Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities

Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities Kishore N Gujjar, Chethan Prathap K N, Hema D, Udaya Kumar A H, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8925377/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract In this study, we have synthesised a novel coumarin derivative via a nucleophilic substitution reaction between 7-amino-4-(trifluoromethyl)coumarin and acyl chlorides. The compound was characterised by NMR (1H and 13C) and FTIR spectroscopy, with structures validated by single-crystal X-ray diffraction. The compound crystallised in the monoclinic crystal system, space group P21/c. Crystal structure and Hirshfeld surface analyses revealed intermolecular C–H···O and N–H···O hydrogen bonds that stabilise the crystal structure, forming \(\:{R}_{2}^{1}\) (6) and \(\:{R}_{2}^{1}\) (7) supramolecular synthons. The geometrical coordinates of the compound was optimised using density functional theory (B3LYP/6-311 + G(d,p)), and, based on the optimised structure, various electronic properties were evaluated. The natural bond orbital (NBO) and quantum theory of atoms in molecule (QTAIM) analyses provided in-depth insights into the interactions exhibited by the compound. Molecular docking studies with protein [PDB:1AE1] demonstrated that the molecule exhibited strong binding affinity, highlighting its potential as an antibacterial agent. ADMET analysis revealed that drug can be orally active. The potential antibacterial activity of the synthesised compound was tested in vitro against 4 selected bacterial strains: Staphylococcus aureus (Gram-positive) and Bacillus subtilis (Gram-positive), and Escherichia coli and Klebsiella pneumonia (Gram-negative). The coumarin derivative showed potential antibacterial activity against the tested bacterial species. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 1. Introduction Coumarin derivatives are an important group of phytochemicals and belong to the benzopyrone family [ 1 ]. There are currently over 1,300 known naturally occurring coumarin derivatives from various plants, bacteria, and fungi [ 2 ]. Over the years, several coumarin derivatives have been synthesised due to their diverse biological functions [ 3 ]. Coumarins have a broad range of pharmacological activities [ 4 ], including anti-clotting [ 5 ], anti-tumour [ 6 ], antipyretic [ 7 ], anti-proliferative [ 8 ], anti-hyperglycaemic [ 9 ], anticoagulant [ 10 ], and analgesic [ 11 ]. Many coumarins exhibit potent antioxidant properties, enabling them to shield cells from oxidative stress and reduce the risk of chronic diseases [ 12 ]. Coumarin derivatives have potential cytotoxic and anticancer properties [ 13 ]. Coumarin base antimicrobial agents are the most potent weapons in the fight against bacterial infections [ 14 ]. Structural modifications of coumarin derivatives lead to molecular templates for a novel drug. Further, the presence of an amide group contributes promising antibacterial properties. Hence, by coupling them with coumarin derivatives, we can enhance their antimicrobial efficacy. This strategy leverages the potential synergistic effects of combining two distinct bioactive moieties within a single molecular framework [ 15 ]. Prompted by these intriguing findings, we have synthesised novel coumarin derivative 4-fluoro-N-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl) benzamide . The synthesised compound was characterised by NMR and FTIR spectroscopy, and their structures were confirmed by single-crystal X-ray diffraction analysis. Hirshfeld surface and energy framework analysis were employed to analyse the crystal structure and intermolecular interactions. DFT calculations were performed to obtain the optimised geometries of the compound, which were used to elucidate the FMOs and MEPs of the molecule. HOMO-LUMO energy values and energy gap are used to determine the Global reactivity parameter. NBO analysis was carried out to obtain information on intramolecular charge transfer via hyperconjugative interactions. QTAIM- and RDG-based NCI isosurface studies have been carried out to investigate short- to long-range interactions between non-bonded atoms. Molecular docking has also been performed against the protein tropinone reductase-I complex with NADP (PDB: 1AE1) to examine the synthesised compound's antibacterial activity. ADMET studies were carried out to predict the pharmacological properties of the synthesised compound. 2. Experimental section 2.1 Instrumentation and Chemicals The chemicals used for the synthesis of the coumarin derivatives were purchased from Sigma-Aldrich and used without further purification. The 1 H and 13 C NMR spectra were recorded on a BUKER 400MHz Bruker spectrometer. Chemical shifts are measured in parts per million (ppm) compared to TMS. Using Perkin Elmer 100 FT-IR, the FTIR spectrum of the compound was recorded. 2.2 Synthesis 7-Amino-4-(trifluoromethyl)-2H-chromene-2-one, upon reaction with acyl chloride via nucleophilic substitution, yielded the compound (Scheme 1 ). Equimolar amounts (5 mmol) of the reactants were stirred in 30 ml of absolute ethanol, followed by refluxing at 80°C for 8 hr. To monitor the reaction progress, thin-layer chromatography was performed on precoated silica on aluminium plates. Then the obtained precipitate is filtered, dried, and kept for slow evaporation in dimethylformamide, which forms block-shaped, light-yellow crystals. 2.2.1. Synthesis of 4-fluoro- N -(2-oxo-4-(trifluoro methyl) -2 H -chromen-7-yl) benzamide A solid compound with a yield of 91.5% was formed by reacting 7-amino-4-(trifluoromethyl)-2H- chromene-2-one (0.25 g, 1.081mmol), 4-fluoro benzoyl chloride (0.171 g, 1.081 mmol) and pyridine (0.2565 g, 3.243 mmol). The obtained product was crystallised from dimethylformamide, yielding light-yellow crystals. 1 H NMR (DMSO- d 6 , 400 MHz) δ: 10.772 (s, 1H, -CO-NH), 8.02 (m, 3H, Ar-H), 7.77 (dd, 1H, Ar-H), 7.66 (dd, 1H, Ar-H), 7.33 (m, 2H, Ar-H), 6.86 (s, 1H, Coumarin-H). 13 C NMR (DMSO- d 6 , 100.6 MHz) δ: 109.93, 109.10, 115.05, 115.89, 116.11, 117.47, 120.69, 125.74, 130.93, 131.09, 131.18, 143.80, 154.95, 159.21, 165.81, 166.09. IR (KBr, cm − 1 ): 3372.94, 1708.12, 1581.86, 1138.20. 2.3 X-ray diffraction studies Defect-free, good-quality crystals were selected for single-crystal X-ray diffraction studies. A Rigaku XtaLAB mini diffractometer operating at 293 K with MoKα radiation (wavelength 0.71073 Å) was used to obtain the diffraction data. The X-ray intensity data were collected with samples at a distance of 50 mm from the detector, with an exposure time of 3 seconds and a scan width of 0.5 \(\:^\circ\:\) [ 16 ]. The intensity data were processed using Crystal Clear software [ 17 ]. The crystal structure of the molecule was determined using SHELX [ 18 ] as implemented in Olex2 [ 19 ], using the direct method and full-matrix least-squares on F 2 [ 20 ]. PLATON [ 21 ] was used for geometric computations, and MERCURY [ 22 ] was employed to visualise the structure. Table 1 contains information on the refinement and structure parameters. Table 1 Summary of crystal data and structure refinement of novel compound. CCDC deposit No. 2331338 Empirical Formula C17H9F4NO3 Formula weight 351.25 Wavelength (Å) 0.71073 Crystal system, space group Monoclinic, P 2 1 / c Unit cell dimensions a (Å) b (Å) c (Å) β (º) 7.063(9) 23.139(3) 9.254(11) 105.216(13) Volume Å 3 1459.5(3) Z 4 Density (calculated) in Mg m − 3 1.599 Absorption coefficient (mm − 1 ) 0.973 F 000 712 Crystal size (mm) 0.28 x 0.26 x 0.24 θ range for data collection 1.8º to 28.2º Index ranges −9 ≤ h ≤ 8; −30 ≤ k ≤ 27; −12 ≤ l ≤ 11 Reflections collected 11475 Independent reflections 3367 [ R int = 0.0792] Data/restraints/parameters 2313 / 0 / 227 Goodness-of-fit on F 2 1.023 Final [ I > 2σ( I) ] R 1 = 0.0593 w R 2 = 0.1558 R indices (all data) R 1 = 0.0791, w R 2 = 0.1751 Largest diff. peak and hole 0.251 and − 0.241 e Å 3 2.4 Hirshfeld surface analysis Hirshfeld surface (HS) analysis is an effective way to explore the characteristics of intermolecular interactions within a crystal structure through fingerprint plots [ 23 ]. The crystal structure obtained from single-crystal X-ray diffraction was used as input for HS analysis. The normalised contact distance dnorm enables the identification of regions that play a vital role in intermolecular interactions. On the d norm -mapped Hirshfeld surface, the red and blue regions denote shorter and longer contacts, respectively, and the white region represents contacts within the van der Waals radii [ 24 , 25 ]. The normalised distance d norm is calculated using the distance to the closest external contact ( d e ) and the distance to the closest interior contact ( d i ) from a given point on the HR surface [ 26 ]. Crystal Explorer 21 software is used to accomplish the entire computation [ 27 ]. The energy framework analysis provides details on the types of interactions exhibited by the crystal structure. The overall interaction energy was calculated by generating a molecular cluster around the chosen molecule with a radius of 20.0 Å. The Crystal Explorer 21 program was employed to do the energy framework analysis using the B3LYP/6-311 + G(d,p) functional basis set [ 28 ]. The overall interaction energy is composed of several components, including dispersion, polarisation, repulsion, and electrostatic energy. These energies are colour-coded with red for electrostatic energy, green for dispersive energy, and blue for total interaction energy in the molecular cluster [ 29 ]. 2.5 Computational studies Computational techniques for evaluating electronic structure are widely used to predict and understand the properties of molecular systems [ 30 ]. The GAUSSIAN 16W program package was used to perform the theoretical computations [ 31 ], and the results were visualised using Gauss View 6.0.16. The geometrical coordinates of the compound was optimised using DFT with the hybrid B3LYP functional and the 6-311 + G(d,p) basis set [ 32 , 34 ]. Various chemical reactivity descriptors, which play a significant role in evaluating the physical and chemical properties of the molecule, were calculated from the energies of the highest occupied and lowest unoccupied molecular orbitals [ 35 ]. NBO analysis was carried out using the NBO 3.1 program. [ 36 ]. The MULTIWFN application was employed to study topology and to perform non-covalent interactions (NCI) analysis. The findings were visualised using the VMD 1.9.1 program [ 37 , 38 ]. 2.6 Molecular Docking Studies The synthesised molecule was screened for biological activity using molecular docking to reveal their comprehensive interactions with the protein [ 39 ]. The AutoDock Vina 1.2.0 software was used to conduct molecular docking studies [ 40 ]. The tropinone reductase-I complex with NADP (PDB:1AE1) was collected under code 1AE1 as a protein target from the PDB [ 41 ]. For interaction studies, the molecule with the highest scores from the largest cluster were selected. All images (close and hydrogen-bond interactions) were generated using Discovery Studio Visualizer [ 42 ]. 2.7 Biological evaluation The agar well diffusion method was employed to determine the antibacterial activity of the title compound against the four selected bacterial strains: Staphylococcus aureus (Gram-positive) and Bacillus subtilis (Gram-positive), and Escherichia coli and Klebsiella pneumonia (Gram-negative). A subculture of bacterial strains at a volume of 200 µL, equivalent to 106 CFU/mL, was uniformly spread onto the surface of a petri dish containing 20 mL of nutrient agar using a sterile cotton swab, and wells were punched using a sterile gel borer. On the agar, five wells with a diameter of 7mm each were created for the bacterial strains. The first well was designated as the negative control and loaded with 100 µL of DMSO, to which the sample was dissolved at concentrations of 100 µg/mL, 200 µg/mL, and 300 µg/mL. The second well served as the positive control and contained 100µL of Ampicillin (an antibiotic). The rest of the wells contained 100 µL of the test drug at the above-mentioned concentrations. Subsequently, the plates were incubated at 37°C for 24 hours to promote bacterial growth, after which the zone of inhibition surrounding the wells was measured. The concentration of the positive control used was 0.1 mg/mL. 3. Results and discussions 3.1 Single crystal structure analysis The crystal structure analysis reveals that the coumarin compound crystallise in a monoclinic crystal system and in the P 2 1 /c space group with Z = 4. The ORTEP diagrams with 50% probability are shown in Fig. 1 . The dihedral angles between the coumarin moiety and the terminal benzene rings are 4.82°, indicating slight non-planarity. A torsion angle of -177.5° confirms a -anti-periplanar configuration. The selected bond lengths, bond angles, and torsion angles are summarised in Table 2 . The sigplan score of 0.002 reflects the slight non-planarity of the fluorobenzene ring (C1, C2, C3, C5, C6, C7). The fused coumarin rings (O23, C14, C15, C20, C21, C24) and (C11, C12, C13, C14, C24, C25) have sigplan values of 0.020 and 0.009, with maximum deviations of 0.001(2) Å and 0.004(2) Å for atoms C15 and C11, respectively. The hydrogen bond geometries are shown in Table 3 . The intermolecular interactions C6-H6···O22 and N10-H10···O22 resulted in the formation of \(\:{R}_{2}^{1}\) (6) supramolecular synthons. Whereas, the N10-H10···O22 and C12-H12···O22 interactions resulted in the formation of \(\:{R}_{2}^{1}\) (7) synthons. Further, these hydrogen bonds connect the molecule to form a 1D chain along the b-axis, as shown in Fig. 2 . The molecule possesses one N-H···O and two C-H···O types of intermolecular hydrogen bonds, as well as C-H···O and C-H···F types of intramolecular hydrogen bonds, which contribute to the stability of the molecular structures. The interactions involve C8-O9···Cg1 (centroid of the benzene ring: C1, C2, C3, C5, C6, C7) with O···Cg distance of 3.7022(17) Å and an angle of 72.14(12)° (1- x , 1- y , 1- z ). These O···Cg interactions are illustrated in Fig. 3 Table 2 List of the bond lengths, bond angles, and torsional angles of coumarin derivative, determined by experimental (XRD) and theoretical (DFT) studies. Atoms Bond length (Å) Atoms Bond angles (°) Atoms Torsional angles (°) XRD DFT XRD DFT XRD DFT C1-C2 1.376(3) 1.3888 C3-C2-C1 118.7(2) 118.48 F4-C3-C5-C6 179.8(2) 179.73 O9-C8 1.219(2) 1.2179 C5-C3-C2 122.6(2) 122.41 C8-C7-C5-C6 179.4(2) 178.79 C7-C1 1.397(3) 1.4006 C7-C1-C2 121.0(2) 120.82 C5-C3-C2-C1 0.2(3) 0.26 C8-C7 1.498(3) 1.5004 C11-C12-C13 121.2(2) 120.83 O9-C8-C7-C6 -175.4(2) -154.33 C14-C15 1.443(3) 1.4075 C14-C13-C12 121.1(2) 120.92 C20-C15-C16-F17 -120.0(2) -120.31 C11-C25 1.386(3) 1.3944 C15-C20-C21 121.3(2) 121.73 C14-C13-C12-C11 1.2(3) 0.02 C24-C14 1.400(3) 1.4075 C24-O23-C21 122.4(1) 123.07 C14-C15-C16-F18 -58.3(2) -59.57 N10-C11 1.406(2) 1.4009 C11-N10-C8 128.0(2) 128.73 C16-C15-C20-C21 -177.4(2) -179.99 O23-C21 1.364(2) 1.3643 O23-C24-C14 120.9(2) 121.57 C24-C14-C13-C12 -0.0(3) -0.03 F4-C3 1.352(2) 1.3502 N10-C11-C25 123.7(2) 123.47 O23-C24-C25-C11 -177.3(2) -179.95 F19-C16 1.331(2) 1.3438 F4-C3-C2 119.1(2) 118.86 O22-C21-C20-C15 174.4(2) 179.97 Correlation coefficient 0.9817 Correlation coefficient 0.9900 Correlation coefficient 0.9988 Table 3 . Information on hydrogen bond interactions exhibited by the coumarin derivative. N10-H10 \(\:\cdots\:\) O22 0.86 2.22 3.046 (2) 160 x, y, -1 + z C1-H1 \(\:\cdots\:\) O9 0.93 2.41 2.770 (2) 168 Intra C6-H6 \(\:\cdots\:\) O22 0.93 2.42 3.327(3) 100 x, y, -1 + z C12-H12 \(\:\cdots\:\) O22 0.93 2.36 3.186(2) 147 x, y, -1 + z C13-H13 \(\:\cdots\:\) F17 0.93 2.55 3.049(2) 116 Intra C20-H20 \(\:\cdots\:\) F19 0.93 2.31 2.677(3) 103 Intra C25-H25 \(\:\cdots\:\) O9 0.93 2.23 2.829(2) 121 Intra Figure 3 O … Cg interactions of the coumarin derivative. 3.2 Non-covalent interaction analysis 3.2.1 Hirshfeld surface and interaction energy analysis To explore and visualise the intermolecular interactions of the coumarin derivative, HS studies were performed, and surfaces were mapped over the dnorm range (-0.3885 to 1.5014). Two slightly dim red spots indicate the C6 \(\:-\) H6 \(\:\cdots\:\) O22 and C12 \(\:-\) H12 \(\:\cdots\:\) O22 interaction, which leads to the formation of \(\:{R}_{2}^{1}\left(6\right)\) and \(\:{R}_{2}^{1}\left(7\right)\) supramolecular synthon. A comparative bar graph and 2D fingerprint plot to visualise the role of several intermolecular interactions that depend on the chemical environment of donor and acceptor molecule of coumarin derivative are shown in Fig. 4 . H \(\:\cdots\:\) F interactions ( 22.5%) is found to be the highest contributors to the total Hirshfeld surface and H \(\:\cdots\:\) H interaction (15.1%) are found to be the second highest contribution to the surface. The O \(\:\cdots\:\) H intermolecular interactions for molecule (15.6%) is also one of the major contributors to the total Hirshfeld surface due to the presence of N \(\:-\) H \(\:\cdots\:\) O and C \(\:-\) H \(\:\cdots\:\) O hydrogen bonds (H \(\:\cdots\:\) O distance: 2.22 Å -2.42 Å). An energy framework (Table 4 and Fig. 5 ) was used to examine the intermolecular interactions in the coumarin derivative crystal. The interaction energies were obtained with scale factors (k ele = 1.057, k pol = 0.740, k dis = 0.871, k rep = 0.618), which were used to calculate the electrostatic (E ele ), polarization (E po l), dispersion (E dis ), and repulsion (E rep ) components. The maximum interaction energy was observed at R = 3.87 Å with an interaction energy of -76.15 kJ mol⁻¹. The total interaction energy of the molecular cluster is -224.73 kJ mol⁻¹. The major contribution to the interaction energy comes from dispersion forces, which are − 200.24 kJ mol⁻¹. The electrostatic force also supports the packing of the crystal, with an energy of -91.74 kJ mol⁻¹. Table 4 : Molecular interaction energies (conversion factors k ele = 1.057, k pol = 0.740, k dis = 0.871, k rep = 0.618) of the cluster of molecule of coumarin derivative. 3.3 Computational studies 3.3.1. HOMO-LUMO analysis Analysis of the frontier molecular orbitals plays a significant role in understanding chemical reactions and the electric and optical characteristics of molecule. The electron-donor and electron receptor modes of the molecule are represented by the E HOMO and E LUMO , respectively. The most important indicator of the stability of the molecule is the energy gap between HOMO and LUMO. Molecule with higher band-gap energies are more stable, less reactive, and chemically harder. The frontier molecular orbitals of the molecule were calculated with the 6-311 + G(d,p) basic set using DFT-B3LYP [ 43 ]. The molecular orbitals distribution with the HOMO-LUMO energy gap for the compound is shown in Fig. 6 . The energy gap between the HOMO and LUMO levels of the compound is 4.0529 eV. Compound with smaller energy gaps are referred to as soft molecule and are highly reactive. The lobes of HOMO display charge density localised around the coumarin moiety, and those of LUMO are positioned over the fluoride benzene rings. Calculated energies of HOMO and LUMO, energy band gap, and the global chemical reactivity descriptors for the compound are tabulated in Table 5 . A negative chemical potential indicates that the synthesised molecule are stable. Table 5 Calculated frontier molecular orbitals energy values and quantum molecular descriptors of coumarin derivative. E HOMO -6.8654 E LUMO -2.8126 Energy gap (eV) 4.0529 Ionisation potential (I) 6.8654 Electron affinity (A) 2.8126 Electronegativity (χ) 4.8390 Chemical potential(µ) -4.8390 Global hardness (η) 2.0264 Global softness (σ) 0.4935 Electrophilicity (ω) 5.7776 3.3.2 Molecular Electrostatic Potential Surface Analysis The MEP surface represents the charge distribution on the molecular surface. The MEP plot is a crucial chemical descriptor that provides information on a molecule's electrophilic and nucleophilic sites using distinct colour codes: green denotes regions of zero potential, blue indicates regions of most nucleophilic reactivity, and red indicates regions of most electrophilic reactivity [ 44 , 45 ]. MEP of the synthesised molecule was plotted for an order of -0.07548 a.u. to 0.07548 a.u using the DFT/6-311 + G(d,P) (Fig. 7 ), nucleophilic reactive place is spread over the coumarin moiety, and the electrophilic reactive place focuses on hydrogens of carbon atoms with fluorine atoms. 3.3.3 Perturbation theory energy analysis: Donor acceptor interactions The NBO analysis provides a useful way to examine the chemical properties of bonding, as well as attributes such as basicity, stability, reactivity, and intra- and intermolecular charge transfer [ 46 ]. The NBO method, represented by the stabilisation energy E(2), provides insight into the interaction between empty orbitals that act as acceptors and filled orbitals that act as donors. The NBO 3.1 program [ 47 , 48 ], included with the Gaussian16W software, has been used for NBO calculations. where \(\:{F}_{ij}\) is the diagonal natural bonding orbital Fock matrix element, \(\:{E}_{i}\wedge\:{E}_{j}\) are diagonal elements, \(\:{q}_{i}is\) the donor orbital occupancy. The NBO analysis results are listed in Table 6 . The hyperconjugative interactions due to the orbital overlap σ (C2-H2) over antibonding σ*(C25-H25), π* (C7- C6), σ*(C15-C16), σ*(C21-C20) and σ*(C15-C20) with stabilization energy of 3466.39, 695.4,311.33, 246,25 and 200.9 kcal/mol respectively. σ (C1-C2) bond as donor and σ*(C25-H25), σ*(C7-C6) antibonding as accepter participates in charge transfer with stabilisation energy 644.78 and 169.38 kcal/mol, respectively. The other important interactions involve the interactions of σ (C3-C2) with σ*(C25-H25), σ* (C7-C6), and σ*(C15-C16), which participate in charge transfer with stabilisation energies of 630.03, 167.9, and 148.43 kcal/mol, respectively. Table 6 Second-order perturbation theory analysis of Fock matrix in NBO basis for coumarin derivative. \(\:\sigma\:\) C2-H2 1.97701 \(\:\sigma\:\) * C 25- H25 0.01373 3466.39 0.11 0.546 \(\:\sigma\:\) C2-H2 1.97701 \(\:\pi\:\) * C7-C6 0.38325 695.4 0.17 0.334 \(\:\sigma\:\) C1-C2 1.97434 \(\:\sigma\:\) * C25- H25 0.01373 644.78 0.36 0.434 \(\:\sigma\:\) C3-C2 1.98085 \(\:\sigma\:\) * C25-H25 0.01373 630.03 0.38 0.440 \(\:\sigma\:\) C2-H2 1.97701 \(\:\sigma\:\) * C15- C16 0.0588 311.33 0.54 0.370 \(\:\sigma\:\) C2-H2 1.97701 \(\:\sigma\:\) * C2-C20 0.05669 246.25 0.64 0.358 \(\:\sigma\:\) C2-H2 1.97701 \(\:\sigma\:\) * C15-C20 0.01741 200.9 0.74 0.345 \(\:\sigma\:\) C1-C2 1.97434 \(\:\pi\:\) * C7-C6 0.38325 169.38 0.42 0.263 \(\:\sigma\:\) C3-C2 1.98085 \(\:\pi\:\) * C7-C6 0.38325 167.9 0.44 0.269 \(\:\sigma\:\) C3-C2 1.98085 \(\:\sigma\:\) * C15-C16 0.0588 148.43 0.82 0.315 a E(2) energy of hyper-conjugative interactions. b Energy difference between donor and acceptor i and j NBO orbitals. c F(i,j) Fock matrix element between i and j NBO orbitals. 3.3.4 QTAIM analysis Quantum theory of atoms in molecule provides insight into the nature of bonds in molecule via bond critical paths. The software Multiwfn 3.7. was used to perform QTAIM computations to examine the nature and strength of the hydrogen bonds in the synthesised molecule[ 49 ]. Molecule are stabilised through intramolecular interactions, which are seen in the Bond Critical Paths (BCP) between the attractors (atoms). The wavefunction characteristics (energy density and the Laplacian of the electron density at the BCP) are considered along with binding energies (BE). The formula for estimating the binding energy (BE) of an H-bond based on the electron density at BCP is given by BE ≈ − 223.08 × 𝜌(r) + 0.7423. ∇ 2 ρ BCP < 0, H BCP 0, H BCP 0, H BCP > 0 associated with weak hydrogen bond interactions and electrostatic in nature. Interaction energy was another method to determine the strength of hydrogen bonds [ 50 ]. Considering these factors, for the synthesised compound, interactions H1...O9, H13...F17, and H20...F19 are all weak hydrogen bonds and electrostatic in nature. The interaction energy computed at BCP indicates that H1...O9 exhibit more binding energy with energy values − 11.388 kJ/mol. A molecular graph indicating the presence of the BCPs is depicted in Fig. 8 . Table 6 Topological characteristics of interacting atoms in coumarin derivative. Interactions \(\:\rho\:\left(r\right)\) (a.u) \(\:{\nabla\:}^{2}\rho\:\left(r\right)\) (a.u) G(r) (a.u) H(r) (a.u) V(r) (a.u) E int kJ/mol C1–H1..O9 0.01554 0.06526 0.01329 0.00302 -0.01027 -11.388 C13–H13..F17 0.00747 0.03428 0.00695 0.001622 -0.00532 -3.863 C20–H20..F19 0.00745 0.03419 0.00693 0.001621 -0.00530 -3.844 Electron density \(\:(\rho\:\) ), Laplacian of electron density \(\:{\nabla\:}^{2}\rho\:\left(r\right)\) , electron kinetic energy density, G(r) total electron energy density H(r), electron potential energy density V(r), and estimated interaction energy ( E int ). 3.3.5. Reduced density gradient (RDG) RDG is one of the most widely used methods available to investigate non-covalent interactions. There are several spikes in the scatter density plot. By using an RDG isosurface to enclose their real space, the interaction position can be identified. The blue region in the isosurface represents the steric effect, the green region denotes Van der Waals interactions, and the blue regions signify strong, attractive interactions. These interactions rely on the electron density attribute. VMD (Visual Molecular Dynamics) was used to visualise the computations, which were performed with Multiwfn [ 51 ]. Green cloud iso surfaces between C1–H1...O9, C13–H13...F17, C20–H20...F19 indicate the presence of weak hydrogen bonds, and in addition, various interactions that were not evident in the AIM analysis were disclosed by the isosurface diagram. This includes spaces that are green between C25–H25...O9, N10–H10...H6, and C20–H20...F18, confirming the presence of electrostatic interactions and van der Waals interactions. The fluoride group forms weak dispersive dihydrogen (H…H) interactions with the H6 (–CH) and H10 (–NH) atoms of the coumarin moiety, as also evident from the NCI isosurface. Moreover, red spots appear at the middle of aromatic rings, indicating the effect of steric repulsion. NCI-RDG findings supported by HSA and x-ray diffraction analysis. Figure 9 depicts the NCI-RDG scatter map and interaction types for the compound. 3.4 Biological activities Antibacterial activity of synthesised molecule was tested against four reference strains: S. aureus, B. subtilis, E. Coli, and K. pneumoniae. Experimental data are reported in Table 7 . Inhibition zone results indicate that the title compound exhibit strong to moderate antibacterial activity against all tested bacterial strains. Ampicillin (0.5mg/mL) was used as the standard. The molecule exhibited good antibacterial activity against the four tested strains, especially S. B. Subtilis, which is nearly as effective as Ampicillin against the same strain. Table 7 Showing zone of inhibition of coumarin derivative against tested organisms Concentration in µg/mL Zone of inhibition measured in mm Staphylococcus aureus Bacillus subtilis Escherichia coli Klebsiella pneumonia 100 11.4 10.5 12.3 12.3 200 12 11.4 13.3 13.7 300 12.6 12.4 15.8 14.6 Ampicillin 18.8 22.4 18.6 21.4 3.5 Molecular docking Molecular docking is an essential technique used to investigate the binding affinity of compound with the target protein. The protein tropinone reductase-I complex with NADP (PDB:1AE1) has shown efficacy against various bacterial pathogens, such as Staphylococcus aureus and Escherichia coli, and was chosen to investigate the antibacterial properties of the ligand. [ 52 ]. Docking studies showed that the binding component of the molecule interacts with the active site of tropinone reductase-I with NADP, and that the molecule interacts with the active site through five hydrogen bonds. showed a good binding affinity with protein scoring − 9.9 kcal/mol. Ligand and protein interaction through different amino residues of THR206, GLY202, TYR171, ILE33, LEU208, GLY108, GLY34, LYS31, ALA107, and ILE204. The trifluoromethyl group interact with amino acid residues THR206 and ILE204 through hydrogen bonds with a distance of 2.712 Å and 2.53 Å, respectively. TYR171 shows interaction with the oxygen of the benzoyl group, and ILE33, LEU208, and the residue interact with the benzene ring of the coumarin moiety at distances of 2.45 Å, 3.96 Å, and 3.46 Å, respectively. GLY108 and GLY34 interact with the hydrogen and oxygen atoms of the amide bond. Figure 10 shows the docking pose and the associated ligand and two-dimensional interaction of the 1AE1 protein for the molecule. 3.6 ADMET parameters and toxicity studies ADMET properties were predicted to evaluate the physicochemical and pharmacokinetic features of the synthesised molecule. These evaluations play a vital role in the utilisation of the molecule as a drug [ 53 ]. The ADMET parameters have been evaluated using pkCSM and the SwissADME online tool; both tools provide highly accurate value predictions [ 54 , 55 ]. The six physicochemical parameters, lipophilicity (LIPO), size (SIZE), polarity (POLAR), flexibility (FLEX), insolubility (INSOLU), and insaturation (INSATU) are taken into account by the bioavailability radar to evaluate drug-likeness and ADMET profiling shown in Fig. 11 . The predicted result indicated that the molecule has a good solubility potential in water (-4.158 log mol/L) and high gastrointestinal absorption (90.99%), which would make it more appropriate for oral use. Compound are capable of inhibiting cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C19, CYP2C9), indicating that it hinders the body from metabolising xenobiotics. Log BB values of 0.003 and log PS values of -1.708 revealed that the molecule have better blood-brain barrier (BBB) and central nervous system (CNS) penetration. The Physicochemical and Pharmacokinetics parameters of coumarin derivates are shown in Table 8 . These findings demonstrate that the molecule exhibits strong ADMET properties, which are vital for drug-like behaviour. After applying Lipinski's filters and based on the anticipated pharmacokinetic characteristics, the compound possess favourable drug-like properties and could be potential drug candidates for further studies. Table 8 Physicochemical and pharmacokinetic parameters of coumarin derivatives using SWISSADME and pkCSM tools. HBD: Number of hydrogen bond donor, HBA: Number of hydrogen bond acceptor Physicochemical parameters Values Molecular weight (MW < 500) 351.25 g/mol HBA (HBA < 10) 7 HBD (HBD < 5) 1 Rotatable bond count 4 PSA 59.31 Å 2 Molar Refractivity 81.66 Lipinski’s rule of five followed, violation Yes ,0 Pharmacokinetics Absorption Water solubility -4.158 Caco2 permeability 1.418 Intestinal absorption (human) 90.995 Skin Permeability -2.755 P-glycoprotein substrate Yes P-glycoprotein I inhibitor Yes P-glycoprotein II inhibitor Yes Distribution VDss (human) -0.236 Fraction unbound (human) 0.125 BBB permeability 0.003 CNS permeability -1.708 Metabolism CYP2D6 substrate No CYPA4 substrate Yes CYP1A2 inhibitior Yes CYP2C19 inhibitior Yes CYP2C9 inhibitior Yes CYP2D6 inhibitior No CYPA4 inhibitior Yes Excretion Total Clearance 0.347 Renal OCT2 substrate No Toxicity AMES toxicity Yes Max. tolerated dose (human) 0.17 hERG I inhibitor No hERG II inhibitor Yes Oral Rat Acute Toxicity (LD50) 2.842 Oral Rat Chronic Toxicity (LOAEL) 1.577 Hepatotoxicity Yes Skin Sensitisation No T. Pyriformis toxicity 0.833 Minnow toxicity 0.075 5. Conclusion In the present paper, a novel 7-amino-4-(trifluoromethyl)-2H-chromene-2-one derivative was synthesised and characterised by 1H and 13C NMR and FTIR spectroscopy to confirm the product formation and the presence of important functional groups. Structural analysis revealed that the compound crystallises in the P2 1 /c space group, Hirshfeld surface analysis showed that H…F and H…H interactions contribute to about 40% of total interactions and play a significant role in stabilising the crystal and formation of \(\:{R}_{2}^{1}\) (6), \(\:{R}_{2}^{1}\) (7) supramolecular synthons. Interaction energies show that the C-H⋯O hydrogen bond plays a very important role in the highest interaction energy. Geometrical optimisation molecule was performed. Geometrical parameters showed strong agreement with single-crystal XRD results. HOMO, LUMO, and energy gaps between them were examined. AIM calculations reveal that the title molecule exhibits weak hydrogen bonds and electrostatic interactions. The molecular docking analysis revealed that the coumarin derivative showed strong interactions with protein 1AE1, with a binding affinity of -9.9 kcal/mol. ADMET analysis showed that the coumarin derivative is orally active, with good intestinal absorption and permeability. The title compound exhibited strong antibacterial activity compared with the standard antibiotic used in this study. Declarations Funding “The authors recived no financial support for the research, authorship, and/or publication of this article.” Author Contribution Kishore- Dtata analysis, Manuscrpit writing.Hema - Synthesis. Data analysis, Editing, software engagement.Uday- Characterisation.Lokanath N K-Charctersiation facility.Vinay- ProofreadingNarasimha -Biological activitiesHanumanthappa- Biological activities Chethan Prathap- Data analysis, Proofreading. 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J Med Chem 58(9):4066–4072 Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(1):42717 Scheme 1 Scheme 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Scheme 1: Synthesis of the novel 7-amino-4-(trifluoromethyl)-2H-chromene-2-one benzamide derivative. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 May, 2026 Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviewers invited by journal 19 Mar, 2026 Editor assigned by journal 24 Feb, 2026 Submission checks completed at journal 24 Feb, 2026 First submitted to journal 20 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8925377","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":609890269,"identity":"d8f849d5-c073-467b-adbd-be765fdff8d2","order_by":0,"name":"Kishore N Gujjar","email":"","orcid":"","institution":"Department of Physics, University College of Science, Tumkur University","correspondingAuthor":false,"prefix":"","firstName":"Kishore","middleName":"N","lastName":"Gujjar","suffix":""},{"id":609890270,"identity":"fc9e5889-e029-4e1c-ac23-2765c9582345","order_by":1,"name":"Chethan Prathap K 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2","display":"","copyAsset":false,"role":"figure","size":113262,"visible":true,"origin":"","legend":"\u003cp\u003eFormation of a hydrogen bond-mediated 1D chain along the b axis and supramolecular structure with R½(6) R½(7) ring motif.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/848dd418a1b16d73a361e1ff.png"},{"id":105564827,"identity":"f5ea49d5-ae24-4d86-8cd1-ba9229c530df","added_by":"auto","created_at":"2026-03-27 12:50:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":104812,"visible":true,"origin":"","legend":"\u003cp\u003eO … Cg interactions of the coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/e5614ac5f19c82c45caaa451.png"},{"id":105289744,"identity":"5528b29c-a1f8-4c5b-9c3c-388d13c8d8b2","added_by":"auto","created_at":"2026-03-24 11:59:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":368578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ed\u003c/em\u003e\u003csub\u003enorm \u003c/sub\u003esurface map and fingerprint plot depicting different interactions of coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/272278f1b27c045b72cb5954.png"},{"id":105289745,"identity":"578c13ac-78f7-4675-b4b7-f6f92c38f948","added_by":"auto","created_at":"2026-03-24 11:59:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":241903,"visible":true,"origin":"","legend":"\u003cp\u003eThe graphical visualisation of the energy framework of the coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/cb5fab5d145e55bf0a8ef61b.png"},{"id":105565332,"identity":"b7030330-7784-4dc8-a52f-7ed6ab649c22","added_by":"auto","created_at":"2026-03-27 12:52:56","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":141192,"visible":true,"origin":"","legend":"\u003cp\u003eFrontier molecular orbitals distribution on coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/bed013a57d0b36b13f615f43.png"},{"id":105289747,"identity":"6e3a8356-d298-4f3a-8857-2e0f1bb7e6f4","added_by":"auto","created_at":"2026-03-24 11:59:21","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":48527,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular electrostatic potential map of coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/fcd259939efcc2b625f88e02.png"},{"id":105289746,"identity":"73375108-529a-4a08-845b-0421f5762df3","added_by":"auto","created_at":"2026-03-24 11:59:21","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":53420,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular graph indicating the presence of the BCPs of coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/ecf5ecab66a21b3094f39062.png"},{"id":105564870,"identity":"27cee9f8-c9b3-4785-a25d-ad7507d23ce7","added_by":"auto","created_at":"2026-03-27 12:51:09","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":92311,"visible":true,"origin":"","legend":"\u003cp\u003eNCI - RDG scatter map and interactiontypes in coumarin.\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/1c44829a94a684ffa27877d9.png"},{"id":105289751,"identity":"0badb489-71d6-4776-abaa-b3f68f1650b2","added_by":"auto","created_at":"2026-03-24 11:59:22","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":278391,"visible":true,"origin":"","legend":"\u003cp\u003eDocking pose and the associated ligand and two-dimensional interaction of the 1AE1 and protein for coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/71586d8097512b536d404ea1.png"},{"id":105903897,"identity":"3681c5ce-af1a-40f9-94f5-df4d056c17e1","added_by":"auto","created_at":"2026-04-01 09:57:09","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":51007,"visible":true,"origin":"","legend":"\u003cp\u003eBioavailability radar for coumarin coumarin derivative.\u003c/p\u003e","description":"","filename":"floatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/147872c93f0e0fbb815dfa55.png"},{"id":105906327,"identity":"518b00cd-7ff6-4e7f-b8c9-9d0c3a89e82f","added_by":"auto","created_at":"2026-04-01 10:19:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3141254,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/c725e631-5982-4d10-818c-ba6d7d3365c2.pdf"},{"id":105289741,"identity":"1bd2ed32-600f-4d29-bf7a-cb36bbe2c80f","added_by":"auto","created_at":"2026-03-24 11:59:21","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":31453,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1:\u003c/strong\u003e Synthesis of the novel 7-amino-4-(trifluoromethyl)-2H-chromene-2-one benzamide derivative.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8925377/v1/2a73bb1294c3df65b23cde6f.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCoumarin derivatives are an important group of phytochemicals and belong to the benzopyrone family [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There are currently over 1,300 known naturally occurring coumarin derivatives from various plants, bacteria, and fungi [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Over the years, several coumarin derivatives have been synthesised due to their diverse biological functions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Coumarins have a broad range of pharmacological activities [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], including anti-clotting [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], anti-tumour [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], antipyretic [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], anti-proliferative [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], anti-hyperglycaemic [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], anticoagulant [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and analgesic [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Many coumarins exhibit potent antioxidant properties, enabling them to shield cells from oxidative stress and reduce the risk of chronic diseases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Coumarin derivatives have potential cytotoxic and anticancer properties [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Coumarin base antimicrobial agents are the most potent weapons in the fight against bacterial infections [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Structural modifications of coumarin derivatives lead to molecular templates for a novel drug. Further, the presence of an amide group contributes promising antibacterial properties. Hence, by coupling them with coumarin derivatives, we can enhance their antimicrobial efficacy. This strategy leverages the potential synergistic effects of combining two distinct bioactive moieties within a single molecular framework [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Prompted by these intriguing findings, we have synthesised novel coumarin derivative 4-fluoro-N-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)\u003cem\u003ebenzamide\u003c/em\u003e. The synthesised compound was characterised by NMR and FTIR spectroscopy, and their structures were confirmed by single-crystal X-ray diffraction analysis. Hirshfeld surface and energy framework analysis were employed to analyse the crystal structure and intermolecular interactions. DFT calculations were performed to obtain the optimised geometries of the compound, which were used to elucidate the FMOs and MEPs of the molecule. HOMO-LUMO energy values and energy gap are used to determine the Global reactivity parameter. NBO analysis was carried out to obtain information on intramolecular charge transfer via hyperconjugative interactions. QTAIM- and RDG-based NCI isosurface studies have been carried out to investigate short- to long-range interactions between non-bonded atoms. Molecular docking has also been performed against the protein tropinone reductase-I complex with NADP (PDB: 1AE1) to examine the synthesised compound's antibacterial activity. ADMET studies were carried out to predict the pharmacological properties of the synthesised compound.\u003c/p\u003e"},{"header":"2. Experimental section","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Instrumentation and Chemicals\u003c/h2\u003e \u003cp\u003eThe chemicals used for the synthesis of the coumarin derivatives were purchased from Sigma-Aldrich and used without further purification. The \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra were recorded on a BUKER 400MHz Bruker spectrometer. Chemical shifts are measured in parts per million (ppm) compared to TMS. Using Perkin Elmer 100 FT-IR, the FTIR spectrum of the compound was recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Synthesis\u003c/h2\u003e \u003cp\u003e7-Amino-4-(trifluoromethyl)-2H-chromene-2-one, upon reaction with acyl chloride via nucleophilic substitution, yielded the compound (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Equimolar amounts (5 mmol) of the reactants were stirred in 30 ml of absolute ethanol, followed by refluxing at 80\u0026deg;C for 8 hr. To monitor the reaction progress, thin-layer chromatography was performed on precoated silica on aluminium plates. Then the obtained precipitate is filtered, dried, and kept for slow evaporation in dimethylformamide, which forms block-shaped, light-yellow crystals.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1. Synthesis of 4-fluoro-\u003cem\u003eN\u003c/em\u003e-(2-oxo-4-(trifluoro methyl) -2\u003cem\u003eH\u003c/em\u003e-chromen-7-yl) benzamide\u003c/h2\u003e \u003cp\u003eA solid compound with a yield of 91.5% was formed by reacting 7-amino-4-(trifluoromethyl)-2H- chromene-2-one (0.25 g, 1.081mmol), 4-fluoro benzoyl chloride (0.171 g, 1.081 mmol) and pyridine (0.2565 g, 3.243 mmol). The obtained product was crystallised from dimethylformamide, yielding light-yellow crystals. \u003csup\u003e1\u003c/sup\u003eH NMR (DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sub\u003e, 400 MHz) δ: 10.772 (s, 1H, -CO-NH), 8.02 (m, 3H, Ar-H), 7.77 (dd, 1H, Ar-H), 7.66 (dd, 1H, Ar-H), 7.33 (m, 2H, Ar-H), 6.86 (s, 1H, Coumarin-H). \u003csup\u003e13\u003c/sup\u003eC NMR (DMSO- \u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sub\u003e, 100.6 MHz) δ: 109.93, 109.10, 115.05, 115.89, 116.11, 117.47, 120.69, 125.74, 130.93, 131.09, 131.18, 143.80, 154.95, 159.21, 165.81, 166.09. IR (KBr, cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e): 3372.94, 1708.12, 1581.86, 1138.20.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.3 X-ray diffraction studies\u003c/h2\u003e \u003cp\u003eDefect-free, good-quality crystals were selected for single-crystal X-ray diffraction studies. A Rigaku XtaLAB mini diffractometer operating at 293 K with MoKα radiation (wavelength 0.71073 \u0026Aring;) was used to obtain the diffraction data. The X-ray intensity data were collected with samples at a distance of 50 mm from the detector, with an exposure time of 3 seconds and a scan width of 0.5\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:^\\circ\\:\\)\u003c/span\u003e\u003c/span\u003e [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The intensity data were processed using \u003cem\u003eCrystal Clear software\u003c/em\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The crystal structure of the molecule was determined using \u003cem\u003eSHELX\u003c/em\u003e [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] as implemented in \u003cem\u003eOlex2\u003c/em\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], using the direct method and full-matrix least-squares on \u003cem\u003eF\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. \u003cem\u003ePLATON\u003c/em\u003e [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] was used for geometric computations, and \u003cem\u003eMERCURY\u003c/em\u003e [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] was employed to visualise the structure. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e contains information on the refinement and structure parameters.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of crystal data and structure refinement of novel compound.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCDC deposit No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2331338\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmpirical Formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC17H9F4NO3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormula weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e351.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWavelength (\u0026Aring;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.71073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrystal system, space group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMonoclinic, \u003cem\u003eP\u003c/em\u003e2\u003csub\u003e1\u003c/sub\u003e/\u003cem\u003ec\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnit cell dimensions\u003c/p\u003e \u003cp\u003e\u003cem\u003ea\u003c/em\u003e (\u0026Aring;)\u003c/p\u003e \u003cp\u003e\u003cem\u003eb\u003c/em\u003e (\u0026Aring;)\u003c/p\u003e \u003cp\u003e\u003cem\u003ec\u003c/em\u003e (\u0026Aring;)\u003c/p\u003e \u003cp\u003e\u003cem\u003eβ\u003c/em\u003e (\u0026ordm;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.063(9)\u003c/p\u003e \u003cp\u003e23.139(3)\u003c/p\u003e \u003cp\u003e9.254(11)\u003c/p\u003e \u003cp\u003e105.216(13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume \u0026Aring;\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1459.5(3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDensity (calculated) in Mg m\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsorption coefficient (mm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003csub\u003e000\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e712\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrystal size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.28 x 0.26 x 0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eθ\u003c/em\u003e range for data collection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.8\u0026ordm; to 28.2\u0026ordm;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex ranges\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;9\u0026thinsp;\u0026le;\u0026thinsp;\u003cem\u003eh\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;8; \u0026minus;30\u0026thinsp;\u0026le;\u0026thinsp;\u003cem\u003ek\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;27; \u0026minus;12\u0026thinsp;\u0026le;\u0026thinsp;\u003cem\u003el\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReflections collected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndependent reflections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3367 [\u003cem\u003eR\u003c/em\u003e\u003csub\u003eint\u003c/sub\u003e = 0.0792]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData/restraints/parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2313 / 0 / 227\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGoodness-of-fit on \u003cem\u003eF\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFinal [\u003cem\u003eI\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;2σ(\u003cem\u003eI)\u003c/em\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e1\u0026thinsp;=\u0026thinsp;0.0593\u003c/p\u003e \u003cp\u003ew\u003cem\u003eR\u003c/em\u003e2\u0026thinsp;=\u0026thinsp;0.1558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e indices (all data)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e1\u0026thinsp;=\u0026thinsp;0.0791,\u003c/p\u003e \u003cp\u003ew\u003cem\u003eR\u003c/em\u003e2\u0026thinsp;=\u0026thinsp;0.1751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLargest diff. peak and hole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.251 and \u0026minus;\u0026thinsp;0.241 e \u0026Aring;\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Hirshfeld surface analysis\u003c/h2\u003e \u003cp\u003eHirshfeld surface (HS) analysis is an effective way to explore the characteristics of intermolecular interactions within a crystal structure through fingerprint plots [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The crystal structure obtained from single-crystal X-ray diffraction was used as input for HS analysis. The normalised contact distance dnorm enables the identification of regions that play a vital role in intermolecular interactions. On the \u003cem\u003ed\u003c/em\u003e\u003csub\u003enorm\u003c/sub\u003e-mapped Hirshfeld surface, the red and blue regions denote shorter and longer contacts, respectively, and the white region represents contacts within the van der Waals radii [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The normalised distance \u003cem\u003ed\u003c/em\u003e\u003csub\u003enorm\u003c/sub\u003e is calculated using the distance to the closest external contact (\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003ee\u003c/em\u003e\u003c/sub\u003e) and the distance to the closest interior contact (\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003ei\u003c/em\u003e\u003c/sub\u003e) from a given point on the HR surface [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. \u003cem\u003eCrystal Explorer 21\u003c/em\u003e software is used to accomplish the entire computation [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe energy framework analysis provides details on the types of interactions exhibited by the crystal structure. The overall interaction energy was calculated by generating a molecular cluster around the chosen molecule with a radius of 20.0 \u0026Aring;. The \u003cem\u003eCrystal Explorer 21\u003c/em\u003e program was employed to do the energy framework analysis using the B3LYP/6-311\u0026thinsp;+\u0026thinsp;G(d,p) functional basis set [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The overall interaction energy is composed of several components, including dispersion, polarisation, repulsion, and electrostatic energy. These energies are colour-coded with red for electrostatic energy, green for dispersive energy, and blue for total interaction energy in the molecular cluster [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Computational studies\u003c/h2\u003e \u003cp\u003eComputational techniques for evaluating electronic structure are widely used to predict and understand the properties of molecular systems [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The \u003cem\u003eGAUSSIAN 16W\u003c/em\u003e program package was used to perform the theoretical computations [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], and the results were visualised using \u003cem\u003eGauss View 6.0.16.\u003c/em\u003e The geometrical coordinates of the compound was optimised using DFT with the hybrid B3LYP functional and the 6-311\u0026thinsp;+\u0026thinsp;G(d,p) basis set [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Various chemical reactivity descriptors, which play a significant role in evaluating the physical and chemical properties of the molecule, were calculated from the energies of the highest occupied and lowest unoccupied molecular orbitals [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. NBO analysis was carried out using the \u003cem\u003eNBO 3.1\u003c/em\u003e program. [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The \u003cem\u003eMULTIWFN\u003c/em\u003e application was employed to study topology and to perform non-covalent interactions (NCI) analysis. The findings were visualised using the \u003cem\u003eVMD 1.9.1\u003c/em\u003e program [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Molecular Docking Studies\u003c/h2\u003e \u003cp\u003eThe synthesised molecule was screened for biological activity using molecular docking to reveal their comprehensive interactions with the protein [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. The \u003cem\u003eAutoDock Vina 1.2.0\u003c/em\u003e software was used to conduct molecular docking studies [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The tropinone reductase-I complex with NADP (PDB:1AE1) was collected under code 1AE1 as a protein target from the PDB [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. For interaction studies, the molecule with the highest scores from the largest cluster were selected. All images (close and hydrogen-bond interactions) were generated using \u003cem\u003eDiscovery Studio Visualizer\u003c/em\u003e [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Biological evaluation\u003c/h2\u003e \u003cp\u003eThe agar well diffusion method was employed to determine the antibacterial activity of the title compound against the four selected bacterial strains: Staphylococcus aureus (Gram-positive) and Bacillus subtilis (Gram-positive), and \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumonia\u003c/em\u003e (Gram-negative). A subculture of bacterial strains at a volume of 200 \u0026micro;L, equivalent to 106 CFU/mL, was uniformly spread onto the surface of a petri dish containing 20 mL of nutrient agar using a sterile cotton swab, and wells were punched using a sterile gel borer. On the agar, five wells with a diameter of 7mm each were created for the bacterial strains. The first well was designated as the negative control and loaded with 100 \u0026micro;L of DMSO, to which the sample was dissolved at concentrations of 100 \u0026micro;g/mL, 200 \u0026micro;g/mL, and 300 \u0026micro;g/mL. The second well served as the positive control and contained 100\u0026micro;L of Ampicillin (an antibiotic). The rest of the wells contained 100 \u0026micro;L of the test drug at the above-mentioned concentrations. Subsequently, the plates were incubated at 37\u0026deg;C for 24 hours to promote bacterial growth, after which the zone of inhibition surrounding the wells was measured. The concentration of the positive control used was 0.1 mg/mL.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and discussions","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Single crystal structure analysis\u003c/h2\u003e \u003cp\u003eThe crystal structure analysis reveals that the coumarin compound crystallise in a monoclinic crystal system and in the P\u003cem\u003e2\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e/c\u003c/em\u003e space group with Z\u0026thinsp;=\u0026thinsp;4. The ORTEP diagrams with 50% probability are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The dihedral angles between the coumarin moiety and the terminal benzene rings are 4.82\u0026deg;, indicating slight non-planarity. A torsion angle of -177.5\u0026deg; confirms a -anti-periplanar configuration. The selected bond lengths, bond angles, and torsion angles are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The sigplan score of 0.002 reflects the slight non-planarity of the fluorobenzene ring (C1, C2, C3, C5, C6, C7). The fused coumarin rings (O23, C14, C15, C20, C21, C24) and (C11, C12, C13, C14, C24, C25) have \u003cem\u003esigplan\u003c/em\u003e values of 0.020 and 0.009, with maximum deviations of 0.001(2) \u0026Aring; and 0.004(2) \u0026Aring; for atoms C15 and C11, respectively. The hydrogen bond geometries are shown in \u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e. The intermolecular interactions C6-H6\u0026middot;\u0026middot;\u0026middot;O22 and N10-H10\u0026middot;\u0026middot;\u0026middot;O22 resulted in the formation of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(6) supramolecular synthons. Whereas, the N10-H10\u0026middot;\u0026middot;\u0026middot;O22 and C12-H12\u0026middot;\u0026middot;\u0026middot;O22 interactions resulted in the formation of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(7) synthons. Further, these hydrogen bonds connect the molecule to form a 1D chain along the b-axis, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The molecule possesses one N-H\u0026middot;\u0026middot;\u0026middot;O and two C-H\u0026middot;\u0026middot;\u0026middot;O types of intermolecular hydrogen bonds, as well as C-H\u0026middot;\u0026middot;\u0026middot;O and C-H\u0026middot;\u0026middot;\u0026middot;F types of intramolecular hydrogen bonds, which contribute to the stability of the molecular structures. The interactions involve C8-O9\u0026middot;\u0026middot;\u0026middot;Cg1 (centroid of the benzene ring: C1, C2, C3, C5, C6, C7) with O\u0026middot;\u0026middot;\u0026middot;Cg distance of 3.7022(17) \u0026Aring; and an angle of 72.14(12)\u0026deg; (1-\u003cem\u003ex\u003c/em\u003e, 1-\u003cem\u003ey\u003c/em\u003e, 1-\u003cem\u003ez\u003c/em\u003e). These O\u0026middot;\u0026middot;\u0026middot;Cg interactions are illustrated in \u003cb\u003eFig.\u0026nbsp;3\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of the bond lengths, bond angles, and torsional angles of coumarin derivative, determined by experimental (XRD) and theoretical (DFT) studies.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAtoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBond length (\u0026Aring;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAtoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eBond angles (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAtoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eTorsional angles (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXRD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDFT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eXRD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDFT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eXRD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDFT\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC1-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.376(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3888\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC3-C2-C1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e118.7(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e118.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eF4-C3-C5-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e179.8(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e179.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eO9-C8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.219(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC5-C3-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e122.6(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e122.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC8-C7-C5-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e179.4(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e178.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC7-C1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.397(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC7-C1-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121.0(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e120.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC5-C3-C2-C1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC8-C7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.498(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC11-C12-C13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121.2(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e120.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eO9-C8-C7-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-175.4(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-154.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC14-C15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.443(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC14-C13-C12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121.1(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e120.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC20-C15-C16-F17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-120.0(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-120.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC11-C25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.386(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC15-C20-C21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121.3(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e121.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC14-C13-C12-C11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.2(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC24-C14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.400(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC24-O23-C21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e122.4(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e123.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC14-C15-C16-F18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-58.3(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-59.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN10-C11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.406(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC11-N10-C8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128.0(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e128.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC16-C15-C20-C21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-177.4(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-179.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eO23-C21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.364(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO23-C24-C14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120.9(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e121.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eC24-C14-C13-C12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.0(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4-C3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.352(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3502\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN10-C11-C25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e123.7(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e123.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eO23-C24-C25-C11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-177.3(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-179.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF19-C16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.331(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF4-C3-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e119.1(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e118.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eO22-C21-C20-C15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e174.4(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e179.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCorrelation coefficient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCorrelation coefficient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eCorrelation coefficient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTable 3\u003c/b\u003e. Information on hydrogen bond interactions exhibited by the coumarin derivative.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN10-H10\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO22\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.22\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.046 (2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ex, y, -1\u0026thinsp;+\u0026thinsp;z\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC1-H1\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.770 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC6-H6\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.327(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ex, y, -1\u0026thinsp;+\u0026thinsp;z\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC12-H12\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.186(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ex, y, -1\u0026thinsp;+\u0026thinsp;z\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC13-H13\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eF17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.049(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC20-H20\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eF19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.677(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC25-H25\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.829(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFigure 3\u003c/strong\u003e \u003cp\u003eO \u0026hellip; Cg interactions of the coumarin derivative.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Non-covalent interaction analysis\u003c/h2\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1 Hirshfeld surface and interaction energy analysis\u003c/h2\u003e \u003cp\u003eTo explore and visualise the intermolecular interactions of the coumarin derivative, HS studies were performed, and surfaces were mapped over \u003cem\u003ethe dnorm range\u003c/em\u003e (-0.3885 to 1.5014). Two slightly dim red spots indicate the C6\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:-\\)\u003c/span\u003e\u003c/span\u003eH6\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO22 and C12\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:-\\)\u003c/span\u003e\u003c/span\u003eH12\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO22 interaction, which leads to the formation of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\left(6\\right)\\)\u003c/span\u003e\u003c/span\u003e and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\left(7\\right)\\)\u003c/span\u003e\u003c/span\u003e supramolecular synthon. A comparative bar graph and 2D fingerprint plot to visualise the role of several intermolecular interactions that depend on the chemical environment of donor and acceptor molecule of coumarin derivative are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e. H\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eF interactions ( 22.5%) is found to be the highest contributors to the total Hirshfeld surface and H\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eH interaction (15.1%) are found to be the second highest contribution to the surface. The O\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eH intermolecular interactions for molecule (15.6%) is also one of the major contributors to the total Hirshfeld surface due to the presence of N\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:-\\)\u003c/span\u003e\u003c/span\u003eH\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO and C\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:-\\)\u003c/span\u003e\u003c/span\u003eH\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO hydrogen bonds (H\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\cdots\\:\\)\u003c/span\u003e\u003c/span\u003eO distance: 2.22 \u0026Aring; -2.42 \u0026Aring;). An energy framework (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e) was used to examine the intermolecular interactions in the coumarin derivative crystal. The interaction energies were obtained with scale factors (k\u003csub\u003eele\u003c/sub\u003e = 1.057, k\u003csub\u003epol\u003c/sub\u003e = 0.740, k\u003csub\u003edis\u003c/sub\u003e = 0.871, k\u003csub\u003erep\u003c/sub\u003e = 0.618), which were used to calculate the electrostatic (E\u003csub\u003eele\u003c/sub\u003e), polarization (E\u003csub\u003epo\u003c/sub\u003el), dispersion (E\u003csub\u003edis\u003c/sub\u003e), and repulsion (E\u003csub\u003erep\u003c/sub\u003e) components. The maximum interaction energy was observed at R\u0026thinsp;=\u0026thinsp;3.87 \u0026Aring; with an interaction energy of -76.15 kJ mol⁻\u0026sup1;. The total interaction energy of the molecular cluster is -224.73 kJ mol⁻\u0026sup1;. The major contribution to the interaction energy comes from dispersion forces, which are \u0026minus;\u0026thinsp;200.24 kJ mol⁻\u0026sup1;. The electrostatic force also supports the packing of the crystal, with an energy of -91.74 kJ mol⁻\u0026sup1;.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Molecular interaction energies (conversion factors k\u003csub\u003eele\u0026nbsp;\u003c/sub\u003e= 1.057, k\u003csub\u003epol\u003c/sub\u003e = 0.740, k\u003csub\u003edis\u003c/sub\u003e = 0.871, k\u003csub\u003erep\u003c/sub\u003e = 0.618) of the cluster of molecule of coumarin derivative.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"724\" height=\"186\"\u003e\u003c/p\u003e\n\n \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Computational studies\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1. HOMO-LUMO analysis\u003c/h2\u003e \u003cp\u003eAnalysis of the frontier molecular orbitals plays a significant role in understanding chemical reactions and the electric and optical characteristics of molecule. The electron-donor and electron receptor modes of the molecule are represented by the E\u003csub\u003eHOMO\u003c/sub\u003e and E\u003csub\u003eLUMO\u003c/sub\u003e, respectively. The most important indicator of the stability of the molecule is the energy gap between HOMO and LUMO. Molecule with higher band-gap energies are more stable, less reactive, and chemically harder. The frontier molecular orbitals of the molecule were calculated with the 6-311\u0026thinsp;+\u0026thinsp;G(d,p) basic set using DFT-B3LYP [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The molecular orbitals distribution with the HOMO-LUMO energy gap for the compound is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The energy gap between the HOMO and LUMO levels of the compound is 4.0529 eV. Compound with smaller energy gaps are referred to as soft molecule and are highly reactive. The lobes of HOMO display charge density localised around the coumarin moiety, and those of LUMO are positioned over the fluoride benzene rings. Calculated energies of HOMO and LUMO, energy band gap, and the global chemical reactivity descriptors for the compound are tabulated in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e. A negative chemical potential indicates that the synthesised molecule are stable.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCalculated frontier molecular orbitals energy values and quantum molecular descriptors of coumarin derivative.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE\u003csub\u003eHOMO\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.8654\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE\u003csub\u003eLUMO\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.8126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnergy gap (eV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIonisation potential (I)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.8654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectron affinity (A)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectronegativity (χ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8390\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemical potential(\u0026micro;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.8390\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal hardness (η)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal softness (σ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.4935\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectrophilicity (ω)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7776\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Molecular Electrostatic Potential Surface Analysis\u003c/h2\u003e \u003cp\u003eThe MEP surface represents the charge distribution on the molecular surface. The MEP plot is a crucial chemical descriptor that provides information on a molecule's electrophilic and nucleophilic sites using distinct colour codes: green denotes regions of zero potential, blue indicates regions of most nucleophilic reactivity, and red indicates regions of most electrophilic reactivity [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. MEP of the synthesised molecule was plotted for an order of -0.07548 a.u. to 0.07548 a.u using the DFT/6-311\u0026thinsp;+\u0026thinsp;G(d,P) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e), nucleophilic reactive place is spread over the coumarin moiety, and the electrophilic reactive place focuses on hydrogens of carbon atoms with fluorine atoms.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e3.3.3 Perturbation theory energy analysis: Donor acceptor interactions\u003c/h2\u003e \u003cp\u003eThe NBO analysis provides a useful way to examine the chemical properties of bonding, as well as attributes such as basicity, stability, reactivity, and intra- and intermolecular charge transfer [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. The NBO method, represented by the stabilisation energy E(2), provides insight into the interaction between empty orbitals that act as acceptors and filled orbitals that act as donors. The \u003cem\u003eNBO 3.1\u003c/em\u003e program [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], included with the Gaussian16W software, has been used for NBO calculations.\u003c/p\u003e \u003cp\u003ewhere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{F}_{ij}\\)\u003c/span\u003e\u003c/span\u003e is the diagonal natural bonding orbital Fock matrix element, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{E}_{i}\\wedge\\:{E}_{j}\\)\u003c/span\u003e\u003c/span\u003e are diagonal elements, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{q}_{i}is\\)\u003c/span\u003e\u003c/span\u003e the donor orbital occupancy. The NBO analysis results are listed in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe hyperconjugative interactions due to the orbital overlap σ (C2-H2) over antibonding σ*(C25-H25), π* (C7- C6), σ*(C15-C16), σ*(C21-C20) and σ*(C15-C20) with stabilization energy of 3466.39, 695.4,311.33, 246,25 and 200.9 kcal/mol respectively. σ (C1-C2) bond as donor and σ*(C25-H25), σ*(C7-C6) antibonding as accepter participates in charge transfer with stabilisation energy 644.78 and 169.38 kcal/mol, respectively. The other important interactions involve the interactions of σ (C3-C2) with σ*(C25-H25), σ* (C7-C6), and σ*(C15-C16), which participate in charge transfer with stabilisation energies of 630.03, 167.9, and 148.43 kcal/mol, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecond-order perturbation theory analysis of Fock matrix in NBO basis for coumarin derivative.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2-H2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97701\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC 25- H25\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01373\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3466.39\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2-H2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pi\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC7-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.38325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e695.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.334\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC1-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC25- H25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e644.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC3-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.98085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC25-H25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e630.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.440\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2-H2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC15- C16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0588\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e311.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.370\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2-H2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC2-C20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.05669\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e246.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2-H2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC15-C20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC1-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.97434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pi\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC7-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.38325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e169.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC3-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.98085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pi\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC7-C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.38325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e167.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC3-C2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.98085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sigma\\:\\)\u003c/span\u003e\u003c/span\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC15-C16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0588\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e148.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eE(2) energy of hyper-conjugative interactions.\u003c/p\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003eEnergy difference between donor and acceptor i and j NBO orbitals.\u003c/p\u003e \u003cp\u003e\u003csup\u003ec\u003c/sup\u003eF(i,j) Fock matrix element between i and j NBO orbitals.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.3.4 QTAIM analysis\u003c/h2\u003e \u003cp\u003eQuantum theory of atoms in molecule provides insight into the nature of bonds in molecule via bond critical paths. The software \u003cem\u003eMultiwfn 3.7.\u003c/em\u003e was used to perform QTAIM computations to examine the nature and strength of the hydrogen bonds in the synthesised molecule[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Molecule are stabilised through intramolecular interactions, which are seen in the Bond Critical Paths (BCP) between the attractors (atoms). The wavefunction characteristics (energy density and the Laplacian of the electron density at the BCP) are considered along with binding energies (BE). The formula for estimating the binding energy (BE) of an H-bond based on the electron density at BCP is given by BE\u0026thinsp;\u0026asymp;\u0026thinsp;\u0026minus;\u0026thinsp;223.08 \u0026times; \u0026#120588;(r)\u0026thinsp;+\u0026thinsp;0.7423. \u0026nabla;\u003csup\u003e2\u003c/sup\u003eρ\u003csub\u003eBCP\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0, H\u003csub\u003eBCP\u003c/sub\u003e \u0026lt; 0 associated with strong hydrogen bond interaction and covalent in nature, \u0026nabla;\u003csup\u003e2\u003c/sup\u003eρ\u003csub\u003eBCP\u003c/sub\u003e \u0026gt;\u0026thinsp;0, H\u003csub\u003eBCP\u003c/sub\u003e \u0026lt; 0 associated with intermediate type hydrogen bonds and partially covalent, \u0026nabla;\u003csup\u003e2\u003c/sup\u003eρ\u003csub\u003eBCP\u003c/sub\u003e \u0026gt;\u0026thinsp;0, H\u003csub\u003eBCP\u003c/sub\u003e \u0026gt; 0 associated with weak hydrogen bond interactions and electrostatic in nature. Interaction energy was another method to determine the strength of hydrogen bonds [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Considering these factors, for the synthesised compound, interactions H1...O9, H13...F17, and H20...F19 are all weak hydrogen bonds and electrostatic in nature. The interaction energy computed at BCP indicates that H1...O9 exhibit more binding energy with energy values\u0026thinsp;\u0026minus;\u0026thinsp;11.388 kJ/mol. A molecular graph indicating the presence of the BCPs is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTopological characteristics of interacting atoms in coumarin derivative.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInteractions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\rho\\:\\left(r\\right)\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(a.u)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\nabla\\:}^{2}\\rho\\:\\left(r\\right)\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(a.u)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eG(r)\u003c/p\u003e \u003cp\u003e(a.u)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eH(r)\u003c/p\u003e \u003cp\u003e(a.u)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eV(r)\u003c/p\u003e \u003cp\u003e(a.u)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eE\u003c/em\u003e\u003csub\u003eint\u003c/sub\u003e\u003c/p\u003e \u003cp\u003ekJ/mol\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC1\u0026ndash;H1..O9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.01554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00302\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.01027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-11.388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC13\u0026ndash;H13..F17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00695\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001622\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.00532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-3.863\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC20\u0026ndash;H20..F19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.00530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-3.844\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eElectron density \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:(\\rho\\:\\)\u003c/span\u003e\u003c/span\u003e), Laplacian of electron density \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\nabla\\:}^{2}\\rho\\:\\left(r\\right)\\)\u003c/span\u003e\u003c/span\u003e, electron kinetic energy density, G(r) total electron energy density H(r), electron potential energy density V(r), and estimated interaction energy (\u003cem\u003eE\u003c/em\u003e\u003csub\u003eint\u003c/sub\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e3.3.5. Reduced density gradient (RDG)\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eRDG is one of the most widely used methods available to investigate non-covalent interactions. There are several spikes in the scatter density plot. By using an RDG isosurface to enclose their real space, the interaction position can be identified. The blue region in the isosurface represents the steric effect, the green region denotes Van der Waals interactions, and the blue regions signify strong, attractive interactions. These interactions rely on the electron density attribute. \u003cem\u003eVMD\u003c/em\u003e (Visual Molecular Dynamics) was used to visualise the computations, which were performed with Multiwfn [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Green cloud iso surfaces between C1\u0026ndash;H1...O9, C13\u0026ndash;H13...F17, C20\u0026ndash;H20...F19 indicate the presence of weak hydrogen bonds, and in addition, various interactions that were not evident in the AIM analysis were disclosed by the isosurface diagram. This includes spaces that are green between C25\u0026ndash;H25...O9, N10\u0026ndash;H10...H6, and C20\u0026ndash;H20...F18, confirming the presence of electrostatic interactions and van der Waals interactions. The fluoride group forms weak dispersive dihydrogen (H\u0026hellip;H) interactions with the H6 (\u0026ndash;CH) and H10 (\u0026ndash;NH) atoms of the coumarin moiety, as also evident from the NCI isosurface. Moreover, red spots appear at the middle of aromatic rings, indicating the effect of steric repulsion. NCI-RDG findings supported by HSA and x-ray diffraction analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e9\u003c/span\u003e depicts the NCI-RDG scatter map and interaction types for the compound.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Biological activities\u003c/h2\u003e \u003cp\u003eAntibacterial activity of synthesised molecule was tested against four reference strains: S. aureus, B. subtilis, E. Coli, and K. pneumoniae. Experimental data are reported in Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. Inhibition zone results indicate that the title compound exhibit strong to moderate antibacterial activity against all tested bacterial strains. Ampicillin (0.5mg/mL) was used as the standard.\u003c/p\u003e \u003cp\u003eThe molecule exhibited good antibacterial activity against the four tested strains, especially S. B. Subtilis, which is nearly as effective as Ampicillin against the same strain.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eShowing zone of inhibition of coumarin derivative against tested organisms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConcentration in \u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eZone of inhibition measured in mm\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStaphylococcus aureus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBacillus subtilis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEscherichia\u003c/p\u003e \u003cp\u003ecoli\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKlebsiella pneumonia\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmpicillin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Molecular docking\u003c/h2\u003e \u003cp\u003eMolecular docking is an essential technique used to investigate the binding affinity of compound with the target protein. The protein \u003cem\u003etropinone reductase-I\u003c/em\u003e complex with NADP (PDB:1AE1) has shown efficacy against various bacterial pathogens, such as Staphylococcus aureus and Escherichia coli, and was chosen to investigate the antibacterial properties of the ligand. [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Docking studies showed that the binding component of the molecule interacts with the active site of tropinone reductase-I with NADP, and that the molecule interacts with the active site through five hydrogen bonds. showed a good binding affinity with protein scoring\u0026thinsp;\u0026minus;\u0026thinsp;9.9 kcal/mol. Ligand and protein interaction through different amino residues of THR206, GLY202, TYR171, ILE33, LEU208, GLY108, GLY34, LYS31, ALA107, and ILE204. The trifluoromethyl group interact with amino acid residues THR206 and ILE204 through hydrogen bonds with a distance of 2.712 \u0026Aring; and 2.53 \u0026Aring;, respectively. TYR171 shows interaction with the oxygen of the benzoyl group, and ILE33, LEU208, and the residue interact with the benzene ring of the coumarin moiety at distances of 2.45 \u0026Aring;, 3.96 \u0026Aring;, and 3.46 \u0026Aring;, respectively. GLY108 and GLY34 interact with the hydrogen and oxygen atoms of the amide bond. Figure\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e10\u003c/span\u003e shows the docking pose and the associated ligand and two-dimensional interaction of the 1AE1 protein for the molecule.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003e3.6 ADMET parameters and toxicity studies\u003c/h2\u003e \u003cp\u003eADMET properties were predicted to evaluate the physicochemical and pharmacokinetic features of the synthesised molecule. These evaluations play a vital role in the utilisation of the molecule as a drug [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. The ADMET parameters have been evaluated using pkCSM and the SwissADME online tool; both tools provide highly accurate value predictions [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The six physicochemical parameters, lipophilicity (LIPO), size (SIZE), polarity (POLAR), flexibility (FLEX), insolubility (INSOLU), and insaturation (INSATU) are taken into account by the bioavailability radar to evaluate drug-likeness and ADMET profiling shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e11\u003c/span\u003e. The predicted result indicated that the molecule has a good solubility potential in water (-4.158 log mol/L) and high gastrointestinal absorption (90.99%), which would make it more appropriate for oral use. Compound are capable of inhibiting cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C19, CYP2C9), indicating that it hinders the body from metabolising xenobiotics. Log BB values of 0.003 and log PS values of -1.708 revealed that the molecule have better blood-brain barrier (BBB) and central nervous system (CNS) penetration. The Physicochemical and Pharmacokinetics parameters of coumarin derivates are shown in Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e. These findings demonstrate that the molecule exhibits strong ADMET properties, which are vital for drug-like behaviour. After applying Lipinski's filters and based on the anticipated pharmacokinetic characteristics, the compound possess favourable drug-like properties and could be potential drug candidates for further studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePhysicochemical and pharmacokinetic parameters of coumarin derivatives using SWISSADME and pkCSM tools. HBD: Number of hydrogen bond donor, HBA: Number of hydrogen bond acceptor\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysicochemical parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValues\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolecular weight (MW\u0026thinsp;\u0026lt;\u0026thinsp;500)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e351.25 g/mol\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBA (HBA\u0026thinsp;\u0026lt;\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBD (HBD\u0026thinsp;\u0026lt;\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRotatable bond count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.31 \u0026Aring;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolar Refractivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLipinski\u0026rsquo;s rule of five followed, violation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes ,0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePharmacokinetics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbsorption\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWater solubility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaco2 permeability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal absorption (human)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.995\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin Permeability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-glycoprotein substrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-glycoprotein I inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-glycoprotein II inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistribution\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVDss (human)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFraction unbound (human)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBBB permeability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNS permeability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.708\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMetabolism\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYP2D6 substrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYPA4 substrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYP1A2 inhibitior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYP2C19 inhibitior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYP2C9 inhibitior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYP2D6 inhibitior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYPA4 inhibitior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExcretion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Clearance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.347\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal OCT2 substrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eToxicity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMES toxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMax. tolerated dose (human)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehERG I inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehERG II inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Rat Acute Toxicity (LD50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.842\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Rat Chronic Toxicity (LOAEL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.577\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatotoxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin Sensitisation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT. Pyriformis\u0026nbsp;toxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinnow toxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn the present paper, a novel 7-amino-4-(trifluoromethyl)-2H-chromene-2-one derivative was synthesised and characterised by 1H and 13C NMR and FTIR spectroscopy to confirm the product formation and the presence of important functional groups. Structural analysis revealed that the compound crystallises in the P2\u003csub\u003e1\u003c/sub\u003e/c space group, Hirshfeld surface analysis showed that H\u0026hellip;F and H\u0026hellip;H interactions contribute to about 40% of total interactions and play a significant role in stabilising the crystal and formation of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(6), \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(7) supramolecular synthons. Interaction energies show that the C-H⋯O hydrogen bond plays a very important role in the highest interaction energy. Geometrical optimisation molecule was performed. Geometrical parameters showed strong agreement with single-crystal XRD results. HOMO, LUMO, and energy gaps between them were examined. AIM calculations reveal that the title molecule exhibits weak hydrogen bonds and electrostatic interactions. The molecular docking analysis revealed that the coumarin derivative showed strong interactions with protein 1AE1, with a binding affinity of -9.9 kcal/mol. ADMET analysis showed that the coumarin derivative is orally active, with good intestinal absorption and permeability. The title compound exhibited strong antibacterial activity compared with the standard antibiotic used in this study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e\u0026ldquo;The authors recived no financial support for the research, authorship, and/or publication of this article.\u0026rdquo;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKishore- Dtata analysis, Manuscrpit writing.Hema - Synthesis. Data analysis, Editing, software engagement.Uday- Characterisation.Lokanath N K-Charctersiation facility.Vinay- ProofreadingNarasimha -Biological activitiesHanumanthappa- Biological activities Chethan Prathap- Data analysis, Proofreading.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are avilable from the corresponding author upon reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTsivileva OM, Koftin OV (2023) Fungal coumarins: biotechnological and pharmaceutical aspects. Stud Nat Prod Chem 78:441\u0026ndash;479\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenugopala KN, Rashmi V, Odhav B (2013) Review on natural coumarin lead compounds for their pharmacological activity. 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Sci Rep 7(1):42717\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-chemical-crystallography","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocc","sideBox":"Learn more about [Journal of Chemical Crystallography](http://link.springer.com/journal/10870)","snPcode":"10870","submissionUrl":"https://submission.nature.com/new-submission/10870/3","title":"Journal of Chemical Crystallography","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8925377/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8925377/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this study, we have synthesised a novel coumarin derivative via a nucleophilic substitution reaction between 7-amino-4-(trifluoromethyl)coumarin and acyl chlorides. The compound was characterised by NMR (1H and 13C) and FTIR spectroscopy, with structures validated by single-crystal X-ray diffraction. The compound crystallised in the monoclinic crystal system, space group P21/c. Crystal structure and Hirshfeld surface analyses revealed intermolecular C\u0026ndash;H\u0026middot;\u0026middot;\u0026middot;O and N\u0026ndash;H\u0026middot;\u0026middot;\u0026middot;O hydrogen bonds that stabilise the crystal structure, forming \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(6) and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{2}^{1}\\)\u003c/span\u003e\u003c/span\u003e(7) supramolecular synthons. The geometrical coordinates of the compound was optimised using density functional theory (B3LYP/6-311\u0026thinsp;+\u0026thinsp;G(d,p)), and, based on the optimised structure, various electronic properties were evaluated. The natural bond orbital (NBO) and quantum theory of atoms in molecule (QTAIM) analyses provided in-depth insights into the interactions exhibited by the compound. Molecular docking studies with protein [PDB:1AE1] demonstrated that the molecule exhibited strong binding affinity, highlighting its potential as an antibacterial agent. ADMET analysis revealed that drug can be orally active. The potential antibacterial activity of the synthesised compound was tested in vitro against 4 selected bacterial strains: Staphylococcus aureus (Gram-positive) and Bacillus subtilis (Gram-positive), and Escherichia coli and Klebsiella pneumonia (Gram-negative). The coumarin derivative showed potential antibacterial activity against the tested bacterial species.\u003c/p\u003e","manuscriptTitle":"Synthesis, Structural Elucidation and DFT studies of Novel Coumarin derivative with Docking, ADMET analysis and Antibacterial activities","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-24 11:59:10","doi":"10.21203/rs.3.rs-8925377/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"180292752756085683812479010650429136486","date":"2026-05-18T19:02:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-31T22:19:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"138370078839097051838630730373675070546","date":"2026-03-21T13:49:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T19:26:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-24T12:47:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-24T12:45:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Chemical Crystallography","date":"2026-02-20T11:09:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-chemical-crystallography","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocc","sideBox":"Learn more about [Journal of Chemical Crystallography](http://link.springer.com/journal/10870)","snPcode":"10870","submissionUrl":"https://submission.nature.com/new-submission/10870/3","title":"Journal of Chemical Crystallography","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b7fb4490-0194-4d63-9a19-170cf15c3ecc","owner":[],"postedDate":"March 24th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"180292752756085683812479010650429136486","date":"2026-05-18T19:02:42+00:00","index":28,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-24T11:59:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-24 11:59:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8925377","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8925377","identity":"rs-8925377","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}