Computational study and quantum – chemical investigation on bambuterol hydrochloride compound drug: ADFT approach

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S.S. Alblozy, Ahmed A. K. Mohammed, refaat M. Mahfouz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2767196/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The main objective of the study is to provide deep knowledge of structural and reactivity features of bambuterol hydrochloride (BB.HCl) drug compound. Theoretical calculations are done by the density functional theory (DFT) method with RB3LYP/6–31 + G (d) level and basis set. The computational study by DFT was used to explore HOMO –LUMO energies, global reactivity parameters, NLO using the aforementioned level of theory and basis set. The nature of the hydrogen and halogen bonding interactions was analyzed by NBO, AIM, and RDG analysis. Electron localization function (ELF) analysis provides new insight into the chemical bonding of bambuterol hydrochloride. The pharmaceutical potential of the drug has been considered by molecular docking procedure. Bambuterol hydrochloride Computational study DFT calculations Geometry optimization docking procedure Vibration spectroscopy 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 Bambuterol hydrochloride (BB.HCl), (RS)-5-(2-tert-butylamino-1 hydroxyethyl)-m-phenylene bis(dimethyl carbamate) hydrochloride, Figure(1) is an orally effective long-acting sympathomimetic drug with predominantly-adrenergic activity (B1-agonist)[ 1 ].It is widely used for asthma and chronic obstructive pulmonary disease [ 2 – 4 ]. It is an ester prodrug of β2 adrenergic agonist terbutaline[ 5 , 6 ].The drug has been estimated by solid state NMR spectroscopy, GC-MS, potentiometric titration, andactive enantiomer with more efficiency over the (S)-bambuterol hydrochloride enantiomerin the treatment of asthma[ 7 ]. For understanding the pharmacological reactions and elucidation of the geometric structure parameters of biomolecular compounds, DFT was shown to be a powerful method. Bambuterol hydrochlorideis a directly acting sympathomimetic agent and predominantly shows adrenergic activity[ 8 ]. It is considered biscarbamate ester form and acts as a prodrug of terbutaline which is β2 adrenergic agonist. It exhibits pre-systemic stability till concentration in the lung tissues, afterwards, it begins hydrolysis into terbutaline by butyrylcholinesterase[ 9 ]. In the present study, efforts have been taken to predict the description of the molecular geometry, natural bond orbital (NBO) analysis, and hydrogen bonding interactions, AIM, ELF, RDG, and FT-IR spectroscopic study of bambuterol hydrochloride. Figure (1) 2. Computational Methods DFT computations have been performed using the Gaussian 09 program package[ 10 ].The geometry optimization and conformational analysis on the single molecule were performed using RB3LYPlevel with 6–31 + G (d) basis set to achieve the optimal conditions for structural parameters calculations and ground state optimization in the gas phase. The dispersion corrected DFT (DFT-D3) approach used by Grimme etal. was employed in this study to give better results for non-covalent interactions[ 11 ].Frequency calculations for the optimized structure of bambuterol hydrochloride showed That there are no imaginary frequencies, which confirms that they are true minima. The chemical reactivity has been predicted in view of HOMO-LUMO gap and reactivity descriptors. The stability of the title compound has been analyzed in light of natural bond order (NBO) analysis.The chemical activity has been measured in terms of molecular electrostatic potential (MEP) analysis. The activity and stability of the compound have been further investigated with regards to the nature of non-covalent interactions through atoms in molecules (AIM) approach, electron localization function, electrostatic potential map and reduced–density gradient (RDG) have been performed by Multiwfn program. To get visual animation for the verification of the normal modes of Gauss View 6 was fallen back on. 3. Result And Dissuasion 3.1 Computationalstudies 3.1.1Optimization The geometrical optimized parameters of bambuterol hydrochloride computed by RB3LYP level with 6–31 + G (d) basis are listed in Table (1). The corresponding structure together with the labeling of atoms is shown in Figure (2). the overall geometry has a non-planar structure. The geometry of the benzene ring is seen to be perturbed due to different substituents on the benzene ring.The symmetry of the ring is distorted yielding ring angles greater than 120 at the points of substitutions. Figure (2) Table (1) 3.1.2 Mulliken analysis Charge distributions of the molecule have been computed by performing Mulliken analysis[ 12 ]. The theoretical calculations of atomic charges play an important role in the application of quantum mechanical calculations to molecular systems. The calculated results reveal that the biggest values of negative charge are noticed for O5, Cl57, and C9. The carbon atoms of the methyl groups are positively charged. Almost very similar values of positive charges are noticed for all hydrogen atoms forming CH 3 groups. The highest value of the positive charge is located on H56connected to N6 (N6 –H56). 3.1.3 Frontier molecular orbitals (FMOs) and density of states (DOS) The highest occupied molecular orbital (HOMO)and the lowest unoccupied molecular orbital(LUMO) of the title compound are computed with the same level of DFT theory and are shown pictorially in Figure (3) The compositions of both HOMO and LUMO were calculated by Becke method via the Multiwfn program. From Figure (3) it could be seen that the HOMO result from thelone pair present on the chloride atom contributes to the HOMO by 96.7%.The LUMO result mainly from the aromatic system (benzene ring), with a contribution of 78%. The chemical reactivity of the title compound would be assessed based on the global reactivity descriptors. The energy of the HOMO and LUMO is directly related to ionization potential (IP) and electron affinity (EA). Figure (3) The value of IP and EA are given according to Koopman ’ s theorem[ 13 ]. IP= -HOMO EA = -LUMO The values of IP and EA can be used to deduce the global reactivity descriptors including chemical potential (µ), chemical hardness ( η ), chemical softness(S), electronegativity (X), and electrophilic index (ω) according to the following equations. µ = - [(IP + EA)/2] η = (IP-EA)/2 S = 1/2 η X = (IP + EA)/2 ω = µ 2 / 2 η According to the values in Table 2 , (E)/ (Nmax) is -1.707eV, and the maximal charge acceptance Nmax is 1.203eV. These values reveal the drug's intramolecular charge transfer as well as its ability to interact with and bind to β1-adrenergic receptors. Chemical hardness ( η ) and electron transfer energy (E) are 2.836 and − 2.055 eV, respectively. These findings suggest that the charge transfer process in the drug and bioactivity formation of intermolecular interaction with 1-adrenergic receptors and blocking is permissible[ 14 ]. Table (2) The Multiwfn program was used to plot each total, partial, and overlap density state (TDOS, PDOS, and OPDOS). Figures (4) depicts these plots. The curve maps of broadened partial DOS (PDOS) and overlap population DOS (OPDOS) for the title molecule is very useful for visualizing atomic orbitals of different fragments and have significant contributions to the corresponding MOs and chemical bonding. Figure 4 depicts the fragments of the title molecule and their PDOS and OPDOS only in the valence MOs range. The left axis represents TDOS and PDOS, while the right axis represents OPDOS, and the vertical dashed line indicates the position of the HOMO. Red, blue, magenta, brown, and yellow have been observed to have the highest contribution to valence MOs, with comparable amounts of contribution. The green curve represents the OPDOS between fragments 1, and 2, and its positive part indicates that MOs in the corresponding energy range exhibit bonding properties between two fragments (e.g. the one at -0.231 a.u which corresponds to MO 108). Figure (4) 3.1.4 Molecular electrostatic potential (MEP) map To forecast reactivity, find places for nucleophilic and electrophilic attacks on the molecule, and lastly assess the biological recognition process and hydrogen bonding interactions, one can use the concept of molecular electrostatic potential (MEP), which is connected to electron density[ 15 ].Drug-receptor interactions and the electrostaticpotential (ESP) V(r) have both been extensively studied[ 16 , 17 ]. Figures (5) depicts the 3D ESP map of the investigated molecule to determine the different electrostatic potential values at both electrophilic and nucleophilic sites. The most electrostatically positive, most negatively charged, and zero electrostatic potential regions are represented by the colors blue, red, and white on the MEP surface, respectively. The figure shows 5 surface maxima for positive potential sites surrounding the hydrogen atoms and 4 surface minima for the negative potential sites on chlorine and oxygen atoms. The global minimum on the surface (-49.9 kcal/mol) is located on Cl57. While the location of the surface's global maxima (+ 46.8 kcal/mol) is located on H27. We note that the strongest nucleophilic and electrophilic sites, as well as the global maximum and minimum, are found in the vicinity of hydrogen chloride. According to the MEP map, the region that contains the hydrogen chloride molecule has a significant biological activity, plays a more significant role than any other location in the recognition of the drug in biological systems, and can establish halogen bonds. Figure (5) 3.1.5 Reduced Density Gradient Equation(1) gives the reduced density gradient (RDG), which is a fundamental dimensionless quantity derived from the density and its first derivative[ 18 ]. $${\text{RDG(}}r{\text{)}}=\frac{1}{{2{{\left( {3{\pi ^2}} \right)}^{\frac{1}{3}}}}}\frac{{\nabla \rho (r)}}{{\rho {{(r)}^{\frac{4}{3}}}}}$$ (1) Large negative values of sign (λ 2 ) in RDG tails indicate attractive interactions (such as dipole-dipole or hydrogen bonding); if the sign (λ 2 ) is large and positive, the interaction is non-bonding (steric effect). Near-zero values indicate very weak van der Waals interactions. Multiwfn was used to generate the RDG of the BB.HCl structures,whichwerethen plotted using the VMD program[ 19 ]. Figures (6 ) depicts these results. Figure (6) Green colors represent van der Waals interactions, while the red color represents strong repulsion. Inside the ring, repulsive interactions were observed, while van der Waals interactions were observed between the hydrogen atoms.The blue colors in BB.HCl indicates hydrogen bonding and halogen bonding interactions[ 20 ]. 3.1.6 Natural bond orbital (NBO) analysis Natural bond orbital analysis of bambuterol hydrochloride molecule is performed using NBO 3.1 module as implemented in Gaussian 09 program to confirm the charge transfer and conjugation interaction within the molecule. A Second order perturbation approach Fock matrix gives an examination of the energetic importance of electron transfer from the donor (Lewis-type NBOs) to accepter (non-Lewis NBOs). The stabilization energy,E (2) , represents the degree of electron transfer from donor to acceptor known as the degree of electron delocalization[ 21 ]. E (2) = △E i j = q i j = \(\frac{F {(i, j )}^{2}}{Ej-Ei}\) Where q ij is donor orbital occupancy, F (i, j) is the off–diagonal Fock matrix element, E j and E i are the diagonal element (orbital energies). E (2 ) value can represent (reflect) the intensity of electron donor and electron acceptor and the degree of conjugation of the structure. The occupancy and energies of (i) and (j) with △ E ij of the most significant lone pair (LP) and boning to anti-bonding \({BD}^{*}(\) σ*⁄ \({\pi }^{*}\) ) are given in table (3). It can be seen from table (3) that the majority of the contributions to the stability of the drug comes from lone pair interaction donor (NBO (i)) with anti-bonding BD * orbitals acceptor (NBO j )significant contributions of lP (1) N7⟶ \({\sigma }^{*}\) (O4 – C21) and lP (1) N8⟶ \({\sigma }^{*}\) (O5 – C22). Table (3) The other significant interactions gave a stronger stabilization energy value of 220.31and 231.09 kJ/mol to the structure are the interaction between the antibonding of C16–C19 and C18 –C20 respectively. Significant contribution to the stabilization energy could be added by LP (4) Cl57⟶ LP * H27 of 102.55 value of E 2 (i) . 3.1.7 The electron localization function (ELF) ELF provides important information on the electron environment, chemical bonding, and atomic shell on the surface of the molecule. The colored map of ELF drawn by Multiwfn software is shown in Figure (7) higher values of ELF plotted between the range 0.85 − 1.0 Bohr indicate the strong localization of electrons and formation of covalent bonds, whereas lower values lie between 0.0 and 0.4 Bohr denote the strong delocalization of electrons. From the ELF color map, we observe highly localized areas surrounding hydrogen atoms indicated by red color. Delocalized electrons predicated around oxygen and carbon atoms are shown in blue. The high value of electron localization occurs between the carbon atoms in the ring with the hydrogen atoms due to the overlap of the SP orbitals of carbon with the S orbital of hydrogen. Deformation of the ELF distribution around the oxygen is due to hydrogen and halogen bond interactions. Figure (7) The 3D plot of ELF for bambuterol hydrochloride is shown in Figure (8). the monosynaptic basin is associated with the lone pair whereas the disynaptic basin belongs to covalent interaction. The monosynaptic lone pair regions of oxygen, nitrogen, and chloride occupy more space. While the disynaptic associated with OH, NH, and CH occupy less space due to halogen and hydrogen bond interactions. Figure (8) 3.1.8 Vibration analysis. The molecule contains 57 atoms and hence 165 modes of vibrations. These 165 normal modes of vibrations are distributed among the symmetry specie as follow, considering C 2 point symmetry. ┌vibration =111 \({A}^{{\prime }}\) + 54 \({A}^{"}\) \({A}^{{\prime }}\) and \({A}^{"}\) represent the vibrations which lie within in plane and out of plane, respectively. In C 2 group, the symmetry of the molecule is a non-planar structure and has the 165 modes in irreducible representation. The calculated vibrations wavenumbers are higher than experimental values for the majority of the normal modes due to the environment of performing vibrations (gas phase for theoretical and solid state for experimental), and the fact that the experimental values are inharmonic wave numbers while the calculated values are harmonic ones. Therefore, the computed wavenumbers are scaled down using a scaling factor of 0.9608 to discard the anharmonicity present in the real system. The methyl group makes a significant contribution to the vibration spectrum of bambuterol hydrochloride since the molecule contains 7 methyl groups. Therefore, we will discuss the assignment of methyl group vibrations in detail. Nine fundamental modes of vibrations can be associated with each methyl group: two asymmetric stretching, one symmetric stretching, two asymmetric deformations, one symmetric deformation, two rocking vibrations, and one torsion mode of vibration. The computed (scaled) vibrations of the methyl group together with the experimentally observed frequencies and the assignments ate present in table (4) . Table (4) 3.1.9 AIM calculations . Atoms in molecules (AIM) theory is a convenient method to analyze the hydrogen bonding and other interactions in various molecular systems and has been extensively used to classify and understand bonding interactions in terms of quantum mechanical parameters and their derivatives as electron density (𝞺). The theory of AIM efficiently describes H-bonding and it ' s a concept without borders. One of the advantages of this theory is that one can obtain information on the change in electron density distribution as the result of their bond formation or complex formation[ 22 ]. The molecular graph of the molecule using AIM theory is shown in Figure (9) the topological parameters of non-covalent interactions are grouped in a table (5). AIM results show that bambuterol hydrochloride is characterized by 4BCPs of non-covalent character. Two describing hydrogen bonding, and two characters halogen bonding interactions. According to the values of the parameters reported in table (5 ). We can classify the non-covalent interactions as weak hydrogen and halogen bonding interaction except for N6-H27……Cl57 strong bonding interactions [ 23 ]. Figure (9) Table (5) 3.1.10 Nonlinear optical effects and first hyper polarizability . NLO is at the cutting edge of current research because it provides the critical functions of frequency shifting, optical modulation, optical switching, optical logic, and optical memory for emerging technologies such as telecommunications, signal processing, and optical interconnections[ 24 , 25 ]. The prediction of non-linear optical (NLO) properties of a molecule by quantum chemistry plays an important role in the design of materials in modern communication technology[ 25 ]. Organic molecules, in particular, are being studied due to their higher NLO susceptibilities caused by electron cloud movement from donor to acceptor, rapid NLO response times, high laser damage thresholds, and low dielectric constants. Table (6) shows the dipole moment, polarizability, and first hyper polarizability components of the title compound which invariant are calculated with a numerical derivative of the dipole moment using RB3LYP/6–31 + G(d) level of DFT. The total static dipole moment, average linear polarizability, anisotropy of polarizability, and first hyper polarizability can be calculated using the equations below [ 25 ]. µ = (µ x 2 + µ y 2 + µ z 2 ) 1\2 α = \(\frac{1}{3}\) ( α xx + α yy + α zz ) △ α = \(\frac{1}{\surd 2}\) [ ( α xx - α yy ) 2 + ( α yy - α zz ) 2 + ( α zz - α xx ) 2 + 6 α xx 2 ] 1\2 β = [ ( β xxx + β xyy + β xzz ) 2 + (β yyy + β xxy + β yzz ) 2 + ( β zzz + β xxz + β yyz ) 2 ] 1\2 Table (6) The calculated values of total static dipole moment µ, the average linear polarizability α ,the anisotropy of the polarizability ∆α ,and the first hyper polarizability β using the RB3LYP/6-31+G(d) level of DFTmethodare8.5Debye,297.5 a.u,540.42 a.uand2.676×10 -30 e.s.u, respectively. Urea is one of the prototypical molecules used in the study of the NLO properties of molecular systems, and it is frequently used as a threshold value for comparative purposes. The values of µ, α, and β obtained with the RB3LYP/6-31+G(d)method for urea are 1.373 Debye, 3.831 Å 3 and 3.729×10 -31 cm 5 e.s.u. -1 , respectively[26] . The title compound's first hyper polarizability is 8 times that of urea. The title compound may be a potential candidate in the development of NLO materials based on the magnitude of its first hyper polarizability. As a result, this molecule could serve as a potential building block for nonlinear optical materials. 3.1.11. Molecular docking Molecular modelling and visualization were performed on Human butyrylcholinesterase using Molecular Operating Environment (MOE) 2019.01. The structure of Human butyrylcholinesterase in complex with thioflavine T obtained from the RCSB Protein Data Bank (PDB ID: 6esy). Bambuterol was prepared with the standard protocol in MOE 2019 and the energy of the docked compound was minimized with gradient RMSE of 0.0001kcal/mol. Then, butyrylcholinesterase structure was prepared by using the MOE QuickPrep protocol. The docking was done using the method of Alpha triangle placement with Amber10: EHT forcefield. Refinement was performed with Forcefield and scored using the Affinity dG scoring system. 3.1.11.1. Results Docking protocol was validated by re-docking of the co-crystalized thioflavine T at the active site of butyrylcholinesterase (PDB ID: 6esy), Fig. (10). the re-docking rmsd = 1.2363 Å and binding score = -6.81 Kcal.mol-1. All the key interactions accomplished by the co-crystalized ligand with the key amino acids in the binding site is reproducible using the followed docking setup, mentioned in the experimental section. The validated docking setup was then used to investigate the ligand-receptor interactions and binding patterns for bambuterol hydrochloride (score = -7.24 Kcal.mol-1), Figure (11). The amino acid residues involved in interaction at binding site with co-crystallized thioflavine T are Ser53, Ile55, Trp56 and Asn57[ 27 ], where the main interactions are H-bonding with amino acid residues through oxygen atom of pyranose ring and attached OH groups. In addition, amidic NH group formed π-H bond with indole ring of Trp56 residue. Figure (10) Figure (11) The docking investigation showed that bambuterol hydrochloride depicted the same interactions as thioflavine T at different poses, but the common residues are Ile55, Trp56 and Asn57 and these amino acid residues as discussed before are essential for inhibition of butyrylcholinesterase enzyme. Beside these amino acids, bambuterol hydrochloride interacts with other amino acids as extra binding interactions Table (7) that are mainly H-bonding which induced and driven by carbamate ester group with Thr59, Lys60, Asn63 residues and H-bonding between primaryNH2 group and Asp54 residue and all that justified the lower binding score and higher affinity of bambuterol than thioflavine T towards butyrylcholinesterase enzyme. Table (7) Conclusion In the present work, a computational study using RB3LYP/ 6-31 G(d) level of the DFT method has been used to calculate the geometrical parameters of the optimized structure for bambuterol hydrochloride. The lowering of the HOMO-LUMO energy gap indicates the charge transfer interaction which leads to the NLO activity.AIM, NBO, ELF, and RDG topological analysis have been reported to study the properties of hydrogen and halogen bonds in the title compound. The MEP map shows that the negative potential sites are located on oxygen and chlorine atom. Atomic charges analysis by Mullikan charge revealed similar values of positive charges for all hydrogen atoms forming methyl groups. The validated docking setup was used to investigate the ligand-receptor interactions and binding patterns for bambuterol (score = -7.24 Kcal.mol -1 ).The computed (scaled) frequencies of the methyl groups usingRB3LYP/6-31+G(d) level of DFT display a good agreement with the experimental FT-IR spectrum of the BB.HCl. Declarations Acknowledgments: This work is a part of Walaa.S.S.Alblozy M.Sc. thesis. The authors like to thank Assiut University for the official, technical and financial support. The authors also acknowledge a generous allocation of computer time granted by SHARCNET, a partner consortium in the Compute Canada national HPC platform. Author contributions: all authors contributed to the conceptualization and realization of the study Walaa.S.S.Alblozy carried out the computations and analysis of result Refaat M. 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Selected geometrical parameters of Bambuterol hydrochloride obtained by RB3LYP /6-31+G(d) levels of DFT Bond lengths(A°) by RB3LYP /6-31+G(d) Bond angles(°) by RB3LYP /6-31+G(d) Dihedral angles (°) by RB3LYP /6-31+G(d) O2 - C18 1.39 O4 - C21 1.21 O3 – C22 1.37 N7 – C21 1.36 N7 - C23 1.46 N8 – C22 1.36 N6 – C10 1.49 Cl57 – H42 1.87 Cl57-H32 3.19 O4 - C21- N7 125.8 O2 - C21- O4 123.39 O3 – C19 - C20 116.3 O2 - C17 - C18 116.8 C18-O2 –C21 118.5 C19-O3–C22 118.95 C21-N7-C24 124.17 C22- N7-C25 118.6 O2–C20- C18 121.20 O5–C22- N8 125.6 C22-N8-C26 124.2 C21 O3 C22 O5 4.67 C15C17 C18 O2 -176.8 C22O3 C19 C20 70.49 C18 C20 C19 O3 -176.19 C22 O3 C19 C15 52.55 C25 N8 C22 O3 -173.99 C15C11C10 N6 -165.11 Table 2. Thereactivityparametersfor bambuterol hydrochloride Chemical reactivity descriptor Value Ionization potential (I) 6.248 eV Electron affinity (A) 0.578 eV Electronegativity (𝝌) 3.414 eV Chemical potential (𝝁) -3.414V Chemical hardness(η) 2.836 eV Chemical softness(𝑺) 0.352 eV Electrophilicity index(𝝎) 2.055 eV Energy change(𝚫𝑬) -2.055 eV Maximalchargeacceptance(𝚫𝑵 𝒎𝒂 ) 1.203 eV ΔE/Δ max -1.707 eV Table 3. Second order perturbation analysis of the Fock matrix of bambuterol hydrochloride F (i,j) a.u E j -E i a.u. E (2)a kcal/mol Acceptor j Donor i 0.059 0.37 10.71 C16-C19 LP(2)O3 (1) 0.130 0.58 35.92 O2-C21 LP(2)O4 (2) 0.117 0.72 22.60 N7- C21 LP(2)O4 (3) 0.130 0.58 35.62 O3- C22 LP(2)O5 (4) 0.117 0.72 22.60 N8- C22 LP(2)O5 (5) 0.113 0.35 45.57 O4- C21 LP(1)N7 (6) 0.112 0.36 43.99 O5- C22 LP(1)N8 (7) 0.190 0.36 102.55 LP * H27 LP(4)Cl57 (8) 0.082 0.01 220.31 C15-C17 BD(2) * C18-C20 (9) 0.082 0.01 231.09 C15-C17 BD(2) * C16-C19 (10) Table 4. The observed FT-IR and computed frequencies atRB3LYP /6-31+G(d) level of DFT of bambuterol hydrochloride(methyl groups vibrations) Assignment Exp. intensity Scaled computed NO ע asy (CH3) 3002 37.36 3008 3134 1 ע sy (CH3) 2898 119.99 2909 3031 2 S asy (CH3) 1446 88.65 1424 1484 3 S sy (CH3) 1359 105.86 1379 1437 4 𝞺 asy (CH3) 1140 601.4 1136 1189 5 𝞺 sy (CH3) 1002 62.61 1017 1064 6 ע asy ⟶asymmetric stretching ע sy ⟶symmetric stretching S asy ⟶asymmetric deformation S sy ⟶symmetric deformation 𝞺 asy ⟶asymmetric rocking 𝞺 sy ⟶ symmetric rocking Table 5. topological parameters of the non –covalent interactions of BB.HCl E bond kJ/mol. ELF (a.u) V ( r ) a.u Localization potential 𝞺 (r) a.u∇ 2 Laplacian of the electron density 𝞺 (r) a.u Electron density interactions -19.7 0.08778 -0.01506 0.061778 0.001682 O1 –H42…CL57 -57.95 0.30722 -0.044249 0.10121 -0.009472 N6 – H27...CL57 -18.73 0.03816 -0.014301 0.08193 0.003090 C21 – O2 …H48 -18.36 0.038257 -0.01402 0.082101 0.003095 C26 – H54….O3 Table 6. Calculated dipolemoment µ (Debye),polarizability (α) and thefirst hyperpolarizability (β) components(a.u.) of BB.HCl Values components values components 246.283 -303.285 -3.73170 -146.087 -26.1894 -142.729 -62.19 28.1994 - β xxx β xyy β xzz β yyy β xxy β yzz β zzz β xxz β yyz 5.81840 -1.48979 -6.12364 308.136 307.742 222.910 4.89543 1.15448 0.199889 µ x µ y z µ a xx a yy a zz a xy a xz a yz Table 7. Energy scores (kcal/mol) and interactions for Bambuterol hydrochloride Compound Energy score (S) (kcal/mol) Amino acids involved in interaction Thioflavine T -6.81 Ser53, Ile55, Trp56, Asn57 Bambuterol -7.24 Ser53, Ile55, Trp56, Asn57, Asp54, Thr59, Lys60, Asn63 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-2767196","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":189052203,"identity":"0426d7db-256d-4428-ba87-216426ed0ff2","order_by":0,"name":"Walaa. S.S. Alblozy","email":"","orcid":"","institution":"Assiut University","correspondingAuthor":false,"prefix":"","firstName":"Walaa.","middleName":"S.S.","lastName":"Alblozy","suffix":""},{"id":189052204,"identity":"7a3afb77-8d9c-4e11-9e75-9151726e3a28","order_by":1,"name":"Ahmed A. K. Mohammed","email":"","orcid":"","institution":"Assiut University","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"A. K.","lastName":"Mohammed","suffix":""},{"id":189052205,"identity":"502f9815-46e3-40a8-a8fd-78b2866936bf","order_by":2,"name":"refaat M. Mahfouz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYFACHoYPQFIOwmEjTgvjDCBpTLqWxAaitZhPO3uw4WNbXXr/jNwDDB/KDjPw8y/Ar0Xmdl5i48w2ttwZN/ISGGecO8wgOeMBfi0S0jnmj3nbeHIbbuQYMPO2HWYwuHGAoBbDZt42iXR5kJa/QC32RGoxSDAAaWEE2cLfQFhL44xzCYYbz7wxONhzLp1H4gZ+HWAtDR/K6uTljucYPvhRZi3H30/AYSgApJaHQSKBBC0QwE+KLaNgFIyCUTASAADVKkIzeeK6+AAAAABJRU5ErkJggg==","orcid":"","institution":"Assiut University","correspondingAuthor":true,"prefix":"","firstName":"refaat","middleName":"M.","lastName":"Mahfouz","suffix":""}],"badges":[],"createdAt":"2023-04-02 09:14:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2767196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2767196/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":35394485,"identity":"9d8b7ef4-08eb-465e-9f53-224af2bd6069","added_by":"auto","created_at":"2023-04-06 14:23:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27980,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular structure of bambuterol hydrochloride\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/3868e7205a8e3265fc738029.png"},{"id":35394493,"identity":"6bc466a7-be7f-4205-918e-ee76cb13283e","added_by":"auto","created_at":"2023-04-06 14:23:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151764,"visible":true,"origin":"","legend":"\u003cp\u003eOptimized structures with numbering of atoms of Bambuterol hydrochloride.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/5853c327a46058ab9114b288.png"},{"id":35396893,"identity":"b9c28ab4-b347-4d24-96c6-d58905821975","added_by":"auto","created_at":"2023-04-06 14:39:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":213937,"visible":true,"origin":"","legend":"\u003cp\u003eThe atomic orbital compositions of the frontier molecular orbitals of BB.HCl calculated by the Becke method. Percentage contributions to the HOMO and LUMO are given in blue and red colors respectively.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/4a398e071823982192d1df6b.png"},{"id":35394486,"identity":"109c00f5-615e-45b7-85c0-2e4f05082e27","added_by":"auto","created_at":"2023-04-06 14:23:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":90403,"visible":true,"origin":"","legend":"\u003cp\u003ePopulation density of state (TDOS), partial density of state (PDOS) for\u003c/p\u003e\n\u003cp\u003eFragments of BB. Hcl and overlap density of state (OPDOS) for frag.1 and frag.2.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/5ca2767dae7797f1ed19d5bb.png"},{"id":35396889,"identity":"e42a090b-32c5-4531-8962-25a94d6a6cc9","added_by":"auto","created_at":"2023-04-06 14:39:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":432089,"visible":true,"origin":"","legend":"\u003cp\u003e3D molecular electrostatic potential map for BB.HCl along with the values of its electrostatic and vdW surfaces.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/a8bf0dabe992bfaa6ef438ba.png"},{"id":35396892,"identity":"7ba150d4-2f34-4c64-969e-d67a70d5ace6","added_by":"auto","created_at":"2023-04-06 14:39:31","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":168906,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Plots of the RDG versus the electron density (ρ) multiplied by the sign λ\u003csub\u003e2\u003c/sub\u003e for BB.HCL (b) the surfaces are colored on a blue-green-red scale according to values of sign λ\u003csub\u003e2\u003c/sub\u003e. Blue indicates strong attractive interactions; red indicates strong repulsion (steric effect) and green indicates van der Waalsinteractions.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/75ef1eec604ac7e382f77be2.png"},{"id":35398031,"identity":"00136617-eec7-4bd9-8c5d-8f7d220e2843","added_by":"auto","created_at":"2023-04-06 14:47:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":563267,"visible":true,"origin":"","legend":"\u003cp\u003eELF color map of BB.HCL.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/48e2ba1e8a5db0446312b225.png"},{"id":35394491,"identity":"b4574bb9-a723-4e2c-8bee-dee0d86dd6cc","added_by":"auto","created_at":"2023-04-06 14:23:31","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":218166,"visible":true,"origin":"","legend":"\u003cp\u003e3D Plots of electron localization function (ELF) isosurfaces for BB.HCL\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/66afc4eb944bfc53e8f0925f.png"},{"id":35395748,"identity":"5c8dd477-583f-4d3a-b332-2e6a97604417","added_by":"auto","created_at":"2023-04-06 14:31:30","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":175382,"visible":true,"origin":"","legend":"\u003cp\u003eBond critical points (BCP) for BB.HCl using AIM analysis.\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/f30a00c89c4220c0154894f1.png"},{"id":35395751,"identity":"9d7b6b9c-e450-4af2-8529-214e0584ba4d","added_by":"auto","created_at":"2023-04-06 14:31:31","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":163789,"visible":true,"origin":"","legend":"\u003cp\u003e2D and 3d interactions of Thioflavine T.\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/152c860865097f48ff5bd25c.png"},{"id":35398723,"identity":"16888e20-b4e8-4f0d-aa70-33b4929a0760","added_by":"auto","created_at":"2023-04-06 14:55:31","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":166724,"visible":true,"origin":"","legend":"\u003cp\u003e2D and 3d interactions of Bambuterol hydrocloride.\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/d0dbc5ed3a5cb38ad584bf5d.png"},{"id":35454825,"identity":"a5606c2a-878e-49a8-9a4e-a8ca01972dba","added_by":"auto","created_at":"2023-04-07 15:59:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2616163,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2767196/v1/58243388-1868-492d-a2de-e0a26bcb7495.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Computational study and quantum – chemical investigation on bambuterol hydrochloride compound drug: ADFT approach","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBambuterol hydrochloride (BB.HCl), (RS)-5-(2-tert-butylamino-1 hydroxyethyl)-m-phenylene bis(dimethyl carbamate) hydrochloride, \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eFigure(1)\u003c/span\u003e is an orally effective long-acting sympathomimetic drug with predominantly-adrenergic activity (B1-agonist)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].It is widely used for asthma and chronic obstructive pulmonary disease [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It is an ester prodrug of β2 adrenergic agonist terbutaline[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].The drug has been estimated by solid state NMR spectroscopy, GC-MS, potentiometric titration, andactive enantiomer with more efficiency over the (S)-bambuterol hydrochloride enantiomerin the treatment of asthma[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. For understanding the pharmacological reactions and elucidation of the geometric structure parameters of biomolecular compounds, DFT was shown to be a powerful method. Bambuterol hydrochlorideis a directly acting sympathomimetic agent and predominantly shows adrenergic activity[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is considered biscarbamate ester form and acts as a prodrug of terbutaline which is β2 adrenergic agonist. It exhibits pre-systemic stability till concentration in the lung tissues, afterwards, it begins hydrolysis into terbutaline by butyrylcholinesterase[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In the present study, efforts have been taken to predict the description of the molecular geometry, natural bond orbital (NBO) analysis, and hydrogen bonding interactions, AIM, ELF, RDG, and FT-IR spectroscopic study of bambuterol hydrochloride.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure (1)\u003c/b\u003e \u003c/p\u003e"},{"header":"2. Computational Methods","content":"\u003cp\u003eDFT computations have been performed using the Gaussian 09 program package[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].The geometry optimization and conformational analysis on the single molecule were performed using RB3LYPlevel with 6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G (d) basis set to achieve the optimal conditions for structural parameters calculations and ground state optimization in the gas phase. The dispersion corrected DFT (DFT-D3) approach used by Grimme etal. was employed in this study to give better results for non-covalent interactions[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].Frequency calculations for the optimized structure of bambuterol hydrochloride showed That there are no imaginary frequencies, which confirms that they are true minima. The chemical reactivity has been predicted in view of HOMO-LUMO gap and reactivity descriptors. The stability of the title compound has been analyzed in light of natural bond order (NBO) analysis.The chemical activity has been measured in terms of molecular electrostatic potential (MEP) analysis. The activity and stability of the compound have been further investigated with regards to the nature of non-covalent interactions through atoms in molecules (AIM) approach, electron localization function, electrostatic potential map and reduced\u0026ndash;density gradient (RDG) have been performed by Multiwfn program. To get visual animation for the verification of the normal modes of Gauss View 6 was fallen back on.\u003c/p\u003e"},{"header":"3. Result And Dissuasion","content":"\u003cdiv class=\"Section2\" id=\"Sec4\"\u003e\n \u003ch2\u003e3.1 Computationalstudies\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003e3.1.1Optimization\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe geometrical optimized parameters of bambuterol hydrochloride computed by RB3LYP level with 6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G (d) basis are listed in\u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eTable (1).\u003c/span\u003e The corresponding structure together with the labeling of atoms is shown in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (2).\u003c/span\u003ethe overall geometry has a non-planar structure. The geometry of the benzene ring is seen to be perturbed due to different substituents on the benzene ring.The symmetry of the ring is distorted yielding ring angles greater than 120 at the points of substitutions.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (2)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(1)\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv class=\"Section3\" id=\"Sec5\"\u003e\n \u003ch2\u003e3.1.2 Mulliken analysis\u003c/h2\u003e\n \u003cp\u003eCharge distributions of the molecule have been computed by performing Mulliken analysis[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. The theoretical calculations of atomic charges play an important role in the application of quantum mechanical calculations to molecular systems. The calculated results reveal that the biggest values of negative charge are noticed for O5, Cl57, and C9. The carbon atoms of the methyl groups are positively charged. Almost very similar values of positive charges are noticed for all hydrogen atoms forming CH\u003csub\u003e3\u003c/sub\u003e groups. The highest value of the positive charge is located on H56connected to N6 (N6 \u0026ndash;H56).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec6\"\u003e\n \u003ch2\u003e3.1.3 Frontier molecular orbitals (FMOs) and density of states (DOS)\u003c/h2\u003e\n \u003cp\u003eThe highest occupied molecular orbital (HOMO)and the lowest unoccupied molecular orbital(LUMO) of the title compound are computed with the same level of DFT theory and are shown pictorially in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (3)\u003c/span\u003e The compositions of both HOMO and LUMO were calculated by Becke method via the Multiwfn program. From \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (3)\u003c/span\u003e it could be seen that the HOMO result from thelone pair present on the chloride atom contributes to the HOMO by 96.7%.The LUMO result mainly from the aromatic system (benzene ring), with a contribution of 78%. The chemical reactivity of the title compound would be assessed based on the global reactivity descriptors. The energy of the HOMO and LUMO is directly related to ionization potential (IP) and electron affinity (EA).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (3)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe value of IP and EA are given according to Koopman\u003csup\u003e\u0026rsquo;\u003c/sup\u003es theorem[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eIP= -HOMO\u003c/p\u003e\n \u003cp\u003eEA = -LUMO\u003c/p\u003e\n \u003cp\u003eThe values of IP and EA can be used to deduce the global reactivity descriptors including chemical potential (\u0026micro;), chemical hardness (\u003cem\u003e\u0026eta;\u003c/em\u003e), chemical softness(S), electronegativity (X), and electrophilic index (\u0026omega;) according to the following equations.\u003c/p\u003e\n \u003cp\u003e\u0026micro; = - [(IP\u0026thinsp;+\u0026thinsp;EA)/2]\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026eta;\u003c/em\u003e = (IP-EA)/2\u003c/p\u003e\n \u003cp\u003eS\u0026thinsp;=\u0026thinsp;1/2 \u003cem\u003e\u0026eta;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eX = (IP\u0026thinsp;+\u0026thinsp;EA)/2\u003c/p\u003e\n \u003cp\u003e\u0026omega; = \u0026micro;\u003csup\u003e2\u003c/sup\u003e/ 2 \u003cem\u003e\u0026eta;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eAccording to the values in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, (E)/ (Nmax) is -1.707eV, and the maximal charge acceptance Nmax is 1.203eV. These values reveal the drug\u0026apos;s intramolecular charge transfer as well as its ability to interact with and bind to \u0026beta;1-adrenergic receptors.\u003c/p\u003e\n \u003cp\u003eChemical hardness (\u003cem\u003e\u0026eta;\u003c/em\u003e) and electron transfer energy (E) are 2.836 and \u0026minus;\u0026thinsp;2.055 eV, respectively. These findings suggest that the charge transfer process in the drug and bioactivity formation of intermolecular interaction with 1-adrenergic receptors and blocking is permissible[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(2)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe Multiwfn program was used to plot each total, partial, and overlap density state (TDOS, PDOS, and OPDOS). Figures (4) depicts these plots. The curve maps of broadened partial DOS (PDOS) and overlap population DOS (OPDOS) for the title molecule is very useful for visualizing atomic orbitals of different fragments and have significant contributions to the corresponding MOs and chemical bonding. Figure \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e depicts the fragments of the title molecule and their PDOS and OPDOS only in the valence MOs range. The left axis represents TDOS and PDOS, while the right axis represents OPDOS, and the vertical dashed line indicates the position of the HOMO. Red, blue, magenta, brown, and yellow have been observed to have the highest contribution to valence MOs, with comparable amounts of contribution. The green curve represents the OPDOS between fragments 1, and 2, and its positive part indicates that MOs in the corresponding energy range exhibit bonding properties between two fragments (e.g. the one at -0.231 a.u which corresponds to MO 108).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (4)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec7\"\u003e\n \u003ch2\u003e3.1.4 Molecular electrostatic potential (MEP) map\u003c/h2\u003e\n \u003cp\u003eTo forecast reactivity, find places for nucleophilic and electrophilic attacks on the molecule, and lastly assess the biological recognition process and hydrogen bonding interactions, one can use the concept of molecular electrostatic potential (MEP), which is connected to electron density[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e].Drug-receptor interactions and the electrostaticpotential (ESP) V(r) have both been extensively studied[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. Figures (5) depicts the 3D ESP map of the investigated molecule to determine the different electrostatic potential values at both electrophilic and nucleophilic sites. The most electrostatically positive, most negatively charged, and zero electrostatic potential regions are represented by the colors blue, red, and white on the MEP surface, respectively. The figure shows 5 surface maxima for positive potential sites surrounding the hydrogen atoms and 4 surface minima for the negative potential sites on chlorine and oxygen atoms. The global minimum on the surface (-49.9 kcal/mol) is located on Cl57. While the location of the surface\u0026apos;s global maxima (+\u0026thinsp;46.8 kcal/mol) is located on H27. We note that the strongest nucleophilic and electrophilic sites, as well as the global maximum and minimum, are found in the vicinity of hydrogen chloride. According to the MEP map, the region that contains the hydrogen chloride molecule has a significant biological activity, plays a more significant role than any other location in the recognition of the drug in biological systems, and can establish halogen bonds.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec8\"\u003e\n \u003ch2\u003e3.1.5 Reduced Density Gradient\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003eEquation(1)\u003c/strong\u003e gives the reduced density gradient (RDG), which is a fundamental dimensionless quantity derived from the density and its first derivative[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\n \u003cdiv class=\"Equation\" id=\"Equ1\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e$${\\text{RDG(}}r{\\text{)}}=\\frac{1}{{2{{\\left( {3{\\pi ^2}} \\right)}^{\\frac{1}{3}}}}}\\frac{{\\nabla \\rho (r)}}{{\\rho {{(r)}^{\\frac{4}{3}}}}}$$\u003c/div\u003e\n \u003cdiv class=\"EquationNumber\"\u003e(1)\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eLarge negative values of sign (\u0026lambda;\u003csub\u003e2\u003c/sub\u003e) in RDG tails indicate attractive interactions (such as dipole-dipole or hydrogen bonding); if the sign (\u0026lambda;\u003csub\u003e2\u003c/sub\u003e ) is large and positive, the interaction is non-bonding (steric effect).\u003c/p\u003e\n \u003cp\u003eNear-zero values indicate very weak van der Waals interactions. Multiwfn was used to generate the RDG of the BB.HCl structures,whichwerethen plotted using the VMD program[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. Figures\u0026nbsp;(6\u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003e)\u003c/span\u003e depicts these results.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (6)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGreen colors represent van der Waals interactions, while the red color represents strong repulsion. Inside the ring, repulsive interactions were observed, while van der Waals interactions were observed between the hydrogen atoms.The blue colors in BB.HCl indicates hydrogen bonding and halogen bonding interactions[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec9\"\u003e\n \u003ch2\u003e3.1.6 Natural bond orbital (NBO) analysis\u003c/h2\u003e\n \u003cp\u003eNatural bond orbital analysis of bambuterol hydrochloride molecule is performed using NBO 3.1 module as implemented in Gaussian 09 program to confirm the charge transfer and conjugation interaction within the molecule. A Second order perturbation approach Fock matrix gives an examination of the energetic importance of electron transfer from the donor (Lewis-type NBOs) to accepter (non-Lewis NBOs). The stabilization energy,E\u003csub\u003e(2)\u003c/sub\u003e, represents the degree of electron transfer from donor to acceptor known as the degree of electron delocalization[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eE\u003c/em\u003e \u003csub\u003e\u0026nbsp;\u003cem\u003e(2)\u003c/em\u003e\u0026nbsp;\u003c/sub\u003e \u003cem\u003e= △E\u003c/em\u003e\u003csub\u003e\u003cem\u003ei j\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e= q\u003c/em\u003e \u003csub\u003e\u003cem\u003ei j\u003c/em\u003e\u003c/sub\u003e \u003cem\u003e=\u003c/em\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{F {(i, j )}^{2}}{Ej-Ei}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eWhere q \u003csub\u003eij\u003c/sub\u003e is donor orbital occupancy, \u003cem\u003eF (i, j)\u003c/em\u003e is the off\u0026ndash;diagonal Fock matrix element, E\u003csub\u003ej\u003c/sub\u003e and \u003cem\u003eE\u003c/em\u003e\u003csub\u003e\u003cem\u003ei\u003c/em\u003e\u003c/sub\u003eare the diagonal element (orbital energies).\u003cem\u003eE\u003c/em\u003e \u003csub\u003e\u003cem\u003e(2\u003c/em\u003e)\u003c/sub\u003e value can represent (reflect) the intensity of electron donor and electron acceptor and the degree of conjugation of the structure. The occupancy and energies of (i) and (j) with △\u003cem\u003eE\u003c/em\u003e\u003csub\u003e\u003cem\u003eij\u003c/em\u003e\u003c/sub\u003eof the most significant lone pair (LP) and boning \u003cimg src=\"data:image/png;base64,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\" width=\"39\" height=\"22\"\u003e to anti-bonding \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({BD}^{*}(\\)\u003c/span\u003e\u003c/span\u003e\u0026sigma;*\u0026frasl;\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\pi }^{*}\\)\u003c/span\u003e\u003c/span\u003e) are given in table (3). It can be seen from \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003etable (3)\u003c/span\u003e that the majority of the contributions to the stability of the drug comes from lone pair interaction donor (NBO (i)) with anti-bonding BD\u003csup\u003e*\u003c/sup\u003e orbitals acceptor (NBO\u003csub\u003ej\u003c/sub\u003e)significant contributions of \u003cem\u003elP\u003c/em\u003e(1) N7⟶\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\sigma }^{*}\\)\u003c/span\u003e\u003c/span\u003e(O4 \u0026ndash; C21) and \u003cem\u003elP\u003c/em\u003e(1) N8⟶\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\sigma }^{*}\\)\u003c/span\u003e\u003c/span\u003e(O5 \u0026ndash; C22).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(3)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe other significant interactions gave a stronger stabilization energy value of 220.31and 231.09 kJ/mol to the structure are the interaction between the antibonding of C16\u0026ndash;C19 and C18 \u0026ndash;C20 respectively. Significant contribution to the stabilization energy could be added by \u003cem\u003eLP\u003c/em\u003e (4) Cl57⟶\u003cem\u003eLP\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003eH27 of 102.55 value of E\u003csub\u003e2 (i)\u003c/sub\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec10\"\u003e\n \u003ch2\u003e3.1.7 The electron localization function (ELF)\u003c/h2\u003e\n \u003cp\u003eELF provides important information on the electron environment, chemical bonding, and atomic shell on the surface of the molecule. The colored map of ELF drawn by Multiwfn software is shown in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (7)\u003c/span\u003e higher values of ELF plotted between the range 0.85 \u0026minus;\u0026thinsp;1.0 Bohr indicate the strong localization of electrons and formation of covalent bonds, whereas lower values lie between 0.0 and 0.4 Bohr denote the strong delocalization of electrons. From the ELF color map, we observe highly localized areas surrounding hydrogen atoms indicated by red color. Delocalized electrons predicated around oxygen and carbon atoms are shown in blue. The high value of electron localization occurs between the carbon atoms in the ring with the hydrogen atoms due to the overlap of the SP orbitals of carbon with the S orbital of hydrogen. Deformation of the ELF distribution around the oxygen is due to hydrogen and halogen bond interactions.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (7)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe 3D plot of ELF for bambuterol hydrochloride is shown in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (8).\u003c/span\u003ethe monosynaptic basin is associated with the lone pair whereas the disynaptic basin belongs to covalent interaction. The monosynaptic lone pair regions of oxygen, nitrogen, and chloride occupy more space. While the disynaptic associated with OH, NH, and CH occupy less space due to halogen and hydrogen bond interactions.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec11\"\u003e\n \u003ch2\u003e3.1.8 Vibration analysis.\u003c/h2\u003e\n \u003cp\u003eThe molecule contains 57 atoms and hence 165 modes of vibrations. These 165 normal modes of vibrations are distributed among the symmetry specie as follow, considering C\u003csub\u003e2\u003c/sub\u003e point symmetry.\u003c/p\u003e\n \u003cp\u003e\u003csub\u003e┌vibration\u003c/sub\u003e =111\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({A}^{{\\prime }}\\)\u003c/span\u003e\u003c/span\u003e+ 54\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({A}^{\u0026quot;}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u0026nbsp;\u003cspan class=\"mathinline\"\u003e\\({A}^{{\\prime }}\\)\u003c/span\u003e\u0026nbsp;\u003c/span\u003eand \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({A}^{\u0026quot;}\\)\u003c/span\u003e\u003c/span\u003e represent the vibrations which lie within in plane and out of plane, respectively. In C\u003csub\u003e2\u003c/sub\u003e group, the symmetry of the molecule is a non-planar structure and has the 165 modes in irreducible representation. The calculated vibrations wavenumbers are higher than experimental values for the majority of the normal modes due to the environment of performing vibrations (gas phase for theoretical and solid state for experimental), and the fact that the experimental values are inharmonic wave numbers while the calculated values are harmonic ones. Therefore, the computed wavenumbers are scaled down using a scaling factor of 0.9608 to discard the anharmonicity present in the real system. The methyl group makes a significant contribution to the vibration spectrum of bambuterol hydrochloride since the molecule contains 7 methyl groups. Therefore, we will discuss the assignment of methyl group vibrations in detail. Nine fundamental modes of vibrations can be associated with each methyl group: two asymmetric stretching, one symmetric stretching, two asymmetric deformations, one symmetric deformation, two rocking vibrations, and one torsion mode of vibration. The computed (scaled) vibrations of the methyl group together with the experimentally observed frequencies and the assignments ate present in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003etable (4)\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(4)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec12\"\u003e\n \u003ch2\u003e\u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003e3.1.9 AIM calculations\u003c/span\u003e.\u003c/h2\u003e\n \u003cp\u003eAtoms in molecules (AIM) theory is a convenient method to analyze the hydrogen bonding and other interactions in various molecular systems and has been extensively used to classify and understand bonding interactions in terms of quantum mechanical parameters and their derivatives as electron density (𝞺). The theory of AIM efficiently describes H-bonding and it\u003csup\u003e\u0026apos;\u003c/sup\u003es a concept without borders. One of the advantages of this theory is that one can obtain information on the change in electron density distribution as the result of their bond formation or complex formation[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]. The molecular graph of the molecule using AIM theory is shown in \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eFigure (9)\u003c/span\u003e the topological parameters of non-covalent interactions are grouped in a table (5). AIM results show that bambuterol hydrochloride is characterized by 4BCPs of non-covalent character. Two describing hydrogen bonding, and two characters halogen bonding interactions. According to the values of the parameters reported \u003cstrong\u003ein table (5\u003c/strong\u003e). We can classify the non-covalent interactions as weak hydrogen and halogen bonding interaction except for N6-H27\u0026hellip;\u0026hellip;Cl57 strong bonding interactions [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (9)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec13\"\u003e\n \u003ch2\u003e\u003cstrong\u003e3.1.10 Nonlinear optical effects and first hyper polarizability\u003c/strong\u003e.\u003c/h2\u003e\n \u003cp\u003eNLO is at the cutting edge of current research because it provides the critical functions of frequency shifting, optical modulation, optical switching, optical logic, and optical memory for emerging technologies such as telecommunications, signal processing, and optical interconnections[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. The prediction of non-linear optical (NLO) properties of a molecule by quantum chemistry plays an important role in the design of materials in modern communication technology[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Organic molecules, in particular, are being studied due to their higher NLO susceptibilities caused by electron cloud movement\u003c/p\u003e\n \u003cp\u003efrom donor to acceptor, rapid NLO response times, high laser damage thresholds, and low dielectric constants. \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eTable\u0026nbsp;(6)\u003c/span\u003e shows the dipole moment, polarizability, and first hyper polarizability components of the title compound which invariant are calculated with a numerical derivative of the dipole moment using RB3LYP/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G(d) level of DFT. The total static dipole moment, average linear polarizability, anisotropy of polarizability, and first hyper polarizability can be calculated using the equations below [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026micro; = (\u0026micro;\u003c/strong\u003e \u003csub\u003e\u0026nbsp;\u003cstrong\u003ex\u003c/strong\u003e\u0026nbsp;\u003c/sub\u003e \u003csup\u003e\u0026nbsp;\u003cstrong\u003e2\u003c/strong\u003e\u0026nbsp;\u003c/sup\u003e \u003cstrong\u003e+ \u0026micro;\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/sub\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003cstrong\u003e+ \u0026micro;\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003ez\u003c/strong\u003e\u003c/sub\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003cstrong\u003e)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e1\\2\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026alpha; \u003cstrong\u003e=\u003c/strong\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{1}{3}\\)\u003c/span\u003e\u003c/span\u003e \u003cstrong\u003e(\u003c/strong\u003e \u0026alpha;\u003csub\u003e\u003cstrong\u003exx\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;\u003cstrong\u003e+\u003c/strong\u003e\u0026thinsp;\u0026alpha;\u003csub\u003e\u003cstrong\u003eyy\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;\u003cstrong\u003e+\u003c/strong\u003e\u0026thinsp;\u0026alpha;\u003csub\u003e\u003cstrong\u003ezz\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e△\u003c/strong\u003e\u0026alpha; \u003cstrong\u003e=\u003c/strong\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{1}{\\surd 2}\\)\u003c/span\u003e\u003c/span\u003e \u003cstrong\u003e[ (\u003c/strong\u003e\u0026alpha;\u003csub\u003e\u003cstrong\u003exx\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e-\u003c/strong\u003e \u0026alpha;\u003csub\u003e\u003cstrong\u003eyy\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003csub\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e(\u003c/strong\u003e\u0026alpha;\u003csub\u003e\u003cstrong\u003eyy\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e-\u003c/strong\u003e \u0026alpha;\u003csub\u003e\u003cstrong\u003ezz\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003cstrong\u003e+ (\u003c/strong\u003e \u0026alpha;\u003csub\u003e\u003cstrong\u003ezz\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e-\u003c/strong\u003e \u0026alpha;\u003csub\u003e\u003cstrong\u003exx\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003cstrong\u003e+ 6\u003c/strong\u003e\u0026alpha;\u003csub\u003e\u003cstrong\u003exx\u003c/strong\u003e\u003c/sub\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e \u003cstrong\u003e]\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e1\\2\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026beta; \u003cstrong\u003e=\u003c/strong\u003e[ ( \u0026beta;\u003csub\u003e\u003cstrong\u003exxx\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003exyy\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003exzz\u003c/sub\u003e )\u003csup\u003e2\u003c/sup\u003e + (\u0026beta;\u003csub\u003eyyy\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003exxy\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003eyzz\u003c/sub\u003e)\u003csup\u003e2\u003c/sup\u003e + ( \u0026beta;\u003csub\u003ezzz\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003exxz\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;\u0026beta;\u003csub\u003eyyz\u003c/sub\u003e )\u003csup\u003e2\u003c/sup\u003e ]\u003csup\u003e1\\2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(6)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe calculated values\u0026nbsp;of total static dipole moment \u0026micro;, the average linear polarizability \u0026alpha; ,the anisotropy of the polarizability ∆\u0026alpha; ,and the first hyper polarizability \u0026beta; using the\u0026nbsp;RB3LYP/6-31+G(d)\u0026nbsp;level of DFTmethodare8.5Debye,297.5 a.u,540.42 a.uand2.676\u0026times;10\u003csup\u003e-30\u003c/sup\u003ee.s.u, respectively.\u003c/p\u003e\n \u003cp\u003eUrea is one of the prototypical molecules used in the study of the NLO properties of molecular systems, and it is frequently used as a threshold value for comparative purposes. \u0026nbsp;The values of \u0026micro;, \u0026alpha;, and \u0026beta; obtained with the RB3LYP/6-31+G(d)method for urea are 1.373 Debye, 3.831 \u0026Aring;\u003csup\u003e3\u003c/sup\u003e and 3.729\u0026times;10\u003csup\u003e-31\u003c/sup\u003e cm\u003csup\u003e5\u003c/sup\u003e e.s.u.\u003csup\u003e-1\u003c/sup\u003e, respectively[26]\u003cstrong\u003e.\u003c/strong\u003eThe title compound\u0026apos;s first hyper polarizability is 8 times that of urea. The title compound may be a potential candidate in the development of NLO materials based on the magnitude of its first hyper polarizability. As a result, this molecule could serve as a potential building block for nonlinear optical materials.\u003c/p\u003e\n \u003cp\u003e\u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003e\u003cstrong\u003e3.1.11. Molecular docking\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eMolecular modelling and visualization were performed on Human butyrylcholinesterase using Molecular Operating Environment (MOE) 2019.01. The structure of Human butyrylcholinesterase in complex with thioflavine T obtained from the RCSB Protein Data Bank (PDB ID: 6esy). Bambuterol was prepared with the standard protocol in MOE 2019 and the energy of the docked compound was minimized with gradient RMSE of 0.0001kcal/mol. Then, butyrylcholinesterase structure was prepared by using the MOE QuickPrep protocol. The docking was done using the method of Alpha triangle placement with Amber10: EHT forcefield. Refinement was performed with Forcefield and scored using the Affinity dG scoring system.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3.1.11.1. Results\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDocking protocol was validated by re-docking of the co-crystalized thioflavine T at the active site of butyrylcholinesterase (PDB ID: 6esy), Fig. (10). the re-docking rmsd\u0026thinsp;=\u0026thinsp;1.2363 \u0026Aring; and binding score = -6.81 Kcal.mol-1. All the key interactions accomplished by the co-crystalized ligand with the key amino acids in the binding site is reproducible using the followed docking setup, mentioned in the experimental section. The validated docking setup was then used to investigate the ligand-receptor interactions and binding patterns for bambuterol hydrochloride (score = -7.24 Kcal.mol-1), Figure (11). The amino acid residues involved in interaction at binding site with co-crystallized thioflavine T are Ser53, Ile55, Trp56 and Asn57[\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e], where the main interactions are H-bonding with amino acid residues through oxygen atom of pyranose ring and attached OH groups. In addition, amidic NH group formed \u0026pi;-H bond with indole ring of Trp56 residue.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (10)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFigure (11)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe docking investigation showed that bambuterol hydrochloride depicted the same interactions as thioflavine T at different poses, but the common residues are Ile55, Trp56 and Asn57 and these amino acid residues as discussed before are essential for inhibition of butyrylcholinesterase enzyme. Beside these amino acids, bambuterol hydrochloride interacts with other amino acids as extra binding interactions Table\u0026nbsp;(7) that are mainly H-bonding which induced and driven by carbamate ester group with Thr59, Lys60, Asn63 residues and H-bonding between primaryNH2 group and Asp54 residue and all that justified the lower binding score and higher affinity of bambuterol than thioflavine T towards butyrylcholinesterase enzyme.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable (7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the present work, a computational study using RB3LYP/ 6-31 G(d) level of the DFT method has been used to calculate the geometrical parameters of the optimized structure for bambuterol hydrochloride. The lowering of the HOMO-LUMO energy gap indicates the charge transfer interaction which leads to the NLO activity.AIM, NBO, ELF, and RDG topological analysis have been reported to study the properties of hydrogen and halogen bonds in the title compound. The MEP map shows that the negative potential sites are located on oxygen and chlorine atom. \u0026nbsp;Atomic charges analysis by Mullikan charge revealed similar values of positive charges for all hydrogen atoms forming methyl groups.\u003c/p\u003e\n\u003cp\u003eThe validated docking setup was used to investigate the ligand-receptor interactions and binding patterns for bambuterol (score = -7.24 Kcal.mol\u003csup\u003e-1\u003c/sup\u003e).The computed (scaled) frequencies of the methyl groups usingRB3LYP/6-31+G(d) level of DFT display a good agreement with the experimental FT-IR spectrum of the BB.HCl.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThis work is a part of\u003cstrong\u003e\u0026nbsp;Walaa.S.S.Alblozy\u003c/strong\u003e M.Sc. thesis. The authors like to thank Assiut University for the official, technical and financial support. The authors also acknowledge a generous allocation of computer time granted by SHARCNET, a partner consortium in the Compute Canada national HPC platform.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eall authors contributed to the conceptualization and realization of the study Walaa.S.S.Alblozy carried out the computations and analysis of result\u003cstrong\u003e\u0026nbsp;Refaat M. Mahfouz\u003c/strong\u003e wrote the first draft and reviewed the results.\u0026nbsp;\u003cstrong\u003eAhmed A. K. Mohammed\u003c/strong\u003e\u0026nbsp;contributed in computational and analysis of the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: the authors have declared that there is no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSweetman SC. 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Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study. \u003cem\u003eMolecules\u003c/em\u003e. 2017 Nov 29,22(12):2098.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Selected geometrical parameters of Bambuterol hydrochloride obtained by RB3LYP /6-31+G(d) \u0026nbsp; levels of DFT\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBond lengths(A\u0026deg;) by RB3LYP /6-31+G(d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBond angles(\u0026deg;) by RB3LYP /6-31+G(d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDihedral angles (\u0026deg;) \u0026nbsp;by RB3LYP /6-31+G(d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003eO2 - C18 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1.39\u003c/p\u003e\n \u003cp\u003eO4 - C21 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.21\u003c/p\u003e\n \u003cp\u003eO3 \u0026ndash; C22 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.37\u003c/p\u003e\n \u003cp\u003eN7 \u0026ndash; C21 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.36\u003c/p\u003e\n \u003cp\u003eN7 - \u0026nbsp;C23 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.46\u003c/p\u003e\n \u003cp\u003eN8 \u0026ndash; C22 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.36\u003c/p\u003e\n \u003cp\u003eN6 \u0026ndash; C10 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.49\u003c/p\u003e\n \u003cp\u003eCl57 \u0026ndash; H42 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1.87\u003c/p\u003e\n \u003cp\u003eCl57-H32 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003eO4 - C21- N7 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 125.8\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eO2 - C21- O4 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;123.39\u003c/p\u003e\n \u003cp\u003eO3 \u0026ndash; C19 - C20 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 116.3\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eO2 - \u0026nbsp;C17 - C18 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 116.8\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC18-O2 \u0026ndash;C21 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 118.5\u003c/p\u003e\n \u003cp\u003eC19-O3\u0026ndash;C22 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;118.95\u003c/p\u003e\n \u003cp\u003eC21-N7-C24 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;124.17\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC22- N7-C25 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;118.6\u003c/p\u003e\n \u003cp\u003eO2\u0026ndash;C20- C18 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;121.20\u003c/p\u003e\n \u003cp\u003eO5\u0026ndash;C22- \u0026nbsp;N8 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;125.6\u003c/p\u003e\n \u003cp\u003eC22-N8-C26 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;124.2 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.333333333333336%\"\u003e\n \u003cp\u003eC21 O3 \u0026nbsp;C22 \u0026nbsp; \u0026nbsp; O5 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;4.67 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC15C17 \u0026nbsp;C18 \u0026nbsp; \u0026nbsp; O2 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -176.8\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC22O3 C19 C20 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 70.49\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC18 C20 C19 O3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-176.19\u003c/p\u003e\n \u003cp\u003eC22 O3 \u0026nbsp;C19 C15 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;52.55\u003c/p\u003e\n \u003cp\u003eC25 \u0026nbsp;N8 C22 O3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -173.99\u003c/p\u003e\n \u003cp\u003eC15C11C10 N6 \u0026nbsp; \u0026nbsp; \u0026nbsp;-165.11 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;2.\u0026nbsp;Thereactivityparametersfor bambuterol hydrochloride\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemical reactivity descriptor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eIonization potential \u003cem\u003e(I)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e6.248 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eElectron affinity \u003cem\u003e(A)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e0.578 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eElectronegativity (𝝌)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e3.414 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eChemical potential (𝝁)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e-3.414V\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eChemical hardness(\u0026eta;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e2.836 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eChemical softness(𝑺)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e0.352 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eElectrophilicity index(𝝎)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e2.055 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eEnergy change(𝚫𝑬)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e-2.055 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003eMaximalchargeacceptance(𝚫𝑵\u003csub\u003e𝒎𝒂\u003c/sub\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e1.203 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.91869918699187%\"\u003e\n \u003cp\u003e\u0026Delta;E/\u0026Delta; \u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.08130081300813%\"\u003e\n \u003cp\u003e-1.707 eV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Second order perturbation analysis of the Fock matrix of bambuterol hydrochloride\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"653\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003eF (i,j) a.u \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003eE\u003csub\u003ej\u003c/sub\u003e-E\u003csub\u003ei\u003c/sub\u003e a.u.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003eE\u003csup\u003e(2)a\u0026nbsp;\u003c/sup\u003ekcal/mol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003eAcceptor j\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"22.93577981651376%\"\u003e\n \u003cp dir=\"LTR\"\u003eDonor \u0026nbsp;i\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003e0.059\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e0.37\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e10.71\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cem\u003eC16-C19\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(2)O3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e(1)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003e0.130\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e0.58\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e35.92\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cem\u003eO2-C21\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(2)O4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e(2)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003e0.117\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e0.72\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e22.60\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cem\u003eN7- C21\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(2)O4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e(3)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.130\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e35.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;O3- C22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(2)O5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.117\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e22.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;N8- C22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(2)O5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.113\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e45.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;O4- C21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(1)N7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.112\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e43.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;O5- C22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(1)N8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp; (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.190\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e102.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e H27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003eLP(4)Cl57\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.082\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e220.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003eC15-C17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003eBD(2)\u003csup\u003e*\u003c/sup\u003eC18-C20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.302752293577981%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.082\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.795107033639145%\"\u003e\n \u003cp dir=\"LTR\"\u003e231.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.217125382262996%\"\u003e\n \u003cp dir=\"LTR\"\u003eC15-C17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.749235474006117%\"\u003e\n \u003cp dir=\"LTR\"\u003eBD(2)\u003csup\u003e*\u003c/sup\u003eC16-C19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.186544342507645%\"\u003e\n \u003cp dir=\"LTR\"\u003e(10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4. The observed FT-IR and computed frequencies atRB3LYP /6-31+G(d) level of DFT of bambuterol hydrochloride(methyl groups vibrations)\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"532\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cu\u003eAssignment\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cu\u003eExp.\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eintensity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eScaled\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ecomputed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eNO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003eע\u003c/span\u003e\u003csub\u003easy\u0026nbsp;\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e3002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e37.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e3008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e3134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003eע\u003c/span\u003e\u003csub\u003esy\u0026nbsp;\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e2898\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e119.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e2909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e3031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003eS\u003csub\u003easy\u0026nbsp;\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1446\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e88.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e1424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003eS\u003csub\u003e\u0026nbsp;sy\u0026nbsp;\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e105.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e1379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003e𝞺\u003csub\u003easy\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e601.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e1136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.804511278195488%\"\u003e\n \u003cp dir=\"LTR\"\u003e𝞺\u003csub\u003esy\u003c/sub\u003e(CH3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.857142857142858%\"\u003e\n \u003cp dir=\"LTR\"\u003e62.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.669172932330827%\"\u003e\n \u003cp dir=\"LTR\"\u003e1017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.977443609022556%\"\u003e\n \u003cp dir=\"LTR\"\u003e1064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.714285714285714%\"\u003e\n \u003cp dir=\"LTR\"\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan dir=\"RTL\"\u003eע\u003c/span\u003e\u003csub\u003easy\u0026nbsp;\u003c/sub\u003e⟶asymmetric stretching\u003c/p\u003e\n\u003cp\u003e\u003cspan dir=\"RTL\"\u003eע\u003c/span\u003e\u003csub\u003esy\u0026nbsp;\u003c/sub\u003e⟶symmetric stretching\u003c/p\u003e\n\u003cp\u003eS\u003csub\u003easy\u0026nbsp;\u003c/sub\u003e⟶asymmetric deformation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eS\u003csub\u003esy\u0026nbsp;\u003c/sub\u003e⟶symmetric deformation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e𝞺\u003csub\u003easy\u003c/sub\u003e⟶asymmetric\u0026nbsp;rocking\u003c/p\u003e\n\u003cp\u003e\u003cspan dir=\"LTR\"\u003e𝞺\u003c/span\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003esy\u003c/span\u003e\u003c/sub\u003e\u003cspan dir=\"LTR\"\u003e⟶\u003c/span\u003e\u003cspan dir=\"LTR\"\u003esymmetric\u003c/span\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;rocking\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5. topological parameters of the non \u0026ndash;covalent interactions of BB.HCl\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"652\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.950920245398773%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003e\u003csub\u003ebond\u0026nbsp;\u003c/sub\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;kJ/mol.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eELF (a.u)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eV ( r ) a.u\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLocalization potential\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.865030674846626%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;𝞺\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e(r) a.u\u0026nabla;\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLaplacian of the electron density\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.33128834355828%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e𝞺\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e(r) a.u\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eElectron density\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.779141104294478%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003einteractions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.950920245398773%\"\u003e\n \u003cp dir=\"LTR\"\u003e-19.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.08778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e-0.01506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.865030674846626%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.061778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.33128834355828%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.001682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.779141104294478%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eO1 \u0026ndash;H42\u0026hellip;CL57\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.950920245398773%\"\u003e\n \u003cp dir=\"LTR\"\u003e-57.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.30722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e-0.044249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.865030674846626%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.10121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.33128834355828%\"\u003e\n \u003cp dir=\"LTR\"\u003e-0.009472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.779141104294478%\"\u003e\n \u003cp dir=\"LTR\"\u003eN6 \u0026ndash; H27...CL57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.950920245398773%\"\u003e\n \u003cp dir=\"LTR\"\u003e-18.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.03816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e-0.014301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.865030674846626%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.08193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.33128834355828%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.003090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.779141104294478%\"\u003e\n \u003cp dir=\"LTR\"\u003eC21 \u0026ndash; O2 \u0026hellip;H48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.950920245398773%\"\u003e\n \u003cp dir=\"LTR\"\u003e-18.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.038257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.036809815950921%\"\u003e\n \u003cp dir=\"LTR\"\u003e-0.01402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.865030674846626%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.082101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.33128834355828%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.003095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.779141104294478%\"\u003e\n \u003cp dir=\"LTR\"\u003eC26 \u0026ndash; H54\u0026hellip;.O3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 6. Calculated dipolemoment \u003cem\u003e\u0026micro;\u003c/em\u003e (Debye),polarizability\u003cem\u003e(\u0026alpha;)\u003c/em\u003eand thefirst hyperpolarizability\u003cem\u003e\u0026nbsp;(\u0026beta;)\u003c/em\u003e components(a.u.) of BB.HCl\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"635\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.652996845425868%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eValues\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.86435331230284%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003ecomponents\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.820189274447948%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003evalues\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.662460567823345%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003ecomponents\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.652996845425868%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e246.283\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-303.285\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-3.73170\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-146.087\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-26.1894\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-142.729\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-62.19\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e28.1994\u003c/span\u003e\u003c/em\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.86435331230284%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003exxx\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003exyy\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003exzz\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta; \u003csub\u003eyyy\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003exxy\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003eyzz\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003ezzz\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003exxz\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026beta;\u003csub\u003eyyz\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.820189274447948%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e5.81840\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-1.48979\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e-6.12364\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e308.136\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e307.742\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e222.910\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e4.89543\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e1.15448\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e0.199889\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.662460567823345%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026micro;\u003csub\u003ex\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026micro;\u003csub\u003ey\u003c/sub\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003ez\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u0026micro;\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003exx\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003eyy\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003ezz\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003exy\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003exz\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003ea\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003cem\u003e\u003csub\u003e\u003cspan dir=\"LTR\"\u003eyz\u003c/span\u003e\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eTable 7. Energy scores (kcal/mol) and interactions for Bambuterol hydrochloride\u003c/span\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eCompound\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eEnergy score (S) (kcal/mol)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"35.80246913580247%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eAmino acids involved in interaction\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eThioflavine T\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e-6.81\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"35.80246913580247%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eSer53, Ile55, Trp56, Asn57\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eBambuterol\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.098765432098766%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e-7.24\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"35.80246913580247%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003eSer53, Ile55, Trp56, Asn57, Asp54, Thr59, Lys60, Asn63\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bambuterol hydrochloride, Computational study, DFT calculations, Geometry optimization, docking procedure, Vibration spectroscopy","lastPublishedDoi":"10.21203/rs.3.rs-2767196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2767196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe main objective of the study is to provide deep knowledge of structural and reactivity features of bambuterol hydrochloride (BB.HCl) drug compound. Theoretical calculations are done by the density functional theory (DFT) method with RB3LYP/6\u0026ndash;31\u0026thinsp;+\u0026thinsp;G (d) level and basis set. The computational study by DFT was used to explore \u003cem\u003eHOMO \u0026ndash;LUMO\u003c/em\u003e energies, global reactivity parameters, \u003cem\u003eNLO\u003c/em\u003e using the aforementioned level of theory and basis set. The nature of the hydrogen and halogen bonding interactions was analyzed by NBO, AIM, and RDG analysis. Electron localization function (ELF) analysis provides new insight into the chemical bonding of bambuterol hydrochloride. The pharmaceutical potential of the drug has been considered by molecular docking procedure.\u003c/p\u003e","manuscriptTitle":"Computational study and quantum – chemical investigation on bambuterol hydrochloride compound drug: ADFT approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-06 14:23:25","doi":"10.21203/rs.3.rs-2767196/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f39443ef-4e41-4b75-a423-f56678d3f647","owner":[],"postedDate":"April 6th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-04-07T15:59:27+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-06 14:23:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2767196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2767196","identity":"rs-2767196","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}