Utility of Zn12O12 Nanocage for The Elimination of Ciprofloxacin From Drinking Water Using DFT Simulations

Utility of Zn12O12 Nanocage for The Elimination of Ciprofloxacin From Drinking Water Using DFT Simulations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Utility of Zn 12 O 12 Nanocage for The Elimination of Ciprofloxacin From Drinking Water Using DFT Simulations Qaisar Ali, Hamad Khan, Salman Khan, Mahtab Alam, Ajmal Shah, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9432981/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract According to the biochemical theory, the development of pollutants like antibiotics is a worldwide issue since they foster antibiotic resistance. A detailed DFT analysis was carried out to examine the adsorption capabilities of the Zn 12 O 12 nanocage for ciprofloxacin (CIP). Five optimal structures of Zn 12 O 12 -CIP complexes, named CMP-1 to CMP-5. CMP-3 show best adsorption energy of 48.9929 kcal/mol, represent the best interaction without any structural deformation of the nanocage. The mechanism by which the interaction takes place is that CIP molecules are bound to Zn and O atoms of the nanocage by their F and O atoms respectively. FMO indicated that the bandgap of the entire range of Zn 12 O 12 CIP complexes on adsorption reduce to make the complexes more reactive and to verify the favorable adsorption characteristics. The NBO analysis revealed that the CMP-3 complex had the highest charge transfer of = 0.139e with the minimum bond distance of 1.92 Å and 1.25 Å respectively. The presence of covalent and weak electrostatic interaction between nanocage and CIP molecules was confirmed by QTAIM, NCI and RDG analysis. The thermodynamic assessment showed that adsorption of the process is spontaneous. The nanocage of Zn 12 O 12 is easily regenerated, makes the nanocage a potential application in the real world concerning the aspects of environmental remediation. Physical sciences/Chemistry Earth and environmental sciences/Environmental sciences Physical sciences/Materials science Physical sciences/Nanoscience and technology DFT Ciprofloxacin Adsorptions Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION Antibiotics are widely used in the management of a broad spectrum of infections with the inclusion of those of the urinary tract, respiratory system, and central nervous system 1 . Ciprofloxacin (CIP) is a broad-spectrum antibiotic comprising of Fluoroquinolone, which is one of the most common agents used in the treatment of various bacterial infections 2 . At the same time, a significant portion of the ciprofloxacin administered to a patient is excreted via urine and thus, the drug continuously enters the water body due to its partial metabolism in the human body 3 . The significant routes through which it has been caused in water masses include discharges like hospital effluents, pharmaceutical manufacturing, and domestic sewage 4 , 5 . The fact that ciprofloxacin remains in aquatic system is alarming because it may cause severe health conditions in all human beings and animals which include glycemic responses, seizures, gastrointestinal disorders, bacterial resilience and tendon disorders 6 . A ciprofloxacin is highly soluble in aqueous at a wide the pH scale, and its molecular structure is stable, which is why the drug is resistant to natural decay, making it hard to eliminate in polluted water 7 . Different treatment methods have also been studied in the remediation of ciprofloxacin among them are, biological degradation 8 , photolysis 9 , membrane separation methods 10 , ion exchange processing 11 , and chemical oxidation methods 12 . In spite of the stated benefits, these methods are frequently limited by such negative factors as high operation costs, low selectivity, and low efficiency that prevent the application of such methods on a large-scale level 13 – 15 . However, over the last few years, nanomaterials have become a potential candidate in the context of the environmental application due to their peculiar physicochemical characteristics 16 – 25 . Both zinc oxide (ZnO) has shown impressive potential in the field of sensing, catalysis and adsorption, as well as their potential to interact with diverse molecules 26 – 33 . Recently, it was observed that a B 12 N 12 nanocage can be useful as an adsorbent, and the removal of CIP is effective with the assistance of it 34 . Here, the given work studies the adsorption of ciprofloxacin on Zn 12 O 12 nanocage by using the density functional theory (DFT) calculations. The paper sheds light on the adsorption mechanism and studied it with the help of frontier molecular orbital (FMO), natural bond orbital (NBO), and charge transfer assessment, and the determination of the dipole moment. Moreover, non-covalent interaction (NCI) and reduced density gradient (RDG) are utilized to explain the nature of interactions. The method of solvent effect considerations is done with the polarizable continuum model (PCM), whereas thermodynamic parameters and regeneration potential are determined to evaluate the efficiency and reusability of Zn 12 O 12 nanocages as ciprofloxacin adsorbents. RESULTS AND DISCUSSIONS Geometries Optimization Of Zn 12 O 12 Nanocage Ciprofloxacin And Complexes The computed structure of Zn 12 O 12 nanocage, determined through the computational method described above, was seen to consist of six four-membered rings (4 MRs), and eight six-membered rings (6 MRs) as shown in Fig. 1 . The analysis indicated two types of bonds in the nanocage which are: Zn-O bonds in both 4MRs and 6MRs, and Zn-Zn bonds in the 4MRs and have a bond length of about 1.90 Å and 1.80 Å respectively. The increased ZnO bonds length in the 4MRs than the 6MRs is due to higher angular strain in the smaller ring system which is in line with other previous results. The bond angle analysis revealed that the O-Zn-O and Zn-O-Zn angles in 6MRs and 4MRs are 126.19° and 92.16° and 111.96° and 86.40° respectively. These data are coherent with the earlier documented information, which validates the geometrical characteristics of the nanocage 53 , 54 . The electronic properties of the nanocage are indicated by the molecular electrostatic potential (MEP) map of Fig. 1 . The yellow and red areas around the oxygen atoms are sites of negative electrostatic potentials and so, they represent the electrophilic sites. On the contrary, the atoms of Zinc are surrounded by blue areas which represent positive potential, and which imply that they are nucleophilic. Through this, the hypothesis is that the O atoms of Zn 12 O 12 are likely to interact with the hydrogen atom of the hydroxyl group (OH) in the CIP molecule (designated in blue on the MEP map), whereas Zn atoms are also likely to interact with the O atoms of the two carbonyl groups (indicated in red on the MEP map). Moreover, another possible interaction site of Zn atoms is the fluorine atom in CIP depicted with a light red colour, as well, due to its partial negative nature. Molecular complexes were formed using these predicted sites of interactions which were subsequently analyzed. In order to investigate the adsorption characteristics of CIP on Zn 12 O 12 , it was decided to have five configurations (CMP-1 to CMP-5) as single structures, which were optimized using the identical computational approach. These geometries are depicted in Fig. 3 and were summarized in Table 1 . The interactions form in the most stable complex with the help of the O, H, and F atoms of CIP and the C = O functional groups which interact with Zn and O atoms in the nanocage. The greatest adsorption was observed in the CMP-3 geometry, with both carbonyl O atom and hydroxyl H atom of CIP bonded with Zn atoms of Zn 12 O 12 . The adsorption energies in all five configurations were higher than 11 kcal/mol, which indicated chemisorption. CMP-3 had the highest adsorption energy of about − 48.993 kcal/mol, which means that it is the most stable complex. The lengths of bonds in the complexes indicate strong interactions: CMP-1 had the bond length of 1.99 Å and 2.21 Å, CMP-2 had 1.98 Å, and the interaction CMP-3-Zn and CMP-3-O had the bond length values of 1.92Å and 1.25 Å, respectively. Bond distances were found to be 2.18Å and 2.07Å in CMP-4 and CMP-5 respectively. It is interesting to note that the tiniest bond lengths were observed in CMP-3 (1.25Å in H-O and 1.92Å in O-Zn), which supports the fact that CMP-3 was the most stable geometry with the highest adsorption energy. It was found that bond elongation under interaction occurred in a number of complexes which indicates strong interaction. The two C = O bonds were found to have been elongated in CMP-1 by 0.02Å and 0.002Å respectively against their original bond lengths of 1.99Å and 2.22Å. In case of CMP-2 and CMP-3, 0.03Å and 0.04 Å bond elongations in C = O group were observed. On the same note, CMP-4 and CMP-5 showed a similar elongation of C-F and C-O bonds, with a bond distance of 0.03Å and 0.04Å, respectively, following interaction with Zn atoms. The hydrogen bond in CMP-3 is elongated by 0.2Å indicating a very strong interaction which also confirms the high stability of this structure. The cumulative bond elongation values of C = O and H-O are 0.04Å and 0.2Å, respectively indicating the high adsorption stability and energetics of CMP-3. Table 1 Adsorption energy, HOMO-LUMO (FMO) and Charge transfer (NBO) analysis. System E ad (kcal/mol) E LUMO (eV) E HOMO (eV) E g (eV) Q (e) Zn 12 O 12 ------------- -2.84713 -6.93918 4.092050 --------- Ciprofloxacin ------------- -1.20900 -5.70596 4.496956 --------- CMP-1 -39.3726 -2.29501 -5.68936 3.394350 -0.087 CMP-2 -39.3255 -2.04766 -6.11495 4.067288 -0.097 CMP-3 -48.9929 -2.51107 -5.83630 3.325233 -0.139 CMP-4 -23.6022 -2.47460 -6.14189 3.667280 -0.003 CMP-5 -33.4816 -2.66781 -5.93209 3.264280 -0.053 Frontier molecular orbitals (FMO) analysis and Density of state (DOS) Analysis The sensing response of the Zn 12 O 12 nanocage to the ciprofloxacin (CIP) was additionally investigated using the frontier molecular orbital (FMO) and density of states (DOS) theories. The display of the HOMO and LUMO are shown in Fig. 4 together with their respective DOS spectra of the free Zn 12 O 12 nanocage and its complex with CIP. It is noteworthy that upon complex formation, a reduction in HOMO energy levels (E HOMO ) was observed as well as changes in the energy bandgap were experienced, as is presented in Table 1 . The CMP-5 and CMP-3 configurations had the least energy distance of 3.264280 eV, 3.325233 eV (respectively), as illustrated in Fig. 3 . These lower values of the bandgaps are suggestive of high orbital interaction implying that these configurations become more stable. Conversely CMP-2 illustrated the greatest energy gap which is approximately 4.067288 eV meaning comparatively weak interaction in this complex. The HOMO-LUMO gap value tends to decrease in general when the conduction electrons are more available thus improving the electrical conductivity of the system. This gain in conductivity helps in the production of an electrical signal hence enhances the sensitivity of the nanocage in detecting CIP. Moreover, the decreasing of E HOMO is the indication of the decreasing electronation energy and, consequently, the values of chemical reactivity and sensing of the Zn 12 O 12 nanocage to CIP molecules. As Fig. 3 shows, the FMO orbitals can be visualised with the oxygen atoms of the Zn 12 O 12 nanocage being localized in the LUMO orbital whereas the HOMO orbitals are localized in the zinc atoms. With CIP complexation, a major redistribution of orbital was found. The LUMO orbitals are localized on the nanocage, and HOMO defaults towards the CIP molecule in the resulting complexes, indicating that there exist intermolecular interactions and attractive forces between the two entities Specifically, the color areas visualized in Fig. 3 would indicate the localization of the LUMO orbitals at the interacting atoms in CMP-1, CMP-2 and CMP-3. The orbital distributions are highly consistent with the adsorption energy (Eads) estimates supporting the fact that there was actually effective orbital overlap and strong interaction between the Zn 12 O 12 nanocage and the CIP drug molecules. Reduce Density Gradient (RDG) Analysis and Noncovalent Interaction (NCI) analysis Reduced density gradient (RDG) analysis was used to determine the nature and strength of interactions between the ciprofloxacin (CIP) molecule and the Zn 12 O 12 nanocage. Figure 5 shows the plots of RDG against sign (λ 2 )ρ, as well as, non-covalent interaction (NCI) isosurfaces. The technique offers important knowledge of both effective and weak interactions that take place in molecular complexes. The NCI isosurfaces are identified by various color-codes to indicate various types of interactions. Green zones are associated with van der Waals forces, blue areas are associated with hydrogen bonding and red areas are associated with strong steric repulsion. The existence of Van der waals interactions is verified by the green-colored isosurfaces that are present around the RDG spikes in all five CIP-Zn 12 O 12 complexes. CMP-3 exhibits different blue isosurface features indicating that there are important hydrogen bonding or partially hydrogen bonds between the hydrogen atom of the hydroxyl group of the CIP and the oxygen atom on the nanocage. On the same note, the blue spot on the RDG plot on CMP-4 indicates an interaction between a zinc atom of Zn 12 O 12 and the fluorine atom of CIP. Evident of these interactions is the visualization of green isosurfaces between the C = O oxygen atoms, CIP and Zn atoms, Zn 12 O 12 , CMP-1, CMP-2 and CMP-3 between the oxygen atom and nanocage in these NCI plots and the presence of green arrows. Also, there are some green patches in between which the molecule of CIP itself is dispensed, which indicates the possibility of intramolecular van der Waals forces. These are observed at several points of atoms and they sum up to the total adsorption energy (Eads), which supports the contribution of weak non-covalent forces that stabilize the drug-nanocage complexes. Quantum Theory of Atom In Molecule (QTAIM) Analysis To further confirm the type of intermolecular interactions between the Zn 12 O 12 nanocage and the ciprofloxacin (CIP) drug molecule, the Quantum Theory of Atoms in Molecules (QTAIM) analysis was performed using the Gaussian software suite. Figure 4 gives the topological results in graphical form. The characterization of covalent and electrostatic interactions between electrons can also be done with QTAIM that examines several electron density properties at bond critical points (BCPs), including the electron density (ρb), Laplacian of the electron density (∇2ρb), kinetic electron energy density (Gb), local potential energy density (Vb), and total energy density (Hb). Types of interaction are classified according to the sign of ∇²ρb and Hb, and the size of the -Gb/Vb ratio. Negative Hb values (generally treated as a shared-electron interaction) are generally known as covalent interactions, whereas positive values of Hb (of ∇²ρb and Hb) are usually referred to as electrostatic or closed-shell interaction. The structures of the complexes between Zn 12 O 12 − CIP complexes were analyzed to determine the similarities in interaction characteristics at the BCPs 57, 29, 69, 72, and 83 with negative values obtained respectively as indicated in Table 2 . These hint on the existence of covalent contributions to the bonding. However, there was a positive Hb value in BCP 55 in CMP-1, and it denotes a closed-shell electrostatic interaction at that particular site, and is further confirmed by the fact that -Gb/Vb ratio is more than unity. Also, the finding of positive 002 -b with negative levels of Hb at BCPs 57, 29, 69, 72, and 83 indicate that there are a combination of weak electrostatic and covalent interactions in these sites. This conclusion is supported by -Gb/Vb ratios falling in the range of 0.5 to 1.0 which suggests that there are both partial covalent and partial electrostatic interactions. The BCP 51 in CMP-3 is highly hydrogen bonded as indicated by rho b is high and the -Gb/Vb ratio is even lower, below 0.5, as well as indicates highly covalent interactions. The value of highest electron density at BCP 69 also proves that CMP-3 has the strongest interaction of his whole set of configurations, as well as its best adsorption energy (Eads). This is further observed in CMP-2 that has higher values of ρb at BCP 29 and CMP-1 that has high levels of densities at BCP 57. The Eads of CMP-1 is higher but this can be explained by the fact that two BCPs (57 and 55) contribute to it. On the other hand, BCP 72 has the least value of ρb meaning that this bond is the weakest and most unstable in all complexes. These find their way into agreement with the calculated adsorption energies as well as variations of the bond lengths in the past analyses. Table 2 Quantum Theory OF Atom In Molecule QTIAM Analysis. System Zn 12 O 12 BCP Density of all electrons (ρb) laplacian (∇2ρb) kinetic electron density Gb Potential energy density Vb Energy density Hb -Gb/Vb CMP-1 57 0.071300 0.336007 0.105036 -0.126070 -0.021034 0.83316 55 0.037884 0.202514 0.049943 -0.049257 0.000685 1.01392 CMP-2 29 0.074241 0.332523 0.106581 -0.130031 -0.023450 0.81966 CMP-3 69 0.093506 0.401112 0.137055 -0.173832 -0.036777 0.78843 51 0.147488 -0.182077 0.089715 -0.224950 -0.135235 0.39882 CMP-4 72 0.037742 0.208252 0.053236 -0.054409 -0.001173 0.97844 CMP-5 83 0.060437 0.269235 0.081010 -0.094713 -0.013702 0.85532 Natural Bond Orbital (Nbo) Analysis Of Zno Nanocage And Their Complexes With CIP Natural Bond Orbital (NBO) analysis was used to determine the degree and direction of the charge transfer that took place between the ciprofloxacin (CIP) drug and the Zn 12 O 12 nanocage. They were calculated at the B3LYP/ 6-31G(d, p) on the optimized structures of the complexes Zn 12 O 12 -CIP. The same values of the population change of charge transfers are given in Table 1 , which shows that the net change of the electron density spreads opposite between the CIP molecule and the Zn 12 O 12 nanocage. The electronegative atoms (oxygen and fluorine in the CIP drug and Zn 12 O 12 nanocage) have partial negative charges in the isolated molecules (monomers), and the hydrogen atoms in CIP and the zinc atoms in the nanocage have partial positive charges. On complexation, the partial charges on the oxygen atom of CIP moieties are raised whereas the electron charges on zinc atoms are deprotonated implying that electrons move onto the nanocage and away on to the CIP molecule. As an example, the charge of the oxygen atom on CMP-1 increases to -0.652 e after complexing with the free CIP molecule which was − 0.565 e indicating that there is a change of -0.087 e. Equally, the oxygen atoms of CMP-2 and CMP-3 witness a rise in charge which are − 0.565 e, -0.572 e to -0.662 e, -0.710 e respectively. These changes validate a net transfer of a charge between the Zn atoms in Zn 12 O 12 as well as the oxygen atoms of the carbonyl groups in the CIP molecule. In CMP-4, the fluorine atom has a very small change in charge ( -0.334 e -0.337 e), this shows that the interaction of the atom is weak and the geometry is also a little less stable than other complexes. Conversely, CMP-5 (ZnO-Com-E) the oxygen atom of the hydroxyl (O-H) group of the molecule shows a big change in charge as it changes to a negative value which is -0.807 e instead of the initial negative value of -0.748 e indicating the significant redistribution of charge during adsorption. On the whole, the experiments with charge transfers observed indicate strong interactions of CIP and Zn 12 O 12 nanocage. The findings confirm the finding that Zn 12 O 12 is adsorbent and probably capable of eliminating CIP in aqueous solutions. Moreover, the obtained results of NBO are well in line with the calculated adsorption energies (Eads), which gives some consistent evidence of the sensing and adsorption properties of the nanocage. Electron density differences (EDD) analysis To further confirm the stability of the interactions between the Zn 12 O 12 nanocage and ciprofloxacin (CIP) molecule, EDD analysis was employed in order to strengthen the results of Natural Bond Orbital (NBO) analysis. Creating the resulting EDD isosurfaces as in Fig. 6 , provides insight into where there is accumulation and depletion of electron density and provides an insight into the nature of bonding between the adsorbent and the adsorbate. The EDD plots of all the five complexes show a strong blue and green isosurface loop on the interface between the Zn 12 O 12 nanocage and CIP molecule indicating that the interactions between the molecules are strong which supports that there are stable and stable complexions that formed. It is interesting to note that CMP-1, CMP-2 as well as CMP-3 show large areas of green isosurface which cover the interacting atoms to the effect of making the atomic boundaries loss clear. This implies that there is a large extent of redistribution of electrons and overlapping of electrons orbitals that explains an increase in stability of these structures. In all the complexes, the appearance of clear blue and green loops at the contacts of the molecule of the drug and nanocage indicates strong chemisorption. The potential observed orbital overlap is in agreement with strong binding interactions and as such it supports the trends in the charge transfer that were seen in the NBO analysis. These data confirm the stability of the complexes and underline the efficiency of Zn 12 O 12 nanocages in forming the long-term interactions with CIP molecule. Effect Of Solvent And Dipole Moment Analysis To analyze how the solvent environment impacts the interaction behavior of the Zn 12 O 12 nanocage and the ciprofloxacin (CIP) drug, all the previous optimization complexes were re-optimized in aqueous phase with the help of the polarizable continuum model (PCM) as the part of the computation framework. The values of adsorption energies of both the dry samples and their wet samples are tabulated in Table 3 . The solvent effects introduced showed a slight decrease in the adsorption energies of most of the complexes as compared to the gas-phase calculations 60. It is worth noting that complexes CMP-1 and CMP-4 were both highly stable in aqueous and vacuum environment which means that they have strong binding properties even when solvated. The system with the highest adsorption energy in aqueous medium was the CMP-3, which was found to be with − 43.2013 kcal/mol per mole indicating that a preferred configuration of the complex existed in water. Besides the energy determinations, there was a variation in the dipole moments, which were also examined in order to determine the interaction process between the nanocage and CIP drug further. The isolated Zn 12 O 12 nanocage and the CIP molecule have dipole moments of about 0.000173 and 9.702292 Debye, respectively. When complexes were formed, the dipole moments enhanced significantly in all the systems as it is reported in Table 3 . This increment in polarity implies the improved redistribution of charges and other hints on the adsorption capacity and efficiency of them Zn 12 O 12 nanocage to the CIP drug. Table 3 Adsorption energy in Solvent And Dipole Moment (DM) Analysis. System Eads (gas medium) Eads (water medium) DM (Debye) Zn 12 O 12 ------------- ------------- 0.000173 Ciprofloxacin ------------- ------------- 9.702292 CMP-1 -39.3726 -41.1865 20.430222 CMP-2 -39.3255 -38.0160 16.290770 CMP-3 -48.9929 -43.2013 8.581503 CMP-4 -23.6022 -23.9422 11.715527 CMP-5 -33.4816 -27.4871 8.743845 Thermodynamics Analysis The thermodynamic analysis will provide very important information on the viability and nature of the adsorption phenomenon. The calculated values of enthalpy change (∆H) and Gibbs free energy change (∆G) of all Zn 12 O 12 CIP complexes were negative as indicated by Table 3 . The presence of these negative values proves that the adsorption process is exothermic in nature. In addition, the negative ∆G values result in the fact that the interaction is a spontaneous occurrence under the conditions described. The results of the thermodynamic calculations are close to the findings of energetic calculations, which support the clarity and feasibility of the adsorption process under consideration. Recovery time calculation The efficiency of the adsorbent to be regenerated is also one of the important variables defining the practical applicability of the adsorbent, and the lower the recovery time the greater the reusability. To determine this, the recovery time of all five complexes of Zn 12 O 12 -CIP were determined at 298.15K and 350.0 K. The recovery time of CMP-1, CMP-2, CMP-3, CMP-4, and CMP-5 were found to be 7.27 x 10 − 7, 6.71 x 10 − 6, 8.20 x 10 − 3, 2 x 10 − 5 and 3.49 x 10 − 1 seconds at 298.15 K, respectively. On raising the temperature to 350 K, recovery times decreased much to 3.85 x 10 12, 3.60 x 10 12, 3.92 x 10 18, 5.47 x 10 2 and 8.08 x 10 8 seconds respectively as shown in Fig. 7 . The implication of these findings is that an increase in temperatures also promotes the process of regeneration. All in all, the short regeneration times especially at high temperatures are indicative of Zn 12 O 12 nanocage as a very efficient and reusable adsorbent in the removal of ciprofloxacin (CIP) in aqueous environment. COMPUTATIONAL DETIALS It is well known that Density Functional Theory (DFT) is accurate, reliable, and has a high level of computer efficiency when it comes to the study of the overall structure of a material and its electronic characteristics [35,36,37,38,39]. The optimization of the molecular form of ciprofloxacin (CIP) as well as Zn 12 O 12 nanocage was performed in this work with the help of the GAMESS 40 software suite with the use of the B3LYP functional and a combination of 6-31G(d,p) basis set. To correctly take into consideration the effects of long-range dispersion, the method of the DFT-D3 correction, which was created by Grimme 41 , was applied. Based on the relation, the adsorption energy of CIP on the Zn 12 O 12 nanocage under gas and aqueous conditions was obtained. $$\:{E}_{ads}={E}_{complex}-({E}_{M1}+{E}_{M2})$$ Ecomplex the overall energy of the CIP Zn 12 O 12 system, and E M1 and E M2 are the energy of the free ciprofloxacin molecule and Zn 12 O 12 nanocage, respectively. Frontier molecular orbital (FMO) 42 and density of states (DOS) were carried out to investigate the electronic properties and sensing mechanism. The expression was used to calculate the HOMO LUMO energy gap (Eg). $$\:{E}_{g}={E}_{LUMO}-{E}_{HOMO}$$ E LUMO , E HOMO Is the energy of the lowest and highest unoccupied and occupied molecular orbitals, respectively. Visualization was done in Visual Molecular Dynamics (VMD) 43 and reduced density gradient (RDG) mapping by Multiwfn 44 program was used to analyze non-covalent interactions. Topology was also studied electron density topology parameters based on the Quantum Theory of Atoms in Molecules (QTAIM) method to determine bond critical point (BCP) parameters by the B3LYP wavefunctions 45 . Natural Bond Orbital (NBO) 46 analysis on the Gaussian 16 framework was used to study the charge transfer processes but electron density difference (EDD) 47 maps were produced using Multiwfn to visualize the redistribution of charge during adsorption. Thermodynamic parameters 48 , enthalpy changes (∆H) 49 and Gibbs free energy (∆G) 50 were calculated by the following relations. $$\:\varDelta\:{H}_{ads}={H}_{Complex}-{H}_{(M1+M2)}$$ $$\:\varDelta\:{G}_{ad}=\varDelta\:{H}_{ad}-T\varDelta\:{S}_{ad}$$ $$\:\varDelta\:{G}_{ad}=\varDelta\:{H}_{ad}-T\left[\right({S}_{\left(complex\right)}-({S}_{adsorbent}+{S}_{adsorbate})]$$ Where ∆H and ∆G are the total electronic and thermal enthalpy and Gibbs free energy at standard conditions (298.15 K and 1 atm), and S is entropy. The solvent effect on adsorption of CIP was simulated by Polarizable Continuum Model (PCM) 51 in order to model the aqueous interactions. Besides, regeneration experiment was conducted at 298.15 K and 350 K to determine the thermal stability and reusability of the Zn 12 O 12 nanocage 52 . Declarations Competing Interests The authors confirm that they have no Competing interests. Funding declaration This work was supported by the Ongoing Research Funding Program (ORF-2026-235), King Saud University, Riyadh, Saudi Arabia. Author Contribution Q.A, H.K and F.A have conceptualized and carried out the simulations and interpreted the results, M.K, A,S and M.A helped in Editing Drafting and designing. Q.A, A.F.A and S.K have performed the Grammar revision and Analysis of Results. The manuscript was revised by all Authors. Acknowledgement This work was supported by the Ongoing Research Funding Program (ORF-2026-235), King Saud University, Riyadh, Saudi Arabia. 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Introduction to QTAIM and beyond. in Advances in quantum chemical topology beyond QTAIM 1–19 (Elsevier, (2023). Glendening, E. D., Landis, C. R. & Weinhold, F. Natural bond orbital theory: Discovering chemistry with NBO7. Complement Bond Anal 129–156 (2021). Bithe, S. A., Hasan, M., Oishi, A. A., Dhali, P. & Roy, D. To understand the miglitol adsorption behavior on BC3, BN, and GNS nanosheets using DFT and QTAIM analysis for drug delivery applications. Phys. Scr. 98 , 75010 (2023). Ojha, J. K., Ramesh, G. & Reddy, B. V. Structure, chemical reactivity, NBO, MEP analysis and thermodynamic parameters of pentamethyl benzene using DFT study. Chem. Phys. Impact . 7 , 100280 (2023). Khodiev, M. K. et al. Estimation of electrostatic and covalent contributions to the enthalpy of H-bond formation in H-complexes of 1, 2, 3-benzotriazole with proton-acceptor molecules by IR spectroscopy and DFT calculations. J. King Saud Univ. 35 , 102530 (2023). Yasin, G. et al. Defects-engineered tailoring of tri-doped interlinked metal-free bifunctional catalyst with lower gibbs free energy of OER/HER intermediates for overall water splitting. Mater. Today Chem. 23 , 100634 (2022). Seenithurai, S. & Chai, J. D. TAO-DFT with the polarizable continuum model. Nanomaterials 13 , 1593 (2023). Wu, H. et al. Adsorption and sensing properties of Janus MoSTe materials for characteristic gases (CO, C2H2, C2H4, CH4) in power transformers: A DFT study. Int. J. Hydrogen Energy . 102 , 1253–1266 (2025). Abd El-Mageed, H. R. Zinc oxide nanoclusters and nanoparticles as a drug carrier for cisplatin and nedaplatin anti-cancer drugs, insights from DFT methods and MC simulation. Mol. Phys. 119 , e1842533 (2021). Munsif, S. et al. Sensing behavior of pristine and TM-decorated Zn12O12 nanocage towards toxic formaldehyde, phosgene and thiophosgene gases. J. Inorg. Organomet. Polym. Mater. 34 , 2351–2365 (2024). Additional Declarations No competing interests reported. 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04:25:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9432981/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9432981/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108514364,"identity":"5710b8ac-76a9-4d4b-94ac-afb72c72af45","added_by":"auto","created_at":"2026-05-05 13:15:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1594534,"visible":true,"origin":"","legend":"\u003cp\u003eMEP and Optimized geometries of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and CIP.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/56909d0cf8ed4822f59d5dc8.png"},{"id":108804556,"identity":"e946ad78-e724-4ba5-8a54-8f62ae8328c8","added_by":"auto","created_at":"2026-05-08 15:21:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2738718,"visible":true,"origin":"","legend":"\u003cp\u003eOptimized complexes Of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage with CIP.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/75bc45b83243a219c19bdb9e.png"},{"id":108804707,"identity":"d3abeb80-69c2-43b6-88d5-df52d2b0d10f","added_by":"auto","created_at":"2026-05-08 15:22:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6336620,"visible":true,"origin":"","legend":"\u003cp\u003eHOMO-LUMO (FMO) and Density of State (DOS) analysis.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/437799219ff081ce4fdbec95.png"},{"id":108514366,"identity":"0d1e991b-ef78-44a4-a580-971f15182c19","added_by":"auto","created_at":"2026-05-05 13:15:34","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":8241423,"visible":true,"origin":"","legend":"\u003cp\u003eQuantum Theory OF Atom In Molecule (QTAIM) Analysis.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/35b447114fff757467033153.png"},{"id":108804583,"identity":"86a40d25-b9da-4f4a-91e1-124b46791f5a","added_by":"auto","created_at":"2026-05-08 15:21:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2362654,"visible":true,"origin":"","legend":"\u003cp\u003eReduce Density Gradient (RDG) and Non-covalent Interaction (NCI) Analysis.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/2d840591da68bc2df2b1af3f.png"},{"id":108514367,"identity":"c3fee1b2-f643-452f-94c8-3434168b9128","added_by":"auto","created_at":"2026-05-05 13:15:34","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":339996,"visible":true,"origin":"","legend":"\u003cp\u003eRecovery time graph For Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12 \u003c/sub\u003eNanocage.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/7854694315649f1f4444cf69.png"},{"id":108803948,"identity":"579e61cb-efd1-433f-8ae1-fa0cc5de6ff0","added_by":"auto","created_at":"2026-05-08 15:12:17","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":2847691,"visible":true,"origin":"","legend":"\u003cp\u003eElectron Density differences (EDD) Analysis.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/7b590bcfdbfde0b78e0660d8.png"},{"id":108809657,"identity":"364eb82f-8d46-40f2-9608-2cc2b819448e","added_by":"auto","created_at":"2026-05-08 15:54:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":24918180,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9432981/v1/e9dde0bc-2146-494e-9159-4df0e4d9c530.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eUtility of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e Nanocage for The Elimination of Ciprofloxacin From Drinking Water Using DFT Simulations\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAntibiotics are widely used in the management of a broad spectrum of infections with the inclusion of those of the urinary tract, respiratory system, and central nervous system \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Ciprofloxacin (CIP) is a broad-spectrum antibiotic comprising of Fluoroquinolone, which is one of the most common agents used in the treatment of various bacterial infections \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. At the same time, a significant portion of the ciprofloxacin administered to a patient is excreted via urine and thus, the drug continuously enters the water body due to its partial metabolism in the human body \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The significant routes through which it has been caused in water masses include discharges like hospital effluents, pharmaceutical manufacturing, and domestic sewage \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The fact that ciprofloxacin remains in aquatic system is alarming because it may cause severe health conditions in all human beings and animals which include glycemic responses, seizures, gastrointestinal disorders, bacterial resilience and tendon disorders \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. A ciprofloxacin is highly soluble in aqueous at a wide the pH scale, and its molecular structure is stable, which is why the drug is resistant to natural decay, making it hard to eliminate in polluted water \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Different treatment methods have also been studied in the remediation of ciprofloxacin among them are, biological degradation \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, photolysis \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, membrane separation methods \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, ion exchange processing \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, and chemical oxidation methods \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In spite of the stated benefits, these methods are frequently limited by such negative factors as high operation costs, low selectivity, and low efficiency that prevent the application of such methods on a large-scale level \u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. However, over the last few years, nanomaterials have become a potential candidate in the context of the environmental application due to their peculiar physicochemical characteristics \u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Both zinc oxide (ZnO) has shown impressive potential in the field of sensing, catalysis and adsorption, as well as their potential to interact with diverse molecules \u003csup\u003e\u003cspan additionalcitationids=\"CR27 CR28 CR29 CR30 CR31 CR32\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Recently, it was observed that a B\u003csub\u003e12\u003c/sub\u003eN\u003csub\u003e12\u003c/sub\u003e nanocage can be useful as an adsorbent, and the removal of CIP is effective with the assistance of it \u003csup\u003e34\u003c/sup\u003e. Here, the given work studies the adsorption of ciprofloxacin on Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage by using the density functional theory (DFT) calculations. The paper sheds light on the adsorption mechanism and studied it with the help of frontier molecular orbital (FMO), natural bond orbital (NBO), and charge transfer assessment, and the determination of the dipole moment. Moreover, non-covalent interaction (NCI) and reduced density gradient (RDG) are utilized to explain the nature of interactions. The method of solvent effect considerations is done with the polarizable continuum model (PCM), whereas thermodynamic parameters and regeneration potential are determined to evaluate the efficiency and reusability of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocages as ciprofloxacin adsorbents.\u003c/p\u003e"},{"header":"RESULTS AND DISCUSSIONS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eGeometries Optimization Of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e Nanocage Ciprofloxacin And Complexes\u003c/h2\u003e\n \u003cp\u003eThe computed structure of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage, determined through the computational method described above, was seen to consist of six four-membered rings (4 MRs), and eight six-membered rings (6 MRs) as shown in Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The analysis indicated two types of bonds in the nanocage which are: Zn-O bonds in both 4MRs and 6MRs, and Zn-Zn bonds in the 4MRs and have a bond length of about 1.90 \u0026Aring; and 1.80 \u0026Aring; respectively. The increased ZnO bonds length in the 4MRs than the 6MRs is due to higher angular strain in the smaller ring system which is in line with other previous results. The bond angle analysis revealed that the O-Zn-O and Zn-O-Zn angles in 6MRs and 4MRs are 126.19\u0026deg; and 92.16\u0026deg; and 111.96\u0026deg; and 86.40\u0026deg; respectively. These data are coherent with the earlier documented information, which validates the geometrical characteristics of the nanocage \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. The electronic properties of the nanocage are indicated by the molecular electrostatic potential (MEP) map of Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The yellow and red areas around the oxygen atoms are sites of negative electrostatic potentials and so, they represent the electrophilic sites. On the contrary, the atoms of Zinc are surrounded by blue areas which represent positive potential, and which imply that they are nucleophilic. Through this, the hypothesis is that the O atoms of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e are likely to interact with the hydrogen atom of the hydroxyl group (OH) in the CIP molecule (designated in blue on the MEP map), whereas Zn atoms are also likely to interact with the O atoms of the two carbonyl groups (indicated in red on the MEP map). Moreover, another possible interaction site of Zn atoms is the fluorine atom in CIP depicted with a light red colour, as well, due to its partial negative nature. Molecular complexes were formed using these predicted sites of interactions which were subsequently analyzed. In order to investigate the adsorption characteristics of CIP on Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e, it was decided to have five configurations (CMP-1 to CMP-5) as single structures, which were optimized using the identical computational approach. These geometries are depicted in Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and were summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The interactions form in the most stable complex with the help of the O, H, and F atoms of CIP and the C\u0026thinsp;=\u0026thinsp;O functional groups which interact with Zn and O atoms in the nanocage. The greatest adsorption was observed in the CMP-3 geometry, with both carbonyl O atom and hydroxyl H atom of CIP bonded with Zn atoms of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e. The adsorption energies in all five configurations were higher than 11 kcal/mol, which indicated chemisorption. CMP-3 had the highest adsorption energy of about\u0026thinsp;\u0026minus;\u0026thinsp;48.993 kcal/mol, which means that it is the most stable complex. The lengths of bonds in the complexes indicate strong interactions: CMP-1 had the bond length of 1.99 \u0026Aring; and 2.21 \u0026Aring;, CMP-2 had 1.98 \u0026Aring;, and the interaction CMP-3-Zn and CMP-3-O had the bond length values of 1.92\u0026Aring; and 1.25 \u0026Aring;, respectively. Bond distances were found to be 2.18\u0026Aring; and 2.07\u0026Aring; in CMP-4 and CMP-5 respectively. It is interesting to note that the tiniest bond lengths were observed in CMP-3 (1.25\u0026Aring; in H-O and 1.92\u0026Aring; in O-Zn), which supports the fact that CMP-3 was the most stable geometry with the highest adsorption energy. It was found that bond elongation under interaction occurred in a number of complexes which indicates strong interaction. The two C\u0026thinsp;=\u0026thinsp;O bonds were found to have been elongated in CMP-1 by 0.02\u0026Aring; and 0.002\u0026Aring; respectively against their original bond lengths of 1.99\u0026Aring; and 2.22\u0026Aring;. In case of CMP-2 and CMP-3, 0.03\u0026Aring; and 0.04 \u0026Aring; bond elongations in C\u0026thinsp;=\u0026thinsp;O group were observed. On the same note, CMP-4 and CMP-5 showed a similar elongation of C-F and C-O bonds, with a bond distance of 0.03\u0026Aring; and 0.04\u0026Aring;, respectively, following interaction with Zn atoms. The hydrogen bond in CMP-3 is elongated by 0.2\u0026Aring; indicating a very strong interaction which also confirms the high stability of this structure. The cumulative bond elongation values of C\u0026thinsp;=\u0026thinsp;O and H-O are 0.04\u0026Aring; and 0.2\u0026Aring;, respectively indicating the high adsorption stability and energetics of CMP-3.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdsorption energy, HOMO-LUMO (FMO) and Charge transfer (NBO) analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSystem\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eE\u003csub\u003ead\u003c/sub\u003e (kcal/mol)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eE\u003csub\u003eLUMO\u003c/sub\u003e (eV)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eE\u003csub\u003eHOMO\u003c/sub\u003e (eV)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eE\u003csub\u003eg\u003c/sub\u003e (eV)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eQ (e)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eZn\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e-------------\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.84713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-6.93918\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e4.092050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e---------\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCiprofloxacin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-------------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-1.20900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-5.70596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e4.496956\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e---------\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-39.3726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.29501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-5.68936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e3.394350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e-0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-39.3255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.04766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-6.11495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e4.067288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e-0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-48.9929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.51107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-5.83630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e3.325233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e-0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-23.6022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.47460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-6.14189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e3.667280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-33.4816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-2.66781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e-5.93209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e3.264280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e-0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eFrontier molecular orbitals (FMO) analysis and Density of state (DOS) Analysis\u003c/h3\u003e\n\u003cp\u003eThe sensing response of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage to the ciprofloxacin (CIP) was additionally investigated using the frontier molecular orbital (FMO) and density of states (DOS) theories. The display of the HOMO and LUMO are shown in Fig. \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e together with their respective DOS spectra of the free Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and its complex with CIP. It is noteworthy that upon complex formation, a reduction in HOMO energy levels (E\u003csub\u003eHOMO\u003c/sub\u003e) was observed as well as changes in the energy bandgap were experienced, as is presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The CMP-5 and CMP-3 configurations had the least energy distance of 3.264280 eV, 3.325233 eV (respectively), as illustrated in Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. These lower values of the bandgaps are suggestive of high orbital interaction implying that these configurations become more stable. Conversely CMP-2 illustrated the greatest energy gap which is approximately 4.067288 eV meaning comparatively weak interaction in this complex. The HOMO-LUMO gap value tends to decrease in general when the conduction electrons are more available thus improving the electrical conductivity of the system. This gain in conductivity helps in the production of an electrical signal hence enhances the sensitivity of the nanocage in detecting CIP. Moreover, the decreasing of E\u003csub\u003eHOMO\u003c/sub\u003e is the indication of the decreasing electronation energy and, consequently, the values of chemical reactivity and sensing of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage to CIP molecules. As Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows, the FMO orbitals can be visualised with the oxygen atoms of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage being localized in the LUMO orbital whereas the HOMO orbitals are localized in the zinc atoms. With CIP complexation, a major redistribution of orbital was found. The LUMO orbitals are localized on the nanocage, and HOMO defaults towards the CIP molecule in the resulting complexes, indicating that there exist intermolecular interactions and attractive forces between the two entities Specifically, the color areas visualized in Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e would indicate the localization of the LUMO orbitals at the interacting atoms in CMP-1, CMP-2 and CMP-3. The orbital distributions are highly consistent with the adsorption energy (Eads) estimates supporting the fact that there was actually effective orbital overlap and strong interaction between the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and the CIP drug molecules.\u003c/p\u003e\n\u003ch3\u003eReduce Density Gradient (RDG) Analysis and Noncovalent Interaction (NCI) analysis\u003c/h3\u003e\n\u003cp\u003eReduced density gradient (RDG) analysis was used to determine the nature and strength of interactions between the ciprofloxacin (CIP) molecule and the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage. Figure \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the plots of RDG against sign (\u0026lambda;\u003csub\u003e2\u003c/sub\u003e)\u0026rho;, as well as, non-covalent interaction (NCI) isosurfaces. The technique offers important knowledge of both effective and weak interactions that take place in molecular complexes. The NCI isosurfaces are identified by various color-codes to indicate various types of interactions. Green zones are associated with van der Waals forces, blue areas are associated with hydrogen bonding and red areas are associated with strong steric repulsion. The existence of Van der waals interactions is verified by the green-colored isosurfaces that are present around the RDG spikes in all five CIP-Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e complexes. CMP-3 exhibits different blue isosurface features indicating that there are important hydrogen bonding or partially hydrogen bonds between the hydrogen atom of the hydroxyl group of the CIP and the oxygen atom on the nanocage. On the same note, the blue spot on the RDG plot on CMP-4 indicates an interaction between a zinc atom of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e and the fluorine atom of CIP. Evident of these interactions is the visualization of green isosurfaces between the C\u0026thinsp;=\u0026thinsp;O oxygen atoms, CIP and Zn atoms, Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e, CMP-1, CMP-2 and CMP-3 between the oxygen atom and nanocage in these NCI plots and the presence of green arrows. Also, there are some green patches in between which the molecule of CIP itself is dispensed, which indicates the possibility of intramolecular van der Waals forces. These are observed at several points of atoms and they sum up to the total adsorption energy (Eads), which supports the contribution of weak non-covalent forces that stabilize the drug-nanocage complexes.\u003c/p\u003e\n\u003ch3\u003eQuantum Theory of Atom In Molecule (QTAIM) Analysis\u003c/h3\u003e\n\u003cp\u003eTo further confirm the type of intermolecular interactions between the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and the ciprofloxacin (CIP) drug molecule, the Quantum Theory of Atoms in Molecules (QTAIM) analysis was performed using the Gaussian software suite. Figure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e gives the topological results in graphical form. The characterization of covalent and electrostatic interactions between electrons can also be done with QTAIM that examines several electron density properties at bond critical points (BCPs), including the electron density (\u0026rho;b), Laplacian of the electron density (\u0026nabla;2\u0026rho;b), kinetic electron energy density (Gb), local potential energy density (Vb), and total energy density (Hb). Types of interaction are classified according to the sign of \u0026nabla;\u0026sup2;\u0026rho;b and Hb, and the size of the -Gb/Vb ratio. Negative Hb values (generally treated as a shared-electron interaction) are generally known as covalent interactions, whereas positive values of Hb (of \u0026nabla;\u0026sup2;\u0026rho;b and Hb) are usually referred to as electrostatic or closed-shell interaction. The structures of the complexes between Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12 \u0026minus;\u003c/sub\u003eCIP complexes were analyzed to determine the similarities in interaction characteristics at the BCPs 57, 29, 69, 72, and 83 with negative values obtained respectively as indicated in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. These hint on the existence of covalent contributions to the bonding. However, there was a positive Hb value in BCP 55 in CMP-1, and it denotes a closed-shell electrostatic interaction at that particular site, and is further confirmed by the fact that -Gb/Vb ratio is more than unity. Also, the finding of positive 002 -b with negative levels of Hb at BCPs 57, 29, 69, 72, and 83 indicate that there are a combination of weak electrostatic and covalent interactions in these sites. This conclusion is supported by -Gb/Vb ratios falling in the range of 0.5 to 1.0 which suggests that there are both partial covalent and partial electrostatic interactions. The BCP 51 in CMP-3 is highly hydrogen bonded as indicated by rho b is high and the -Gb/Vb ratio is even lower, below 0.5, as well as indicates highly covalent interactions. The value of highest electron density at BCP 69 also proves that CMP-3 has the strongest interaction of his whole set of configurations, as well as its best adsorption energy (Eads). This is further observed in CMP-2 that has higher values of \u0026rho;b at BCP 29 and CMP-1 that has high levels of densities at BCP 57. The Eads of CMP-1 is higher but this can be explained by the fact that two BCPs (57 and 55) contribute to it. On the other hand, BCP 72 has the least value of \u0026rho;b meaning that this bond is the weakest and most unstable in all complexes. These find their way into agreement with the calculated adsorption energies as well as variations of the bond lengths in the past analyses.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eQuantum Theory OF Atom In Molecule QTIAM Analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSystem\u003c/p\u003e\n \u003cp\u003eZn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eBCP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eDensity of all electrons\u003c/p\u003e\n \u003cp\u003e(\u0026rho;b)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003elaplacian (\u0026nabla;2\u0026rho;b)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003ekinetic electron density\u003c/p\u003e\n \u003cp\u003eGb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003ePotential energy density\u003c/p\u003e\n \u003cp\u003eVb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003eEnergy density\u003c/p\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e-Gb/Vb\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.071300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.336007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.105036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.126070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.021034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.83316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.037884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.202514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.049943\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.049257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e0.000685\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e1.01392\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.074241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.332523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.106581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.130031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.023450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.81966\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.093506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.401112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.137055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.173832\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.036777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.78843\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.147488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e-0.182077\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.089715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.224950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.135235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.39882\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.037742\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.208252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.053236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.054409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.001173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.97844\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e0.060437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.269235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\n \u003cp\u003e0.081010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\n \u003cp\u003e-0.094713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\n \u003cp\u003e-0.013702\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e0.85532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003eNatural Bond Orbital (Nbo) Analysis Of Zno Nanocage And Their Complexes With CIP\u003c/h3\u003e\n\u003cp\u003eNatural Bond Orbital (NBO) analysis was used to determine the degree and direction of the charge transfer that took place between the ciprofloxacin (CIP) drug and the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage. They were calculated at the B3LYP/ 6-31G(d, p) on the optimized structures of the complexes Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e-CIP. The same values of the population change of charge transfers are given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, which shows that the net change of the electron density spreads opposite between the CIP molecule and the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage. The electronegative atoms (oxygen and fluorine in the CIP drug and Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage) have partial negative charges in the isolated molecules (monomers), and the hydrogen atoms in CIP and the zinc atoms in the nanocage have partial positive charges. On complexation, the partial charges on the oxygen atom of CIP moieties are raised whereas the electron charges on zinc atoms are deprotonated implying that electrons move onto the nanocage and away on to the CIP molecule. As an example, the charge of the oxygen atom on CMP-1 increases to -0.652 e after complexing with the free CIP molecule which was \u0026minus;\u0026thinsp;0.565 e indicating that there is a change of -0.087 e. Equally, the oxygen atoms of CMP-2 and CMP-3 witness a rise in charge which are \u0026minus;\u0026thinsp;0.565 e, -0.572 e to -0.662 e, -0.710 e respectively. These changes validate a net transfer of a charge between the Zn atoms in Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e as well as the oxygen atoms of the carbonyl groups in the CIP molecule. In CMP-4, the fluorine atom has a very small change in charge ( -0.334 e -0.337 e), this shows that the interaction of the atom is weak and the geometry is also a little less stable than other complexes. Conversely, CMP-5 (ZnO-Com-E) the oxygen atom of the hydroxyl (O-H) group of the molecule shows a big change in charge as it changes to a negative value which is -0.807 e instead of the initial negative value of -0.748 e indicating the significant redistribution of charge during adsorption. On the whole, the experiments with charge transfers observed indicate strong interactions of CIP and Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage. The findings confirm the finding that Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e is adsorbent and probably capable of eliminating CIP in aqueous solutions. Moreover, the obtained results of NBO are well in line with the calculated adsorption energies (Eads), which gives some consistent evidence of the sensing and adsorption properties of the nanocage.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eElectron density differences (EDD) analysis\u003c/h2\u003e\n \u003cp\u003eTo further confirm the stability of the interactions between the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and ciprofloxacin (CIP) molecule, EDD analysis was employed in order to strengthen the results of Natural Bond Orbital (NBO) analysis. Creating the resulting EDD isosurfaces as in Fig. \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, provides insight into where there is accumulation and depletion of electron density and provides an insight into the nature of bonding between the adsorbent and the adsorbate. The EDD plots of all the five complexes show a strong blue and green isosurface loop on the interface between the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and CIP molecule indicating that the interactions between the molecules are strong which supports that there are stable and stable complexions that formed. It is interesting to note that CMP-1, CMP-2 as well as CMP-3 show large areas of green isosurface which cover the interacting atoms to the effect of making the atomic boundaries loss clear. This implies that there is a large extent of redistribution of electrons and overlapping of electrons orbitals that explains an increase in stability of these structures. In all the complexes, the appearance of clear blue and green loops at the contacts of the molecule of the drug and nanocage indicates strong chemisorption. The potential observed orbital overlap is in agreement with strong binding interactions and as such it supports the trends in the charge transfer that were seen in the NBO analysis. These data confirm the stability of the complexes and underline the efficiency of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocages in forming the long-term interactions with CIP molecule.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eEffect Of Solvent And Dipole Moment Analysis\u003c/h3\u003e\n\u003cp\u003eTo analyze how the solvent environment impacts the interaction behavior of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and the ciprofloxacin (CIP) drug, all the previous optimization complexes were re-optimized in aqueous phase with the help of the polarizable continuum model (PCM) as the part of the computation framework. The values of adsorption energies of both the dry samples and their wet samples are tabulated in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The solvent effects introduced showed a slight decrease in the adsorption energies of most of the complexes as compared to the gas-phase calculations 60. It is worth noting that complexes CMP-1 and CMP-4 were both highly stable in aqueous and vacuum environment which means that they have strong binding properties even when solvated. The system with the highest adsorption energy in aqueous medium was the CMP-3, which was found to be with \u0026minus;\u0026thinsp;43.2013 kcal/mol per mole indicating that a preferred configuration of the complex existed in water. Besides the energy determinations, there was a variation in the dipole moments, which were also examined in order to determine the interaction process between the nanocage and CIP drug further. The isolated Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage and the CIP molecule have dipole moments of about 0.000173 and 9.702292 Debye, respectively. When complexes were formed, the dipole moments enhanced significantly in all the systems as it is reported in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. This increment in polarity implies the improved redistribution of charges and other hints on the adsorption capacity and efficiency of them Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage to the CIP drug.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdsorption energy in Solvent And Dipole Moment (DM) Analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSystem\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eEads (gas medium)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eEads (water medium)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eDM (Debye)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eZn\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-------------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-------------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e0.000173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCiprofloxacin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-------------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-------------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e9.702292\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-39.3726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-41.1865\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e20.430222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-39.3255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-38.0160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e16.290770\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-48.9929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-43.2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e8.581503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-23.6022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-23.9422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e11.715527\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCMP-5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e-33.4816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e-27.4871\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e8.743845\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003eThermodynamics Analysis\u003c/h3\u003e\n\u003cp\u003eThe thermodynamic analysis will provide very important information on the viability and nature of the adsorption phenomenon. The calculated values of enthalpy change (∆H) and Gibbs free energy change (∆G) of all Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e CIP complexes were negative as indicated by Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The presence of these negative values proves that the adsorption process is exothermic in nature. In addition, the negative ∆G values result in the fact that the interaction is a spontaneous occurrence under the conditions described. The results of the thermodynamic calculations are close to the findings of energetic calculations, which support the clarity and feasibility of the adsorption process under consideration.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eRecovery time calculation\u003c/h2\u003e\n \u003cp\u003eThe efficiency of the adsorbent to be regenerated is also one of the important variables defining the practical applicability of the adsorbent, and the lower the recovery time the greater the reusability. To determine this, the recovery time of all five complexes of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e-CIP were determined at 298.15K and 350.0 K. The recovery time of CMP-1, CMP-2, CMP-3, CMP-4, and CMP-5 were found to be 7.27 x 10\u0026thinsp;\u0026minus;\u0026thinsp;7, 6.71 x 10\u0026thinsp;\u0026minus;\u0026thinsp;6, 8.20 x 10\u0026thinsp;\u0026minus;\u0026thinsp;3, 2 x 10\u0026thinsp;\u0026minus;\u0026thinsp;5 and 3.49 x 10\u0026thinsp;\u0026minus;\u0026thinsp;1 seconds at 298.15 K, respectively. On raising the temperature to 350 K, recovery times decreased much to 3.85 x 10 12, 3.60 x 10 12, 3.92 x 10 18, 5.47 x 10 2 and 8.08 x 10 8 seconds respectively as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. The implication of these findings is that an increase in temperatures also promotes the process of regeneration. All in all, the short regeneration times especially at high temperatures are indicative of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage as a very efficient and reusable adsorbent in the removal of ciprofloxacin (CIP) in aqueous environment.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"COMPUTATIONAL DETIALS","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003cp\u003eIt is well known that Density Functional Theory (DFT) is accurate, reliable, and has a high level of computer efficiency when it comes to the study of the overall structure of a material and its electronic characteristics [35,36,37,38,39]. The optimization of the molecular form of ciprofloxacin (CIP) as well as Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage was performed in this work with the help of the GAMESS\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e software suite with the use of the B3LYP functional and a combination of 6-31G(d,p) basis set. To correctly take into consideration the effects of long-range dispersion, the method of the DFT-D3 correction, which was created by Grimme \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, was applied. Based on the relation, the adsorption energy of CIP on the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage under gas and aqueous conditions was obtained.\u003c/p\u003e\n \u003cdiv id=\"Equa\" class=\"Equation\"\u003e\n \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e$$\\:{E}_{ads}={E}_{complex}-({E}_{M1}+{E}_{M2})$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eEcomplex the overall energy of the CIP Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e system, and E\u003csub\u003eM1\u003c/sub\u003e and E\u003csub\u003eM2\u003c/sub\u003e are the energy of the free ciprofloxacin molecule and Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage, respectively.\u003c/p\u003e\n \u003cp\u003eFrontier molecular orbital (FMO)\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e and density of states (DOS) were carried out to investigate the electronic properties and sensing mechanism. The expression was used to calculate the HOMO LUMO energy gap (Eg).\u003c/p\u003e\n \u003cdiv id=\"Equb\" class=\"Equation\"\u003e\n \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e$$\\:{E}_{g}={E}_{LUMO}-{E}_{HOMO}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eE\u003csub\u003eLUMO\u003c/sub\u003e, E\u003csub\u003eHOMO\u003c/sub\u003e Is the energy of the lowest and highest unoccupied and occupied molecular orbitals, respectively.\u003c/p\u003e\n \u003cp\u003eVisualization was done in Visual Molecular Dynamics (VMD)\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e and reduced density gradient (RDG) mapping by Multiwfn\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e program was used to analyze non-covalent interactions. Topology was also studied electron density topology parameters based on the Quantum Theory of Atoms in Molecules (QTAIM) method to determine bond critical point (BCP) parameters by the B3LYP wavefunctions \u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. Natural Bond Orbital (NBO)\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e analysis on the Gaussian 16 framework was used to study the charge transfer processes but electron density difference (EDD)\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e maps were produced using Multiwfn to visualize the redistribution of charge during adsorption.\u003c/p\u003e\n \u003cp\u003eThermodynamic parameters\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e, enthalpy changes (∆H)\u003csup\u003e49\u003c/sup\u003e and Gibbs free energy (∆G)\u003csup\u003e50\u003c/sup\u003e were calculated by the following relations.\u003c/p\u003e\n \u003cdiv id=\"Equc\" class=\"Equation\"\u003e\n \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e$$\\:\\varDelta\\:{H}_{ads}={H}_{Complex}-{H}_{(M1+M2)}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Equd\" class=\"Equation\"\u003e\n \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equd\" name=\"EquationSource\"\u003e$$\\:\\varDelta\\:{G}_{ad}=\\varDelta\\:{H}_{ad}-T\\varDelta\\:{S}_{ad}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Eque\" class=\"Equation\"\u003e\n \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Eque\" name=\"EquationSource\"\u003e$$\\:\\varDelta\\:{G}_{ad}=\\varDelta\\:{H}_{ad}-T\\left[\\right({S}_{\\left(complex\\right)}-({S}_{adsorbent}+{S}_{adsorbate})]$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eWhere ∆H and ∆G are the total electronic and thermal enthalpy and Gibbs free energy at standard conditions (298.15 K and 1 atm), and S is entropy. The solvent effect on adsorption of CIP was simulated by Polarizable Continuum Model (PCM)\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e in order to model the aqueous interactions. Besides, regeneration experiment was conducted at 298.15 K and 350 K to determine the thermal stability and reusability of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage \u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors confirm that they have no Competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding declaration\u003c/h2\u003e \u003cp\u003eThis work was supported by the Ongoing Research Funding Program (ORF-2026-235), King Saud University, Riyadh, Saudi Arabia.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eQ.A, H.K and F.A have conceptualized and carried out the simulations and interpreted the results, M.K, A,S and M.A helped in Editing Drafting and designing. Q.A, A.F.A and S.K have performed the Grammar revision and Analysis of Results. The manuscript was revised by all Authors.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThis work was supported by the Ongoing Research Funding Program (ORF-2026-235), King Saud University, Riyadh, Saudi Arabia.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of the article is available within the article\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDicu-Andreescu, I., Penescu, M. N., C\\uapuș\\ua, C. \u0026amp; Verzan, C. Chronic kidney disease, urinary tract infections and antibiotic nephrotoxicity: are there any relationships? \u003cem\u003eMed. (B Aires)\u003c/em\u003e. \u003cb\u003e59\u003c/b\u003e, 49 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShariati, A. et al. 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Mater.\u003c/em\u003e \u003cb\u003e34\u003c/b\u003e, 2351\u0026ndash;2365 (2024).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"DFT, Ciprofloxacin, Adsorptions","lastPublishedDoi":"10.21203/rs.3.rs-9432981/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9432981/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAccording to the biochemical theory, the development of pollutants like antibiotics is a worldwide issue since they foster antibiotic resistance. A detailed DFT analysis was carried out to examine the adsorption capabilities of the Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e nanocage for ciprofloxacin (CIP). Five optimal structures of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e-CIP complexes, named CMP-1 to CMP-5. CMP-3 show best adsorption energy of 48.9929 kcal/mol, represent the best interaction without any structural deformation of the nanocage. The mechanism by which the interaction takes place is that CIP molecules are bound to Zn and O atoms of the nanocage by their F and O atoms respectively. FMO indicated that the bandgap of the entire range of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e CIP complexes on adsorption reduce to make the complexes more reactive and to verify the favorable adsorption characteristics. The NBO analysis revealed that the CMP-3 complex had the highest charge transfer of =\u0026thinsp;0.139e with the minimum bond distance of 1.92 \u0026Aring; and 1.25 \u0026Aring; respectively. The presence of covalent and weak electrostatic interaction between nanocage and CIP molecules was confirmed by QTAIM, NCI and RDG analysis. The thermodynamic assessment showed that adsorption of the process is spontaneous. The nanocage of Zn\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e12\u003c/sub\u003e is easily regenerated, makes the nanocage a potential application in the real world concerning the aspects of environmental remediation.\u003c/p\u003e","manuscriptTitle":"Utility of Zn12O12 Nanocage for The Elimination of Ciprofloxacin From Drinking Water Using DFT Simulations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-05 13:15:29","doi":"10.21203/rs.3.rs-9432981/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-04T08:39:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-01T18:21:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T01:01:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221451416374677263634706229036901523350","date":"2026-04-25T16:15:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-25T01:32:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180301416891027053921359258249517322919","date":"2026-04-25T00:09:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181831901505966920587219813070865278141","date":"2026-04-24T10:04:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162823388321938057352302601227987656082","date":"2026-04-24T09:00:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-24T08:09:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-24T07:26:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-24T07:17:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-22T01:32:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-04-22T01:26:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"61591930-b50e-47a1-b3af-7f2be25706bd","owner":[],"postedDate":"May 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":67562131,"name":"Physical sciences/Chemistry"},{"id":67562132,"name":"Earth and environmental sciences/Environmental sciences"},{"id":67562133,"name":"Physical sciences/Materials science"},{"id":67562134,"name":"Physical sciences/Nanoscience and technology"}],"tags":[],"updatedAt":"2026-05-21T06:54:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-05 13:15:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9432981","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9432981","identity":"rs-9432981","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}