A DFT-D4 investigation of the complexation phenomenon between pentachlorophenol and β-cyclodextrin published by Ural Federal University eISSN 2411-1414 chimicatechnoacta.ru ARTICLE 2023, vol. 10(2), No. 202310209 DOI: 10.15826/chimtech.2023.10.2.09 1 of 7 A DFT-D4 investigation of the complexation phenomenon between pentachlorophenol and β-cyclodextrin Zoubir Kabouche a, Youghourta Belhocine b * , Tahar Benlecheb a, Ibtissem Meriem Assaba bc, Abdelkarim Litim a, Rabab Lalalou b, Asma Mechhoud b a: Laboratory of Sensors, Instrumentations and Process (LCIP), University of Abbes Laghrour, Khenchela 40000, Algeria b: Laboratory of catalysis, bioprocess and environment, Department of Process Engineering, Faculty of Technology, University of 20 August 1955, Skikda 21000, Algeria c: LRPCSI-Laboratoire de Recherche sur la Physico-Chimie des Surfaces et Interfaces, University of 20 August 1955, Skikda 21000, Algeria * Corresponding author: y.belhocine@univ-skikda.dz This paper belongs to a Regular Issue. Abstract Density functional theory (DFT) calculations based on the BLYP-D4 and PBEh-3c composite methods were performed for investigating the encap- sulation mode of pentachlorophenol (PCP) inside the cavity of β-cyclodex- trin (β-CD). Different quantum chemical parameters such as HOMO, LUMO, and HOMO–LUMO gap were calculated. Complexation energies were computed at the molecular level to provide insight into the inclusion of PCP inside the β-CD cavity. The Independent gradient model (IGM) ap- proach was applied to characterize the non-covalent interactions that oc- curred during the complex (PCP@β-CD) formation. Two modes of inclu- sion were considered in this work (modes A and B). Calculated complexa- tion energies as well as the changes in enthalpy, entropy, and free Gibbs energy exhibit negative values for both modes A and B, indicating a ther- modynamically favorable process. Weak Van der Waals interactions and one strong intermolecular hydrogen bond act as the main driving forces behind the stabilization of the formed most stable complex. This study was carried out to explore the potential use of the β-CD as a host macrocycle for sensing and capturing pentachlorophenol. Keywords β-cyclodextrin pentachlorophenol inclusion complex non-covalent interactions environmental pollution Received: 25.02.23 Revised: 15.04.23 Accepted: 21.04.23 Available online: 28.04.23 Key findings ● The complexation process between β-cyclodextrin and pentachlorophenol is spontaneous, exothermic and enthalpy- driven. ● Pentachlorophenol is partially included in the β-cyclodextrin cavity. ● Stabilization of Pentachlorophenol@β-cyclodextrin complex is due to hydrogen bonding and Van der Waals interactions. ● The sensing potential of β-cyclodextrin towards pentachlorophenol could be used for environmental monitoring. © 2023, the Authors. This article is published in open access under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 1. Introduction The host-guest chemistry has paved the way for the devel- opment of supramolecular nanoarchitectures [1] with practi- cal applications such as molecular recognition, drug delivery and electrochemical biosensing [2–4]. Host–guest assemblies consist of guest molecules bound to the host molecules through non-covalent interactions (van der Waals forces, hy- drogen bonding, hydrophobic effect, π···π stacking interac- tions, etc.). Among the different classes of macrocyclic systems, calixarenes [5], pillararenes [6], cucurbiturils [7], and, in particular, cyclodextrins [8–10] are the widely used host molecules in host-guest chemistry. The usefulness of these host molecules lies in their ability to enhance the solu- bility, stability and bioavailability of poorly water-soluble guests through the complexation process [11, 12]. Cyclodextrins (CDs) represent a family of cyclic oligo- saccharides with unique properties that belong to the cage molecules family; they are usually used as host systems able to be complexed with a wide variety of guests. On the http://chimicatechnoacta.ru/ https://doi.org/10.15826/chimtech.2023.10.2.09 http://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0003-3876-8683 https://crossmark.crossref.org/dialog/?doi=https://doi.org/10.15826/chimtech.2023.10.2.09&domain=pdf&date_stamp=2023-04-28 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 2 of 7 DOI: 10.15826/chimtech.2023.10.2.09 other hand, CDs are inexpensive and eco-friendly, which makes them suitable for use in several industries [13]. CDs are considered as semi-natural products synthesized by simple enzymatic conversion of starch and containing six to twelve glucopyranose units [14–16]; they possess a hydro- philic peripheral surface and hydrophobic interior cavity with an overall truncated cone shape [17, 18]. α-, β-, and γ- cyclodextrins, composed, respectively, of six, seven, and eight glucopyranose units, represent the three mains com- mon cyclodextrins [19]. Pentachlorophenol (PCP) is an industrial prevalent wood preservative used since 1936, particularly, in utility poles and railway ties [20]. Its widespread use has caused environment pollution. Indeed, the PCP was listed among the 126 priority pollutants by the European Community as well as the United States Environmental Protection Agency (USEPA) [21] and was classified as a potentially carcino- genic compound by USEPA and International Agency for Re- search on Cancer (IARC) [22]. Its use has been, therefore, severely regulated in many countries since 1987, except for the preservation of wood that is limited to industrial uses [23]. Consequently, the biodegradation of this toxic sub- stance has attracted growing interest among scientists and researchers with the aim of developing experimental meth- ods for the removal of PCP. An alternative method for the capture of PCP molecules through the supramolecular chemistry concept consists in the encapsulation of PCP by host macrocyclic systems such as cyclodextrins, cucurbiturils, calixarenes, etc. The com- plexation of guest molecules in the cavity of host systems, particularly, β-cyclodextrin, induces modifications in the physicochemical properties of the guests [24, 25]. Theoretical investigations of the host-guest interactions were the subject of several studies with the aim of under- standing the complexation behavior at molecular level by determining the forces involved in the stabilization of guest molecules inside the cavities of the macrocyclic hosts. For this purpose, different quantum chemical methods ranging from semi-empirical ones such as AM1, PM3, PM6 and PM7 [26–28] to density functional theory based approaches [29– 31] were employed. In this paper, we performed a theoretical study based on the density functional theory (DFT) method, aiming at in- vestigating the inclusion phenomenon between the β-cy- clodextrin (β-CD) host system and the pentachlorophenol (PCP) guest molecule. The formation of a 1:1 stoichiometry complex was the subject of a previous experimental study [32], while the present work constitutes a complementary approach to rationalizing the inclusion phenomenon. 2. Computational procedure ORCA code (version 4.2.1) [33, 34] was utilized to perform DFT calculations. The whole complexation process consists of full geometry optimization of the initial generated com- plexes formed between pentachlorophenol (PCP) and β- cyclodextrin (β-CD) in vacuum using BLYP-D4 functional [35–39] associated with the def2-SVP basis set. A geomet- rical counterpoise correction scheme (gCP) [40] was ap- plied to account for the basis set superposition error (BSSE). Based on the approach proposed by Liu and Guo [41], the center of PCP (guest) and β-CD (host) was set as the center of the coordinate system (0 Å). The guest mole- cule, PCP, was translated with a step of 1 Å from –8 to +8 Å along the Z-axis, resulting thus in two possible inclusion modes on the side of the wider rim of the β-CD, denoted A or B. These modes correspond to the inclusion orientation of the PCP through β-CD cavity by its terminal chloro group or its hydroxy group (OH), respectively, as represented in Figure 1 (a and b) using the visualization application Jmol [42]. For a more precise inspection of the lowest energy conformations, we explored and included more initial con- formations in the vicinity of the most stable configurations. Thus, a step of 0.5 Å was considered for A and B modes along the Z-axis in the ranges [0–8 Å] and [2–8 Å], respec- tively. A total of 48 possible conformations were obtained and fully optimized in vacuum at BLYP-D4/def2-SVP-gCP level of theory, without any symmetry constraints. The complexation energies were calculated using equa- tion (1): ΔEComplexation = EComplex(PCP@β–CD)–(EPCP + Eβ–CD), (1) where ΔEcomplexation, EcomplexPCP@β–CD, EPCP, and Eβ–CD repre- sent, respectively, the complexation energy, the optimized energies of the complex, the free PCP, and the free β-CD. Figure 1 Schematic illustration of the inclusion complexation con- formations (Mode A) (a) and Mode B (b). Atomic color code: carbon (grey), hydrogen (white), oxygen (red), chlorine (green). https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 3 of 7 DOI: 10.15826/chimtech.2023.10.2.09 The most stable configurations correspond to the structures with the lowest complexation energies. The obtained most stable structures calculated at BLYP-D4/def2-SVP-gCP level of theory for A and B modes were subsequently reoptimized with the more accurate global hybrid PBEh-3c [43] func- tional in both vacuum and aqueous phase. Calculations in water solvent were performed with the SMD solvation model [44]. Then, the most stable geometry associated with the lowest energy structure was subjected to further anal- yses, such as non-covalent interactions (NCIs) characteri- zation with independent gradient model based on the Hirshfeld partitioning scheme (IGMH) [45, 46] using Mul- tiwfn code [47] and VMD program for visualization [48]. 3. Results and Discussion 3.1. DFT-calculations of complexation energies The most stable configuration corresponds to the lowest en- ergy of all the optimized conformations calculated at DFT/BLYP-D4/def2-SVP-gcp level of theory. Figure 2 re- ports the values of the computed complexation energy for the A and B modes for each optimized conformation. The energy profiles obtained for all configurations in both modes (A and B) exhibit negative complexation energy values, pointing out a thermodynamically favorable pro- cess. Full geometry optimization was followed by frequency calculations to verify that the obtained structures are true minima. Overall, the complexation energies are globally less negative for the A and B configurations located at the negative positions of Z-axis (from –8 Å to –1 Å), whereas more negative values of the complexation energies are ob- served in the interval of positive values of z axis points. The most stable configurations for A and B modes are located at Z = 7.5 and 6.5 Å, with the respective complexa- tion energies of –121.39 and –123.79 kJ/mol. The re-optimi- zation at PBEh-3c level yielded complexation energies of –69.00 and –70.66 kJ/mol in vacuum and –21.02 and –29.53 kJ/mol in water solvent for 7.5 A and 6.5 B configu- rations, respectively, with the complex PCP@β-CD of B mode being more stable than that of A mode. Figure 2 Energy profile of the complexation between PCP and β- CD (A and B modes). The complexation process is thermodynamically more favorable in vacuum than in the water solvent. The struc- tural analysis of the most stable PCP@β-CD complex con- figuration (mode B at 6.5 Å) calculated with PBEh-3c in vac- uum shows the partial pentachlorophenol encapsulation in- side the β-CD cavity, as illustrated in Figure 3. It is worth mentioning that the least stable structure lo- cated at Z = –1 Å for A mode with a complexation energy of –4.05 kJ/mol corresponds structurally to the inclusion of the PCP into the β-CD cavity, as shown in Figure 4. Indeed, the β-CD cavity is not sufficiently large to encapsulate com- pletely the PCP guest within; the total inclusion of PCP in- volves strong elongation and flattening of β-CD. The obtained results suggest that the stability of the mo- lecular association between PCP and β-CD is enhanced by the partial encapsulation of the PCP guest. The inclusion of PCP depends mainly on the cavity size of β-CD. 3.2. Quantum electronic parameters The energies of the frontier molecular orbitals (HOMO and LUMO), and the molecular HOMO–LUMO gap of the most stable inclusion complex were computed at DFT/PBEh-3c level in vacuum, and the obtained results are shown in Table 1. Figure 3 Side view of the most stable configuration of the complex PCP@β-CD showing the partial encapsulation of PCP inside β-CD cavity. Figure 4 Front view of the least stable configuration of the complex PCP@β-CD. https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 4 of 7 DOI: 10.15826/chimtech.2023.10.2.09 The HOMO–LUMO energy gap is reduced from 9.915 eV for the host molecule β-CD to 6.883 eV after complexation by a percentage variation of about 30.58%, indicating, thus, the potential use of β-CD as a host for PCP detection. The HOMO and LUMO of the most stable PCP@β-CD complex was visu- alized with IboView program [49, 50] and represented in Fig- ure 5. Both HOMO and LUMO are almost entirely delocalized over the fused PCP molecule. The HOMO–LUMO energy gap can be used as an indica- tor of kinetic stability. A large energy separation is associ- ated with a low chemical reactivity and high kinetic stabil- ity. Upon the complexation, the decrease in the HOMO– LUMO gap of the PCP@β-CD complex (6.88 eV) in compar- ison with β-CD alone (9.92 eV) indicates that PCP@β-CD complex is more reactive and less stable than β-CD. 3.3. Characterization of the intermolecular non- covalent interactions The IGMH analysis was performed to provide insights into the nature of the intermolecular non-covalent interactions involved in the stabilization of the PCP@β-CD complex. The IGMH plots are colored according to the occurring intermo- lecular interactions. Green and blue colors denote, respec- tively, weak Van der Waals and hydrogen-bond interac- tions. The IGMH isosurface of the most stable PCP@β-CD complex (Figure 6) was calculated using Multiwfn and vis- ualized with the VMD program. The topological analysis shows that green areas associ- ated with Van der Waals interactions dominated the calcu- lated isosurface; the presence of a one hydrogen bond is re- vealed by the blue disc, as represented in Figure 6, indicat- ing that both weak Van der Waals interactions and the sin- gle intermolecular hydrogen bond act as attractive forces for the stabilization of PCP@β-CD complex. 3.4. Statistical thermodynamic calculations The thermodynamic parameters were calculated at PBEh- 3c level of theory in vacuum using frequency calculation analysis for the most stable configuration. Table 1 Frontier orbitals and HOMO–LUMO gap for β-CD, PCP, and PCP@β-CD system. Parameters β-CD PCP PCP@β-CD EHOMO –8.107 –7.841 –7.762 ELUMO 1.808 –0.854 –0.879 ΔEgap 9.915 6.988 6.883 Figure 5 HOMO and LUMO orbitals of PCP@β-CD complex. The enthalpy, entropy, and Gibbs free energy changes [51, 52] of the complexation process of PCP with β-CD at standard temperature and pressure values (298.15 K and 1 atm) are reported in Table 2. The calculated ΔG° value is negative, showing that the complexation process is sponta- neous. In addition, the negative values of enthalpy and en- tropy changes (ΔH° and ΔS°) indicated that the process is enthalpy-controlled and exothermic in nature. 3.5. Natural orbital bond (NBO) analysis of inter- molecular interactions The NBO approach [53] provides useful insights for describ- ing and determining the nature of the different donor-ac- ceptor interactions that occur in the molecular systems. The NBO analysis was carried out on the relaxed geometry of the most stable complex at M06-2X/def2-TZVPP [54–56] level of theory in vacuum using Gaussian 09 program [57]. The structural analysis (Figure 7) shows the presence of one strong hydrogen bond having a stabilization energy of 139.03 kJ/mol, formed between hydrogen atom H (160) of terminal CHO group of β-CD as the donor and oxygen atom O (121) of the PCP as the acceptor with a short distance of 1.62 Å. Figure 6 The IGMH isosurface (isovalue 0.005 a.u.) of the PCP@β- CD complex. Figure 7 The significant intermolecular hydrogen bonds for the PCP@β-CD complex. https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 5 of 7 DOI: 10.15826/chimtech.2023.10.2.09 Table 2 Energetic and thermodynamic parameters of the complexa- tion process calculated at PBEh-3c levels of theory in vacuum. Thermodynamic Parameters Energetic values ΔH° (kJ/mol) –66.85 ΔG° (kJ/mol) –1.25 ΔS° (kJ/mol) –65.61 4. Limitations Performing DFT calculations using several functionals and several basis sets is useful for comparison purposes; how- ever, the high computational and time cost of such calcula- tions are the limiting factors. 5. Conclusion The energetic and electronic properties of the complexation process between pentachlorophenol (PCP) and β-cyclodex- trin were computationally studied using DFT approach. The main conclusions of the present investigation can be stated as follows: ‒ Calculated thermodynamic parameters exhibit nega- tive enthalpy, entropy and Gibbs energy changes, indicating that the complexation process is spontaneous, exothermic and enthalpy-driven. ‒ The configuration located at Z = 6.5 Å for B mode represents the most stable configuration with a complexa- tion energy of –70.66 kJ/mol as calculated with PBEh-3c in vacuum. ‒ The structural analysis showed that PCP penetrates partially the β-cyclodextrin cavity. ‒ Hydrogen bonding and Van der Waals interactions were found by IGMH analysis to be the main driving forces for the formation and stabilization of the PCP@β-CD com- plex. ‒ Upon complexation, a significant hydrogen bond was formed at a short distance of 1.62 Å with a stabilization en- ergy of 139.03 kJ/mol. ‒ After complexation, the HOMO–LUMO energy gap decreased by a percentage of 30.58%, suggesting the poten- tial application of the β-CD host system for the encapsula- tion of PCP. The results of this study revealed the sensing potential of β-cyclodextrin as a suitable host in electronic devices based on biosensors for the detection, capture and encap- sulation of pentachlorophenol. This work could serve as a starting point for more deep experimental studies for de- veloping effective biosensors for environmental concerns. ● Supplementary materials No supplementary materials are available. ● Funding This research had no external funding. ● Acknowledgments None. ● Author contributions Conceptualization: Y.B, T.B. Data curation: Z.K, R.L, A.M. Formal Analysis: I.M.A, Z.K, A.L. Funding acquisition: Y.B. Investigation: R.L. A.M. Methodology: Y.B., T.B. Project administration: Y.B. Resources: I.M.A., Z.K., A.L. Software: Y.B., Z.K, A.L. Supervision: Y.B., T.B. Validation: Y.B. Visualization: R.L., A.M., Z.K., A.L. Writing – original draft: Y.B., I.M.A., Z.K. Writing – review & editing: Y.B. ● Conflict of interest The authors declare no conflict of interest. ● Additional information Author ID: Y. Belhocine, Scopus ID 54917426000. Websites: University of khenchela, https://univ-khenchela.com; University of Skikda, https://www.univ-skikda.dz/in- dex.php/en. References 1. Mattia E, Otto S. Supramolecular systems chemistry. Nat Nanotechnol. 2015;10:111–119. doi:10.1038/nnano.2014.337 2. Kolesnichenko IV, Anslyn EV. Practical applications of supra- molecular chemistry. Chem Soc Rev. 2017;46:2385–2390. doi:10.1039/C7CS00078B 3. Ma X, Zhao Y. Biomedical applications of supramolecular sys- tems based on host–guest interactions. Chem Rev. 2014;115:7794–7839. doi:10.1021/cr500392w 4. Sambrook MR, Notman S. Supramolecular chemistry and chemical warfare agents: From fundamentals of recognition to catalysis and sensing. Chem Soc Rev. 2013;42:9251–9267. doi:10.1039/C3CS60230C 5. Bohmer V. Calixarenes, Macrocycles with (Almost) Unlimited Possibilities. Angew Chem Int Ed Engl. 1995;34:713–725. doi:10.1002/anie.199507131 6. Chen JF, Ding JD, Wei TB. Pillararenes: Fascinating planar chiral macrocyclic arenes. Chem Commun. 2021;57:9029– 9039. doi:10.1039/D1CC03778A 7. Gerasko OA, Samsonenko DG, Fedin VP. Supramolecular chemistry of cucurbiturils. Russ Chem Rev. 2002;71:741–760. doi:10.1070/RC2002v071n09ABEH000748 8. Crini G. Review: a history of cyclodextrins. Chem Rev. 2014;114:10940–10975. doi:10.1021/cr500081p 9. Del Valle EM. Cyclodextrins and their uses: a review. Process Biochem. 2004;39(9):1033-1046. doi:10.1016/S0032- 9592(03)00258-9 https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 http://www.scopus.com/inward/authorDetails.url?authorID=54917426000&partnerID=MN8TOARS https://univ-khenchela.com/ https://www.univ-skikda.dz/index.php/en https://www.univ-skikda.dz/index.php/en https://www.nature.com/articles/nnano.2014.337 https://pubs.rsc.org/en/content/articlelanding/2017/cs/c7cs00078b https://pubs.acs.org/doi/full/10.1021/cr500392w https://pubs.rsc.org/en/content/articlelanding/2013/cs/c3cs60230c https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.199507131 https://pubs.rsc.org/en/content/articlelanding/2021/cc/d1cc03778a https://pubs.rsc.org/en/content/articlelanding/2002/rc/rc020741 https://pubs.acs.org/doi/full/10.1021/cr500081p https://doi.org/10.1016/S0032-9592(03)00258-9 https://doi.org/10.1016/S0032-9592(03)00258-9 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 6 of 7 DOI: 10.15826/chimtech.2023.10.2.09 10. Crini G, Fourmentin S, Fenyvesi É, Torri G, Fourmentin M, Morin-Crini N. Cyclodextrins from molecules to applications. Environ Chem Lett. 2018;16:1361–1375. doi:10.1007/s10311-018-0763-2 11. Gidwani B, Vyas A. Pharmacokinetic study of solid-lipid-na- noparticles of altretamine complexed epichlorohydrin-β-cy- clodextrin for enhanced solubility and oral bioavailability. Int J Biol Macromol. 2017;101:24–31. doi:10.1016/j.ijbiomac.2017.03.047 12. Alizadeh N, Malakzadeh S. Changes in chemical stability and bioactivities of curcumin by forming inclusion complexes of beta- and Gama-cyclodextrins. J Polym Res. 2020;27:42. doi:10.1007/s10965-019-1994-z 13. Yadav M, Thakore S, Jadeja R. A review on remediation tech- nologies using functionalized Cyclodextrin. Environ Sci Pollut Res. 2022;29:236–250. doi:10.1007/s11356-021-15887-y 14. Roy I, Stoddart JF. Cyclodextrin metal–organic frameworks and their applications. Acc Chem Res. 2021;54(6):1440–1453. doi:10.1021/acs.accounts.0c00695 15. Liu Y, Lin T, Cheng C, Wang Q, Lin S, Liu C, Han X. Research progress on synthesis and application of cyclodextrin poly- mers. Molec. 2021;26(4):1090. doi:10.3390/molecules26041090 16. Bautista-Renedo JM, Hernández-Esparza R, Cuevas-Yañez E, Reyes-Pérez H, Vargas R, Garza J, González-Rivas N. Defor- mations of cyclodextrins and their influence to form inclu- sion compounds. Int J Quantum Chem. 2021;122(6):e26859. doi:10.1002/qua.26859 17. Tian B, Hua S, Tian Y, Liu J. Cyclodextrin-based adsorbents for the removal of pollutants from wastewater: a review. En- viron Sci Pollut Res. 2021;28:1317–1340. doi:10.1007/s11356- 020-11168-2 18. Majd M, Yazdanpanah M, Bayatloo MR, Nojavan S. Recent ad- vances and applications of cyclodextrins in magnetic solid phase extraction. Talanta. 2021;229:122296. doi:10.1016/j.talanta.2021.122296 19. Nelumdeniya NRM, Ranatunga RJKU. Complex forming be- haviour of α, β and γ-cyclodextrins with varying size probe particles in silico. Ceylon J Sci. 2021;50(5):329–339. doi:10.4038/cjs.v50i5.7922 20. United States Environmental Protection Agency. Pentachloro- phenol. Available from: https://www.epa.gov/ingredients- used-pesticide-products/pentachlorophenol, Accessed on 03 August 2022. 21. United States Environmental Protection Agency. Priority Pol- lutant List, 2014. Available from: https://www.epa.gov/sites/default/files/2015-09/docu- ments/priority-pollutant-list-epa.pdf, Accessed on 03 August 2022. 22. Agency for Toxic Substances and Disease Registry (ATSDR), 2001. Toxicological Profile for Pentachlorophenol Atlanta, GA: U.S. Available from: https://semspub.epa.gov/work/10/100006534.pdf, Accessed on 03 August 2022. 23. Kraševec I, Nemeček N, Lozar Štamcar M, Kralj Cigić I, Prosen H. Non-destructive detection of pentachlorophenol residues in historical wooden objects. Polymers. 2021;13(7):1052. doi:10.3390/polym13071052 24. Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical for- mulations I: structure and physicochemical properties, for- mation of complexes, and types of complex. Drug Discov To- day. 2016;21:356–362. doi:10.1016/j.drudis.2015.11.017 25. Iacovino R, Rapuano F, Caso JV, Russo A, Lavorgna M, Russo C, Isidori M, Russo L, Malgieri G, Isernia C. β-Cyclodextrin in- clusion complex to improve physicochemical properties of pi- pemidic acid: Characterization and bioactivity evaluation. Int J Mol Sci. 2013;14:13022–13041. doi:10.3390/ijms140713022 26. Bakó I, Jicsinszky L. Semiempirical calculations on cyclodex- trins. J Incl Phenom Macrocycl Chem. 1994;18:275–289. doi:10.1007/BF00708734 27. Bouhadiba A, Belhocine Y, Rahim M, Djilani I, Nouar L, Khatmi DE. Host-guest interaction between tyrosine and β- cyclodextrin: Molecular modeling and nuclear studies. J Mol Liq. 2017;233:358–363. doi:10.1016/j.molliq.2017.03.029 28. Fifere A, Marangoci N, Maier SS, Coroaba A, Maftei D, Pin- teala M. Theoretical study on β-cyclodextrin inclusion com- plexes with propiconazole and protonated propiconazole. Beilstein J Org Chem. 2012;8:2191–2201. doi:10.3762/bjoc.8.247 29. Mazurek AH, Szeleszczuk Ł. Current status of quantum chem- ical studies of cyclodextrin host–guest Complexes. Molecules 2022;27:3874. doi:10.3390/molecules27123874 30. Mesri N, Belhocine Y, Messikh N, Sayede A, Mouffok B. Mo- lecular DFT investigation on the inclusion complexation of Benzo[a]pyrene with γ-Cyclodextrin. Macroheterocycles 2021;14(2):164–170. doi:10.6060/mhc210337m 31. Oqmhula K, Hongo K, Maezono R, Ichibha T. Ab Initio evalua- tion of complexation energies for cyclodextrin-drug inclusion complexes. ACS Omega 2020;5:19371–19376. doi:10.1021/acsomega.0c01059 32. Hanna K, de Brauer C, Germain P. Cyclodextrin-enhanced sol- ubilization of pentachlorophenol in water. J Environ Manag. 2004;71(1):1–8. doi:10.1016/j.jenvman.2004.01.001 33. Neese F. The ORCA program system. Wiley Interdiscip. Rev. Comput Mol Sci. 2012;2:73–78. doi:10.1002/wcms.81 34. Neese F. Software update: the ORCA program system, version 4.0. WIREs. Comput Mol Sci. 2017;8:e1327. doi:10.1002/wcms.1327 35. Becke AD. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A. 1988;38:3098– 3100. doi:10.1103/PhysRevA.38.3098 36. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B. 1988;37:785–789. doi:10.1103/PhysRevB.37.785 37. Caldeweyher E, Ehlert S, Hansen A, Neugebauer H, Spicher S, Bannwarth C, Grimme S. A generally applicable atomic- charge dependent London dispersion correction. J Chem Phys. 2019;150:154122. doi:10.1063/1.5090222 38. Belhocine Y, Rahali S, Allal H, Assaba IM, Ghoniem MG, Ali FAM. A dispersion corrected DFT investigation of the inclu- sion complexation of dexamethasone with β-Cyclodextrin and molecular docking study of its potential activity against COVID-19. Molec. 2021;26:7622. doi:10.3390/molecules26247622 39. Litim A, Belhocine Y, Benlecheb T, Ghoniem MG, Kabouche Z, Ali FAM, Abdulkhair BY, Seydou M, Rahali S. DFT-D4 Insight into the Inclusion of Amphetamine and Methamphetamine in Cucurbit[7]uril: Energetic, Structural and Biosensing Proper- ties. Molec. 2021;26:7479. doi:10.3390/molecules26247479 40. Kruse H, Grimme S. A geometrical correction for the inter- and intra-molecular basis set superposition error in Hartree- Fock and density functional theory calculations for large sys- tems. J Chem Phys. 2012;136:154101. doi:10.1063/1.3700154 41. Liu L, Guo QX. Use of quantum chemical methods to study cy- clodextrin chemistry. J Incl Phenom Macrocycl Chem. 2004;50:95–103. doi:10.1007/s10847-003-8847-3 42. Jmol: an open-source Java viewer for chemical structures in 3D. Available from: http://www.jmol.org/ 43. Grimme S, Brandenburg JG, Bannwarth C, Hansen A. Con- sistent structures and interactions by density functional the- ory with small atomic orbital basis sets. J Chem Phys. 2015;143:054107. doi:10.1063/1.4927476 44. Marenich AV, Cramer CJ, Truhlar DG. Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J Phys Chem B 2009;113(18):6378–6396. doi:10.1021/jp810292n 45. Lefebvre C, Khartabil H, Boisson JC, Contreras-García J, Piquemal JP, Hénon E. The Independent Gradient Model: A New Approach for Probing Strong and Weak Interactions in Molecules from Wave Function Calculations. ChemPhysChem 2018;19:724–735. doi:10.1002/cphc.201701325 https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 https://link.springer.com/article/10.1007/s10311-018-0763-2 https://doi.org/10.1016/j.ijbiomac.2017.03.047 https://link.springer.com/article/10.1007/s10965-019-1994-z https://link.springer.com/article/10.1007/s11356-021-15887-y https://pubs.acs.org/doi/abs/10.1021/acs.accounts.0c00695 https://www.mdpi.com/1420-3049/26/4/1090 https://onlinelibrary.wiley.com/doi/10.1002/qua.26859 https://link.springer.com/article/10.1007/s11356-020-11168-2 https://link.springer.com/article/10.1007/s11356-020-11168-2 https://www.sciencedirect.com/science/article/abs/pii/S0039914021002174 https://cjs.sljol.info/articles/abstract/10.4038/cjs.v50i5.7922/ https://www.epa.gov/ingredients-used-pesticide-products/pentachlorophenol https://www.epa.gov/ingredients-used-pesticide-products/pentachlorophenol https://www.epa.gov/sites/default/files/2015-09/documents/priority-pollutant-list-epa.pdf https://www.epa.gov/sites/default/files/2015-09/documents/priority-pollutant-list-epa.pdf https://semspub.epa.gov/work/10/100006534.pdf https://www.mdpi.com/2073-4360/13/7/1052 https://www.sciencedirect.com/science/article/abs/pii/S1359644615004523 https://www.mdpi.com/1422-0067/14/7/13022 https://link.springer.com/article/10.1007/BF00708734 https://www.sciencedirect.com/science/article/abs/pii/S0167732216338582 https://www.beilstein-journals.org/bjoc/articles/8/247 https://www.mdpi.com/1420-3049/27/12/3874 https://macroheterocycles.isuct.ru/en/mhc210337m https://pubs.acs.org/doi/10.1021/acsomega.0c01059 https://www.sciencedirect.com/science/article/pii/S0301479704000180 https://wires.onlinelibrary.wiley.com/doi/10.1002/wcms.81 https://journals.aps.org/pra/abstract/10.1103/PhysRevA.38.3098 https://journals.aps.org/prb/abstract/10.1103/PhysRevB.37.785 https://aip.scitation.org/doi/10.1063/1.5090222 https://www.mdpi.com/1420-3049/26/24/7622 https://www.mdpi.com/1420-3049/26/24/7479 https://aip.scitation.org/doi/10.1063/1.3700154 https://link.springer.com/article/10.1007/s10847-003-8847-3 http://www.jmol.org/ https://aip.scitation.org/doi/10.1063/1.4927476 https://pubs.acs.org/doi/10.1021/jp810292n https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cphc.201701325 Chimica Techno Acta 2023, vol. 10(2), No. 202310209 ARTICLE 7 of 7 DOI: 10.15826/chimtech.2023.10.2.09 46. Lu T, Chen Q. Independent gradient model based on Hirshfeld partition: A new method for visual study of interactions in chemical systems. J Comput Chem. 2022;43:539–555. doi:10.1002/jcc.26812 47. Lu T, Chen F. Multiwfn: a multifunctional wavefunction ana- lyzer. J Comput Chem. 2012;33:580–592. doi:10.1002/jcc.22885 48. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dy- namics. J Mol Graph. 1996;14:33–38. doi:10.1016/0263- 7855(96)00018-5 49. Knizia G. Intrinsic atomic orbitals: An unbiased bridge be- tween quantum theory and chemical concepts. J Chem Theory Comput. 2013;9(11):4834–4843. doi:10.1021/ct400687b 50. Knizia G, Klein JE. Electron flow in reaction mechanisms—Re- vealed from first principles. Angew Chem Int Ed. 2015;54(18):5518–5522. doi:10.1002/anie.201410637 51. González GB, Espinoza JM. Thermodynamic and reactivity as- pect of β-cyclodextrine inclusion complexes with coumarin derivatives. J Chil Chem Soc. 2022;67(2):5514–5520. doi:10.4067/S0717-97072022000205514 52. Belhocine Y, Bouhadiba A, Rahim M, Nouar L, Djilani I, Khatmi DE. Inclusion complex formation of β-Cyclodextrin with the nonsteroidal anti-inflammatory drug flufenamic acid: computational study. Macroheterocycles. 2018;11(2):203–209. doi:10.6060/mhc170829b 53. Reed AE, Curtiss LA, Weinhold F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev. 1998;88:899–926. doi:10.1021/cr00088a005 54. Zhao Y, Truhlar DG. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, non- covalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Account. 2008;120:215–241. doi:10.1007/s00214-007-0310-x 55. Weigend F. Accurate Coulomb-fitting basis sets for H to Rn. Phys Chem Chem Phys. 2006;8:1057–1065. doi:10.1039/B515623H 56. Weigend F, Ahlrichs R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy. Phys Chem Chem Phys. 2005;7:3297–3305. doi:10.1039/B508541A 57. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09, Revision D.01, Gaussian Inc., Wallingford (CT), 2013. https://doi.org/10.15826/chimtech.2023.10.2.09 https://doi.org/10.15826/chimtech.2023.10.2.09 https://onlinelibrary.wiley.com/doi/10.1002/jcc.26812 https://onlinelibrary.wiley.com/doi/abs/10.1002/jcc.22885 https://www.sciencedirect.com/science/article/abs/pii/0263785596000185 https://www.sciencedirect.com/science/article/abs/pii/0263785596000185 https://pubs.acs.org/doi/10.1021/ct400687b https://onlinelibrary.wiley.com/doi/10.1002/anie.201410637 https://www.scielo.cl/scielo.php?pid=S0717-97072022000205514&script=sci_arttext https://macroheterocycles.isuct.ru/en/mhc170829b https://pubs.acs.org/doi/10.1021/cr00088a005 https://link.springer.com/article/10.1007/s00214-007-0310-x https://pubs.rsc.org/en/content/articlelanding/2006/cp/b515623h https://pubs.rsc.org/en/content/articlelanding/2005/cp/b508541a