Quantum Chemical Calculations on Fentanyl Used as Potent Analgesic

Year 2021, Volume: 2 Issue: 2, 62 - 75, 18.12.2021

Sümeyya Serin , Tuğba Utku , Gulsen Kaya

https://doi.org/10.46572/naturengs.1022735

Abstract

This current study dealt with the quantum chemical analysis on fentanyl compound, which is a potent synthetic analgesic. First of all, the geometry optimizations were carried out via Density Functional Theory (DFT) and Hartree-Fock (HF) methods in both the gas and the water phase. The B3LYP functional and the HF method were used with the 6-31G (d,p) and 6-31++G (d,p) basis sets. Computed structural parameters were compared with the data available in the literature and consistent results were obtained for all four different methodologies. Charge distributions of each atom of fentanyl were obtained by Mulliken and natural population analysis. Accompanied by calculated molecular descriptors, the results of frontier molecular orbital (FMO) analysis and natural bond orbital (NBO) analysis were reported. Finally, molecular electrostatic potential (MEP) analysis has been performed to estimate reactive sites for electrophilic and nucleophilic attack. Total density, ESP, MEP, and contour maps were visualized at B3LYP/6-31++G (d,p) level of theory.

Keywords

Fentanyl, DFT, Atomic Charges, NBO, HOMO-LUMO

References

• [1] Smialek, J.E., Levine, B., Chin, L., Wu, S.C., Jenkins, A. J. (1994). A Fentanyl Epidemic İn Maryland, J. Forensic Sci., 39(1): 159-164.
• [2] Morgan, E.G., Mikhail, M.S., Murray, M.J., Larson, C.P. (2002). Clinical Anesthesiology, New York, Mc Graw Hill Co., 127–77: 819- 48.
• [3] Stanley, T.H. (1992). The History and Development of The Fentanyl Series, J Pain Symptom Manage, 7:3–7.
• [4] Ronald, D.M. (2010). Miller’s Anesthesia, Seventh Edition, Churchill Livingstone Elsevier, 795-803.
• [5] Asadi, Z., Esrafili, M.D., Vessally, E., Asnaashariisfahani, M., Yahyaei, S., Khani, A. (2017). A structural study of fentanyl by DFT calculations, NMR and IR spectroscopy, Journal of Molecular Structure, 1128:552-562.
• [6] Leonardi, J., Haddad, A., Green, O., Birke, R.L., Kubic, T., Kocak, A., Lombardi, J.L. (2017). SERS, Raman, and DFT analyses of fentanyl and carfentanil: Toward detection of trace samples, J Raman Spectrosc., 48:1323–1329.
• [7] Wang, C.H., Terracciano, A.C., Masunov, A.E., Xu, M., Vasu, S.S. (2021). Accurate prediction of terahertz spectra of molecular crystals of fentanyl and its analogs, Scientific Reports, 11:4062.
• [8] Peeters, O.M., Blaton, N.M., De Ranter, C.J., Van Herk, A.M., Goubitz, K. (1979). Crystal and molecular structure of N-[1-(2-phenylethyl)-4-piperidinylium]-N-phenylpropanamide (fentanyl) citrate-toluene solvate, Journal of Crystal and Molecular Structure, Vol. 9, No. 3.
• [9] Ergül, M., Sayın, K., Ataseven, H. (2021). 2-Phenylethyne-1-Sulfonamide Derivatives as New Drugs Candidates for Heat Shock Protein 70 and Doublecortin-like Kinase, Turkish Comp. Theo. Chem. (TC&TC), 5(1): 1-12.
• [10] Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman., J.R., Scalmani, G., Barone, V., Petersson, G.A., Nakatsuji, H., et.al. (2016). Gaussian 16 Rev. B.01, Wallingford, CT.
• [11] Dennington, R., Keith, T.A., Millam, J.M. (2016). Gauss View, Version 6, Semichem Inc., Shawnee Mission.
• [12] Becke, A.D. (1993). A new mixing of Hartree–Fock and local density functional theories. J. Chem. Phys., 98:1372–1377.
• [13] Lee, C., Yang, W., Parr, R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical Review B., 37: 785–789.
• [14] Becke, A.D. (1993). Density‐functional thermochemistry. III. The role of exact exchange, J. Chem. Phys., 98: 5648–5652.
• [15] Marenich, A. V., Cramer, C. J. and Truhlar, D. G. J. Phys. (2009). Chem. B., 113 6378.
• [16] Mulliken, R. S. (1955). J Chem Phys., 1833-1841.
• [17] Fukui, K. (1982). The Role of Frontier Orbitals in chemical reactions, Science, 218: 747–754.
• [18] Serdaroğlu, G. and Elik, M. (2018). A Computational study predicting the chemical reactivity behavior of 1-substituted 9-ethyl-βCCM derivatives: DFT- Based Quantum Chemical Descriptors, Turkish Comp. Theo. Chem. (TC&TC), 2(1): 1-11.
• [19] Sayin, K. and Üngördü, A. (2019). Investigations of structural, spectral and electronic properties of enrofloxacin and boron complexes via quantum chemical calculation and molecular docking, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 220: 117102.
• [20] Serdaroğlu, G. and Ortiz, J. V. (2017). Ab Initio Calculations on some Antiepileptic Drugs such as Phenytoin, Phenobarbital, Ethosuximide and Carbamazepine., Struct. Chem., 28: 957-964.
• [21] Üngördü, A. and Sayin, K. (2019). Quantum chemical calculations on sparfloxacin and boron complexes, Chemical Physics Letters, 733: 136677.
• [22] Weinhold, F., Landis, C.R. and Glendening, E.D. (2016). Int. Rev. Phys. Chem., 35(3): 399-440.
• [23] Reed, A.E., Curtiss, L.A. and Weinhold, F. (1988). Chem. Rev., 88(6): 899-9 26.
• [24] Murray, J.S. and Politzer, P. (2011). The electrostatic potential: an overview, WIREs Comput. Mol. Sci., 1: 153-322.