Solvent Effects on Medicinal Structure and 15N NMR Shielding of Medazepam
محورهای موضوعی :Arezoo Tahan 1 , Fatemeh Alimohammadi 2
1 - Department of Chemistry, Semnan Branch, Islamic Azad University, Semnan, Iran
2 - Department of Chemistry, Shahre Rey Branch, Islamic Azad University, Tehran, Iran
کلید واژه: NBO analysis, Chemical shielding, 1, 4-Benzodiazepines, Polarized Continuum Model (PCM),
چکیده مقاله :
The Density Functional Theory (DFT) and Tomasi’s Polarized Continuum Model (PCM) were used to investigate the effects of solvent dielectric constant on the structural stability and 15N NMR tensors of Medazepam (MDZ) drug. The results revealed that the structural stability of MDZ in polar protic solvents was higher than that in the polar aprotic and non-polar solvents; and its value depended on the solvent dielectric constant and its structure. so that in most cases, relative stability increased by increasing the solvent dielectric constant and the most stable structures were observed in water media at DFT level and in methanol at MP2 level. In this regard, natural bond orbital (NBO) interpretation showed that the tetravalent N1 nucleus of diazepine ring in the MDZ structure had the highest value of negative charge and the resonance energy related to LP (1) N1 → σ* and π* delocalizations among heteroatoms of MDZ structure in the tested solvents. The findings reported that with an increase in the solvent dielectric constant, the resonance energy related to LP (1) N1 → σ* and π* delocalizations increased and the highest value of resonance energy was observed in water media. Furthermore, NMR results represented that the N1 nucleus had a higher value of chemical shielding than the trivalent N4 nucleus in all of the tested media. However, it may be concluded that by increasing the accumulation of negative charge and lone pair electrons participation of nitrogen nuclei in the resonance delocalizations, isotropic chemical shielding around them increase.
1. Kraus G.A., Maeda H., 1994. A direct preparation of 1, 4-benzodiazepines. The synthesis of medazepam and related compounds via a common intermediate. Tetrahedron Lett. 35(49), 9189–9190.
2. Medicines C.O.T.R.O., 1980. Systematic Review Of The Benzodiazepines: Guidelines For Data Sheets On Diazepam, Chlordiazepoxide, Medazepam, Clorazepate, Lorazepam, Oxazepam, Temazepam, Triazolam, Nitrazepam, and Flurazepam. Br Med J. 29, 910–912.
3. Boleloucký Z., Náhunek K., Kamenická V., Kulísková O., Misurec J., Sláma B., 1975. Medazepam, oxazepam and placebo: Clinical and experimental study. Act Nerv Super. 17(4), 277-278 (Praha).
4. Giusti P., Arban R., 1993. Physiological and pharmacological bases for the diverse properties of benzodiazepines and their congeners. Pharmacol Res. 27(3), 201–216.
5. Riss J., Cloyd J., Gates J., Collins S., 2008. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol. Scand. 118(2), 69–86.
6. Muthu S., Prasath M., Balaji R.A., Maheswari J.U., 2012. Thermochemical investigations and vibrational spectroscopic studies of1, 4-benzodiazepines using ab initio and dft methods. Ann Fac Eng Hunedoara. 10(3), 399.
7. El Assyry A., Benali B., Boucetta A., Lakhrissi, B., 2014. Quantum chemical study by Density Functional Theory (DFT) of some benzodiazepine derivatives. J Mater Environ Sci. 5(6), 1860–1867.
8. Millefiori S., Alparone A., 2011. Electronic properties of neuroleptics: ionization energies of benzodiazepines. J Mol Model. 17(2), 281–287.
9. Keerti A.R., Kumar B.A., Parthasarathy T., Uma V., 2005. QSAR studies—potent benzodiazepine γ-secretase inhibitors. Bioorg Med Chem. 13(5), 1873–1878.
10. Lu A., Zhou J., 2004. Pseudoreceptor models and 3d-qsar for imidazobenzodiazepines at gabaa/bzr subtypes α x β3γ2 [x= 1− 3, 5, and 6] via flexible atom receptor model. J Chem Inf Comput Sci. 44(3), 1130–1136.
11. Kawakami J., Hoshi K., Ishiyama A., Miyagishima S., Sato K., 2004. Application of a self-organizing map to quantitative structure–activity relationship analysis of carboquinone and benzodiazepine. Chem Pharm Bull. 52(6), 751–755.
12. Gupta S.P., 2002. Quantitative structure-activity relationship studies on cholecystokinin antagonists. Curr Pharm Des. 8(2), 111–124.
13. Annor-Gyamfi J.K., Jarrett J.M., Osazee J.O., Bialonska D., Whitted C., Palau V.E., Shilabin A.G., 2018. Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines. Heliyon. 4(2), 1–19.
14. Berezhnoy D., Baur R., Gonthier A., Foucaud B., Goeldner M., Sigel E., 2005. Conformational changes at benzodiazepine binding sites of GABAA receptors detected with a novel technique. J Neurochem. 92(4), 859–866.
15. Schove L.T., Perez J.J., Loew G.H., 1994. Molecular determinants of recognition and activation at the cerebellar benzodiazepine receptor site. Bioorg Med Chem. 2(10), 1029–1049.
16. Loew G.H., Nienow J.R., Poulsen M., 1984. Theoretical structure-activity studies of benzodiazepine analogues. Requirements for receptor affinity and activity. Mol Pharmacol. 26(1), 19–34.
17. Karpińska G., Mazurek A.P., Dobrowolski J.C., 2012. On substituent effect on the benzodiazepinone system. Comput Theor Chem. 993(1),13–19.
18. Bronisz K., Ostafin M., Poleshchuk O.K., Mielcarek J., Nogaj B., 2006. Studies of the electronic structure and biological activity of chosen 1,4-benzodiazepines by35Cl NQR spectroscopy and DFT calculations. Chem Phys. 330(1-2), 301–306.
19. al-Hawasli H., Al-Khayat M.A., Al-Mardini M.A., 2012. Development of a validated HPLC method for the separation and analysis of a Bromazepam, Medazepam and Midazolam mixture. J Pharm Anal. 2(6), 484–491.
20. Pape B.E., Ribick M.A., 1977. Analysis of medazepam, diazepam, and metabolites in plasma by gas—liquid chromatography with electrolytic conductivity detection. J Chromatogr A. 136(1), 113–126.
21. Yilmaz B., Akba V., 2009. Rapid and Simple Methods for Determination of Medazepam in Pharmaceutical Preparations using GC-FID and GC-MS. Anal Lett. 42(18), 2978–2985.
22. Crankshaw D.P., Raper C., 1971. The effect of solvents on the potency of chlordiazepoxide, diazepam, medazepam and nitrazepam. J Pharm Pharmacol. 23(5), 313–321.
23. Mihalić M., Šunjić V., Kajfež F., Žinić M., 1977. Quaternization of 2‐aziridino‐5‐chlorobenzophenone, an efficient synthesis of medazepam. J Heterocycl Chem. 14(5), 941–942.
24. Ghalami-Choobar B., Ghiami-Shomami A., Asadzadeh-Khanghah S., 2018. First principles prediction of aqueous acidities of some benzodiazepine drugs. Chem Phys Lett. 706(16), 426–431.
25. Le Petit G.F., 1976. Medazepam pKa determined by spectrophotometric and solubility methods. J Pharm Sci. 65(7), 1094–1095.
26. Mielcarek J., Nowak D.M., Pajzderska A., Peplińska B., Wsicki J., 2011. A hybrid method for estimation of molecular dynamics of diazepam-density functional theory combined with NMR and FT-IR spectroscopy. Int J Pharm. 404(1-2), 19–26.
27. Finner E., Zeugner H., Milkowski W., 1985. Conformation of medazepam in solution. Arch Pharm. (Weinheim). 318(12), 1135–1137.
28. Salari A.A., Talebi Tari M., Noei M., Tahan A., 2017. The ab initio study and NBO interpretation of solvent effects on the structural stability and the chemical reactivity of penicillin-V conformations. Arab J Chem. 10, S2327–S2334.
29. Tahan A., Ahmadinejad N., 2014. Investigation of solvent effects on the stability and 15N NMR shielding of hallucinogenic harmine using the PCM model and NBO interpretation. J Struct Chem. 55(5), 837–842.
30. Tahan A., Khojandi M., Salari A.A., 2015. The theoretical investigation of solvent effects on the relative stability and 15N NMR shielding of antidepressant heterocyclic drug. Russ J Phys Chem A. 90(1), 130–135.
31. Foresman J.B., Keith T.A., Wiberg K.B., Snoonian J., Frisch M.J., 1996. Solvent effects. 5. Influence of cavity shape, truncation of electrostatics, and electron correlation on ab initio reaction field calculations. J Phys Chem. 100(40), 16098–16104.
32. Glendening E.D., Reed A.E., Carpenter J.E., Weinhold F., 1998. NBO Version 3.1, Tci. Univ. Wisconsin, Madison. 65.
33. Reed A.E., Curtiss L.A., Weinhold F., 1988. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev. 88(6), 899–926.
34. Cammi R., Mennucci B., Tomasi J., 1999. Nuclear magnetic shieldings in solution: Gauge invariant atomic orbital calculation using the polarizable continuum model. J Chem Phys. 110(16), 7627–7638.
35. Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Montgomery J.A., Vreven T., Kudin K.N., Burant J.C., 2004. GAUSSIAN 03 software package. Gaussian Inc., Wallingford Google Sch.
36. Martindale W., 1996. The extra pharmacopoeia. ed. Reynolds, J.E.F. London: Royal Pharmaceutical Society.
