Density Functional Theory and Molecular Docking Analysis of Newly Synthesized and Characterized Benzimidazolium Salts

Year 2022, , 52 - 63, 30.06.2022

Elvan Üstün , Neslihan Şahin

https://doi.org/10.54370/ordubtd.1117826

Abstract

Benzimidazoles, an important member of the N-heterocyclic carbenes family, draw attention to their catalytic properties as well as their pharmaceutical activity. Since these molecules are relatively easy to synthesize and derivatize, they are frequently used in the synthesis of species with desired properties and metal complexes of these species. The interactions of these kinds of pharmaceutical molecules with the tissue and blood components are important. The interaction of the bioactive species with serum albumin, which is one of the most important proteins in the blood, is a frequently studied subject and Bovine Serum Albumin is frequently used in these researches. In-silico methods provide many advantages and give important insights before experimental procedures. In this study, two novel benzimidazolium salts were synthesized and characterized. After the structural analysis of the molecules was analyzed by DFT-based calculation methods, the reactivities of the molecules were also examined with Global Reactivity Descriptors. In addition, the interactions of molecules with Bovine Serum Albumin were analyzed by molecular docking methods.

Keywords

DFT, N-heterocyclic carbenes, molecular docking, DFT, benzimidazole, bovine serum albumin

Yeni Sentezlenmiş ve Karakterize Edilmiş Benzimidazolyum Tuzlarının Yoğunluk Fonksiyonel Teorisi ve Moleküler Doking Analizi

Abstract

N-heterosiklik karbenler ailesinin önemli bir üyesi olan benzimidazoller, farmasötik aktivitelerinin yanı sıra katalitik özellikleri ile de dikkat çekmektedir. Bu moleküllerin sentezlenmesi ve türevlendirilmesi nispeten kolay olduğundan, bu bileşikler istenen özelliklere sahip yeni türlerin ve bu türlerin metal komplekslerinin sentezinde sıklıkla kullanılırlar. Bu tür farmasötik moleküllerin doku ve kan bileşenleri ile etkileşimleri önemlidir. Biyoaktif türlerin kandaki en önemli proteinlerden biri olan serum albümini ile etkileşimi sıkça çalışılan bir konudur ve bu araştırmalarda Sığır Serum Albümin sıklıkla kullanılmaktadır. In-siliko yöntemler birçok avantaj sağlar ve deneysel prosedürlerden önce önemli bilgiler verir. Bu çalışmada iki yeni benzimidazolyum tuzu sentezlenmiş ve karakterize edilmiştir. Moleküllerin yapısal analizi DFT tabanlı hesaplama yöntemleri ile analiz edildikten sonra, Global Reaktivite Tanımlayıcıları ile moleküllerin reaktiviteleri de incelenmiştir. Ayrıca moleküllerin Sığır Serum Albümin ile etkileşimleri moleküler doking yöntemleri ile analiz edildi.

Keywords

DFT, N-heterosiklik karbenler, moleküler doking, DFT, benzimidazol, sığır serum albümini

References

• Alinaghi, M., Karami, K., Shahpiri, A., Momtazi-Borojeni, A. A., Abdollahi, E., & Lipkowski, J. (2020). A Pd (II) complex derived from pyridine-2-carbaldehyde oxime ligand: Synthesis, characterization, DNA and BSA interaction studies and in vitro anticancer activity. Journal of Molecular Structure, 1219, 128479. https://doi.org/10.1016/j.molstruc.2020.128479
• Arduengo III, A. J., Harlow, R. L., & Kline, M. (1991). A stable crystalline carbene. Journal of the American Chemical Society, 113(1), 361-363. https://doi.org/10.1021/ja00001a054
• Becke, A. D. (1988). Correlation energy of an inhomogeneous electron gas: A coordinate‐space model. The Journal of Chemical Physics, 88(2), 1053-1062. https://doi.org/10.1063/1.454274
• Bejaoui, L., Brahmia, A., Marzouki, R., Dusek, M., Eigner, V., Serdaroğlu, G., ... & Hassen, R. B. (2020). Synthesis, crystal structure, hirshfeld surface analysis, spectroscopic, biological and first-principles studies of novel aminocoumarins. Journal of Molecular Structure, 1221, 128862. https://doi.org/10.1016/j.molstruc.2020.128862
• Bujacz, A. (2012). Structures of bovine, equine and leporine serum albumin. Acta Crystallographica Section D: Biological Crystallography, 68(10), 1278-1289. https://doi.org/10.1107/S0907444912027047 Dassault Systèmes BIOVIA (2016). Discovery studio modeling environment, release 2017. Dassault Systèmes.
• Feizi-Dehnayebi, M., Dehghanian, E., & Mansouri-Torshizi, H. (2021). A novel palladium (II) antitumor agent: Synthesis, characterization, DFT perspective, CT-DNA and BSA interaction studies via in-vitro and in-silico approaches. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 249, 119215. https://doi.org/10.1016/j.saa.2020.119215
• Furche, F., & Perdew, J. P. (2006). The performance of semilocal and hybrid density functionals in 3 d transition-metal chemistry. The Journal of Chemical Physics, 124(4), 044103. https://doi.org/10.1063/1.2162161
• Goldwasser, P., & Feldman, J. (1997). Association of serum albumin and mortality risk. Journal of Clinical Epidemiology, 50(6), 693-703. https://doi.org/10.1016/S0895-4356(97)00015-2
• Law, C. S., & Yeong, K. Y. (2021). Benzimidazoles in drug discovery: A patent review. ChemMedChem, 16(12), 1861-1877. https://doi.org/10.1002/cmdc.202100004
• Manoharan, S., & Anandan, S. (2014). Cyanovinyl substituted benzimidazole based (D–π–A) organic dyes for fabrication of dye sensitized solar cells. Dyes and Pigments, 105, 223-231. https://doi.org/10.1016/j.dyepig.2014.02.010
• Nair, V., Vellalath, S., & Babu, B. P. (2008). Recent advances in carbon–carbon bond-forming reactions involving homoenolates generated by NHC catalysis. Chemical Society Reviews, 37(12), 2691-2698. https://doi.org/10.1039/B719083M
• Narasimhan, B., Sharma, D., & Kumar, P. (2012). Benzimidazole: A medicinally important heterocyclic moiety. Medicinal Chemistry Research, 21(3), 269-283. https://doi.org/10.1007/s00044-010-9533-9
• Neese, F. (2012). The ORCA program system. Wiley Interdisciplinary Reviews: Computational Molecular Science, 2(1), 73-78. https://doi.org/10.1002/wcms.81
• Neese, F. (2018). Software update: the ORCA program system, version 4.0. Wiley Interdisciplinary Reviews: Computational Molecular Science, 8(1), e1327. https://doi.org/10.1002/wcms.1327
• P Barot, K., Nikolova, S., Ivanov, I., & D Ghate, M. (2013). Novel research strategies of benzimidazole derivatives: a review. Mini reviews in Medicinal Chemistry, 13(10), 1421-1447. https://www.ingentaconnect.com/content/ben/mrmc/2013/00000013/00000010/art00005
• Perepichka, D. F., & Bryce, M. R. (2005). Molecules with exceptionally small HOMO–LUMO gaps. Angewandte Chemie International Edition, 44(34), 5370-5373. https://doi.org/10.1002/anie.200500413
• Peters Jr, T. (1985). Serum albumin. Advances in Protein Chemistry, 37, 161-245. https://doi.org/10.1016/S0065-3233(08)60065-0
• Phillips, J. C. (1961). Generalized Koopmans' Theorem. Physical Review, 123(2), 420. https://doi.org/10.1103/PhysRev.123.420
• Rani, J. J., Jayaseeli, A. M. I., Rajagopal, S., Seenithurai, S., Chai, J. D., Raja, J. D., & Rajasekaran, R. (2021). Synthesis, characterization, antimicrobial, BSA binding, DFT calculation, molecular docking and cytotoxicity of Ni (II) complexes with Schiff base ligands. Journal of Molecular Liquids, 328, 115457. https://doi.org/10.1016/j.molliq.2021.115457 Şahin, N., Üstün, E., Tutar, U., Çelik, C., Gürbüz, N., & Özdemir, İ. (2021). Antimicrobial activity, inhibition of biofilm formation, and molecular docking study of novel Ag-NHC complexes. Journal of Organometallic Chemistry, 954, 122082. https://doi.org/10.1016/j.jorganchem.2021.122082
• Serdaroğlu, G., Şahin, N., Şahin-Bölükbaşı, S., & Üstün, E. (2022). Novel Ag (I)-NHC complex: Synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies. Zeitschrift für Naturforschung C, 77(1-2), 21-36. https://doi.org/10.1515/znc-2021-0130
• Serdaroğlu, G., Şahin, N., Üstün, E., Tahir, M. N., Arıcı, C., Gürbüz, N., & Özdemir, İ. (2021). PEPPSI type complexes: Synthesis, x-ray structures, spectral studies, molecular docking and theoretical investigations. Polyhedron, 204, 115281. https://doi.org/10.1016/j.poly.2021.115281
• Spasov, A. A., Yozhitsa, I. N., Bugaeva, L. I., & Anisimova, V. A. (1999). Benzimidazole derivatives: Spectrum of pharmacological activity and toxicological properties (A review). Pharmaceutical Chemistry Journal, 33(5), 232-243. https://doi.org/10.1007/BF02510042
• Velık, J., Baliharova, V., Fink-Gremmels, J., Bull, S., Lamka, J., & Skálová, L. (2004). Benzimidazole drugs and modulation of biotransformation enzymes. Research in Veterinary Science, 76(2), 95-108. https://doi.org/10.1016/j.rvsc.2003.08.005
• Vijayaraj, R., Subramanian, V., & Chattaraj, P. K. (2009). Comparison of global reactivity descriptors calculated using various density functionals: A QSAR perspective. Journal of Chemical Theory and Computation, 5(10), 2744-2753. https://doi.org/10.1021/ct900347f
• Yadav, G., & Ganguly, S. (2015). Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review. European Journal of Medicinal Chemistry, 97, 419-443. https://doi.org/10.1016/j.ejmech.2014.11.053