A Theoretical Study of 2-hydroxyethyl Substituted NHC Precursors Containing ortho–, meta– and para– methylbenzyl: Global Reactivity Descriptors and Prediction of Biological Activities

Year 2021, Volume: 11 Issue: 1, 258 - 267, 01.03.2021

Duygu Barut Celepci

https://doi.org/10.21597/jist.756249

Cited By: 1

Abstract

In this work, three 2-hydroxyethyl substituted N-heterocyclic carbene (NHC) precursors containing ortho–, meta– and para– methylbenzyl fragments are characterized theoretically. Theoretical calculations are performed to gain insight into these three molecules’ electronic properties (HOMO-LUMO energy, MEP and global reactivity descriptors) and biological behaviors. Also, atomic charges are calculated and molecular orbital analysis is performed. In order to investigate the stability of the molecules resulting from hyperconjugative interactions and charge delocalization, natural bond orbital (NBO) analysis is used. A predictive study for the biological activities is carried out using PASS (prediction of activity spectra for biologically active structures) online software. Biological activity predictions showed the substance P antagonist, analgesic and antiinflammatory activities of the compounds.

Keywords

N-heterocyclic precursors, DFT, PASS online

References

• Anonymous, 2014. Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource. http://www.way2drug.com/PASSOnline/.
• Balachandran V, Parimala K, 2012. Tautomeric purine forms of 2-amino-6-chloropurine (N9H10 and N7H10): Structures, vibrational assignments, NBO analysis, hyperpolarizability, HOMO–LUMO study using B3 based density functional calculations, Spectrochimica Acta A 96:340-351.
• Chattaraj PK, Nath S, Maiti B, 2003. Computational Medicinal Chemistry for Drug Discovery. Marcel Dekker. New York.
• Choudhary VK, Bhatt AK, Dash D, Sharma N, 2019. DFT Calculations on Molecular Structures, HOMO–LUMO Study, Reactivity Descriptors and Spectral Analyses of Newly Synthesized Diorganotin (IV) 2-Chloridophenylacetohydroxamate Complexes, Journal of Computational Chemistry 40:2354-2363.
• Dennington R, Keith TA, Millam JM, 2016. GaussView, Version 6, Semichem Inc. Shawnee Mission. KS.
• Dragutan V, Dragutan I, Delaude L, Demonceau A, 2007. NHC–Ru complexes—Friendly catalytic tools for manifoldchemical transformations. Coordination Chemistry Reviews 251:765-794.
• Erdemir F, Barut Celepci D, Aktaş A, Taslimi P, Gök Y, Karabıyık H, Gülçin İ, 2018. 2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, a-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties, Journal of Molecular Structure 1155:797-806.
• Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, Pogodin PV, Poroikov VV, 2014. Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource, Chemistry of Heterocyclic Compounds 50:444-457.
• Filimonov DA, Poroikov VV, 2008. RSC Publishing. Cambridge. 182-216.
• Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, et al. 2010. Gaussian 09 Revision B.01. Gaussian, Inc. Wallingford CT.
• Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Weinhold F, 1995. NBO Version 3.1. Theoretical Chemistry Institute. University of Wisconsin. Maddison.
• Gunasekaran S, Balaji RA, Kumeresan S, Anand G, Srinivasan S, 2008. Experimental and theoretical investigations of spectroscopic properties of N-acetyl-5-methoxytryptamine, Canadian Journal of Analytical Sciences and Spectroscopy 53:149-162.
• Hopkinson MN, Richter C, Schedler M, Glorius F, 2014. An overview of N-heterocyclic carbenes. Nature 510:485-496.
• Lakshmi A, Balachandran V, 2013. Rotational isomers, NBO and spectral analyses of N-(2-hydroxyethyl) phthalimide based on quantum chemical calculations, Journal of Molecular Structure 1033:40-50.
• Meenakshi R, 2017. Spectral investigations, DFT based global reactivity descriptors, Inhibition efficiency and analysis of 5-chloro-2-nitroanisole as π-spacer with donor-acceptor variations effect for DSSCs performance, Journal of Molecular Structure 1127:694-707.
• Mendoza-Huizar LH, 2014. Chemical Reactivity of Quinmerac Herbicide Through the Fukui Function, Acta Chimica Slovenica 61:694-702.
• Nirmala M, Viswanathamurthi P, 2016. Design and synthesis of ruthenium(II) OCO pincer type NHC complexes and their catalytic role towards the synthesis of amides, Journal of Chemical Sciences 128:9-21.
• Okulik N, Jubert AH, 2005. Theoretical Analysis of the Reactive Sites of Non–steroidal Anti–inflammatory Drugs, Internet Electronic Journal of Molecular Design 4:17-21.
• Sarı Y, Aktaş A, Taslimi P, Gök Y, Gülçin İ, 2018. Novel N‐propylphthalimide‐ and 4‐vinylbenzyl‐substituted benzimidazole salts: Synthesis, characterization, and determination of their metal chelating effects and inhibition profiles against acetylcholinesterase and carbonic anhydrase enzymes. Journal of Biochemical and Molecular Toxicology 32:e22009.
• Xavier RJ, Gobinath E, 2012. FT-IR, FT-Raman, ab initio and DFT studies, HOMO–LUMO and NBO analysis of 3-amino-5-mercapto-1,2,4-triazole, Spectrochimica Acta A. Molecular and Biomolecular Spectroscopy 86:242-251.
• Zou T, Lok CN, Wan PK, Zhang ZF, Fung SK, Che CM, 2018. Anticancer metal-N heterocyclic carbene complexes of gold, platinum and palladium. Current Opinion in Chemical Biology 43:30-36.