Synthesis, Structural Investigation, Hirshfeld Surface Analysis, and Biological Evaluation of N-(3-Cyanothiophen-2-yl)-2-(thiophen-2-yl)acetamide

Şükriye Çakmak; Sevgi Kansiz; Mohammad Azam; Cem Cüneyt Ersanlı; Önder İdil; Aysel Veyisoğlu; Hasan Yakan; Halil Kütük; Arunabhiram Chutia

doi:10.1021/acsomega.2c00318

Synthesis, Structural Investigation, Hirshfeld Surface Analysis, and Biological Evaluation of N-(3-Cyanothiophen-2-yl)-2-(thiophen-2-yl)acetamide

ACS Omega. 2022 Mar 21;7(13):11320-11329. doi: 10.1021/acsomega.2c00318. eCollection 2022 Apr 5.

Authors

Şükriye Çakmak¹, Sevgi Kansiz², Mohammad Azam³, Cem Cüneyt Ersanlı⁴, Önder İdil⁵, Aysel Veyisoğlu¹, Hasan Yakan⁶, Halil Kütük⁷, Arunabhiram Chutia⁸

Affiliations

¹ Department of Medical Services and Techniques, Vocational School of Health Services, Sinop University, 57000, Sinop, Turkey.
² Department of Fundamental Sciences, Faculty of Engineering, Samsun University, Samsun, 55420, Turkey.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁴ Department of Physics, Faculty of Arts and Sciences, Sinop University, 5700, Sinop, Turkey.
⁵ Department of Basic Education, Faculty of Education, Amasya University, 05000, Amasya, Turkey.
⁶ Department of Science and Mathematics Education, Ondokuz Mayıs University, 55139, Samsun, Turkey.
⁷ Department of Chemistry, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139, Samsun, Turkey.
⁸ School of Chemistry, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, U.K.

Abstract

In this study, a novel heterocyclic amide derivative, N-(3-cyanothiophen-2-yl)-2-(thiophen-2-yl)acetamide (I), was obtained by reacting 2-aminothiophene-3-carbonitrile with activated 2-(thiophen-2-yl)acetic acid in a N-acylation reaction and characterized by elemental analyses, FT-IR, ¹H and ¹³C NMR spectroscopic studies, and single crystal X-ray crystallography. The crystal packing of I is stabilized by C-H···N and N-H···N hydrogen bonds. In addition, I was investigated computationally using the density functional theory (DFT) method with the B3LYP exchange and correlation functions in conjunction with the 6311++G(d,p) basis set in the gas phase. Fukui function (FF) analysis was also carried out. Electrophilicity-based charge transfer (ECT) method and charge transfer (ΔN) were computed to examine the interactions between I and DNA bases (such as guanine, thymine, adenine, and cytosine). The most important contributions to the Hirshfeld surface are H···H (21%), C···H (20%), S···H (19%), N···H (14%), and O···H (12%). An ABTS antioxidant assay was used to evaluate the in vitro antioxidant activity of I. The compound exhibited moderate antioxidant activity. The antimicrobial activity of the title molecule was investigated under aseptic conditions, using the microdilution method, against Gram-positive and Gram-negative bacterial strains, and it also demonstrated significant activity against yeasts (Candida glabrata ATCC 90030, Candida krusei ATCC 34135). The findings revealed that the molecule possesses significant antioxidant and antimicrobial properties.