Synthesis, Structural Analysis, Antimicrobial Activity and The Molecular Electrostatic Potential Surface (MEP) of 2/3/4-Chloro Benzamide-Spiro[Benzo[B]Thiophene-Dioxolane] Derivatives

Year 2024, Volume: 19 Issue: 1, 53 - 62, 27.05.2024

Naki Çolak , Fatma Şahin , Gülnihal Erten , Sinan Mithat Muhammet

https://doi.org/10.29233/sdufeffd.1413620

Abstract

In this research, 2-amino-4,7-dihydro-5H-spiro[benzo[b]thiophene-6,2'-[1,3]dioxolane]-3-carbonitrile (ST) was synthesized using the Gewald method, starting with 1,4-dioxaspiro[4,5]decan-8-one ketone. The structures of compounds were characterized through FT-IR, 1H-NMR, and 13C-NMR spectra. The antimicrobial properties of the compounds were examined by the disk diffusion process. The compounds (N1-3) did not exhibit effectiveness against the E. Coli (ATCC) and S. Aureus (ATCC) bacteria. The molecular electrostatic potential surface (MEP) of all compounds was calculated via DFT calculations based on the optimized geometries at the B3LYP/6-31G (d,p) level of theory. Negative potential regions were located over the oxygen and nitrogen atoms, whereas positive potential regions were identified over the oxygen and sulfur atoms. Conceptually, computations of the molecular structures of the compounds were carried out using molecular modeling software, specifically GaussView 5.0 and the GAUSSIAN 09 package programs. Additionally, computations were performed for the HOMO and LUMO molecular orbitals of isolated molecules in the gas phase. Molecular electrostatic potential (MEP) surfaces were used to visualize potential interactions between receptors and ligands over the steady-state geometries of the molecules and to highlight the electrophilic and nucleophilic regions of the molecules.

Keywords

Amino Thiophene, Spiro Compounds, Benzamide Derivatives, Molecular Electrostatic Potential Surface

Supporting Institution

Hitit University

Project Number

Project No FEF 19001.23.003

Thanks

Hitit University Scientific Research Projects Coordination Office under Project No FEF 19001.23.003

References

• O. Raubenheimer, “Friedrich Wöhler and the centenary of synthesis”, The Journal of the American Pharmaceutical Association, 17, 973-980, 1928. https://doi.org/10.1002/jps.3080171008.
• R. A. Kyle and M. A. Shampo, “Justus von Liebig—leading teacher of organic chemistry”, Mayo Clinic Proceedings, 76, 921-922, 2001. https://doi.org/10.4065/76.9.921.
• R. J. Ouellette and J. D. Rawn, “Amines and amides”, in Organic chemistry study guide, Editors: R. J. Ouellette and J. D. Rawn, Elsevier, 2015, pp. 465-494. https://doi.org/10.1016/B978-0-12-801889-7.00023-6.
• R. Tripathi, J. P. Yadav, P. Pathak, M. H. Almatarneh and A. Verma, “Polymer–drug linking through amide bonds: the chemistry and applications in drug delivery”, in Polymer-Drug Conjugates: Linker Chemistry, Protocols, and Applications. United States: Elsevier Science & Technology, 2023. https://doi.org/10.1016/B978-0-323-91663-9.00007-2.
• A. Sathya, T. Prabhu, S. Ramalingam, “Structural, biological, and pharmaceutical importance of antibiotic agent chloramphenicol”, Heliyon, 6, e03433, 2020. https://doi.org/10.1016/j.heliyon.2020.e03433.
• S. Ghaffari, N. Roshanravan, H. Tutunchi, A. Ostadrahimi, M. Pouraghaei and B. Kafil, “Oleoylethanolamide, a bioactive lipid amide, as a promising treatment strategy for coronavirus/COVID-19”, Archives of Medical Research, 51, 464-467, 2020. https://doi.org/10.1016/j.arcmed.2020.04.006.
• J. Li, F. Yu, Y. Chen and D. Oupický, “Polymeric drugs: Advances in the development of pharmacologically active polymers”, Journal of Controlled Release, 219, 369-382, 2015. https://doi.org/10.1016/j.jconrel.2015.09.043.
• S. Abdolmaleki and M. Ghadermazi, “Novel pyridinedicarboxamide derivatives and a polymeric copper(II) complex: Synthesis, structural characterization, electrochemical behavior, catalytic and cytotoxic studies”, Inorganica Chimica Acta, 461, 221-232, 2017. https://doi.org/10.1016/j.ica.2017.02.023.
• A. Kar, M. A. Rather, M. Mandal and N. Karak, “Elastomeric biodegradable poly(ester amide urethane) as a tough and robust material”, Progress in Organic Coatings, 182, 107684, 2023. https://doi.org/10.1016/j.porgcoat.2023.107684.
• B. Erkuş, H. Özcan and Ö. Zaim, “Synthesis and antimicrobial activity of four new [1+1] condensed furan and thiophene-based cycloheterophane amides”, Journal of Heterocyclic Chemistry, 57 (4), 1956-1962, 2020. http://doi.org/10.1002/jhet.3922.
• S. Bondock, W. Fadaly and M. A. Metwally, “Synthesis and antimicrobial activity of new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety”, European Journal of Medicinal Chemistry, 45 (9), 3692-3701, 2010. https://doi.org/10,1016/j.ejmech.2010.05.0218..
• N. G. Yernale, B. S. Mathada, S. Shivprasad, S. Hiremath, P. Karunakar and A. Venkatesulu, “ Spectroscopic, theoretical and computational investigations of novel benzo [b] thiophene based ligand and its M(II) complexes: As hih portentous antimicrobial and antioxidant agents”, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 302, 123114, 2023. https://doi.org/10.1016/j.saa.2023.123114.
• C. Rangel-Núñez, C. Ramírez-Trujillo, K. Hakkou, A. Suárez-Cruz, I. Molina-Pinilla and M. Bueno-Martínez, “Regiospecific vs. non regiospecific click azide-alkyne polymerization: In vitro study of water-soluble antibacterial poly(amide aminotriazoles” Materials Science and Engineering: C, 125, 2021. 112113. https://doi.org/10.1016/j.msec.2021.112113.
• E. Plebanek, E. Lescrinier, G. Andrei, R. Snoeck, P. Herdewijn and S. De Jonghe, “Emimycin and its nucleoside derivatives: Synthesis and antiviral activity”, European Journal of Medicinal Chemistry, 144, 93-103, 2018. https://doi.org/10.1016/j.ejmech.2017.12.018.
• C. P. Kaushik, J. Sangwan, R. Luxmi, D. Kumar, D. Kumar, A. Das, A. Kumar and D. Singh, “Design, synthesis, anticancer and antioxidant activities of amide linked 1,4-disubstituted 1,2,3-triazoles”, Journal of Molecular Structure (Part A), 1226, 129255, 2021. https://doi.org/10.1016/j.molstruc.2020.129255.
• A. Marzo, L. Dal Bo, N. Ceppi Monti, F. Crivelli, S. Ismaili, C. Caccia, C. Cattaneo and R. G. Fariello, “Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity”, Pharmacological Research, 50, 77-85, 2004. https://doi.org/10.1016/j.phrs.2003.12.004.
• Y. Li, Y. Shang, X. Li, Y. Zhang, J. Xie, L. Chen, F. Gao and X. L. Zhou, “Design, synthesis, and biological evaluation of low-toxic lappaconitine derivatives as potential analgesics”, European Journal of Medicinal Chemistry, 243, 114776, 2022. https://doi.org/10.1016/j.ejmech.2022.114776.
• G. A. Gevoryan, N. Z. Hakobyan, S. S. Hovakimyan, A. G. Melkonyan and G. A. Panosyan, “Synthesis and biological activity of β-aminoketones, secondary aminopropanols and oximes of 2-aminothiophen series”, Russian Journal of General Chemistry, 89, 2328-2332, 2019. https://doi.org/10.1134/S1070363219110264.
• W. Kemnitzer, N. Sirisoma, C. May, B. Tseng, J. Drewe and S. X. Cai, “Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers”, Bioorganic&Medicinal Chemistry Letters, 19(3), 3536-3540, 2009. https://doi.org/10.1016/j.bmcl.2009.04.145.
• R. Narlawar, J. R. Lane, M. Doddareddy, J. Lin, J. Brusse and A. P. Ijzerman, “Hybrid ortho/allosteric ligands for the adenosine A1 receptor”, Journal of Medicinal Chemistry, 53(8), 3028-3037, 2010. https://doi.org/10.1021/jm901252a.
• N. Uludağ, G. Serdaroğlu, P. Sugumar, P. Rajkumar, N. Çolak and E. Ercağ, “Synthesis of thiophene derivatives: Substituent effect, antioxidant activity, cyclic voltammetry, molecular docking, DFT, and TD-DFT calculations”, Journal of Molecular Structure, 1257, 132607, 2022. https://doi.org/10.1016/j.molstruc.2022.132607.
• G. Serdaroğlu, N. Uludağ, E. Üstün and N. Çolak, “A novel series of tetrahydrothieno[2,3-c]pyridin-2-yl derivatives: fluorescence spectroscopy and BSA binding, ADMET properties, molecular docking, and DFT studies”, New Journal of Chemistry, 47 (25), 11945-11963, 2023. https://doi.org/10.1039/D3NJ01648J.
• G. Serdaroğlu, N. Uludağ, N. Çolak and P. Rajkumar, “Nitrobenzamido substitution on thiophene-3-carboxylate; Electrochemical investigation, antioxidant activity, molecular docking, DFT calculations”, Journal of Molecular Structure, 1271, 134030, 2023. https://doi.org/10.1016/j.molstruc.2022.134030.
• M. J. Frisch, G. W. Trucks, H. B. Schlegel, G.E. Scuseria, M.A. Robb, J. R. Cheeseman, ..., Gaussian 09, Revision C.01. Wallingford CT: Gaussian Inc., 2009.
• C. Lee, W. Yang and R. G. Parr, “Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density”, Physical Review B, 37, 785-789, 1988. https://doi.org/10.1103/PhysRevB.37.785.
• A. D. Becke, “Density-functional exchange-energy approximation with correct asymptotic behavior”, Physical Review A, 38, 3098-3100, 1988. https://doi.org/10.1103/PhysRevA.38.3098
• T. Koopmans, “Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms”, Physica, 1, 104-113, 1934. https://doi.org/10.1016/S0031-8914(34)90011-2.
• R. G. Pearson, “Chemical hardness and density functional theory”, Journal of Chemical Sciences, 117, 369-377, 2005. https://doi.org/10.1007/BF02708340
• R. G. Parr and R. G. Pearson, “Absolute Hardness: Companion Parameter to Absolute Electronegativity”, Journal of the American Chemical Society, 105, 7512-7516, 1983. https://doi.org/10.1021/ja00364a005.
• R. K. Roy, K. Choho, F. De Proft and P. Geerlings, “Reactivity and stability of aromatic carbonyl compounds using density functional theory-based local and global reactivity descriptors”, Journal of Physical Organic Chemistry, 12, 503-509, 1999. https://doi.org/10.1002/(SICI)1099-1395(199906)12:6<503::AID-POC149>3.0.CO;2-2.