Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand

Fatima Ali al Wagaa; Sahbaa Ali Ahmed

doi:10.18596/jotcsa.1820248

Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand

Abstract

In this work, the Schiff base ligand (COM-IST) was synthesized from the condensation of 6-aminocoumarin and isatin. The new Co(II), Ni(II), Cu(II), and Zn(II) complexes were synthesized from the Schiff base (COM-IST) with the proline (Pro) amino acid as a mixed ligand. The structure of the Schiff base was confirmed by FTIR, ¹H-, and ¹³C-NMR spectroscopy and CHN analysis. Its complexes were confirmed through FTIR, UV-vis spectroscopy, CHN analysis, magnetic susceptibility, XRD, and molar conductivity measurements. The spectral results indicate that the ligands exhibit bidentate behavior in all four complexes, and octahedral geometries are observed in each metal complex. The antibacterial activity of the prepared compounds was tested against various types of Gram-positive and negative bacteria. Molecular docking investigations proved that the ligand had intriguing interactions with the active sites of the receptors (DNA gyrase) for both bacterial strains. Frontier molecular orbitals (FMOs), various quantum chemical descriptors (QCDs), and molecular electrostatic potential (MEP) surfaces were computed using density functional theory (DFT) for the ligand and complex at the B3LYP functional with the 6-31G(++)d,p basis set for the ligand and the LANL2DZ basis set for the complexes.

Keywords

Thanks

The author extends heartfelt appreciation to the Department of Chemistry, College of Sciences, University of Mosul, for their indispensable assistance throughout this research.

References

1. Rodriguez-Enriquez F, Costas-Lago MC, Besada P, Alonso-Pena M, Torres-Terán I, Vina D, Fontenla JÁ, Sturlese M, Moro S, Quezada E, Teran C. Novel coumarin-pyridazine hybrids as selective MAO-B inhibitors for the Parkinson’s disease therapy. Bioorganic Chemistry. 2020 Nov 1;104:104203. Available from:.
2. García-Beltrán O, Mena NP, Aguirre P, Barriga-González G, Galdámez A, Nagles E, Adasme T, Hidalgo C, Núñez MT. Development of an iron-selective antioxidant probe with protective effects on neuronal function. PloS one. 2017 Dec 11;12(12): e0189043. Available from:.
3. Aguirre P, García-Beltrán O, Tapia V, Muñoz Y, Cassels BK, Núñez MT. Neuroprotective effect of a new 7, 8-dihydroxycoumarin-based Fe2+/Cu2+ chelator in cell and animal models of Parkinson’s disease. ACS Chemical Neuroscience. 2017 Jan 18;8(1):178-85‏. Available from:.
4. Shen YuFeng SY, Liu Lei LL, Feng ChenZhang FC, Hu Yang HY, Chen Cheng CC, Wang GaoXue WG, Zhu Bin ZB. Synthesis and antiviral activity of a new coumarin derivative against spring viraemia of carp virus.,Fish & Shellfish Immunology, 2018, 81, 57-66, Available from: .
5. Sahoo CR, Paidesetty SK, Sarathbabu S, Dehury B, Senthil Kumar N, Padhy RN. Molecular dynamics simulation, synthesis, and topoisomerase inhibitory actions of vanillin derivatives: a systematic computational structural integument. Journal of Biomolecular Structure and Dynamics. 2022 Dec 12;40(22):11653-63. Available from:.
6. Cione E, La Torre C, Cannataro R, Caroleo MC, Plastina P, Gallelli L. Quercetin, epigallocatechin gallate, curcumin, and resveratrol: from dietary sources to human microRNA modulation. Molecules. 2019 Dec 23;25(1):63. Available from: .
7. Galvin CJ, Hobson M, Meng JX, Ierokomos A, Ivanov IE, Berger JM, Bryant Z. Single-molecule dynamics of DNA gyrase in evolutionarily distant bacteria, Mycobacterium tuberculosis and Escherichia coli. Journal of Biological Chemistry. 2023 May 1;299(5). Available from: .
8. Khan T, Sankhe K, Suvarna V, Sherje A, Patel K, Dravyakar B. DNA gyrase inhibitors: Progress and synthesis of potent compounds as antibacterial agents. Biomedicine & Pharmacotherapy. 2018 Jul 1;103:923-38.‏ Available from:.

9. Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Applied microbiology and biotechnology. 2011 Nov;92(3):479-97.Available from: .
10. Zala AR, Rajani DP, Kumari P. Synthesis, molecular docking, ADME study, and antimicrobial potency of piperazine-based cinnamic acid bearing coumarin moieties as a DNA gyrase inhibitor. Journal of Biochemical and Molecular Toxicology. 2023 Jan;37(1): e23231.Available from: .
11. Emam SH, Hassan RA, Osman EO, Hamed MI, Abdou AM, Kandil MM, Elbaz EM, Mikhail DS. Coumarin derivatives with potential anticancer and antibacterial activity: Design, synthesis, VEGFR‐2 and DNA gyrase inhibition, and in silico studies. Drug Development Research. 2023 May;84(3):475-99. Available from:.
12. Liu H, Xia DG, Chu ZW, Hu R, Cheng X, Lv XH. Novel coumarin-thiazolyl ester derivatives as potential DNA gyrase Inhibitors: Design, synthesis, and antibacterial activity. Bioorganic chemistry. 2020 Jul 1;100: 103907. Available from: .
13. Khatoon S, Aroosh A, Islam A, Kalsoom S, Ahmad F, Hameed S, Abbasi SW, Yasinzai M, Naseer MM. Novel coumarin-isatin hybrids as potent antileishmanial agents: Synthesis, in silico and in vitro evaluations. Bioorganic Chemistry. 2021 May 1;110: 104816. Available from: .
14. Abd El-Lateef HM, Ali AM, Khalaf MM, Abdou A. New Fe (III), Co (II), Ni (II), Cu (II), and Zn (II) mixed-ligand complexes: structural, DFT, biological, and molecular docking studies. Bulletin of the Chemical Society of Ethiopia. 2024 Jan 23;38(2):397-416. Available from: .
15. Mustafa NA, Ahmed SA. Design, synthesis, characterization, DFT, molecular docking, and in vitro screening of metal chelates incorporating Schiff base. Bulletin of the Chemical Society of Ethiopia. 2024 Sep 16;38(6):1625-38.Available from:.
16. Al-Assafe AY, Al-Quaba RAMS. New series of Ni (II), Cu (II), Zr (IV), Ag (I), and Cd (II) complexes of trimethoprim and diamine ligands: Synthesis, characterization, and biological studies. Indones J Chem. 2024;24(3):812-821.Available from:.
17. Shakir M, Hanif S, Sherwani MA, Mohammad O, Azam M, Al-Resayes SI. Pharmacophore hybrid approach of new modulated bis-diimineCuII/ZnII complexes based on 5-chloro Isatin Schiff base derivatives: Synthesis, spectral studies, and comparative biological assessment. Journal of Photochemistry and Photobiology B: Biology. 2016 Apr 1;157: 39-56. Available from: .
18. Fayed EA, Ebrahim MA, Fathy U, Elawady AM, Khalaf WS, Ramsis TM. Pyrano-coumarin hybrids as potential antimicrobial agents against MRSA strains: Design, synthesis, ADMET, molecular docking studies, as DNA gyrase inhibitors. Journal of Molecular Structure. 2024 Jan 5;1295:136663. Available from:.
19. Malabade R, Gupte V, Mohanasundaram S, Warke RG, Warke GM, Raut TC, Satardekar MR, Mahajan GB. Analytical Performance of Plazomicin E-strips (Ezy MIC™) Compared with Broth Micro-dilution. Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine. 2025 May 31;29(Suppl 1):S107.Available from:.
20. Al-burgus AF, Ali AF, Al-abbasy OY. New spiro-heterocyclic coumarin derivatives as antibacterial agents: design, synthesis, and molecular docking. Chim Techno Acta 2024 Vol 11№ 3. 2024;11(3).Available from:.
21. Al-Gaber MA, Abd El-Lateef HM, Khalaf MM, Shaaban S, Shawky M, Mohamed GG, Abdou A, Gouda M, Abu-Dief AM. Design, synthesis, spectroscopic inspection, DFT, and molecular docking study of metal chelates incorporating azo dye ligand for biological evaluation. Materials. 2023; 16 (3): 897 [Internet]. 2023. Available from:.
22. Mohamed GG, Mahmoud WH, Refaat AM. Nano-azo ligand and its superhydrophobic complexes: synthesis, characterization, DFT, contact angle, molecular docking, and antimicrobial studies. J Chem. 2020; 2020:1-19.Available from:.
23. Sarkar T, Kumar A, Sahoo S, Hussain A. Mixed-ligand cobalt (III) complexes of a naturally occurring coumarin and phenanthroline bases as mitochondria-targeted dual-purpose photochemotherapeutics. Inorganic Chemistry. 2021 Apr 15;60(9):6649-62. Available from: .
24. Kadhim AJ, Shaalan N. Synthesis, Characterization, Biological, and Antioxidant Activity of New Metal Ion Complexes with Schiff Base Derived from 2-Hydroxybenzohydrazide. Indones J Chem. 2024;24(6):1851-1860. Available from:.
25. Xu Z, Zhao SJ, Deng JL, Wang Q, Lv ZS, Fan YL. Design, synthesis, and evaluation of tetraethylene glycol tethered isatin–coumarin hybrids as novel anticancer agents. Journal of Heterocyclic Chemistry. 2019 Feb;56(2):400-5.Available from:.
26. Fan YL, Huang ZP, Liu M. Isatin–coumarin hybrids tethered via diethylene glycol: design, synthesis, and their in vitro antitumor activities. Journal of Heterocyclic Chemistry. 2018 Dec;55(12):2722-6. Available from:.
27. Abdalrazaq E, Jbarah AAQ, Al-Noor TH, Shinain GT, Jawad MM. Synthesis, DFT calculations, DNA interaction, and antimicrobial studies of some mixed ligand complexes of oxalic acid and Schiff base trimethoprim with various metal ions. Indones J Chem. 2022;22(5):1348-1364. Available from:.
28. Yamauchi O, Nakao Y, Nakahara A. Mixed Ligand Copper (II) Complexes of Amino Acids and Related Compounds with Possible Ligand-Ligand Interactions. Bulletin of the Chemical Society of Japan. 1975 Sep;48(9):2572-8.Available from: .
29. Gull P, Hashmi AA. Synthesis, XRD, and spectroscopic characterization of pharmacologically active Cu (II) and Zn (II) complexes. Journal of Molecular Structure. 2017 Jul 5;1139: 264-8. Available from: .
30. Reddy GN, Losetty V, Yadav CH. Synthesis of novel Schiff base metal complexes and their spectroscopic characterization, biological activity, and molecular docking investigation. Journal of Molecular Structure. 2023 Jun 15;1282:135161. Available from:.
31. Loginova NV, Harbatsevich HI, Osipovich NP, Ksendzova GA, Koval'chuk TV, Polozov GI. Metal complexes as promising agents for biomedical applications. Current Medicinal Chemistry. 2020 Sep 1;27(31):5213-49. Available from: .
32. Wu S, Wang M, Liu Z, Fu C. Mechanisms Operating in the Use of Transition Metal Complexes to Combat Antimicrobial Resistance. Microorganisms. 2025 Jul 3;13(7):1570. Available from:.
33. Bufarwa SM, Belaidi M, Abbass LM, Thbayh DK. Anticancer Activity, DFT, Molecular Docking, ADMET, and Molecular Dynamics Simulations Investigations of Schiff Base Derived From 2, 3‐Diaminophenazine and Its Metal Complexes. Applied Organometallic Chemistry. 2025 Jan;39(1): e7953. Available from:.
34. Bufarwa SM, Belaidi M, Abbass LM, Thbayh DK. Anticancer Activity, DFT, Molecular Docking, ADMET, and Molecular Dynamics Simulations Investigations of Schiff Base Derived From 2, 3‐Diaminophenazine and Its Metal Complexes. Applied Organometallic Chemistry. 2025 Jan;39(1):e7953. Available from:.
35. Patel SG, Upadhyay DB, Shah N V, et al. In silico exploration of acetic acid driven multicomponent synthesis: design, characterization, and antioxidant evaluation of spiroacridines and spiroquinolines. RSC Sustain. 2024;2(4):1128-1141.Available from: .

Details

Primary Language

English

Subjects

Bioinorganic Chemistry

Journal Section

Research Article

Authors

Fatima Ali al Wagaa ^*
0009-0005-8222-8387
Iraq

Sahbaa Ali Ahmed This is me
Iraq

Publication Date

May 3, 2026

Submission Date

November 8, 2025

Acceptance Date

March 26, 2026

Published in Issue

Year 2026 Number: 2026-1

DOI

https://doi.org/10.18596/jotcsa.1820248

IZ

https://izlik.org/JA69YF92DG

Cite

RIS / Bibtex

APA

Ali al Wagaa, F., & Ahmed, S. A. (2026). Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand. Journal of the Turkish Chemical Society Section A: Chemistry, 2026-1, 1-14. https://doi.org/10.18596/jotcsa.1820248

AMA

1.Ali al Wagaa F, Ahmed SA. Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand. JOTCSA. 2026;(2026-1):1-14. doi:10.18596/jotcsa.1820248

Chicago

Ali al Wagaa, Fatima, and Sahbaa Ali Ahmed. 2026. “Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base With Proline As a Mixed Ligand”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1: 1-14. https://doi.org/10.18596/jotcsa.1820248.

EndNote

Ali al Wagaa F, Ahmed SA (May 1, 2026) Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand. Journal of the Turkish Chemical Society Section A: Chemistry 2026-1 1–14.

IEEE

[1]F. Ali al Wagaa and S. A. Ahmed, “Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand”, JOTCSA, no. 2026-1, pp. 1–14, May 2026, doi: 10.18596/jotcsa.1820248.

ISNAD

Ali al Wagaa, Fatima - Ahmed, Sahbaa Ali. “Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base With Proline As a Mixed Ligand”. Journal of the Turkish Chemical Society Section A: Chemistry. 2026-1 (May 1, 2026): 1-14. https://doi.org/10.18596/jotcsa.1820248.

JAMA

1.Ali al Wagaa F, Ahmed SA. Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand. JOTCSA. 2026;:1–14.

MLA

Ali al Wagaa, Fatima, and Sahbaa Ali Ahmed. “Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base With Proline As a Mixed Ligand”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1, May 2026, pp. 1-14, doi:10.18596/jotcsa.1820248.

Vancouver

1.Fatima Ali al Wagaa, Sahbaa Ali Ahmed. Synthesis, Spectroscopic Inspection, Antibacterial, Molecular Docking, and DFT Analysis of Metal Chelates Incorporating Coumarin-Isatin Schiff Base with Proline as a Mixed Ligand. JOTCSA. 2026 May 1;(2026-1):1-14. doi:10.18596/jotcsa.1820248