Structural and Spectroscopic Study of New Copper(II) and Zinc(II) Complexes of Coumarin Oxyacetate Ligands and Determination of Their Antimicrobial Activity

Abstract

Tackling antimicrobial resistance is of increasing concern in a post-pandemic world where overuse of antibiotics has increased the threat of another pandemic caused by antimicrobial-resistant pathogens. Derivatives of coumarins, a naturally occurring bioactive compound, and its metal complexes have proven therapeutic potential as antimicrobial agents and in this study a series of copper(II) and zinc(II) complexes of coumarin oxyacetate ligands were synthesised and characterised by spectroscopic techniques (IR, 1H, 13C NMR, UV-Vis) and by X-ray crystallography for two of the zinc complexes. The experimental spectroscopic data were then interpreted on the basis of molecular structure modelling and subsequent spectra simulation using the density functional theory method to identify the coordination mode in solution for the metal ions in the complexes. Interestingly, the solid-state coordination environment of the zinc complexes is in good agreement with the simulated solution state, which has not been the case in our previous studies of these ligands when coordinated to silver(I). Previous studies had indicated excellent antimicrobial activity for Ag(I) analogues of these ligands and related copper and zinc complexes of coumarin-derived ligands, but in this study none of the complexes displayed antimicrobial activity against the clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Candida albicans.

Coumarin-transition metal complexes with biological activity: current trends and perspectives

“…As a result, lipophilicity and, hence, membrane permeation and biological activity tend to increase. As demonstrated by ( Mujahid et al, 2023 ), there are additional factors at play - if biological activity is realized by the metal ion, its particular coordination mode determines whether it is “released” to exhibit its effect. - In terms of “preferred” transition metal ions, researchers seem to focus on “safe bets” such as Pt (II/IV) and Pd(II) (antiproliferative agents) and Cu(II) and Zn(II) (antimicrobial chelates).…”

“…As a result, lipophilicity and, hence, membrane permeation and biological activity tend to increase. As demonstrated by (Mujahid et al, 2023), there are additional factors at play -if biological activity is realized by the metal ion, its particular coordination mode determines whether it is "released" to exhibit its effect. -In terms of "preferred" transition metal ions, researchers seem to focus on "safe bets" such as Pt (II/IV) and Pd(II)…”

“…Mujahid and coworkers synthesized a series of Cu(II) and Zn(II) complexes with previously reported 2-(2-oxo-2H-chromene-substituted-yl)oxy acetic acids as ligands ( Mujahid et al, 2023 ). The complexes were tested for antimicrobial activity against methicillin-resistant S. Aureus , P. Aeruginosa , and C. Albicans .…”

“…Mujahid and coworkers synthesized a series of Cu(II) and Zn(II) complexes with previously reported 2-(2-oxo-2H-chromenesubstituted-yl)oxy acetic acids as ligands (Mujahid et al, 2023).…”