Crystal structure, DFT and Hirshfeld surface studies of a novel zinc(II) ion pair complex based on coumarin Mannich base: In vitro antiproliferative activity

Abstract

Due to their critical biochemical role and low toxicity, zinc(II) complexes have emerged as promising alternatives to platinum-based anticancer agents, and great efforts have been made to describe many complexes with antiproliferative activity. Still, mononuclear anionic zinc(II) complexes remain largely underexplored, particularly those incorporating privileged medicinal scaffolds, such as coumarins. Herein, we report the synthesis, structural characterization, and antiproliferative evaluation of a novel anionic zinc(II) complex [HL]⁺[ZnLCl₂]⁻ derived from 7-Hydroxy-4-methyl-8-(1-pyrrolidinylmethyl)-2H-1-benzopyran-2-one, a ligand that has aroused interest as a potential chemotherapeutic and was previously described by our research group. Single-crystal X-ray diffraction revealed an unusual ionic structure, where the protonated ligand acts as a counterion to a tetrahedral Zn(II) center, which is coordinated to one negatively charged ligand and two chlorides. Hirshfeld surface analysis and Density Functional Theory (DFT) further clarified the anionic complex's non-covalent interactions and electronic properties. The complex showed antiproliferative effects (as assessed by MTT-based viability assay) on HeLa (cervical cancer) and PC3 (prostate cancer) cell lines. These results highlight the critical role of zinc coordination in enhancing bioactivity, and our findings underscore the potential of anionic Zn(II) complexes as tunable platforms for anticancer drug design, expanding the limited repertoire of characterized anionic zinc species and paving the way for further exploration of their therapeutic applications.