Synergistic exploration of antimicrobial potency, cytotoxicity, and molecular mechanisms: A tripartite investigation integrating in vitro, in vivo, and in silico approaches for pyrimidine-based metal (II) complexes

We synthesized and characterized bioactive metal (II) complexes from a pyrimidine-based Schiff base ligand, 4-[2-(4-chlorobenzylidene) hydrazinyl]-7H-pyrrolo[2,3-d]pyrimidine. Through thorough elemental analysis and various physicochemical techniques, we characterized both the ligand and its Zn(II), Cd(II), and Hg(II) complexes. Coordination of the metallic ion was established via nitrogen atoms from the ligand's pyrrolo and pyrimidine rings, yielding tetrahedral complexes of the type [M(PPHpCB)2]. These complexes are identified as non-electrolytes due to their low molar conductance. Furthermore, we investigated the coordination behavior of the pyrimidine-based Schiff base ligand (HPPHpCB) with metal ions through comprehensive spectroscopic analysis. 1H NMR spectral data showed bonding between HPPHpCB and metal ions, while UV spectra confirmed intra-ligand and ligand-to-metal charge transfer transitions, indicating coordination through nitrogen atoms. The determination of tetrahedral geometry for metal complexes confirmed their diamagnetic properties. Analysis using 13C NMR and electrospray ionization mass spectra (ESI-MS) revealed variations in chemical shifts, confirming successful complex formation and elucidating structural modifications, electronic interactions, and metal-ligand coordination modes. Moreover, evaluation of in vitro antimicrobial activities using the minimum inhibitory concentration (MIC) approach revealed significant antibacterial and antifungal activities for Hg(II) and Cd(II) complexes, respectively. The Hg(II) complex displayed superior antioxidant activity, while Zn(II) and Cd(II) complexes also demonstrated considerable potential. In vivo, cytotoxicity assessments against Artemia salina provided insights into the cytotoxic properties of ligands and metal complexes. Computational techniques suggested their potential in combating infectious ailments. Overall, our study establishes the synthesis, characterization, and multifaceted biological activities of metal (II) complexes derived from the pyrimidine-based Schiff base ligand, highlighting their promising role in combating various infectious diseases. The bioactive metal (II) complexes derived from a pyrimidine-based Schiff base ligand have been synthesized and characterized. Their in-vitro antimicrobial (bacteria and fungi), antioxidant, and in-vivo cytotoxic potential, along with those of the ligand, have been investigated. Hg(PPHpCB)2, Cd(PPHpCB)2, and Zn(PPHpCB)2 complexes exhibit greater biological activity compared to their free ligand, as attributed to the role of the metal ion according to Tweedy's chelation theory. Molecular docking simulations have provided insights into specific molecular interactions and binding energies, with Zn(PPHpCB)2 demonstrating notably strong binding affinities. image