Multifunctional Schiff base metal complexes: synthesis, biological activity, and computational insights

The Schiff bases are a class of compounds formed by the condensation of primary amines with aldehydes and ketones to form the azomethine (C=N) group. Due to their ease of preparation, flexibility of chemical structure, and high coordination ability with metal ions, Schiff bases have gained increasing attention in many fields, including coordination chemistry, medicinal chemistry, and materials science. The formation of chelate rings is an important property of Schiff bases that makes them effective building blocks for the synthesis of diverse stable complexes with square-planar, tetrahedral, and octahedral geometries, which are more stable than the corresponding ligands. Apart from these properties, metal complexes of Schiff bases have been proven to be potential candidates for various scientific fields, including antimicrobial, antioxidant, anticancer, catalytic, sensing, and environmental fields. With the advent of modern experimental and computational methods, the Schiff base systems are now better known than ever. Single-crystal X-ray diffraction, Hirshfeld surface analysis, cyclic voltammetry, electron paramagnetic resonance (EPR), and X-ray absorption spectroscopy have been used successfully in such investigations. On the other hand, computational methods like density functional theory (DFT), molecular docking, molecular dynamics simulation, and ADMET studies can be employed to study electronic structures, predict reactivity, and examine biological interactions. However, despite the progress made in all the above-mentioned fields, no unified method to understand the electronic structures, chemical reactivity, and biological interaction properties has been developed as of yet. In particular, most studies tend to explore one aspect of Schiff bases only, which results in a lack of understanding of how to link specific structures with particular biological effects in order to achieve desired functions. Hence, this review provides a critical and comprehensive overview of the recent advances in the design of Schiff base ligands and their metal complexes by highlighting their synthesis and structure, biological activities, and mechanistic behavior, and structure-activity relationship studies using a computational approach.