Ni and Cu complexes of N-(2,6-dichlorophenyl)-N-mesityl formamidine dithiocarbamate structural and functional properties as CYP3A4 potential substrates.

Metal compounds continued to attract diverse applications due to their malleability in several capacities. In this study, we present our findings on the crystal structures and functional properties of Ni and Cu complexes of N'-(2,6-dichlorophenyl)-N-mesitylformamidine dithiocarbamate (L) comprising [Ni-(L)] (1) and [Cu-(L)] (2) with a four-coordinate metal center. We established the two complex structures through H and C nuclear magnetic resonance (NMR), elemental, and single-crystal X-ray analysis. The analyses showed that the two complexes are isomorphous, having P2/c as a space group and a unit-cell similarity index (π) of 0.002. The two complexes conform to a distorted square planar geometry around the metal centers. The calculated and experimental data, including bond lengths, angles, and NMR values, are similar. Hirshfeld surface analysis revealed the variational contribution of the different types of intermolecular contacts driven by the crystal lattice of the two solvated complexes. Our knowledge of the potential biological implication of these structures enabled us to probe the compounds as prospective CYP3A4 inhibitors. This approach mimics current trends in pharmaceutical design and biomedicine by incorporating potentially active molecules into various media to predict their biological efficacies. The simulations show appreciable binding of compounds 1 and 2 to CYP3A4 with average interaction energies of -97 and -87 kcal/mol, respectively. The protein attains at least five conformational states in the three studied models using a Gaussian Mixture Model-based clustering and free energy prediction. Electric field analysis shows the crucial residues to substrate binding at the active site, enabling CYP3A4 structure to function prediction. The predicted inhibition with these Ni and Cu complexes indicates that CYP3A4 overexpression in a diseased state like cancer would reduce, thereby increasing the chemotherapeutic compounds' shelf-lives for adsorption. This multidimensional study addresses various aspects of molecular metal electronics, including their application as substrate-mimicking inhibitors. The outcome would enable further research on bio-metal compounds of critical potential.