Theoretical Exploration of Co and Ln Piroxicam Complexes (Ln = La and Pr), A Quest for Efficient and Safe Therapeutic Agents

ABSTRACT Computational chemistry leverages computer simulation programs and theoretical models to anticipate molecular behavior, reactivity, and fascinating properties of metal complexes. In the current study, previously synthesized piroxicam complexes with Co, La, and Pr were investigated by employing and comparing three different functionals. Geometry optimization in gas and solvent, charge distribution and frontier molecular orbital (FMO), reactivity, stability, and Gibbs free energy in solution were investigated for the respective complexes calculated by employing B3LYP, M06, and M06l functionals through the Gaussian 9. The natural population analysis (NPA) revealed metal to ligand electron back‐donation where the electrophilic active site primarily resides around the nitrogen and oxygen of the sulphonyl group, as affirmed by molecular electrostatic potential (MEP) diagrams. The global reactivity descriptors were analyzed by the computation of FMOs energies. The complexes were found to be stable, validated by large band gap energy, and relatively nonpolar in nature, which endowed them with the lipophilicity to permeate across biological membranes, corroborated by OSIRIS property analyzed through DATA WARRIOR 6. The theoretical calculations concluded that the studied complexes possess a high drug likeness score, an effective lipophilicity value, and biologically active characteristics with no side effects like tumorigenicity, mutagenicity, and irritability. Moreover, the biological interactions endured by metal complexes in the light of current speculative analysis have also been manipulated, crucial for the rational drug design.