Synthesis, TDDFT Calculations and Biological Evaluation of Dicationic Porphyrins as Groove Binders and Antimicrobial Agents

Abstract

AbstractA2B2 porphyrin bearing 2/3‐thienyl and 2‐pyridyl moieties (P1a, P3a) and its dicationic derivatives (P2a, P4a) were synthesized in reasonably good yield. The corresponding Copper (II) (P1‐4 b) and Zinc (II) metallated (P1‐4 c) analogs were obtained by conventional methods. The synthesized compounds were characterized by various spectroscopic techniques, electrochemical studies and thermogravimetric analysis. The Copper (II) porphyrin, P1b is structurally characterized by single‐crystal X‐ray structure analysis. The ground state electronic structure and geometry optimizations are carried out by DFT calculations. The computed TD‐DFT results validate the observed optical bands and spectral features. DNA interaction studies of trans‐dicationic porphyrins were performed using spectroscopic titrations, docking studies, and gel electrophoresis experiments. All porphyrins interact with the calf thymus DNA by outside groove binding mode with self‐stacking, and the highest intrinsic binding constant of 1.29 ± 0.14×106 M‐1 is observed for P4a. Molecular docking studies reveal that the binding energy of porphyrins with DNA is around −10 kcal/mol. The antimicrobial properties of the dicationic derivatives (P2,4 a, b, c) were investigated against E. Coli and S. aureus under light and dark conditions, and the growth inhibitory effect is found to be negligible when unilluminated.