Biocompatible citrate-cysteine complexes of manganese as effective antioxidants: Experimental and computational studies

Many clinical studies have evaluated the ability of sulfur-containing antioxidants to prevent oxidative stress, a major cause of cancer, Parkinson's, and Alzheimer's disease. Cysteine complexes of manganese modified with citric acid were synthesized by a one-pot procedure in two molar ratios and at two different temperatures (90(degrees)C, 140(degrees)C). The synthesized complexes were studied using FT-IR, UV-Vis, NMR, and EDX. At the lower temperature, a hydrogel was formed, and a thiazolopyridine ring was formed at a temperature of 140(degrees)C which was complexed with manganese. Infrared and electronic absorption spectroscopy confirmed that manganese binding occurred via the oxygen atoms of COO. The complexes also exhibited strong fluorescence with excitation/emission peak wavelengths of 350/418 nm. The synthesized compounds showed efficient activity for superoxide scavenging (> 70%), which was evaluated by a pyrogallol autoxidation method. MTT assay studies confirmed the noncytotoxic nature of all the prepared samples. The Gaussian 09 program was used to optimize the structural configurations of the ligands and complexes based on DFT by the B3LYP/6-31+G(d) basis set. To evaluate the softness of both the ligand and the complex, an investigation of the HOMO-LUMO gaps was carried out. In addition, UV-vis spectra of Mn complexes obtained from the time-dependent DFT calculations show a strong peak in the range of 380-390 nm, which is in good agreement with our experimental findings. The results revealed that the oxygen atoms of citrate and cysteine are the most potential sites to interact with the Mn atom. Besides, the calculated average local ionization energies showed that the Mn atom is the most energetically favored and vulnerable site to an electrophilic or free radical attack.