Rhenium (I) tricarbonyl complex with thiosemicarbazone ligand derived from Indole-2-carboxaldehyde: Synthesis, crystal structure, computational investigations, antimicrobial activity, and molecular docking studies

Abstract

Antibiotic resistance is becoming a cause of serious concern to human health causing a significant impact on the global economy. The demand for novel antimicrobial agents is pressing since drug resistance is spreading and making antibiotics less and less effective. There is unrealized antibacterial potential in metal complexes. Among other compounds, rhenium complexes are particularly appealing because of their strong antibacterial activity and minimal in vivo toxicity. In this study, three Re carbonyl thiosemicarbazone (TSC) complexes were synthesized and characterized and their antibacterial potential was evaluated against various types of gram-positive and gram-negative bacteria. The structure of the ligands and their corresponding Re complexes were optimized at the DFT/B3LYP level of theory employing 6–311++G(d,p) and LANL2DZ basis sets for C, H, N, O, S, and Re atoms respectively. The MS studies performed with time show that [fac-[Re(CO)3Br(HL)] was converted into dimer [Re2(CO)6(L)2] in solution and the crystal structure of the dimer [Re2(CO)6(L)2] obtained as the result of dimerization of the complex was solved. Among the three Re TSC complexes, [fac-[Re(CO)3Br(HL1)] exhibits the greatest antibacterial activity against S.aureus with MIC value 0.5 µg/mL. The data obtained showed that the synthesized complexes were ineffective against gram-negative bacteria but showed excellent antibacterial activity against gram-positive S.aureus. The [fac-[Re(CO)3Br(HL2)] complex derived from isatin-β-thiosemicarbazone showed lesser activity than the other two rhenium TSC complexes which were obtained by condensation of indole-2-carboxaldehyde and thiosemicarbazide. Furthermore, the in-silico molecular docking studies revealed that the binding energy of the docked compound [Re(CO)3Br(HL)] with E. Coli and MRSA targets were extremely favorable (-7.18 and -5.67 kcal/mol, respectively which further demonstrates the potential of the synthesized complexes in the development of new antibacterial drugs. The molecular docking studies as well as experimental investigations demonstrate the effect of substituents on the ligand backbone on the antimicrobial activity of the synthesized rhenium carbonyl complexes. The enhanced antibacterial properties of rhenium carbonyl complexes with the TSC ligands in comparison to the ligand alone also suggest a possible synergistic effect of the metal center and the organic ligand.