Antimicrobial Activity of Mononuclear and Bionuclear Nitrite Complexes of Platinum (II) and Platinum (IV)

Abstract

Introduction. Pathogens keep evolving and develop resistance to antimicrobial drugs. As a result, science is constantly searching for new antimicrobial agents. Their complex forms based on organic and inorganic ligands exhibit a stronger synergistic antimicrobial effect, if compared to free ligands. The Scopus database contains 73 thousand scientific articles about antimicrobial activity descriptors published during the last five years. This selection includes ten thousand reviews and three thousand publications that feature the antimicrobial activity of platinum complexes. The research objective was to screen the antimicrobial properties of platinum nitrite complexes. The present paper highlights some of the current domestic and foreign trends in this field of research: the biochemical synthesis of peptides as metabolites of bacteria; the development of anti-biofilm agents that act on the protective systems of pathogens; the creation of antimicrobial nanosystems; the synthesis of antimicrobial surfactants; the synthesis and study of the antimicrobial activity of platinum complexes, etc. The authors also give a brief description of the mechanisms of antibacterial action. Study objects and methods. Five previously synthesized complexes of platinum (II) and platinum (IV), both mononuclear and bionuclear, were tested for antimicrobial activity. The platinum complexes contained terminal and bridged nitrite ligands. The test cultures included Bacillus subtilis and Aspergillus niger. The experiment involved the disk-diffusion method and the macro method of serial dilutions. Results and discussion. All the complexes inhibited the metabolic growth of microorganisms to various degrees. The results depended on the composition and structure of the complex, the number and charge of the coordination centers, the degree of platinum oxidation, and the thermodynamic stability and lability of ligand bonds with the complexing agent. The response to Aspergillus niger proved more pronounced. The Pt+2 nonelectrolyte complex containing both terminal and bridged nitrite ligands was less active than the Pt+2 cationic complex, which contained only bridged NO2– ligands. The highest antibacterial activity belonged to the bionuclear complex of PtIV-PtII [(NH3)2(NO2)2PtIV(µ-NO2)2PtII(NH3)2](NO3)2 in relation to Bacillus subtilis B4647 and Aspergillus niger. The minimum inhibitory concentration (MIC) was > 125 μmol. Conclusion. The complexing resulted in a synergistic effect between the ligand and the complexing substance. The poly-core complexes contain two or more linked platinum centers that can covalently bind to DNA. They form a completely different type of DNA adducts compared to mononuclear complexes, as well as cross-links between DNA chains with fixation on different parts. The octahedral platinum complexes are kinetic and thermodynamically inert. Unlike similar squamous complexes, they proved to be able to act as prodrugs, recovering inside or outside the bacterial cell. The antimicrobial activity of the mixed-valence PtIV-PtII bionuclear complex [(NH3)2 (NO2)2PtIV(µ-NO2)2PtII(NH3)2](NO3)2 produced inhibitory effect comparable to the existing antimicrobial drugs. A further research will focus on composite mixtures of platinum complexes with other existing antimicrobial agents, as well as on other bacterial strains.

Keywords

• antimicrobial activity
• platinum
• ligands
• bacillus subtilis
• aspergillus niger