Rhodium(I) Complexes Containing the N^N^N-Chelating Ligand: Synthesis, Structure, and Biological Activity

Rhodium complexes have garnered extensive attention owing to their inherent potential for biological activity. The catalytic properties of Rh–N^N^N complexes have been investigated extensively, whereas there is a paucity of studies regarding their antitumor activity. In this study, we present four rhodium(I) complexes, each distinguished by a different anion. These complexes incorporate 2,6-bis(1,5-diphenyl-1H-pyrazol-3-yl)pyridine as the tridentate N^N^N-chelating ligand and one carbonyl ligand. These complexes underwent rigorous evaluation for cytotoxicity against a spectrum of human tumor cell lines, including MCF-7, HeLa, and HepG2, alongside a nontumor cell line, HUVEC, employing MTT assays and flow cytometry. Our results unveiled that complex 1 Rh(N^N^N)(CO)Cl exhibited remarkable cytotoxicity and demonstrated a favorable selectivity index against tumor cells, with a particularly notable impact on breast adenocarcinoma (selectivity index = 5.2). To further ascertain its potential utility, we probed the interactions between complex 1 and ctDNA/BSA. Both UV and fluorescence scan data indicated that complex 1 was able to intercalate into ctDNA and bind with BSA. Meanwhile, comprehensive assessments, encompassing the mobility shift assay and the micronucleus test, consistently showed that complex 1 could not induce DNA fragmentation in vitro and the formation of micronucleus in mouse erythrocytes. All of these findings suggest that complex 1 could be a promising antitumor compound.