Rare examples of rhenium(I) tricarbonyl iodido complexes with unsymmetrical bipyridines featuring distinguishable rotamers: From synthesis and solid-state/solution-phase isomerism to biological activity

Abstract

Three novel unsymmetrically substituted 2,2′-bipyridine ligands were prepared by introducing a 2-hydroxyphenyl group at the 6-position and either a 4-methoxyphenyl, 3,4-dimethoxyphenyl or 3,4-methylenedioxyphenyl group at the 4-position, using a modified Kröhnke protocol. Their corresponding rhenium(I) tricarbonyl iodido complexes, fac-[Re(L)(CO)₃I], 1–3, were synthesized and comprehensively characterized by single-crystal X-ray diffraction (SCXRD), ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, cyclic voltammetry (CV), high-resolution mass spectrometry (HRMS), and elemental analysis. The common 6-(2-hydroxyphenyl) moiety predominantly influences the spectroscopic and redox properties of the complexes. SCXRD confirms the facial arrangement of the fac-[Re(CO)₃N₂I] core in all three cases, although solid-state conformational isomerism was observed only in complex 1. In contrast, two NMR-distinguishable isomers are observed in solution for all three complexes. The cytotoxicity of 1–3 was evaluated by MTT assay after 48 h of continuous exposure in several human tumor cell lines (HeLa, PANC-1, MDA-MB-231, A549) and in non-malignant human lung fibroblasts (MRC-5). Notably, all three complexes displayed low-micromolar IC₅₀ values comparable to cisplatin, with the highest activity observed in HeLa cells (5.11–7.45 μM). However, significant activity was also recorded in MRC-5 cells (IC₅₀ = 8.19–8.95 μM), suggesting higher overall toxicity and weaker selectivity compared to cisplatin. Analysis in HeLa cells using bright-field microscopy confirmed a substantial antiproliferative effect.