Luminescent Ruthenium Complexes for Theranostic Applications

Abstract

The water-soluble and visible luminescent complexes <i>cis-</i>[Ru­(L-L)₂(L)₂]²⁺ where L-L = 2,2-bipyridine and 1,10-phenanthroline and L= imidazole, 1-methylimidazole, and histamine have been synthesized and characterized by spectroscopic techniques. Spectroscopic (circular dichroism, saturation transfer difference NMR, and diffusion ordered spectroscopy NMR) and isothermal titration calorimetry studies indicate binding of <i>cis-</i>[Ru­(phen)₂(ImH)₂]²⁺ and human serum albumin occurs via noncovalent interactions with <i>K</i>_b = 9.8 × 10⁴ mol^–1 L, Δ<i>H</i> = −11.5 ± 0.1 kcal mol^–1, and <i>T</i>Δ<i>S</i> = −4.46 ± 0.3 kcal mol^–1. High uptake of the complex into HCT116 cells was detected by luminescent confocal microscopy. Cytotoxicity of <i>cis-</i>[Ru­(phen)₂(ImH)₂]²⁺ against proliferation of HCT116p53^+/+ and HCT116p53^–/– shows IC₅₀ values of 0.1 and 0.7 μmol L^–1. Flow cytometry and western blot indicate RuphenImH mediates cell cycle arrest in the G1 phase in both cells and is more prominent in p53^+/+. The complex activates proapoptotic PARP in p53^–/–, but not in p53^+/+. A cytostatic mechanism based on quantification of the number of cells during the time period of incubation is suggested