Luminescent Ruthenium Complexes
for Theranostic Applications
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Abstract
The water-soluble
and visible luminescent complexes <i>cis-</i>[Ru(L-L)<sub>2</sub>(L)<sub>2</sub>]<sup>2+</sup> 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)<sub>2</sub>(ImH)<sub>2</sub>]<sup>2+</sup> and human serum albumin occurs
via noncovalent interactions with <i>K</i><sub>b</sub> =
9.8 × 10<sup>4</sup> mol<sup>–1</sup> L, Δ<i>H</i> = −11.5 ± 0.1 kcal mol<sup>–1</sup>, and <i>T</i>Δ<i>S</i> = −4.46
± 0.3 kcal mol<sup>–1</sup>. High uptake of the complex
into HCT116 cells was detected by luminescent confocal microscopy.
Cytotoxicity of <i>cis-</i>[Ru(phen)<sub>2</sub>(ImH)<sub>2</sub>]<sup>2+</sup> against proliferation of HCT116p53<sup>+/+</sup> and HCT116p53<sup>–/–</sup> shows IC<sub>50</sub> values
of 0.1 and 0.7 μmol L<sup>–1</sup>. Flow cytometry and
western blot indicate RuphenImH mediates cell cycle arrest in the
G1 phase in both cells and is more prominent in p53<sup>+/+</sup>.
The complex activates proapoptotic PARP in p53<sup>–/–</sup>, but not in p53<sup>+/+</sup>. A cytostatic mechanism based on quantification
of the number of cells during the time period of incubation is suggested