Synthesis, spectroscopic characterization, photochemical and photophysical properties and biological activities of ruthenium complexes with mono- and bi-dentate histamine ligand

Abstract

The monodentate cis-[Ru(phen)₂(hist)₂]²⁺1R and the bidentate cis-[Ru(phen)₂(hist)]²⁺2A complexes were prepared and characterized using spectroscopic (¹H, (¹H–¹H)COSY and (¹H–¹³C)HSQC NMR, UV-vis, luminescence) techniques. The complexes presented absorption and emission in the visible region, as well as a tri-exponential emission decay. The complexes are soluble in aqueous and non-aqueous solution with solubility in a buffer solution of pH 7.4 of 1.14 × 10⁻³ mol L⁻¹ for (1R + 2A) and 6.43 × 10⁻⁴ mol L⁻¹ for 2A and lipophilicity measured in an aqueous–octanol solution of −1.14 and −0.96, respectively. Photolysis in the visible region in CH₃CN converted the starting complexes into cis-[Ru(phen)₂(CH₃CN)₂]²⁺. Histamine photorelease was also observed in pure water and in the presence of BSA (1.0 × 10⁻⁶ mol L⁻¹). The bidentate coordination of the histamine to the ruthenium center in relation to the monodentate coordination increased the photosubstitution quantum yield by a factor of 3. Pharmacological studies showed that the complexes present a moderate inhibition of AChE with an IC₅₀ of 21 μmol L⁻¹ (referred to risvagtini, IC₅₀ 181 μmol L⁻¹ and galantamine IC₅₀ 0.006 μmol L⁻¹) with no appreciable cytotoxicity toward to the HeLa cells (50% cell viability at 925 μmol L⁻¹). Cell uptake of the complexes into HeLa cells was detected by fluorescence confocal microscopy. Overall, the observation of a luminescent complex that penetrates the cell wall and has low cytotoxicity, but is reactive photochemically, releasing histamine when irradiated with visible light, are interesting features for application of these complexes as phototherapeutic agents.