Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives

摘要

The potential chemotherapeutic properties coupled to photochemical transitions make the family offac-[Re(CO)(3)(N,N)X](0/+)(N,N = a bidentate diimine such as 2,2 '-bipyridine (bpy); X = halide, H2O, pyridine derivatives, PR3, etc.) complexes of special interest. We have investigated reactions of the aqua complexfac-[Re(CO)(3)(bpy)(H2O)](CF3SO3) (1) with potential anticancer activity with the amino acidl-cysteine (H(2)Cys), and its derivative N-acetyl-l-cysteine (H(2)NAC), as well as the tripeptide glutathione (H(3)A), under physiological conditions (pH 7.4, 37 degrees C), to model the interaction of1with thiol-containing proteins and enzymes, and the impact of such coordination on its photophysical properties and cytotoxicity. We report the syntheses and characterization offac-[Re(CO)(3)(bpy)(HCys)]center dot 0.5H(2)O (2), Na(fac-[Re(CO)(3)(bpy)(NAC)]) (3), and Na(fac-[Re(CO)(3)(bpy)(HA)])center dot H2O (4) using extended X-ray absorption spectroscopy, IR and NMR spectroscopy, electrospray ionization spectrometry, as well as the crystal structure of {fac-[Re(CO)(3)(bpy)(HCys)]}(4)center dot 9H(2)O (2 + 1.75 H2O). The emission spectrum of 1 displays a variance in Stokes shift upon coordination ofl-cysteine andN-acetyl-l-cysteine. Laser excitation at lambda = 355 nm of methanol solutions of 1-3 was followed by measuring their ability to produce singlet oxygen (O-1(2)) using direct detection methods. The cytotoxicity of1and its cysteine-bound complex 2 was assessed using the MDA-MB-231 breast cancer cell line, showing that the replacement of the aqua ligand on1withl-cysteine significantly reduced the cytotoxicity of the Re(I) tricarbonyl complex. Probing the cellular localization of 1 and 2 using X-ray fluorescence microscopy revealed an accumulation of1in the nuclear and/or perinuclear region, whereas the accumulation of2was considerably reduced, potentially explaining its reduced cytotoxicity.