Photostimulated Anticancer Activity of Mitochondria Localized Rhenium(I) Tricarbonyl Complexes Bearing 1H-imidazo[4,5-f][1,10]phenanthroline Ligands Against MDA-MB-231 Cancer Cells.

We have introduced Re(I) tricarbonyl complexes (ReL1 - ReL6) [Re(CO)(N^N)Cl] where N^N=extensive π conjugated imidazo-[4,5-f][1,10]-phenanthroline derivatives that helps in strong DNA intercalation, enhanced photophysical behavior, increase the π-π* character of T state for PDT and high value of lipophilicity for cell membrane penetration. These complexes exhibited prominent intraligand/ligand-centered (π-π*/LC) absorption bands at λ 260-350 nm and relatively weak metal-to-ligand charge-transfer (MLCT) bands within the λ 350-550 nm range. Among the six synthesized complexes, [(CO)ReCl(K-N,N-2-(4-(1-benzyl-1H-tetrazol-5-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline] (ReL6) exhibited outstanding potency (IC~6 μM, PI>9) under yellow light irradiation compared to dark conditions. Importantly, extremely lipophilic complex ReL6 showed effective penetration through the cell membrane and localized primarily in mitochondria (Pearson's correlation coefficient, PCC=0.918) of MDA-MB-231 cells. Complex ReL6 exhibited more than 9 times higher photo-toxicity in normoxic and hypoxic environment of tumor by inducing O generation (type II PDT), radical generation triggered by NADH oxidation (type I PDT). This complex is a promising candidate for TNBC treatment in hypoxic tumors, with efficacy comparable to photofrin and have demonstrated CO release ability under UV light irradiation.