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)3(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 3π‐π* character of T1 state for PDT and high value of lipophilicity for cell membrane penetration. These complexes exhibited prominent intraligand/ligand‐centered (π ‐ π*/ 1LC) absorption bands at λ 260 ‐ 350 nm and relatively weak metal‐to‐ligand charge‐transfer (1MLCT) bands within the λ 350 ‐ 550 nm range. Among the six synthesized complexes, [(CO)3ReICl(K2‐N,N‐2‐(4‐(1‐benzyl‐1H‐tetrazol‐5‐yl)phenyl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline] (ReL6) exhibited outstanding potency (IC50 ~ 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 1O2 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.