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

• Published in: Chemistry : a European journal 2024-11
• Main Authors: Kar, Binoy, Paira, Priyankar
• Format: Article
• Language: English
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202401720

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 3 π‐π* character of T 1 state for PDT and high value of lipophilicity for cell membrane penetration. These complexes exhibited prominent intraligand/ligand‐centered (π‐π*/ 1 LC) absorption bands at λ 260–350 nm and relatively weak metal‐to‐ligand charge‐transfer ( 1 MLCT) bands within the λ 350–550 nm range. Among the six synthesized complexes, [(CO) 3 Re I Cl(K 2 ‐N,N‐2‐(4‐(1‐benzyl‐1H‐tetrazol‐5‐yl)phenyl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline] ( ReL6 ) exhibited outstanding potency (IC 50 ~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 1 O 2 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.