Mitochondria-Targeted Benzoxazole-Based Platinum Photosensitizer Complexes: Photophysical Properties and Photocytotoxicity Evaluation Against Breast and Gastric Cancer Cells

This study explores platinum(II) phototherapy using cycloplatinated compounds with bidentate 2-(4-substituted) benzoxazole ligands, [Pt(<i>L</i>)(<i>R</i>)(<i>X</i>)] (<b>C1-C5</b>). The compounds were synthesized and fully characterized, and their photophysical, cytotoxic, and phototoxic properties were analyzed. Time-dependent Density Functional Theory (TD-DFT) calculations supported the analysis of the complexes absorption and photoluminescence, with high-energy absorption showing ¹L'LCT/¹MLCT [π(Cl, Me) → π*(C^N)] contributions. Among the complexes, <b>C4</b> (<i>L</i> = C^N, <i>R</i> = κ¹-<i>N</i>-C^N, <i>X</i> = Cl) exhibited the highest quantum yield (Φ_F = 48%) and showed strong antiproliferative activity in breast carcinoma (MCF-7) and gastric adenocarcinoma (AGS) cell lines. <b>C1-C5</b> (<b>C1</b>, <i>L</i> = N^N, <i>R</i> = Cl, <i>X</i> = Cl, <b>C2</b>, <i>L</i> = N^N, <i>R</i> = Me, <i>X</i> = Me; <b>C3</b>, <i>L</i> = C^N, <i>R</i> = DMSO, <i>X</i> = Cl; <b>C4</b>, <i>L</i> = C^N, <i>R</i> = C^N, <i>X</i> = Cl, and <b>C5</b>, <i>L</i> = C^N, <i>X</i> = Me, <i>R</i> = DMSO) also demonstrated potential as photoactivatable agents. Mechanistic studies indicated that the complexes triggered ROS generation, mitochondrial dysfunction, and lysosomal damage, with <b>C4</b> showing promise for photochemotherapeutic treatment of gastric and breast cancer due to its selectivity and effectiveness in targeting mitochondria and lysosomes.