Halogenated Vitamin B 6 -Attached Co(III) Photosensitizers on Polypyridyl Scaffold for Light-Induced Antibacterial Activities

Four novel halogenated vitamin B6-derived Co-(III) complexes viz., Co-(thio-tpy)-(SBVB6)Cl (Co1), Co-(thio-tpy)-(BrSBVB6)Cl (Co2), Co-(thio-tpy)-(ClSBVB6)-Cl (Co3), and Co-(thio-tpy)-(FSBVB6)Cl (Co4), where 4'-(thiophen-2-yl)-2,2':6',2″-terpyridine = thio-tpy, (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)-imino)-methyl)-2-methylpyridin-3-ol = H2SBVB6, (E)-4-(((5-bromo-2-hydroxyphenyl)-imino)-methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol = H2BrSBVB6, (E)-4-(((5-chloro-2-hydroxyphenyl)-imino)-methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol = H2ClSBVB6, and (E)-4-(((5-fluoro-2-hydroxyphenyl)-imino)-methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol = H2FSBVB6 were developed successfully as potential photosensitizers for aPDT (antibacterial photodynamic therapy). The pronounced visible light absorption (ca. 440-490 nm) and excellent stability under visible light render them suitable for aPDT applications. X-ray diffraction data of Co4 revealed a distorted octahedral CoIIIN4O2 coordination core. Further, DFT and TD-DFT calculations provided insights into the electronic structure and HOMO-LUMO energy gaps. Interestingly, all complexes showed good 1O2 and •OH generation potential in a DMSO:H2O (1:99, v/v) under light. Under dark conditions, no notable antibacterial activity was observed; however, the activity was significantly enhanced upon exposure to 400-700 nm (10 J cm-2) light, particularly against Gram-positive bacteria (Staphylococcus aureus), with MIC values lying between 0.09 to 0.46 μg/mL, while no such effect was observed against the Gram-negative (Escherichia coli) bacteria. The light-activated antibacterial activity of Co1-Co4 is likely attributed to their ability to disrupt bacterial cell membranes through reactive oxygen species (ROS)-mediated oxidative stress. Additionally, in silico molecular docking studies help to predict the possible mode of action, binding pattern, and interaction affinities between PBP2a and Co2. Overall, these findings highlight the potential of halogenated vitamin B6-derived Co-(III) complexes as promising next-generation photoresponsive antibacterial agents.