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 (<b>Co1</b>), [Co-(thio-tpy)-(BrSBVB₆)]Cl (<b>Co2</b>), [Co-(thio-tpy)-(ClSBVB₆)]-Cl (<b>Co3</b>), and [Co-(thio-tpy)-(FSBVB₆)]Cl (<b>Co4</b>), where 4'-(thiophen-2-yl)-2,2':6',2″-terpyridine = thio-tpy, (<i>E</i>)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)-imino)-methyl)-2-methylpyridin-3-ol = H₂SBVB₆, (<i>E</i>)-4-(((5-bromo-2-hydroxyphenyl)-imino)-methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol = H₂BrSBVB₆, (<i>E</i>)-4-(((5-chloro-2-hydroxyphenyl)-imino)-methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol = H₂ClSBVB₆, and (<i>E</i>)-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 (<i>ca</i>. 440-490 nm) and excellent stability under visible light render them suitable for aPDT applications. X-ray diffraction data of <b>Co4</b> revealed a distorted octahedral Co^IIIN₄O₂ 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 (<i>Staphylococcus aureus</i>), with MIC values lying between 0.09 to 0.46 μg/mL, while no such effect was observed against the Gram-negative (<i>Escherichia coli</i>) bacteria. The light-activated antibacterial activity of <b>Co1</b>-<b>Co4</b> is likely attributed to their ability to disrupt bacterial cell membranes through reactive oxygen species (ROS)-mediated oxidative stress. Additionally, <i>in silico</i> molecular docking studies help to predict the possible mode of action, binding pattern, and interaction affinities between PBP2a and <b>Co2</b>. Overall, these findings highlight the potential of halogenated vitamin B₆-derived Co-(III) complexes as promising next-generation photoresponsive antibacterial agents.