Ligand-Tuned Mn(I) Complexes with Oxazole, Thiazole, and Selenazole Scaffolds: Synthesis and Mechanistic Insights...

Photoactivated carbon monoxide-releasing molecules (photo-CORMs) enable spatiotemporal control of CO delivery with therapeutic potential. We report a series of ten Mn(I) tricarbonyl complexes (1-10) incorporating oxazole-, thiazole-, and selenazole-based ligands, including π-extended quinoline derivatives. All complexes adopt a fac-{Mn(CO)₃} geometry, and photophysical studies revealed MLCT absorption bands at 416-470 nm, tunable by heteroatom identity and ligand conjugation. Kinetic analyses showed first-order CO release, with thiazole-containing complexes releasing the fastest, oxazole analogs the slowest, and selenazole species intermediate. The pyridine-oxazole complex (1) displayed the slowest and more equivalent of CO release (t_1/2 = 8.17 ± 0.02 s). While pH and temperature exerted minimal influence, solvent polarity and excitation wavelength strongly modulated the CO release rates. Mechanistic investigations combining spectroscopy and TD-DFT confirmed that MLCT excitation weakens Mn-CO backbonding, promoting CO dissociation. In biological studies, all complexes in the dark, after light trigger, and their iCORMs were nontoxic up to 40 μM. The complexes capable of light-triggered CO release have been studied using the CODP-106 probe in HeLa cells. These findings define clear structure-reactivity relationships and identify sulfur- and selenium-containing ligands (such as the ones in 2 and 3) as promising scaffolds for efficient Mn(I) photo-CORMs in biomedical contexts.