Structural Insights into the Photoactivatable CO Release from Mn-CO and Re-CO Complexes for CO Delivery

Two tri-carbonyl complexes, [Mn(CO)3(5cpa)Br] (1) and [Re(CO)3(5cqn)(OCH3)] (2), were synthesized, where 5cpa is 5-Cl-2-picolinic acid and 5cqn is 5-Cl-8-Hydroxyquinoline. Their structures were determined using X-ray diffraction techniques. The electronic absorption and IR spectra of the complexes were experimentally measured and theoretically assigned through density functional theory (DFT) calculations. The photo-induced CO release was verified using time-resolved infrared spectroscopy, and the transfer of CO to hemoglobin (Hb) was monitored by UV-vis spectroscopy. The rate of CO release and transfer from Mn complex1is significantly faster than that from Re complex2. Complex2exhibits higher cytotoxicity against HeLa cells than complex1, with IC50values of 40.1 μM and 10.6 μM for1and2, respectively, which decrease to 16.2 μM and 4.9 μM after photo irradiation. Moreover,1exhibited a stronger binding constant (Kb) with human serum albumin (HSA) than2, with values of 1.6 × 106and 7.0 × 105M−1, respectively. The structures of HSA complex adducts revealed that both the resulting [Mn(CO)3(5cpa)]−and [Re(CO)3(5cqn)]−group coordinate with the N atom of His146, while four additional dissociated Mn-CO groups were observed to bind to HSA for complex1. This study provides insights into the stability, possible metabolic pathways, and potential applications of these carbonyl complexes.