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 complex 1 is significantly faster than that from Re complex 2. Complex 2 exhibits higher cytotoxicity against HeLa cells than complex 1, with IC₅₀ values of 40.1 μM and 10.6 μM for 1 and 2, respectively, which decrease to 16.2 μM and 4.9 μM after photo irradiation. Moreover, 1 exhibited a stronger binding constant (K_b) with human serum albumin (HSA) than 2, with values of 1.6 × 10⁶ and 7.0 × 10⁵ M^-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 complex 1. This study provides insights into the stability, possible metabolic pathways, and potential applications of these carbonyl complexes.