Redox-Tagged Carbon Monoxide-Releasing Molecules (CORMs): Ferrocene-Containing [Mn(C^N)(CO)₄] Complexes as a Promising New CORM Class

Abstract

This study describes the synthesis and characterization of a new class of ferrocene-containing carbon monoxide-releasing molecules (CORMs, 1-3). The ferrocenyl group is both a recognized therapeutically viable coligand and a handle for informative infrared spectroelectrochemistry. Deoxymyoglobin CO-release assays and in situ infrared spectroscopy confirm compounds 2 and 3 as photoCORMs and 1 as a thermal CORM, attributed to the increased sensitivity of the Mn-ferrocenyl bond to protonation in 1. Electrochemical and infrared spectroelectrochemical experiments confirm a single reversible redox couple associated with the ferrocenyl moiety with the Mn tetracarbonyl center showing no redox activity up to +590 mV vs Fc/Fc, though no concomitant CO release was observed in association with the redox activity. The effects of linker length on communication between the Fe and Mn centers suggest that the incorporation of redox-active ligands into CORMs focuses on the first coordination sphere of the CORM. Redox-tagged CORMs could prove to be a useful mechanistic probe; our findings could be developed to use redox changes to trigger CO release.

Spectroscopic and DFT studies of photoactivatable Mn(I) tricarbonyl complexes

“…The selective delivery of CO to the target cells and tissues in vivo is the motivation to develop carbon monoxide releasing molecules (CORMs) as pro‐drugs. The ways by which CORMs can be induced to release CO include change of the redox state and pH . Schmalz group used some enzymes to trigger iron (II) based CORMs .…”

Green‐Light‐Induced PhotoCORM: Lysozyme Binding Affinity towards MnI and ReI Carbonyl Complexes and Biological Activity Evaluation

“…Organic (e.g. α,α‐dialkylaldehydes, and oxalates) and organometallic (borano carboxylates, sila‐carboxylates, and metal carbonyl complexes) compounds have been investigated as CORMs. Different triggering methods have been used to initiate the CO release.…”

“…Different triggering methods have been used to initiate the CO release. This includes change of pH value, and redox state, thermal, enzymatic, and photochemical ways . At first, the ability of [Mn 2 (CO) 10 ] (CORM‐1) and Fe(CO) 5 to release CO upon the exposure to a cold light was investigated by Motterlini et al In 2008, a group of fac ‐Mn(CO) 3 complexes bearing tris(pyrazolyl)methane derivatives was examined by Schatzschneider group as photoinduced CO molecules .…”

“…To decrease the detrimental problems of UV light and to increase the penetration depth of the light into tissues, synthesis of visible‐light triggered CORMs is one of the major challenges in this research area. For the class of metal carbonyl complexes, change of the metal ion (rhenium, manganese, iron, ruthenium, molybdenum, tungsten), and the axial ligand as well as extension of the ancillary ligand conjugation system led to modulation of the M–CO that influence in turn the electron density and consequently the energy of the incident light. Manganese(I) and ruthenium(II) carbonyl complexes have been widely studied in the context of CORMs because of their rich photochemical properties , .…”

“…For the class of metal carbonyl complexes, change of the metal ion (rhenium, manganese, iron, ruthenium, molybdenum, tungsten), and the axial ligand as well as extension of the ancillary ligand conjugation system led to modulation of the M–CO that influence in turn the electron density and consequently the energy of the incident light. Manganese(I) and ruthenium(II) carbonyl complexes have been widely studied in the context of CORMs because of their rich photochemical properties , . By extending the conjugation system of the ancillary ligand, Mascharak and his co‐workers succeed in shift the MLCT band of Mn I and Ru II photoCORMs into the visible region and thus visible‐light LEDs were used as excitation source …”