CO Complexation by Ru(II) and Os(II) Porphyrin Complexes Sheds Light on the Relative Importance of Thermodynamic Stability and Kinetic Lability for CO Poisoning Antidotes

Despite the widespread occurrence of CO poisoning and the number of people left underserved by current treatment options, there are no clinically employed CO poisoning antidotes. Current efforts to develop candidate antidotes have focused on Fe-(II) complexes with a high binding affinity for CO, with small-molecule Fe-(II) porphyrin complexes demonstrating promising potential in this role. The well-established organometallic chemistry of group 8 metals suggests that Ru-(II) and Os-(II) analogs should be able to form even more stable carbonyl adducts than their Fe-(II) congeners. Here, we systematically investigate the impact of changing the group 8 metal on the ability of M-(II) complexes of 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinate (TPPS^6-) to sequester CO, where M = Fe, Ru, or Os. We confirm that the Ru-(II) and Os-(II) complexes do indeed form much more thermodynamically stable carbonyl complexes than the Fe-(II) complex, but the rate of formation is significantly slower. At the low concentrations of free CO present in circulation during CO poisoning, the rate of complexation by Ru-(II) or Os-(II) complexes of TPPS^6- is too slow to be clinically meaningful, highlighting that the lability of Fe-(II) complexes is key to their capacity to function as CO poisoning antidotes.