Cyclodextrin-based Development of Artificial Hemoglobin and Its Use for Antidote Against Gas Poisoning

Abstract

Cyclodextrin functions as a host molecule that can include external guest molecules in its hydrophobic cavity in water. In our laboratory, we have found that per-O-methylated β-cyclodextrin (TMe-β-CD) forms a stable 2:1 inclu­sion complex with 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS). The inclusion complex has a strong hydrophobic cavity around the porphyrin scaffold, similar to the environment of heme in heme proteins. We have synthesized a per-O-methylated β-CD dimer having pyridine linker (Py3CD) to make a biomimetic model compound of hemoglobin (Hb) and myoglobin (Mb). The inclusion complex of Py3CD with iron complex of TPPS (FeTPPS) is the first biomimetic Hb/Mb model complex in water. The complex, hemoCD, showed a very high CO binding affinity in vivo. When hemoCD was injected to animals (mice and rats) after exposure to CO, hemoCD captured CO during circulation and was excreted in urine without showing any toxic effect. These properties seem appropriate for the use of hemoCD as an inject­able antidote against CO poisoning. We have just started the drug development to implement hemoCD as a CO antidote for clinical use.