Synthesis of Artificial Hemoglobin Using Cyclodextrin Dimer and its Approach for Drug Development as an Antidote for CO Gas Poisoning

Per-O-methylated β-cyclodextrin (TMe-β-CD) forms a very stable 2 : 1 inclusion complex with water-soluble 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) in water. The supramolecular complex provides strong hydrophobic cavity to the porphyrin scaffold, which is similar to the environment of heme in heme proteins. In our laboratory, per-O-methylated β-CD dimer having pyridine linker (Py3CD) was synthesized to make a biomimetic model compound of oxygen-binding heme protein like hemoglobin (Hb) and myoglobin (Mb). The inclusion complex of Py3CD with iron complex of TPPS (FeTPPS) is the first and only-one biomimetic complex that functions in water. The complex, named hemoCD, showed a very high CO binding affinity. When hemoCD was injected to rodent animals after exposure to CO gas, hemoCD captured CO during circulation and was excreted in urine without showing any toxic effect. These properties are quite suitable to the use of an antidote against CO poisoning. Our laboratory has started the drug development to implement hemoCD as a CO antidote for clinical use.