Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Exploring the potential of synthetic heme protein models as injectable antidotes against highly toxic gases (121789)

Hiroaki Kitagishi 1 , Qiyue Mao 1 , Atsuki Nakagami 1 , Masahito Kodera 1
  1. Doshisha University, Kyotanabe, KYOTO, Japan

In mammals, small and diffusible diatomic gas molecules such as CO, NO, and H2S have been recognized as the physiologically important signal mediators. These gases are endogenously produced, and the amount of these gases are strictly controlled since excess of these gases show very high toxicity. When inhaled into the body, these gases strongly bind to ferric and ferrous hemes in the heme proteins, thus inhibit aerobic respirations. The safe and injectable gas scavengers would be clinically required as the antidotes for emergency use.

A water-soluble tetrakis(4-sulfonatophenyl)porphyrin iron complex (FeTPPS) has long been used as the simple heme model compound. When FeTPPS was mixed with per-O-methylated cyclodextrin dimer, FeTPPS was encapsulated and isolated in the hydrophobic nanocage in water. We have studied in the past two decades the inclusion complexes, hemoCD, as the water-soluble heme protein model complexes.1 Our investigation revealed that hemoCD could work as the injectable antidote against CO, HCN, and H2S.2,3 The injected hemoCD into animals were rapidly excreted in urine accompanied with the gaseous ligand. Recently hemoCD was found to bind with NO both in ferric and ferrous states to form the stable NO adducts in water.

In this presentation, the basic gas-binding properties of hemoCD and recent progress for the clinical use of hemoCD as the antidote will be shown.

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(1) Kitagishi, H. et al., Chem. Comm. 2021, 57, 148–173.

(2) Mao, Q. et al., PNAS 2023, 120, e2209924120.

(3) Nakagami, A. et al., Sci. Rep. 2024, 14, 29371.