Using Density Functional Theory and Fukui Function to Analyze the Reaction Site of Hemoglobin to CO, O2 and NO

Carbon monoxide poisoning is the most common cause of death from gas poisoning worldwide. About 6,600 people suffer long-term cognitive sequelae from carbon monoxide poisoning each year, with a total cost of about $925 million. Carbon monoxide poisoning has always been a very important problem, but there are many environmental limitations in existing treatment methods, and the effect of treatment often causes sequelae. When a large amount of carbon monoxide enters the human system, it will quickly combine with hemoglobin to form carbon monoxide hemoglobin (COHb). The affinity of carbon monoxide to hemoglobin (Hb) is 200 to 200 times that of oxygen to carbon monoxide hemoglobin. Heme dissociates about 3,600 times faster than oxyhemoglobin, so heme transports oxygen poorly, leading to carbon monoxide poisoning. In biology, the dissociation and binding of CO, O², and NO to hemoglobin are very important. In this study, we performed density functional theory (DFT) and computed the Fukui function to analyze the reaction site of heme with CO, O2, and NO. By comparing the calculations results for heme and different oxygen-containing molecules such as CO, O², and NO, we found the specific reaction sites of ferrous ions and carbon atoms in carbon monoxide molecules. This finding can help us to understand the binding mechanism of COHb. We can further extend the research to design an antidote that can break the carbon monoxide-heme bond quickly. The antidote for carbon monoxide poisoning can achieve the fastest therapeutic effect. Our work can be applied to develop an effective antidote and bring great benefits to the treatment of carbon monoxide poisoning.