MECHANISMS OF REACTIONS OF OXYGEN WITH HEME PROTEINS

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Model compounds for hemoglobin and related hemoproteins will be prepared and the effect of their structure on the dynamics of reaction with dioxygen, carbon monoxide, and isonitriles studied. Geminate recombination of isocyanides, nitric oxide and dioxygen to various model compounds for R- and T-state hemoglobins and hemes with different extents of steric, electronic and polar effects at the site will be studied using femptosecond, picosecond, and nanosecond kinetic methods. Photolysis quantum yields will be determined for correlation with the kinetic studies. Special efforts will be made to determine relative rates of binding and conformational change in both the heme cyclophanes and in heme proteins. New compounds will be designed to explore the effects of porphyrin flexibility, distortion of "stiffness" upon dioxygen and other ligand binding. Cooperatively binding heme compounds now in hand and newly designed systems will be studied with regard to kinetics and equilibria of carbon monoxide and dioxygen binding in order to mimic the cooperativity in hemoglobin. This study will define those characteristics of heme compounds and their environment which control the varied reactivities of such hemes in hemoproteins. This information will provide the means of understanding the cooperativity in hemoglobin, the conformational changes in proteins, and other effects which govern ligand affinity. The cyclophane porphyrins and the dimer heme compounds will also be used to probe the effect of intervening molecular structure on porphyrin-to-porphyrin electron transfer.