Model compounds for the T state of hemoglobin

O₂ binding to a series of ferrous and cobaltous 'picket fence' porphyrins is reported. N-Methylimidazole and covalently attached imidazoles give O₂ binding to ferrous porphyrins with ΔH° = -16.2 kcal/mol (-67.7 kJ/mol) and ΔS° = -40 eu (standard state, 1 atmosphere O₂). Similar studies with cobaltous porphyrins yield ΔH° = -12.8 kcal/mol (-53.5 kJ/mol) and ΔS°= -39 eu. These values match well those of myoglobin and isolated subunits of hemoglobin and their cobalt reconstituted analogues. 1,2-Dimethylimidazole has been successfully used to mimic the presumed restraint of T state hemoglobin. In direct analogy to the decreased cooperativity shown by cobalt-substituted hemoglobin, model cobalt porphyrins show a smaller decrease in O₂ affinity than the analogous iron porphyrins when the axial base is hindered. Thermodynamic data are presented. The molecular mechanism of cooperativity in hemoglobin is discussed.