H-BONDED OXYHEMOGLOBIN MODELS WITH SUBSTITUTED PICKET-FENCE PORPHYRINS - THE MODEL-COMPOUND EQUIVALENT OF SITE-DIRECTED MUTAGENESIS

Iron(II) complexes of picket-fence-type porphyrins having one of the four pivalamide pickets replaced by a substituent capable of H-bonding have been synthesized as models for oxyhemoglobin. This synthetic approach is analogous to site-directed mutagenesis of the distal residues in oxygen-binding hemoproteins. Rate and equilibrium data for dioxygen binding have been determined to evaluate the effect of the H-bonding substituent and to make comparisons with more passive substituents. The effect of H-bonding on the dioxygen affinity under standard conditions (25-degrees-C, toluene solvent, 1,2-dimethylimidazole as axial ligand) is best illustrated by the ca. 10-fold increase observed when one pivalamide substituent of picket-fence porphyrin is replaced by a phenylurea substituent. Other substituents influence dioxygen adduct stability in a variety of ways to reveal that even with an apparently straightforward systematic approach, there can be considerable difficulty in partitioning the various factors that influence O2 affinity. This applies to both model compounds and mutant proteins.