Anthracene Heme Cyclophanes. Steric Effects in CO, O2, and RNC Binding

Article abstract of DOI:10.1021/ja00289a012

Equilibrium constants in benzene solution are reported for binding of imidazoles, CO, O2, and isocyanide to two anthracene heme cyclophanes, Fe(6,6-cyclophane) and Fe(7,7-cyclophane), containing a conformationally mobile anthracene ring strapped symmetrically over the heme.The Fe(6,6-cyclophane) shows an approximately 300-fold reduction in affinity for the diatomic molecules, CO, and O2 compared to unhindered hemes.The Fe(7,7-cyclophane) shows only slight steric effects toward CO and O2 but larger effects with bulky isocyanides.The sizes of the cyclophane cavities are qualitatively probed with isocyanides of varying size.Kinetic data for binding of CO, O2, and tosylmethyl isocyanide to heme cyclophanes when compared to similar data for flat analogues demonstrate that steric effects are manifested primarily in the ligand association rates.This feature of the cyclophane is very similar to observed steric effects in hemoproteins, suggesting that large conformational changes (tilting of the cyclophane cap in the models and movement of distal protein residues in hemoproteins) occur in both prior to the transition state for ligation.Magnitudes of steric effects in hemoproteins and cyclophanes are calculated on the basis of comparison with the unhindered chelated heme model compounds.The nature of the distal steric effect in the Fe(6,6-cyclophane) model compound suggests that the reported bending or tilting of CO in hemoglobins and myoglobin may be of minor chemical significance.