Fine Tuning of Heme Reactivity: Hydrogen-Bonding and Dipole Interactions Affecting Ligand Binding to Hemoproteins

Abstract

Abstract Heme reactivity in hemoproteins is governed by the microenvironment near the ligand binding site. In order to quantify polarity effects on heme ligand binding, the kinetics of O2 and CO binding have been measured for a series of synthetic heme models equipped with a range of groups of varying dipole moments positioned near the heme coordination site. For hemes with polar aprotic groups, both O2 on (k′) and off rates (k) are found to be dependent on the dipole moment. For model systems containing protic groups, the O2 off rate is substantially reduced due to hydrogen bonding with the coordinated O2. The hydrogen-bonding stabilization is estimated to be 0.7 and 1.6 kcal/mol for an alcohol and a secondary amide, respectively. CO binding displays little correlation with a polarity effect; instead it seems to depend upon the size and position of the polar group.