The effect of water on the Fe3+/Fe2+ reduction potential of heme

Hemeproteins can act as catalysts, oxygen carriers or electron conductors. The ferric/ferrous reduction potential E-m7 of iron in the center of the pr osthetic group ranges from negative values for peroxidases to an extreme po sitive value for cytochrome a, with Hb and Mb in the middle [1]. Proteins e xercise their influence on E-m7 in several ways: via substituents at the pe riphery of the chelate structure, via the proximal ligand, and via interact ion with the surrounding medium, amino acid side chains, or polar solvents. Work on recombined proteins and ap-substituted free hemes documented that the first two effects are additive [2]. For the third effect, models of the dielectric media on a molecular level have been successfully applied [3-5] . E-m7 has also been empirically correlated to the degree of heme exposure to water [6-8]. The apoprotein/porphyrin and water/porphyrin interfaces are complementary since water molecules fill any empty space in the crevice an d surround any pertinent part of heme outside the protein boundary. The pre sent work links to this idea by a combination of statistical mechanics simu lations and quantum mechanical calculations comparing heme in water with he me in an apolar environment. Our results show that polarization of the porp hyrin pi-electron cloud by the held from water dipoles influences E-m7 The dominant effect of this and other determinates of iron electron availabilit y is perturbations of delocalized electron density in the porphyrin chelate , reproduced by a model where the prosthetic group is treated as a disc of uniform electron density. The present work is also of interest since the in terfacial energy constitutes the main barrier for heme-protein Separation [ 9-11]. (C) 2000 Academic Press.