Conformational Control of Intramolecular Hydrogen Bonding in Heme Models: Maximal Co~Ⅱ-O_2 Binding in a C-Clamp Porphyrin

摘要

Hydrogen bonding plays a crucial role in heme protein reactions. In myoglobin (Mb) and hemoglobin (Hb), the interaction between the distal histidyl proton and the heme-bound O_2 is considered the most significant factor controlling O_2 binding. In catalase and peroxidase, a H-bond polarizes the peroxy group to facilitate a heterolytic O—O bond cleavage. Likewise, in cytochrome a_3, the presence of a proton donor is an integral part of O_2 reduction. The study of H-bonding effects, therefore, is always a focal point in heme model chemistry. Earlier, such studies were mainly confined to intermolecular interactions such as solvent effects, but more recently, synthetic models equipped with intramolecular proton donors have emerged. While these models clearly established the positive effect of enhancing the O_2 affinity, they have not permitted a closer look at how H-bond geometry and strength would influence the heme—substrate reactions. For example, from X-ray and neutron diffraction data it has been noted that the H-bonding between the distal histidine and Fe—O_2 in Mb and Hb is an oblique one, raising possibilities that the proton could interact with O1 and/or O2. Most model systems available to date, as exemplified by the naphthoic acid model 1, attempt a H-bond at O2 in a linear Fe-O1-O2 • • • H. Apart from this "unnatural" conformation, model 1 also suffers from a fatal fault as it undergoes ring degradation giving rise to an oxaporphyrin. In an effort to address the H-bond conformation issue and to sidestep the catabolism of 1, we relocated the proton donor to an overhanging position. This paper reports the synthesis, structure, and O_2 binding study of this unique model.