New synthetic analogs of heme proteins

Abstract

We have been exploring the chemistry of iron porphyrin complexes as they mimic the O 2 binding, activation and hydrocarbon hydroxylation chemistry associated with hemoglobin, peroxidase, and cytochrome P450. To these ends we have synthesized and characterized a novel ‘bis-pocket’ porphyrin, mesotetrakis(2,4,6-triphenyl)phenylporphyrin. This ‘bis-pocket’ porphyrin offers rigid steric protection on both faces of the porphyrin preventing both oxidative degradation and α-oxo dimerization. The O 2 complexes of our model compound show remarkable thermal stability; reversible oxygenation is observed at temperatures as high as 60 °C. The effects of solvent polarity on CO and O 2 binding show that high polarity favors O 2 binding, but disfavors CO binding. Good correlations are found between ΔG° (O 2), ΔG° (CO), and M with empirical solvent polarity scales ( e.g., ET-30 or π*). Thus, a new means of producing O 2/CO discrimination in heme systems is uncovered. These results help explain the discrepancies between other synthetic analogs and the variety of relative CO and O 2 affinities of heme proteins. In addition, the steric hindrance offered by the ‘bis-pocket’ porphyrin dramatically increase the oxidative robustness of the iron complex to the presence of a wide variety of oxidants including peracids, hydroperoxides, and iodosoarenes. This provides for the first stable analogs of the high oxidation intermediates of the peroxidases and cytochrome P450. The results of the characterization of the highly oxidized intermediate observed suggest a compound I type intermediate. Studies on the shape selective hydroxylation of hydrocarbon substrates with iron and manganese ‘bis-pocket’ porphyrin will also be presented. Other studies on the Mössbauer spectra of iron porphyrin complexes oxidized beyond the Fe(III) state will be related. Specifically, we have investigated the electronic structure of a series of single atom bridged dimers, (FeTPP) 2X n+ where X = O, N, or C and TPP = meso-tetraphenylporphyrinato. In the series of complexes which are two oxidizing equivalents above Fe(III)Fe(III) dimers, we find that changing the bridging atom from O to N or C shifts the site of oxidation from the porphyrin pi system (as in (FeTPP) 2O 2+ to the metal, yielding complexes which can be formally viewed as true Fe(IV) dimers [as in (FeTPP) 2N + and (FeTPP) 2C].