Multiple Low-Lying States for Compound I of P450_camand Chloroperoxidase Revealed from Multireference Ab Initio QM/MM Calculations

Abstract

The hybrid CASPT2/MM approach is employed to systematically study the ground and low-lying excited states of the ultimate active species of the enzymes P450cam and chloroperoxidase (CPO): the oxoiron(IV)-porphyrin cation-radical Por(•+)Fe(IV)═O(Cys) species, the so-called Compound I (Cpd I). The results underscore the fact that the B3LYP/MM method is quite accurate on the most part. However, the CASPT2/MM energies for the ferryl-pentaradicaloid quartet state and the perferryl Fe(V)O doublet and quartet states are significantly lower than the B3LYP/MM results. Thus, while the present CASPT2/MM may still overestimate the stability of these states, nevertheless, taken at its face value, the result raises the question whether these states actually contribute to the reactivity of Cpd I. Our paper tries to grapple with this question in view of (a) the recent speculations that the perferryl Fe(V)O states may be involved in unusual reactivities of Cpd I species (Pan, Z. Z.; Wang, Q.; Sheng, X.; Horner, J. H.; Newcomb, M. J. Am. Chem. Soc. 2009, 131, 2621-2628) and (b) the DFT/MM results which show that the pentaradicaloid states have intrinsically low barriers for H-abstraction (Altun, A.; Shaik, S.; Thiel, W. J. Am. Chem. Soc. 2007, 129, 8978-8987). The application of CASPT2/MM to high valent transition metal states like the perferryl are far from being trivial, and the experience and insight gained in this study are expected to be helpful for future successful application of this type of method to resolve key issues in P450 reactivity.

A GGA+U approach to effective electronic correlations in thiolate-ligated iron-oxo (IV) porphyrin

“…Of these, the E 5/2→1/2 state gap decreases most rapidly. All values of U lying below 5.0 eV correspond to a state ordering consistent with existing DFT and multireference calculations, 7 in which progressively higher spin states lie progressively higher in energy. A spin-state crossover occurs for U > 5.0 eV, whereupon the ground state assumes a sextet configuration.…”

“…2,7 Within this scheme, the π The aforementioned theoretical calculations for Cpd I have largely utilized hybrid density functionals to treat correlated behavior at the metal center. 1,2 Hybrid functionals exhibit quantitative agreement with experiment and provide consistent predictions for reaction mechanism, however, the unsystematic nature of their development can obscure the physical processes underlying their predictions.…”

Progress and Challenges in the Calculation of Electronic Excited States

“…A few steps in this direction can be found in refs. [169,170]. 2 + core-for this the reader is referred to ref.…”

DFT and Ab Initio Study of Iron-Oxo Porphyrins: May They Have a Low-Lying Iron(V)-Oxo Electromer?

“…The iron(V)-oxo electromer of the P450 Cpd I model was indeed captured in some of the DFT studies, but at such a high energy (16À24 kcal/mol) above the iron(IV)-oxo triradicaloid ground state that it was judged as not likely to play any role in the catalytic oxidation pathways. 22,23 Only very recently, Chen et al 24 showed that with multireference ab initio methods (CASPT2) the iron(V)-oxo states appear at lower energies, suggesting that they might be readily accessible at ambient temperatures. Moreover, on the basis of recent theoretical studies, the iron(IV)-oxo pentaradicaloids were also proposed as alternative active species in the catalytic cycle.…”