Multireference and Multiconfiguration Ab Initio Methods in Heme-Related Systems: What Have We Learned So Far?

Abstract

This work reviews the recent applications of ab initio multireference/multiconfiguration (MR/MC) electronic structure methods to heme-related systems, involving tetra-, penta-, and hexa-coordinate species, as well as the high-valent iron-oxo species. The current accuracy of these methods in the various systems is discussed, with special attention to potential sources of systematic errors. Thus, the review summarizes and tries to rationalize the key elements of MR/MC calculations, namely, the choice of the employed active space, especially the so-called double-shell effect that has already been recognized to be important in transition-metal-containing systems, and the impact of these elements on the spin-state energetics of heme species, as well as on the bonding mechanism of small molecules to the heme. It is shown that expansion of the MC wave function into one based on localized orbitals provides a compact and insightful view on some otherwise complex electronic structures. The effects of protein environment on the MR/MC results are summarized for the few available quantum mechanical/molecular mechanical (QM/MM) studies. Comparisons with corresponding DFT results are also made wherever available. Potential future directions are proposed.

Quantum-Mechanical Studies of Reactions Performed by Cytochrome P450 Enzymes

“…12 Recently, there have been quite some interest in using advanced QM methods to study various CYP reactants, in particular compound I. [14][15][16][17][18] Such calculations show that compound I has a complicated electronic structure, with many low-lying excited states. The results indicate that both pentaradicaloid (with five unpaired electrons) and Fe V states are nearly degenerate (within 40 kJ/mol) with the triradicaloid ground state.…”

“…This is important, because both calculations and experiments have implicated these species in the reaction mechanism of the CYPs and indicated that they may lead to reduced barriers compared to the triradicaloid Fe IV state. 8,14,[18][19][20][21][22] Many different quantum-mechanical (QM) methods have been used to study the geometry, electronic structure, and reactivity of the CYPs, ranging from approximate semiempirical methods to high-level multi-reference and coupled-cluster methods. 3,4,17,18 However, the great majority of the calculations have been performed with density-functional theory (DFT).…”

“…8,14,[18][19][20][21][22] Many different quantum-mechanical (QM) methods have been used to study the geometry, electronic structure, and reactivity of the CYPs, ranging from approximate semiempirical methods to high-level multi-reference and coupled-cluster methods. 3,4,17,18 However, the great majority of the calculations have been performed with density-functional theory (DFT). Calibration calculations have indicated that DFT, in particular with hybrid functionals such as B3LYP, give reliable structures and energies, except for the relative energy of the pentaradicaloid and Fe V states of compound I and spin populations of this state.…”

“…Calibration calculations have indicated that DFT, in particular with hybrid functionals such as B3LYP, give reliable structures and energies, except for the relative energy of the pentaradicaloid and Fe V states of compound I and spin populations of this state. 14,17,18,21 Most calculations have been performed for isolated heme models, either in a vacuum or in a homogeneous continuum solvent with a dielectric constant of 4-8.…”

Watching energy transfer in metalloporphyrin heterodimers using stimulated X-ray Raman spectroscopy

“…Porphyrin-based molecules hold a pivotal position in the chemistry of engineered photoactive organic compounds, and extensive electronic structure calculations of monomeric (15) and oligomeric (16,17) porphyrin molecules, porphyrin structures in biomacromolecules (18,19), and quasi-1D and -2D porphyrin systems with infinite sizes have been carried out (13,14,(20)(21)(22)(23). Most applications involve multiporphyrin arrays, either in linear or in cyclic shape, or dendrimers (24).…”