Applications of density functional theory to iron-containing molecules of bioinorganic interest

Abstract

The past decades have seen an explosive growth in the application of density functional theory (DFT) methods to molecular systems that are of interest in a variety of scientific fields. Owing to its balanced accuracy and efficiency, DFT plays particularly useful roles in the theoretical investigation of large molecules. Even for biological molecules such as proteins, DFT finds application in the form of, e.g., hybrid quantum mechanics and molecular mechanics (QM/MM), in which DFT may be used as a QM method to describe a higher prioritized region in the system, while a MM force field may be used to describe remaining atoms. Iron-containing molecules are particularly important targets of DFT calculations. From the viewpoint of chemistry, this is mainly because iron is abundant on earth, iron plays powerful (and often enigmatic) roles in enzyme catalysis, and iron thus has the great potential for biomimetic catalysis of chemically difficult transformations. In this paper, we present a brief overview of several recent applications of DFT to iron-containing non-heme synthetic complexes, heme-type cytochrome P450 enzymes, and non-heme iron enzymes, all of which are of particular interest in the field of bioinorganic chemistry. Emphasis will be placed on our own work.

Characterization of Paramagnetic Reactive Intermediates: Predicting the NMR Spectra of Iron(IV)–Oxo Complexes by DFT

“…4. 8 This complex was investigated in detail by various techniques in order to confirm the presence of the oxoiron radical 6. 34, 40…”

“…Generally,t his complexi sd escribed as an iron(IV)-oxo complex coupledt oaporphyrin p-radical cation (formally derived from one-electron oxidationo ft he porphyrinate dianion P 2À ;P = TMTMP), thus often written as [(Fe IV O)(P + C)]. [4,8] This complex was investigated in detail by varioust echniques in order to confirm the presence of the oxoiron radical. [6,34,40] The electronic structure of compound Ia nd its modelsh as been extensivelyi nvestigated, [5] especially to validate the [(Fe IV O)(P + C)] description.…”

“…The prototypical example is the so‐called “compound I”, an Fe IV O porphyrin believed to be an active intermediate in reactions of oxygenases, such as cytochrome P‐450. The structure and reactivity of compound I have been intensely investigated (also from a computational perspective),5 and it is generally accepted that this species is an Fe IV O porphyrin π‐radical cation 6–8. After reduction of compound I by a substrate in a one‐electron transfer process, a different and less reactive complex (compound II) is formed, which has also been characterized in the reactive cycles of peroxidases 7.…”

“…[4] The prototypical example is the so-called "compound I", an Fe IV =Op orphyrin believed to be an active intermediate in reactions of oxygenases, such as cytochrome P-450.T he structure and reactivity of compound I have been intensely investigated( also from ac omputational perspective), [5] and it is generally accepted that this speciesi s an Fe IV =Op orphyrin p-radical cation. [6][7][8] After reduction of compound Ib yasubstrate in ao ne-electron transfer process, ad ifferent and less reactive complex (compound II) is formed, which has also been characterizedi nt he reactive cycles of peroxidases. [7] Direct characterization of compounds Ia nd II is difficult because of their reactivity.I n1 981, Groves et al obtained the first model of compound Ib yo xidationo fF e III meso-tetramesityl-porphyrin (TMTP) at 198 K. [9] Mçssbauers tudies of compound Ii ndicates an S = 3/2 ground state (formally S = 1f or Fe IV and S = 1/2 for the porphyrin p-cationr adical) for all compound Im odels [10] .…”

Computational ‘microscopy’ of cellular membranes

“…For even larger scales, such as lipidmediated protein organization and whole-cell modelling, supra-coarse-grain resolution or continuum modelling is needed. The figure inserts are (from smallest to largest) -a metallic cofactor with its molecular orbitals (image of the σ* 2 state taken from figure 1A of Hirao et al, 2014); respiratory chain complexes III and IV embedded in a mitochondrial membrane (see Fig. 3); multiple copies of the same proteins self-assembling in the bilayer plane (see groups, therefore effectively reducing the number of particles in a system.…”