Jesse W. Tye

Mechanism of electrocatalytic hydrogen production by a di-iron model of iron–iron hydrogenase: A density functional theory study of proton dissociation constants and electrode reduction potentials

Simple dinuclear iron dithiolates such as (mu-SCH2CH2CH2S)[Fe(CO)3]2, (1) and (mu-SCH2CH2S)[Fe(CO)3]2 (2) are functional models for diiron-hydrogenases, [FeFe]-H2ases, that catalyze the reduction of protons to H2. The mechanism of H2 production with 2 as the catalyst and with both toluenesulfonic (HOTs) and acetic (HOAc) acids as the H+ source in CH3CN solvent has been examined by density functional theory (DFT). Proton dissociation constants (pKa) and electrode reduction potentials (E(o)) are directly computed and compared to the measured pKa of HOTs and HOAc acids and the experimental reduction potentials. Computations show that when the strong acid, HOTs, is used as a proton source the one-electron reduced species 2- can be protonated to form a bridging hydride complex as the most stable structure. Then, this species can be reduced and protonated to form dihydrogen and regenerate 2. This cycle produces H2 via an ECEC process at an applied potential of -1.8 V vs. Fc/Fc+. A second faster process opens for this system when the species produced at the ECEC step above is further reduced and H2 release returns the system to 2- rather than 2, an E[CECE] process. On the other hand, when the weak acid, HOAc, is the proton source a more negative applied reduction potential (-2.2 V vs. Fc/Fc+) is necessary. At this potential two one-electron reductions yield the dianion 2(2-) before the first protonation, which in this case occurs on the thiolate. Subsequent reduction and protonation form dihydrogen and regenerate 2- through an E[ECEC] process.

Refining the Active Site Structure of Iron−Iron Hydrogenase Using Computational Infrared Spectroscopy

Iron-iron hydrogenases ([FeFe]H2ases) are exceptional natural catalysts for the reduction of protons to dihydrogen. Future biotechnological applications based on these enzymes require a precise understanding of their structures and properties. Although the [FeFe]H2ases have been characterized by single-crystal X-ray crystallography and a range of spectroscopic techniques, ambiguities remain regarding the details of the molecular structures of the spectroscopically observed forms. We use density functional theory (DFT) computations on small-molecule computational models of the [FeFe]H2ase active site to address this problem. Specifically, a series of structural candidates are geometry optimized and their infrared (IR) spectra are simulated using the computed C-O and C-N stretching frequencies and infrared intensities. Structural assignments are made by comparing these spectra to the experimentally determined IR spectra for each form. The H red form is assigned as a mixture of an Fe(I)Fe(I) form with an open site on the distal iron center and either a Fe(I)Fe(I) form in which the distal cyanide has been protonated or a Fe(II)Fe(II) form with a bridging hydride ligand. The Hox form is assigned as a valence-localized Fe(I)Fe(II) redox level with an open site at the distal iron. The Hox(air)(ox) form is assigned as an Fe(II)Fe(II) redox level with OH(-) or OOH(-) bound to the distal iron center that may or may not have an oxygen atom bound to one of the sulfur atoms of the dithiolate linker. Comparisons of the computed IR spectra of the (12)CO and (13)CO inhibited form with the experimental IR spectra show that exogenous CO binds terminally to the distal iron center.

Correlation Between Computed Gas-Phase and Experimentally Determined Solution-Phase Infrared Spectra: Models of the Iron-Iron Hydrogenase Enzyme Active Site

Gas‐phase density functional theory calculations (B3LYP, double zeta plus polarization basis sets) are used to predict the solution‐phase infrared spectra for a series of CO‐ and CN‐containing iron complexes. It is shown that simple linear scaling of the computed CO and CN stretching frequencies yields accurate predictions of the the experimentally determined ν(CO) and ν(CN) values for a variety of complexes of different charges and in solvents of varying polarity. As examples of the technique, the resulting correlation is used to assign structures to spectroscopically observed but structurally ambiguous species in two different systems. For the (μ‐SCH2CH2CH2S)[Fe(CO)3]2 complex in tetrahydrofuran solution, our calculations show that the initial electrochemical reduction process leads to a simple one‐electron reduced product with a structure very similar to the (μ‐SCH2CH2CH2S)[Fe(CO)3]2 parent complex. For the iron–iron hydrogenase enzyme active site, our computations show that the absence or presence of a water molecule near the distal iron center (the iron center further from the [4Fe4S] cluster and protein backbone) has very little effect on the predicted infrared spectra.

Density functional theory applied to a difference in pathways taken by the enzymes cytochrome P450 and superoxide reductase: spin States of ferric hydroperoxo intermediates and hydrogen bonds from water.

Cytochrome P450 monooxygenase and superoxide reductase (SOR) have the same first atom coordination shell at their iron active sites: an Fe[N(4)S] center in a square-pyramidal geometry with the sixth coordinate site open for the catalytic reaction. Furthermore, both pass through ferric hydroperoxo intermediates. Despite these similarities, the next step in their catalytic cycle is very different: distal oxygen protonation and O-O cleavage (P450) versus proximal oxygen protonation and H(2)O(2) release (SOR). One of the factors leading to this difference is the spin state of the intermediates. Density functional theory (DFT) applied to models for the ferric hydroperoxo, (SCH(3))(L)Fe(III)-OOH (L = porphyrin for P450 and four imidazoles for SOR), gives different ground spin states; the P450 model with the porphyrin, which contrains the Fe-N distances, prefers a low-spin ground state, whereas the SOR model with four histidines, in which Fe-N bonds are extendable, prefers a high-spin ground state. Their ground spin states lead to geometric and electronic structures that assist in (1) the protonation on distal oxygen for P450, which leads to O-O bond cleavage and formation of the oxo-ferryl, (SCH(3))(L)Fe(IV) horizontal lineO (Cpd I), and H(2)O, and (2) the protonation on proximal oxygen for SOR, which leads to the formation of the ferric hydrogen peroxide, (SCH(3))(L)Fe(III)-HOOH, intermediate before the Fe-O bond cleavage and H(2)O(2) production. Specifically, the quartet ground state of the water-bound oxo-ferryl, (SCH(3))(L)Fe(IV) horizontal lineO...H(2)O, is more stable than the sextet ground state of (SCH(3))(L)Fe(III)-HOOH by -14.29 kcal/mol for the P450 model. Another important factor is the differences in the location of the active site: P450s active site is embedded within the enzyme, whereas SORs active site is exposed to the aqueous environment. In the latter location, water molecules can freely form hydrogen bonds with both proximal and distal oxygen to stabilize the (SCH(3))(L)Fe(III)-HOOH intermediate. When two explicit water molecules are included in the model, the sextet ground state of (SCH(3))(L)Fe(III)-HOOH...2H(2)O is more stable than the quartet ground state of (SCH(3))(L)Fe(IV) horizontal lineO...3H(2)O by -2.14 kcal/mol for the SOR model. Our calculations show that both the spin state, which is controlled by the differences between four N donors in porphyrin versus those in imidazoles, and the degree of solvent exposure of the active sites play important roles in the fate of the (SCH(3))(L)Fe(III)-OOH intermediate, leading to O-O cleavage in one situation (P450) and hydrogen peroxide production in the other (SOR).

SYNERGY BETWEEN THEORY AND EXPERIMENT AS APPLIED TO H/D EXCHANGE ACTIVITY ASSAYS IN [Fe]H2ase ACTIVE SITE MODELS

Publisher Summary This chapter discusses synergy between theory and experiment as applied to H/D exchange activity assays in [Fe] H2ase active site models. The growing importance of computational chemistry in mechanistic inorganic chemistry may be ascribed to the broad accessibility and application of density functional theory and related techniques to large molecules, in this case a diiron complex with 10 to 12 coordination sites filled with diatomic or larger ligands. Hydrogenases are biological catalysts responsible for H 2 uptake or production in which the required H 2 cleavage is established to occur in a reversible and heterolytic manner (H + /H – ). This activity is typically assayed by H/D exchange reactivity in H 2 /D 2 O or H 2 /D 2 / H 2 O mixtures. The observation of inhibition of the H/D exchange reaction by CO and CH 3 CN implicates coordinatively unsaturated intermediates in the H 2 capture process. New experiments are also carried out to test the hypotheses implied by some of the individual steps of the proposed mechanism, which are calculated to be energetically feasible.