Theoretical insights into heme-catalyzed oxidation of cyclohexane to adipic acid.

Adipic acid is a key compound in the chemical industry, where it is mainly used in the production of polymers. The conventional process of its generation requires vast amounts of energy and, moreover, produces environmentally deleterious substances. Thus, there is interest in alternative ways to gain adequate amounts of adipic acid. Experimental reports on a one-pot iron-catalyzed conversion of cyclohexane to adipic acid motivated a theoretical investigation based on density functional theory calculations. The process investigated is interesting because it requires less energy than contemporary methods and does not produce environmentally harmful side products. The aim of the present contribution is to gain insight into the mechanism of the iron-catalyzed cyclohexane conversion to provide a basis for the further development of this process. The rate-limiting step of the process is discussed, but considering the accuracy of the calculations, it is difficult to ensure whether the rate-limiting step is in the substrate oxidation or in the generation of the catalytically active species. It is shown that the slowest step in the substrate oxidation is the conversion of cyclohexanol to cyclohexane-1,2-diol. Hydrogen-atom transfer from one of the OH groups of cyclohexane-1,2-diol makes the intradiol cleavage occur spontaneously.

Mechanism of selective halogenation by SyrB2: a computational study.

The mechanism of the chlorination reaction of SyrB2, a representative α-ketoglutarate dependent halogenase, was studied with computational methods. First, a macromolecular model of the Michaelis complex was constructed using molecular docking procedures. Based on this structure, a smaller model comprising the first- and some of the second-shell residues of iron and a model substrate was constructed and used in DFT investigations on the reaction mechanism. Computed relative energies and Mössbauer isomer shifts as well as quadrupole splittings indicate that the two oxoferryl species observed experimentally are two stereoisomers resulting from an exchange of the coordination sites occupied by the oxo and chloro ligands. In principle both Fe(IV)═O species are reactive and decay to Fe(III)Cl (OH)/carbon radical intermediates via C-H bond cleavage. In the final rebound step, which is very fast and thus precluding equilibration between the two forms of the radical intermediate, the ligand (oxo or chloro) placed closest to the carbon radical (trans to His235) is transferred to the carbon. For the native substrate (L-Thr) the lowest barrier for C-H cleavage was found for an isomer of the oxoferryl species favoring chlorination in the rebound step. CASPT2 calculations for the spin state splittings in the oxoferryl species support the conclusion that once the Fe(IV)═O intermediate is formed, the reaction proceeds on the quintet potential energy surface.

DFT study on the catalytic reactivity of a functional model complex for intradiol-cleaving dioxygenases.

The enzymatic ring cleavage of catechol derivatives is catalyzed by two groups of dioxygenases: extradiol- and intradiol-cleaving dioxygenases. Although having different oxidation state of their nonheme iron sites and different ligand coordinations, both groups of enzymes involve a common peroxy intermediate in their catalytic cycles. The factors that lead to either extradiol cleavage resulting in 2-hydroxymuconaldehyde or intradiol cleavage resulting in muconic acid are not fully understood. Well-characterized model compounds that mimic the functionality of these enzymes offer a basis for direct comparison to theoretical results. In this study the mechanism of a biomimetic iron complex is investigated with density functional theory (DFT). This complex catalyzes the ring opening of catecholate with exclusive formation of the intradiol cleaved product. Several spin states are possible for the transition metal system, with the quartet state found to be of main importance during the reaction course. The mechanism investigated provides an explanation for the observed selectivity of the complex. First, a bridging peroxide is formed, which decomposes to an alkoxy radical by O-O homolysis. In contrast to the subsequent barrier-free intradiol C-C bond cleavage, the extradiol pathway proceeds via the formation of an epoxide, which requires an additional activation barrier.

Observed enhancement of the reactivity of a biomimetic diiron complex by the addition of water - mechanistic insights from theoretical modeling.

The biomimetic diiron complex [Fe(III)Fe(IV)(mu-O)(2)(5-Me(3)-TPA)(2)](ClO(4))(3) (TPA = tris(2-pyridylmethyl)amine) has been found to be capable of oxidizing 9,10-dihydroanthracene in a solution of acetonitrile. Addition of water up to 1 M makes the reaction 200 times faster, suggesting that the water molecule in some way activates the catalyst for more efficient substrate oxidation. It is proposed that the enhanced reactivity results from the coordination of a water molecule to the iron(III) half of the complex, converting the bis-mu-oxo structure of the diiron complex to a ring-opened form where one of the bridging oxo groups is transformed into a terminal oxo group on iron(IV). The suggested mechanism is supported by DFT (B3LYP) calculations and transition state theory. Two different computational models of the diiron complex are used to model the hydroxylation of cyclohexane to cyclohexanol. Model has a bis-mu-oxo diiron core (diamond core) while model represents the "open core" analogue with one bridging mu-oxo group, a terminal oxo ligand on iron(IV), and a water molecule coordinated to iron(III). The computational results clearly suggest that the terminal oxo group is more reactive than the bridging oxo group. The free energy of activation is 7.0 kcal mol(-1) lower for the rate limiting step when the oxidant has a terminal oxo group than when both oxo groups are bridging the irons.

Theoretical investigation on the oxidative chlorination performed by a biomimetic non-heme iron catalyst.

The present study is a part of an effort to understand the mechanism of the oxidative chlorination, as performed by a biomimetic non-heme iron complex. This catalytically active complex is generated from a peroxide and [(TPA)Fe(III)Cl(2)]+ [TPA is tris(2-pyridylmethyl)amine]. The reaction catalyzed by [(TPA)FeCl(2)]+/ROOH involves either [(TPA)ClFe(V)=O](2+) or [(TPA)ClFe(IV)=O]+ as an intermediate. On the basis of density functional theory the reaction of these two possible catalysts with cyclohexane is investigated. A question addressed is how the competing hydroxylation of the substrate is avoided. It is demonstrated that the high-valent iron complex [(TPA)Cl-Fe(V)=O](2+) is capable of stereospecific alkane chlorination, based on an ionic rather than on a radical pathway. In contrast, the results found for [(TPA)ClFe(IV)=O]+ cannot explain the experimental findings. In this case the transition states for chlorination and hydroxylation are energetically too close. The exclusive chlorination of the substrate by Cl-Fe(IV)=O may be explained by an indirect or a direct effect, altering the position of the competing rebound barriers.

Cooperative effects in the activation of molecular oxygen by anionic silver clusters.

A novel size dependence in the adsorption reaction of multiple O2 molecules onto anionic silver clusters Agn- (n = 1-5) is revealed by gas-phase reaction studies in an rf-ion trap. Ab initio theoretical modeling based on DFT method provides insight into the reaction mechanism and finds cooperative electronic and structural effects to be responsible for the size selective reactivity of Agn- clusters toward one or more O2. In particular, Agn- clusters with odd n have paired electrons and therefore bind one O2 only weakly, but they are simultaneously activated to adsorb a strongly bound second oxygen molecule. For the clusters Ag3O4- and Ag5O4-, this cooperative effect results in a superoxo-like, doubly bound O2 subunit with potentially high activity in catalytic silver cluster oxidation processes.