Unraveling the role of water in the stereoselective step of aqueous proline-catalyzed aldol reactions.

A multiscale computational study was performed with the aim of tracing the source of stereoselectivity and disclosing the role of water in the stereoselective step of propionaldehyde aldol self-condensation catalyzed by proline amide in water, a reaction that serves as a model for aqueous organocatalytic aldol condensations. Solvent mixing and hydration behavior were assessed by classical molecular dynamics simulations, which show that the reaction between propanal and the corresponding enamine takes place in a fully hydrated environment. First-principles molecular dynamics simulations were used to study the free-energy profile of four possible reaction paths, each of which yields a different stereoisomer, and high-level static first-principles calculations were employed to characterize the transition states for microsolvated species. The first solvation shell of the oxygen atom of the electrophilic aldehyde at the transition states contains two water molecules, each of which donates one hydrogen bond to the nascent alkoxide and thereby largely stabilizes its excess electron density. The stereoselectivity originates in an extra hydrogen bond donated by the amido group of proline amide in two reaction paths.

Insights on the photomagnetism in copper octacyanomolybdates.

High level ab initio calculations on the photoinduced high-spin molecule [Mo(CN)(2)(CN-Cu(tris(2-aminoethyl)amine)(6)](8+) are reported. The calculations indicate that the mechanism of the photoinduced transformation from a paramagnetic to a ferromagnetic state involves a local Mo d-d transition followed by the deformation of the coordination sphere from dodecahedron to square antiprism. Subsequently, Mo loses a ligand and becomes seven coordinated in a pentagonal bipyramid coordination. The resulting Mo(IV)(S = 1) ion interacts ferromagnetically with the five remaining Cu(II) ions through the cyanide bridges. The estimated coupling is about +50 K and the resulting magnetic susceptibility curve resembles the experimental one taking into account that part of the sample is magnetically deactivated during the measurement. The calculated potential energy profile along the linear interpolated reaction coordinate shows a small barrier for the reverse reaction in agreement with the thermal reversibility of the photoinduced state. Moreover, we find that the reverse reaction can be induced by light.

On the mechanism of the photoinduced magnetism in copper octacyanomolybdates.

Ab initio calculations show that a possible mechanism for the photomagnetism in copper octacyanomolybdate compounds consists of the initial excitation of the diamagnetic Cu(II)-Mo(IV-CS) pair to a Cu(II)-Mo(IV-T) state, whose geometry relaxation stabilizes the magnetic doublet and quartet states.

First half-reaction mechanism of nitric oxide synthase: the role of proton and oxygen coupled electron transfer in the reaction by quantum mechanics/molecular mechanics.

The first half-reaction of nitric oxide synthase (NOS) is investigated by means of quantum mechanical/molecular mechanical (QM/MM) calculations. An energetically feasible arginine hydroxylation path was found only when the iron-oxy complex accepted one proton from an external source. The so formed species has not been considered in heme chemistry; it is described as Por(+*)Fe(III)-OOH and is characterized by the same molecular constituency as the more known ferric-hydroperoxide species, compound 0, but has a cation-radical porphyrin moiety. The reaction itself is found to involve proton coupled electron transfer (PCET) and oxygen coupled electron transfer (OCET) steps en route to the formation of compound I and the ultimate monooxygenation of arginine. The cofactor H(4)B turns out to be a key player in the mechanism acting alternatively as an electron donor (when neutral) and an electron sink (when in its radical-cation state) and, thereby, providing the electron transfer component in the various coupled proton and oxygen transfer steps (see Scheme 4 ). The various pieces of this mechanism account for many of the experimental observations, such as the following: (a) the origins of the second proton supplied to the heme, (b) the elusiveness of compound I, (c) the inactivity of peroxide-shunt pathways in NOS first half-reaction, (d) the inhibition of the H(4)B analogue 4-amino-H(4)B due to protonation at the N3 position, (e) the roles of Trp188 (iNOS numbering) and the crystal water at the active site (W115), and so on. Alternative mechanistic hypotheses are tested and excluded, and a new mechanism for the NOS second half-reaction is proposed.

Compound I in heme thiolate enzymes: a comparative QM/MM study.

This study directly compares the active species of heme enzymes, so-called Compound I (Cpd I), across the heme-thiolate enzyme family. Thus, sixty-four different Cpd I structures are calculated by hybrid quantum mechanical/molecular mechanical (QM/MM) methods using four different cysteine-ligated heme enzymes (P450(cam), the mutant P450(cam)-L358P, CPO and NOS) with varying QM region sizes in two multiplicities each. The overall result is that these Cpd I species are similar to each other with regard to many characteristic features. Hence, using the more stable CPO Cpd I as a model for P450 Cpd I in experiments should be a reasonable approach. However, systematic differences were also observed, and it is shown that NOS stands out in most comparisons. By analyzing the electrical field generated by the enzyme on the QM region, one can see that (a) the protein exerts a large influence and modifies all the Cpd I species compared with the gas-phase situation and (b) in NOS this field is approximately planar to the heme plane, whereas it is approximately perpendicular in the other enzymes, explaining the deviating results on NOS. The calculations on the P450(cam) mutant L358P show that the effects of removing the hydrogen bond between the heme sulfur and L358 are small at the Cpd I stage. Finally, Mossbauer parameters are calculated for the different Cpd I species, enabling future comparisons with experiments. These results are discussed in the broader context of recent findings of Cpd I species that exhibit large variations in the electronic structure due to the presence of the substrate.

Effect of external electric fields on the C-H bond activation reactivity of nonheme iron-oxo reagents.

The effect of external electric fields (EFs) on the reactivity of nonheme iron(IV)-oxo species toward alkanes is investigated computationally using density functional theory. It is shown that an external EF changes the energy landscape of the process and thereby impacts the mechanisms, rates, and selectivities of the reactions, in a manner dependent on the nature of the iron(IV)-oxo/alkane pair. When the iron-oxo species is a good electron acceptor, like N4PyFeO2+, and the alkane is a good electron donor, like toluene, the application of the EF changes the mechanism from hydrogen abstraction to electron transfer. With cyclohexane, which is a poorer electron donor than toluene, the EF promotes hydride transfer and generates a carbocation. However, in the reaction between a poorer electron acceptor TMC(SR)FeO+ and cyclohexane, the EF preserves the hydrogen abstraction/rebound mechanism but improves its features by lowering the barriers for both the C-H activation and rebound steps; larger effects were observed for the quintet-state reaction. In all cases, the EF effect obeys a selection rule; the largest effects are observed when the EF vector is aligned with the Fe=O axis (z) and directed along the molecular dipole. As such, an EF aligned in the direction of the electron flow from substrate to the iron-oxo center lowers the reaction barrier and affects both the reactivity and selectivity of the molecular catalysts.

Ferromagnetic interaction in an asymmetric end-to-end azido double-bridged copper(II) dinuclear complex: a combined structure, magnetic, polarized neutron diffraction and theoretical study.

A new end-to-end azido double-bridged copper(II) complex [Cu(2)L(2)(N(3))2] (1) was synthesized and characterized (L=1,1,1-trifluoro-7-(dimethylamino)-4-methyl-5-aza-3-hepten-2-onato). Despite the rather long Cu-Cu distance (5.105(1) A), the magnetic interaction is ferromagnetic with J= +16 cm(-1) (H=-JS(1)S(2)), a value that has been confirmed by DFT and high-level correlated ab initio calculations. The spin distribution was studied by using the results from polarized neutron diffraction. This is the first such study on an end-to-end system. The experimental spin density was found to be localized mainly on the copper(II) ions, with a small degree of delocalization on the ligand (L) and terminal azido nitrogens. There was zero delocalization on the central nitrogen, in agreement with DFT calculations. Such a picture corresponds to an important contribution of the d(x2-y2) orbital and a small population of the d(z2) orbital, in agreement with our calculations. Based on a correlated wavefunction analysis, the ferromagnetic behavior results from a dominant double spin polarization contribution and vanishingly small ionic forms.