Water-Assisted Oxo Mechanism for Heme Metabolism

A mechanism of heme metabolism by heme oxygenase (HO) is discussed from B3LYP density functional theory calculations. The concerted OH group attack to the α-carbon by the iron−hydroperoxo species is investigated using a model with full protoporphyrin IX to confirm our previous conclusion that this species does not have sufficient oxidizing power for heme oxidation (J. Am. Chem. Soc. 2004, 126, 3672). Calculated activation energies and structures of the intermediates and transition state for this process remain unchanged from those for a small model with porphine in the previous study, which shows that the inclusion of the side chain of the porphyrin ring is not essential in describing the OH group transfer. The activation barrier for a direct oxo attack to the α-carbon by an iron−oxo model is calculated to be 49.8 kcal/mol, the barrier height of which looks very high for the enzymatic reaction under physiological conditions. This large activation energy is due to a highly bent porphyrin structure in the transition state. However, a bridging water molecule plays an important role in reducing the porphyrin distortion in the transition state, resulting in a remarkable decrease of the activation barrier to 13.9 kcal/mol. A whole-enzyme model with about 4000 atoms is constructed to elucidate functions of the protein environment in this enzymatic reaction using QM/MM calculations. The key water molecule is fixed in the protein environment to ensure the low-barrier and regioselective heme oxidation. A water-assisted oxo mechanism of heme oxidation by heme oxygenase is proposed from these calculational results

Photochemical Reversibility of Ring-Closing and Ring-Opening Reactions in Diarylperfluorocyclopentenes

Time dependent density functional theory (TDDFT) is used to study the important factors that control the photoisomerization of diarylperfluorocyclopentenes. The calculations are carried out for free molecules and for diarylperfluorocyclopentenes perturbed by gold atoms. Potential energy surfaces for the cyclization reaction are obtained for the ground state and for the excited states involved in the photoswitching. Analysis of the computed UV/vis spectra, the excitation energies, and the spatial distribution of the frontier orbitals of both unperturbed and perturbed molecules give an inside view of the ring opening and the ring closing. The bonding interaction in the unoccupied orbials is considered to be the driving force for the photochemical cyclization while the antibonding interaction significantly hinders the reaction. The obtained theoretical results are in good agreement with the experimental data and provide an explanation of the one-directional and bidirectional photoswitching of diarylperfluorocyclopentenes attached to gold surface

Comparison of the Reactivity of Bis(μ-oxo)Cu^IICu^III and Cu^IIICu^III Species to Methane

Methane hydroxylation at the dinuclear copper site of particulate methane monooxygenase (pMMO) is studied by using density functional theory (DFT) calculations. The electronic and structural properties of the dinuclear copper species of bis(μ-oxo)CuIICuIII and CuIIICuIII are discussed with respect to the C−H bond activation of methane. The bis(μ-oxo)CuIICuIII species is highly reactive and considered to be an active species for the conversion of methane to methanol by pMMO, whereas the bis(μ-oxo)CuIIICuIII species is unable to react with methane as it is. If a Cu−O bond of the bis(μ-oxo)CuIIICuIII species is cleaved, the resultant CuIIICuIII species, in which only one oxo ligand bridges the two copper ions, can activate methane. However, its energetics for methane hydroxylation is less favorable than that by the bis(μ-oxo)CuIICuIII species. The DFT calculations show that the bis(μ-oxo)CuIICuIII species is more effective for the activation of methane than the bis(μ-oxo)CuIIICuIII species. The reactive bis(μ-oxo)CuIICuIII species can be created either from the electron injection to the bis(μ-oxo)CuIIICuIII species or from the O−O bond cleavage in the μ-η1:η2-peroxoCuICuII species

Competition between Hydrogen Bonding and Dispersion Force in Water Adsorption and Epoxy Adhesion to Boron Nitride: From the Flat to the Curved

Hexagonal boron nitride (h-BN) is a material with excellent thermal conductivity and electrical insulation, used as an additive to various matrices. To increase the affinity of h-BN to them, hydrogen bonds should be formed at the interface. In reality, however, they are not formed; the N atoms are not capable of accepting hydrogen bonds due to the delocalization of their lone pair electrons over the B–N π bonds. To make it form hydrogen bonds, one may need to break the planarity of h-BN so that the orbital overlap in the B–N π bonds can be reduced. This idea is verified with first-principles calculations on the adsorption of a water molecule on hypothetical h-BN surfaces, the planarity of which is broken. One can do it in silico but not in vitro. BN nanotubes (BNNTs) are considered as a more realistic BN surface with nonplanarity. The hydrogen bond is shown to become stronger as the curvature of the tube increases. On the contrary, the strength of the dispersion force acting at the interface becomes weaker. In water adsorption, these two interactions are in competition with each other. However, in epoxy adhesion, the interaction due to dispersion forces is overwhelmingly stronger than that due to hydrogen bonding. The smaller the curvature of the surface, the smaller the distance between more atoms at the interface; thus, the interaction due to dispersion forces maximized

Conversion of Methane to Methanol at the Mononuclear and Dinuclear Copper Sites of Particulate Methane Monooxygenase (pMMO): A DFT and QM/MM Study

Methane hydroxylation at the mononuclear and dinuclear copper sites of pMMO is discussed using quantum mechanical and QM/MM calculations. Possible mechanisms are proposed with respect to the formation of reactive copper−oxo and how they activate methane. Dioxygen is incorporated into the CuI species to give a CuII−superoxo species, followed by an H-atom transfer from a tyrosine residue near the monocopper active site. A resultant CuII−hydroperoxo species is next transformed into a CuIII−oxo species and a water molecule by the abstraction of an H-atom from another tyrosine residue. This process is accessible in energy under physiological conditions. Dioxygen is also incorporated into the dicopper site to form a (μ-η2:η2-peroxo)dicopper species, which is then transformed into a bis(μ-oxo)dicopper species. The formation of this species is more favorable in energy than that of the monocopper−oxo species. The reactivity of the CuIII−oxo species is sufficient for the conversion of methane to methanol if it is formed in the protein environment. Since the σ* orbital localized in the Cu−O bond region is singly occupied in the triplet state, this orbital plays a role in the homolytic cleavage of a C−H bond of methane. The reactivity of the bis(μ-oxo)dicopper species is also sufficient for the conversion of methane to methanol. The mixed-valent bis(μ-oxo)CuIICuIII species is reactive to methane because the amplitude of the σ* singly occupied MO localized on the bridging oxo moieties plays an essential role in C−H activation

Adsorption Site Preference Determined by Triangular Topology: Application of the Method of Moments to Transition Metal Surfaces

The adsorption sites of the top and hollow on the close-packed surfaces of transition metals are well known. In this paper, which site is more preferred for the adsorption of atoms and molecular fragments on the metal surfaces is discussed based on the topology of the adsorption geometry. For this purpose, the method of moments for the electronic density of states is applied to the surface. Adsorption at the hollow site generates a triangular topology, leading to a more negative value of the third moment (μ3) than that at the top site, which generates no triangular topology. When the difference in energy between the two adsorption sites is plotted against the band filling of the metal surface, a characteristic node at around the intermediate band filling can be found. This is a signature that the energy difference curve is controlled by μ3. Roughly speaking, the hollow-site adsorption, which has a more negative μ3 value, takes precedence at low band fillings, while the top site adsorption, which has a less negative μ3 value, takes precedence at high band fillings. One can conclude that an adsorption structure with more three-membered rings on a surface is more stable at low electron counts whereas that with less three-membered rings is more stable at high electron counts. However, if the strength of the metal–adsorbate bond is significantly greater than that of the metal–metal bond, the effect of the second moment (μ2) on the energy difference curve cannot be neglected. The hollow-site adsorption leads to a larger value of μ2 due to the topological feature of a larger coordination number around the adsorbate atom. As a result, the hollow-site adsorption is preferred over the top site at any band filling

Enantioselective Alkylation by Binaphthyl Chiral Phase-Transfer Catalysts: A DFT-Based Conformational Analysis

A conformational search method based on the density functional theory (DFT) was successfully applied to explore a mechanism for the highly enantioselective alkylation by binaphthyl-modifed chiral phase-transfer catalysts. Key interactions that govern the enantioselectivity were analyzed. The computational results are encouraging for further application of the DFT-based conformational search toward the rational design of next-generation asymmetric phase transfer catalysts

Reaction Pathways for the Oxidation of Methanol to Formaldehyde by an Iron−Oxo Species

The reaction mechanism and energetics for the conversion of methanol to formaldehyde by an iron−oxo species, FeO+, is investigated. Three competitive reaction pathways for the catalytic reaction are analyzed from DFT computations at the B3LYP level of theory. In Path 1, the H atom of the OH group of methanol is first abstracted by the oxo group of FeO+ via a four-centered transition state (TS1-1) leading to the intermediate complex HO−Fe+−OCH3, and after that one of the H atoms of the OCH3 group is shifted to the OH ligand via a five-centered transition state (TS1-2) to form the final product complex H2O−Fe+−OCH2. In Path 2, one of the H atoms of the CH3 group of methanol is abstracted by the oxo group via a five-centered transition state (TS2-1) leading to the intermediate complex HO−Fe+−OHCH2, and then the H atom of the OHCH2 group is shifted to the OH ligand via a four-centered transition state (TS2-2) to give the product complex. Unlike Paths 1 and 2, which involve a hydrogen shift, the first step in Path 3 involves a methyl migration that takes place via a four-centered transition state (TS3-1) resulting in the formation of the intermediate complex HO−Fe+−OCH3 and the second half of Path 3 is identical to that of Path 1. From B3LYP computations, Path 1 and Path 2 are competitive in energy and Path 3 is unlikely from the energetic viewpoint. Kinetic isotope effects (kH/kD) for the electronic processes of TS1-1, TS2-1, and TS3-1 are computed and analyzed

Current Rectification through π–π Stacking in Multilayered Donor–Acceptor Cyclophanes

Extended π-stacked molecules have attracted much attention since they play an essential role in both electronic devices and biological systems. In this article electron transport properties of a series of multilayered cyclophanes with the hydroquinone donor and quinone acceptor units in the external positions are theoretically studied with applications to molecular rectifiers in mind. Calculations of electron transport through the π–π stacked structures in the multilayered cyclophanes are performed by using nonequilibrium Green’s function method combined with density functional theory. Calculated transmission spectra show that the conductance decreases exponentially with the length of the molecule with a decay factor of 0.75 Å^–1, which lies for the values between π-conjugated molecules and σ-bonded molecules. Applied bias calculations provide current–voltage curves, which exhibit good rectifying behavior. The rectification mechanism in the coherent transport regime is qualitatively explained by the response of the frontier orbital energy levels, especially LUMO levels, to the applied bias, where the rectifying direction is expected to be opposite to the Aviram–Ratner model. The maximum value of rectification ratio increases with an increase in the number of stacking layers due to the effective separation of the donor and acceptor parts, where effects from the opposite electrodes to the donor and acceptor are negligible. Multilayered donor–acceptor cyclophanes are suitable materials for investigating the relationship among electron transport properties, rectification properties, and molecular length (separation between the donor and acceptor parts)

Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations: Application to Enantioselective Organocatalysis

A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost