Lignin Biodegradation by a Cytochrome P450 Enzyme: A Computational Study into Syringol Activation by GcoA

A recently characterized cytochrome P450 isozyme GcoA activates lignin components through a selective O-demethylation or alternatively an acetal formation reaction. These are important reactions in biotechnology and, because lignin is readily available; it being the main component in plant cell walls. In this work we present a density functional theory study on a large active site model of GcoA to investigate syringol activation by an iron(IV)-oxo heme cation radical oxidant (Compound I) leading to hemiacetal and acetal products. Several substrate-binding positions were tested and full energy landscapes calculated. The study shows that substrate positioning determines the product distributions. Thus, with the phenol group pointing away from the heme, an O-demethylation is predicted, whereas an initial hydrogen-atom abstraction of the weak phenolic O-H group would trigger a pathway leading to ring-closure to form acetal products. Predictions on how to engineer P450 GcoA to get more selective product distributions are given.     

Comparison of Multivariate Matching Methods: Structures,Distances, and Algorithms

Abstract

A comparison and evaluation is made of recent proposals for multivariate matched sampling in observational studies, where the following three questions are answered: (1) Algorithms: In current statistical practice, matched samples are formed using “nearest available” matching, a greedy algorithm. Greedy matching does not minimize the total distance within matched pairs, though good algorithms exist for optimal matching that do minimize the total distance. How much better is optimal matching than greedy matching? We find that optimal matching is sometimes noticeably better than greedy matching in the sense of producing closely matched pairs, sometimes only marginally better, but it is no better than greedy matching in the sense of producing balanced matched samples. (2) Structures: In common practice, treated units are matched to one control, called pair matching or 1–1 matching, or treated units are matched to two controls, called 1–2 matching, and so on. It is known, however, that the optimal structure is a full matching in which a treated unit may have one or more controls or a control may have one or more treated units. Optimal 1 — k matching is compared to optimal full matching, finding that optimal full matching is often much better. (3) Distances: Matching involves defining a distance between covariate vectors, and several such distances exist. Three recent proposals are compared. Practical advice is summarized in a final section.     

Favorski Type Rearrangement in the Lead Tetraacetate Oxidation of Cycloalkanones

The cycloalkanones (1a-lf) have been converted into their corresponding cycloalkane carboxylates (2a-2f) by a lead (IV) acetate promoted rearrangement in presence of perchloric acid in triethyl orthoformate.     

Crystal structures of functional building blocks derived from bis(benzo[b]thiophen‐2‐yl)methane

The syntheses of three bis(benzo[b]thiophen‐2‐yl)methane derivatives, namely bis(benzo[b]thiophen‐2‐yl)methanone, C₁₇H₁₀OS₂, (I), 1,1‐bis(benzo[b]thiophen‐2‐yl)‐3‐(trimethylsilyl)prop‐2‐yn‐1‐ol, C₂₂H₂₀OS₂Si, (II), and 1,1‐bis(benzo[b]thiophen‐2‐yl)prop‐2‐yn‐1‐ol, C₁₉H₁₂OS₂, (III), are described and their crystal structures discussed comparatively. The conformation of ketone (I) and the respective analogues are rather similar for most of the compounds compared. This is true for the interplanar angles, the C_aryl—C_bridge—C_aryl angles and the dihedral angles. The best resemblance is found for a bioisotere of (I), viz. 2,2′‐dinaphthyl ketone, (VII). By way of interest, the crystal packings also reveal similarities between (I) and (VII). In (I), the edge‐to‐face interactions seen between two napthyl residues in (VII) are substituted by S…π contacts between the benzo[b]thiophen‐2‐yl units in (I). In the structures of the bis(benzo[b]thiophen‐2‐yl)methanols, i.e. (II) and (III), the interplanar angles are also quite similar compared with analogues and related active pharmaceutical ingredients (APIs) containing the dithiophen‐2‐ylmethane scaffold, though the dihedral angles show a larger variability and produce unsymmetrical molecules.     

Noetherianity of some degree two twisted commutative algebras

The resolutions of determinantal ideals exhibit a remarkable stability property: for fixed rank but growing dimension, the terms of the resolution stabilize (in an appropriate sense). One may wonder if other sequences of ideals or modules over coordinate rings of matrices exhibit similar behavior. We show that this is indeed the case. In fact, our main theorem is more fundamental in nature: It states that certain large algebraic structures (which are examples of twisted commutative algebras) are noetherian. These are important new examples of large noetherian algebraic structures, and ones that are in some ways quite different from previous examples.     

A lattice Boltzmann model for diffusion of binary gas mixtures that includes diffusion slip

This paper describes the development of a lattice Boltzmann (LB) model for a binary gas mixture, and applications to channel flow driven by a density gradient with diffusion slip occurring at the wall. LB methods for single component gases typically use a non‐physical equation of state in which the relationship between pressure and density varies according to the scaling used. This is fundamentally unsuitable for extension to multi‐component systems containing gases of differing molecular masses. Substantial variations in the species densities and pressures may exist even at low Mach numbers; hence, the usual linearized equation of state for small fluctuations is unsuitable. Also, existing methods for implementing boundary conditions do not extend easily to novel boundary conditions, such as diffusion slip. The new model developed for multi‐component gases avoids the pitfalls of some other LB models. A single computational grid is shared by all the species, and the diffusivity is independent of the viscosity. The Navier–Stokes equation for the mixture and the Stefan–Maxwell diffusion equation are both recovered by the model. Diffusion slip, the non‐zero velocity of a gas mixture at a wall parallel to a concentration gradient, is successfully modelled and validated against a simple one‐dimensional model for channel flow. To increase the accuracy of the scheme, a second‐order numerical implementation is needed. This may be achieved using a variable transformation method that does not increase the computational time. Simulations were carried out on hydrogen and water diffusion through a narrow channel for varying total pressure and concentration gradients. Copyright © 2011 John Wiley & Sons, Ltd.