Comprehensive study of okaspirodiol: characterization, total synthesis, and biosynthesis of a new metabolite from Streptomyces

The new spiro[4.5]acetal okaspirodiol (4) was isolated from Streptomyces sp. G? TS 19 as a secondary metabolite in yields up to 380 mg/L. The structure of this cryptic ketotetrol was elucidated by different methods including X-ray analysis, and its equilibration under mildly acidic conditions furnishing three additional isomers was thoroughly studied. Although metabolite 4 is not the thermodynamically favored isomer, a high-yielding total synthesis was accomplished comprising a stereoselective spiroacetalization under equilibrium conditions. This approach benefits from the important influence of an intramolecular hydrogen bond on the stabilization of the spiro[4.5]acetal moiety. The biosynthesis of 4 was investigated by feeding experiments with 13C-labeled precursors proving its origin from a new type of the rare mixed acetate-glycerol biosynthetic pathway. All results are discussed on the basis of the structural diversity of spiroacetals in nature and their chemical properties.     

Probability density in the complex plane

The correspondence principle asserts that quantum mechanics resembles classical mechanics in the high-quantum-number limit. In the past few years, many papers have been published on the extension of both quantum mechanics and classical mechanics into the complex domain. However, the question of whether complex quantum mechanics resembles complex classical mechanics at high energy has not yet been studied. This paper introduces the concept of a local quantum probability density ρ(z) in the complex plane. It is shown that there exist infinitely many complex contours C of infinite length on which ρ(z) dz is real and positive. Furthermore, the probability integral is finite. Demonstrating the existence of such contours is the essential element in establishing the correspondence between complex quantum and classical mechanics. The mathematics needed to analyze these contours is subtle and involves the use of asymptotics beyond all orders.     

Computational prediction of metabolism: sites, products, SAR, P450 enzyme dynamics, and mechanisms

Metabolism of xenobiotics remains a central challenge for the discovery and development of drugs, cosmetics, nutritional supplements, and agrochemicals. Metabolic transformations are frequently related to the incidence of toxic effects that may result from the emergence of reactive species, the systemic accumulation of metabolites, or by induction of metabolic pathways. Experimental investigation of the metabolism of small organic molecules is particularly resource demanding; hence, computational methods are of considerable interest to complement experimental approaches. This review provides a broad overview of structure- and ligand-based computational methods for the prediction of xenobiotic metabolism. Current computational approaches to address xenobiotic metabolism are discussed from three major perspectives: (i) prediction of sites of metabolism (SOMs), (ii) elucidation of potential metabolites and their chemical structures, and (iii) prediction of direct and indirect effects of xenobiotics on metabolizing enzymes, where the focus is on the cytochrome P450 (CYP) superfamily of enzymes, the cardinal xenobiotics metabolizing enzymes. For each of these domains, a variety of approaches and their applications are systematically reviewed, including expert systems, data mining approaches, quantitative structure-activity relationships (QSARs), and machine learning-based methods, pharmacophore-based algorithms, shape-focused techniques, molecular interaction fields (MIFs), reactivity-focused techniques, protein-ligand docking, molecular dynamics (MD) simulations, and combinations of methods. Predictive metabolism is a developing area, and there is still enormous potential for improvement. However, it is clear that the combination of rapidly increasing amounts of available ligand- and structure-related experimental data (in particular, quantitative data) with novel and diverse simulation and modeling approaches is accelerating the development of effective tools for prediction of in vivo metabolism, which is reflected by the diverse and comprehensive data sources and methods for metabolism prediction reviewed here. This review attempts to survey the range and scope of computational methods applied to metabolism prediction and also to compare and contrast their applicability and performance.     

Largest 4-connected components of 3-connected planar triangulations

Let T_n be a 3-connected n-vertex planar triangulation chosen uniformly at random. Then the number of vertices in the largest 4-connected component of T_n is asymptotic to n/2 with probability tending to 1 as n → ∞. It follows that almost all 3-connected triangulations with n vertices have a cycle of length at least n/2 + o(n).     

Importance Sampling for Backward SDEs

In this article, we explain how the importance sampling technique can be generalized from simulating expectations to computing the initial value of backward stochastic differential equations (SDEs) with Lipschitz continuous driver. By means of a measure transformation we introduce a variance reduced version of the forward approximation scheme by Bender and Denk [4 Bender , C. , and Denk , R. 2007 . A forward scheme for backward SDEs . Stochastic Processes and their Applications 117 ( 12 ): 1793 – 1812 . [Google Scholar]] for simulating backward SDEs. A fully implementable algorithm using the least-squares Monte Carlo approach is developed and its convergence is proved. The success of the generalized importance sampling is illustrated by numerical examples in the context of Asian option pricing under different interest rates for borrowing and lending.     

Impact related changes in mineral properties: Ti-magnetite from basaltic rocks at Lonar crater, India

Samples from vesicular Lonar impactite have been investigated by Mössbauer spectroscopy and SEM in combination with elemental analysis. Observation reveal the new-formation of oxide minerals have occurred with nucleation in particular at the walls of the vesicles interpreted as having formed from condensation of the gas phase having caused the vesicles to form in the first place. Elemental analysis of Ti-magnetites gives very similar compositions irrespective of the oxides grains being vesicle or matrix associated (Fe/Ti ratios approximately 3). The room temperature spectra of the oxides show magnetically ordered components due to A, B, and C sites in the substituted spinel. The occurrence of these ordered components are not in accordance with expectations from the bulk chemical compositions, suggesting the presence of fine scaled intergrowth of Ti-oxide and Ti-magnetite.