Lead optimization mapper: automating free energy calculations for lead optimization

Alchemical free energy calculations hold increasing promise as an aid to drug discovery efforts. However, applications of these techniques in discovery projects have been relatively few, partly because of the difficulty of planning and setting up calculations. Here, we introduce lead optimization mapper, LOMAP, an automated algorithm to plan efficient relative free energy calculations between potential ligands within a substantial library of perhaps hundreds of compounds. In this approach, ligands are first grouped by structural similarity primarily based on the size of a (loosely defined) maximal common substructure, and then calculations are planned within and between sets of structurally related compounds. An emphasis is placed on ensuring that relative free energies can be obtained between any pair of compounds without combining the results of too many different relative free energy calculations (to avoid accumulation of error) and by providing some redundancy to allow for the possibility of error and consistency checking and provide some insight into when results can be expected to be unreliable. The algorithm is discussed in detail and a Python implementation, based on both Schrödinger’s and OpenEye’s APIs, has been made available freely under the BSD license.     

Engaging Copper(III) Corrole as an Electron Acceptor: Photoinduced Charge Separation in Zinc Porphyrin–Copper Corrole Donor–Acceptor Conjugates

An electron‐deficient copper(III) corrole was utilized for the construction of donor–acceptor conjugates with zinc(II) porphyrin (ZnP) as a singlet excited state electron donor, and the occurrence of photoinduced charge separation was demonstrated by using transient pump–probe spectroscopic techniques. In these conjugates, the number of copper corrole units was varied from 1 to 2 or 4 units while maintaining a single ZnP entity to observe the effect of corrole multiplicity in facilitating the charge‐separation process. The conjugates and control compounds were electrochemically and spectroelectrochemically characterized. Computational studies revealed ground state geometries of the compounds and the electron‐deficient nature of the copper(III) corrole. An energy level diagram was established to predict the photochemical events by using optical, emission, electrochemical, and computational data. The occurrence of charge separation from singlet excited zinc porphyrin and charge recombination to yield directly the ground state species were evident from the diagram. Femtosecond transient absorption spectroscopy studies provided spectral evidence of charge separation in the form of the zinc porphyrin radical cation and copper(II) corrole species as products. Rates of charge separation in the conjugates were found to be of the order of 10¹⁰ s^?1 and increased with increasing multiplicity of copper(III) corrole entities. The present study demonstrates the importance of copper(III) corrole as an electron acceptor in building model photosynthetic systems.     

Novel stilbene‐based Fischer base analog of leuco‐TAM – (2E,2′Z)‐{2‐(4‐(E)‐styrylphenyl)propane‐1,3‐diylidene}bis(1,3,3‐trimethylindoline) – derivatives: synthesis and structural consideration by 1D NMR and 2D NMR spectroscopy

We report the synthesis of a series of novel stilbene‐based (St) Fischer base analogs of leuco‐triarylmethane (LTAM) dyes by treating Fischer base with (E)‐4‐styrylbenzaldehyde derivatives. All St‐LTAM molecules examined herein are characterized by 1D and 2D NMR. They were found to exhibit ZE configuration and isomerize to their diastereomers EE and ZZ in 2–3 h. They exhibit type I behavior of diastereomeric isomerization. Copyright © 2015 John Wiley & Sons, Ltd.     

Irregular Shearlet Frames: Geometry and?Approximation Properties

Recently, shearlet systems were introduced as a means to derive efficient encoding methodologies for anisotropic features in 2-dimensional data with a unified treatment of the continuum and digital setting. However, only very few construction strategies for discrete shearlet systems are known so far.     

Successive ionic layer adsorption and reaction of ZnSe shells for ZnO nanowire-based dye-sensitized solar cells

Thin ZnSe layers were deposited on ZnO nanowires by a novel successive ionic layer adsorption and reaction technique in order to solve recombination problems in ZnO nanowire-based dye-sensitized solar cells (DSSCs). Cell efficiency increased from 0.1 to 1.3–1.4% with the deposition of a 9- to13-nm-thick ZnSe shell on ZnO nanowires due to a large increase in J_SC. The dramatic increase in J_SC and cell efficiency is due to the facilitation of electron transfer related to ambipolar diffusion by the formation of a type II band alignment and the suppression of recombination in the presence of the ZnSe shell.     

Impact of Milling on Rice Constituents (Oryza Sativa L.): A Metabolomic Approach

Milling is an influential factor that affects the nutritional components in rice. However, the alteration of rice constituents by milling has not been thoroughly examined. In this study, rice with various degrees of milling was analyzed by gas chromatography–mass spectrometry and high-performance liquid chromatography–mass spectrometry. Principal component analysis and partial least square-discriminant analysis were performed to characterize the nutritional components that have significant changes during milling. The concentrations of sugars and sugar alcohols decreased while the phospholipids increased in accordance with the milling degree. These results provide a contrast to the common idea that brown rice is nutritionally superior to white rice. In conclusion, the knowledge of nutritional alterations related to milling may benefit rice production and consumption.