The importance of protonation and tautomerization in relative binding affinity prediction: a comparison of AMBER TI and Schrödinger FEP

In drug discovery, protonation states and tautomerization are easily overlooked. Through a Merck–Rutgers collaboration, this paper re-examined the initial settings and preparations for the Thermodynamic Integration (TI) calculation in AMBER Free-Energy Workflows, demonstrating the value of careful consideration of ligand protonation and tautomer state. Finally, promising results comparing AMBER TI and Schrödinger FEP+ are shown that should encourage others to explore the value of TI in routine Structure-based Drug Design.     

Hydrostatic Pressure Studies Distinguish Global from Local Protein Motions in C−H Activation by Soybean Lipoxygenase‐1

The proposed contributions of distinct classes of local versus global protein motions during enzymatic bond making/breaking processes has been difficult to verify. We employed soybean lipoxygenase‐1 as a model system to investigate the impact of high pressure at variable temperatures on the hydrogen‐tunneling properties of the wild‐type protein and three single‐site mutants. For all variants, pressure dramatically elevates the enthalpies of activation for the C−H activation. In contrast, the primary kinetic isotope effects (KIEs) for C−H activation and their corresponding temperature dependencies remain unchanged up to ca. 700 bar. The differential impact of elevated hydrostatic pressure on the temperature dependencies of rate constants versus substrate KIEs provides direct evidence for two distinct classes of protein motions: local, isotope‐dependent donor–acceptor distance‐sampling modes, and a more global, isotope‐independent search for productive protein conformational sub‐states.     

Enantioselective Total Synthesis of (+)‐Steenkrotin A and Determination of Its Absolute Configuration

The first enantioselective total synthesis of (+)‐steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh‐catalyzed O?H bond insertion followed by an intramolecular carbonyl‐ene reaction, two sequential SmI₂‐mediated Ueno–Stork and ketyl–olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro‐aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)‐steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis.     

The Synthesis of 1-Phenoxy-3- Arylseleno-2-Propanol

A general and efficient synthetic method of 1-phenoxy-3-arylseleno-2-propanol by reducing diary1 diselenides with sodium borohydride in basic environment and their reaction with epoxypropoxyphenols are described.     

Design and characterization of guided mode resonance filters with the improved structure for facile fabrication

In this study, a guided mode resonance filter with the improved structure for facile fabrication is designed; the properties of the designed filters are simulated by rigorous coupled wave analysis. It is found that the resonance wavelength and spectral linewidth are slightly increased with the increasing of the grating thickness, and seldom changed with the thickness of the grating filling factor, as the parameter error of the grating thickness and the grating filling factor are deviated from the designed value by ±10%, respectively, which are very favorable for simplifying preparation process of the GMR filter.     

Novel Synthetic Approach Toward C‐Substituted Piperazine Derivatives via C‐N Bonds Formation of α‐Bromoarylethanones and Ethanolamine

A new method for the synthesis of novel C‐substituted piperazine derivatives bearing aryl substituents on 2,6‐C positions has been developed by one‐pot three‐component sequential reaction of α‐bromoarylethanones with ethanolamine in the presence of formic acid. The structure of the novel compounds was established by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. In addition, the crystal structure of 4e was determined by single X‐ray crystallography and a possible reaction mechanism was proposed.     

Analysis of total nitrogen and total phosphorus in soil using laser-induced breakdown spectroscopy

Laser-induced breakdown spectroscopy(LIBS) is used to determine the total nitrogen(TN) and total phosphorus(TP) in soil.Quantitative determinations are conducted using the line intensity of the analyte element and element concentration.Calibration models are obtained using ten samples for TN and seven samples for TP.The rest samples are used to validate the results.Strong linear correlations are obtained from the determined TN and TP concentrations.LIBS is a powerful tool for analyzing soil samples to determine nutrient elements by selecting calibration and validation samples with similar matrix composition.     

Template/surfactant free and UV light irradiation assisted fabrication of Mn-Co oxides composite nanorings: Structure and synthesis mechanism

A facile, green, cost effective, and template or surfactant free strategy via a two-step route i.e. UV irradiation followed by dissolution-growth for the controlled synthesis of Mn-Co composite nanorings at room temperature was proposed. The nanorings structures and the process were systematically studied via TEM, HRTEM, EDX and XRD. Bir-MnO_2 nanosheets first formed through the direct photolysis of KMnO_4 under UV light irradiation. This was followed by a dissolution-growth process via the dissolution of Bir-MnO_2 nanosheets by the generated H~+ from the redox reaction between the added Co(NO_3)_2 and residual KMnO_4, as well as the accompanied formation of CoOOH, and Mn-Co composite nanorings. It was found that a balance between the dissolution and growth rate was needed. Suitable pH, KMnO_4 presence and the starting nanosheets like Bir-MnO_2 were the key factors for the formation of nanorings. The obtained Mn-Co nanorings/TiO_2 showed enhanced efficiency for the catalytic oxidation of HCHO. Based on the above understandings, it is believed that the developed dissolution-growth method can be adopted for the designing and preparation of other Mn-Co composite nanostructures which can be further applied for environmental pollution remediation.