Unusual neutral ligand coordination to arsenic and antimony trifluoride

The preparations and spectroscopic characterisation of the hydrolytically unstable As(III) complexes, [AsF(3)(OPR(3))(2)] (R = Me or Ph) and [AsF(3){Me(2)P(O)CH(2)P(O)Me(2)}] are described and represent the first examples of complexes of AsF(3) with neutral ligands. The crystal structure of [AsF(3){Me(2)P(O)CH(2)P(O)Me(2)}] contains dimers with bridging diphosphine dioxide, but there are also long contacts between the dimers to neighbouring phosphine oxide groups, completing a very distorted six-coordination at arsenic and producing a weakly associated polymer structure. The reaction of AsF(3) with OAsPh(3) affords Ph(3)AsF(2), and no arsine oxide complex was formed. Reaction of SbF(3) with OER(3) (R = Me or Ph, E = P or As), Me(2)P(O)CH(2)P(O)Me(2) and Ph(2)P(O)(CH(2))(n)P(O)Ph(2) (n = 1 or 2) in MeOH produces [SbF(3)(OER(3))(2)], [SbF(3){Me(2)P(O)CH(2)P(O)Me(2)}] and [SbF(3){Ph(2)P(O)(CH(2))(n)P(O)Ph(2)}] respectively. The X-ray structures reveal that the complexes contain square pyramidal SbF(3)O(2) cores with apical F and cis disposed pnictogen oxides. However, whilst [SbF(3)(OER(3))(2)] (R = Ph: E = P or As; R = Me: E = As) and [SbF(3){Ph(2)P(O)CH(2)P(O)Ph(2)}] are monomeric, [SbF(3){Me(2)P(O)CH(2)P(O)Me(2)}] is a dimer with bridging diphosphine dioxides producing a twelve-membered ring, and [SbF(3){Ph(2)P(O)(CH(2))(2)P(O)Ph(2)}] is a chain polymer with diphosphine dioxide bridges. In the OAsR(3) reactions with SbF(3), R(3)AsF(2) are also formed. Notably the Sb-O(P) bonds are shorter than As-O(P), despite the covalent radii (As < Sb), consistent with very weak coordination of the AsF(3). IR and multinuclear ((1)H, (19)F and (31)P) NMR data are reported and discussed. BiF(3) does not react with pnictogen oxide ligands under similar conditions and halide exchange of bismuth chloro complexes with Me(3)SnF gave BiF(3).     

‘Fixed charge’ chemical derivatization and data dependant multistage tandem mass spectrometry for mapping protein surface residue accessibility

Protein surface accessible residues play an important role in protein folding, protein-protein interactions and protein-ligand binding. However, a common problem associated with the use of selective chemical labeling methods for mapping protein solvent accessible residues is that when a complicated peptide mixture resulting from a large protein or protein complex is analyzed, the modified peptides may be difficult to identify and characterize amongst the largely unmodified peptide population (i.e., the ‘needle in a haystack’ problem). To address this challenge, we describe here the development of a strategy involving the synthesis and application of a novel ‘fixed charge’ sulfonium ion containing lysine-specific protein modification reagent, S,S′-dimethylthiobutanoylhydroxysuccinimide ester (DMBNHS), coupled with capillary HPLC-ESI-MS, automated CID-MS/MS, and data-dependant neutral loss mode MS³ in an ion trap mass spectrometer, to map the surface accessible lysine residues in a small model protein, cellular retinoic acid binding protein II (CRABP II). After reaction with different reagent:protein ratios and digestion with Glu-C, modified peptides are selectively identified and the number of modifications within each peptide are determined by CID-MS/MS, via the exclusive neutral loss(es) of dimethylsulfide, independently of the amino acid composition and precursor ion charge state (i.e., proton mobility) of the peptide. The observation of these characteristic neutral losses are then used to automatically ‘trigger’ the acquisition of an MS³ spectrum to allow the peptide sequence and the site(s) of modification to be characterized. Using this approach, the experimentally determined relative solvent accessibilities of the lysine residues were found to show good agreement with the known solution structure of CRABP II.     

Iodine-catalyzed cycloalkenylation of dihydroquinolines and arylamines through a reaction with cyclic ketones under neat conditions

An iodine-catalyzed direct cycloalkenylation of dihydroquinolines and arylamines has been developed. This method consists of a Friedel–Crafts reaction between dihydroquinolines (or arylamines) and cyclic ketones in which the double bond is selectively generated throughout the course of the reaction resulting in a direct cycloalkenylation, under neat conditions.     

Mass Spectral Analyses of Trimethylsilyl Glucuronic Acids

Mass spectral analysis of carbohydrates has become an important tool for the biological chemist^1–3 and the use of mass spectrometers interfaced with gas-liquid chromatographs has provided a convenient method of study for volatile derivatives of carbohydrates. Several groups^4–7 have accomplished separations of the various isomeric trimethylsilyl (TMSi) esters and ethers of the glucuronic acids. The present work utilizes a gas-liquid chromatograph-mass spectrometer to examine the previously unreported mass spectra of pertrimethylsilylated glucuronic acids and these spectra are compared to the previously reported⁸ spectra of the pemethylated glucuronic acids.     

Geographical influences of an emerging network of gang rivalries

We propose an agent-based model to simulate the creation of street gang rivalries. The movement dynamics of agents are coupled to an evolving network of gang rivalries, which is determined by previous interactions among agents in the system. Basic gang data, geographic information, and behavioral dynamics suggested by the criminology literature are integrated into the model. The major highways, rivers, and the locations of gangs’ centers of activity influence the agents’ motion. We use a policing division of the Los Angeles Police Department as a case study to test our model. We apply common metrics from graph theory to analyze our model, comparing networks produced by our simulations and an instance of a Geographical Threshold Graph to the existing network from the criminology literature.     

Halogenation of 2-Hydroxynicotinic Acid

A convenient method to prepare 5-halo-2-hydroxy-nicotinic acid is described.     

Stereoselective Remote Functionalization via Palladium-Catalyzed Redox-Relay Heck Methodologies

Exploration of novel, three-dimensional chemical space is of growing interest in the drug discovery community and with this comes the challenge for synthetic chemists to devise new stereoselective methods to introduce chirality in a rapid and efficient manner. This Minireview provides a timely summary of the development of palladium-catalyzed asymmetric redox-relay Heck-type processes. These reactions represent an important class of transformation for the selective introduction of remote stereocenters, and have risen to prominence over the past decade. Within this Minireview, the vast scope of these transformations will be showcased, alongside applications to pharmaceutically relevant chiral building blocks and drug substances. To complement this overview, a mechanistic summary and discussion of the current limitations of the transformation are presented, followed by an outlook on future areas of investigation.     

How well does molecular simulation reproduce environment-specific conformations of the intrinsically disordered peptides PLP,TP2 and ONEG?

Understanding the conformational ensembles of intrinsically disordered proteins and peptides (IDPs) in their various biological environments is essential for understanding their mechanisms and functional roles in the proteome, leading to a greater knowledge of, and potential treatments for, a broad range of diseases. To determine whether molecular simulation is able to generate accurate conformational ensembles of IDPs, we explore the structural landscape of the PLP peptide (an intrinsically disordered region of the proteolipid membrane protein) in aqueous and membrane-mimicking solvents, using replica exchange with solute scaling (REST2), and examine the ability of four force fields (ff14SB, ff14IDPSFF, CHARMM36 and CHARMM36m) to reproduce literature circular dichroism (CD) data. Results from variable temperature (VT) ¹H and Rotating frame Overhauser Effect SpectroscopY (ROESY) nuclear magnetic resonance (NMR) experiments are also presented and are consistent with the structural observations obtained from the simulations and CD. We also apply the optimum simulation protocol to TP2 and ONEG (a cell-penetrating peptide (CPP) and a negative control peptide, respectively) to gain insight into the structural differences that may account for the observed difference in their membrane-penetrating abilities. Of the tested force fields, we find that CHARMM36 and CHARMM36m are best suited to the study of IDPs, and accurately predict a disordered to helical conformational transition of the PLP peptide accompanying the change from aqueous to membrane-mimicking solvents. We also identify an α-helical structure of TP2 in the membrane-mimicking solvents and provide a discussion of the mechanistic implications of this observation with reference to the previous literature on the peptide. From these results, we recommend the use of CHARMM36m with the REST2 protocol for the study of environment-specific IDP conformations. We believe that the simulation protocol will allow the study of a broad range of IDPs that undergo conformational transitions in different biological environments.

A protocol for simulating intrinsically disordered peptides in aqueous and hydrophobic solvents is proposed. Results from four force fields are compared with experiment. CHARMM36m performs the best for the simulated IDPs in all environments.     

Ermakov systems,Noether's theorem and the Sarlet-Bahar method

We derive invariants for a nonlinear equation of motion containing arbitrary functions. The method employed is the recently discussed direct method of Sarlet and Bahar. The resulting invariants are a special case of Ermakov invariants. We compare these results to the results obtained by applying Noether's theorem to the same equation of motion.     

Permutation groups generated by cycles of fixed length

Combinatorial conditions on a set of cycles of fixed degree inS _n are studied, so that they generateA _n orS _n . It is shown thatA _n orS _n is so generated if and only if a graph associated with the set of cycles is connected, provided two of the cycles satisfy certain, not too restrictive, criteria. As a corollary, the minimum number of cycles of degreem ≧ 2 that generateA _n or S_n is determined.