STEREOCHEMICAL PROPERTIES OF THE 1-CHLORO-1- PHENYL-2,5-DIMETHYL-2-PHOSPHOLENIUM ION AND DERIVED OXIDE AND PHOSPHINE

Abstract

The cycloaddition of phenylphosphonous dichloride and trans, trans-2,4-hexadiene, or the addition of chlorine to trans-1-phenyl-cis-2,5-dimethyl-3-phospholene, gave 1-chloro-1-phenyl-2,5-dimethyl-2-phospholenium chloride. This compound shows no evidence in its ³¹P and ¹H nmr spectra for the existence of cis, trans isomers, yet on hydrolysis or dehalogenation with magnesium the resulting oxide and phosphine, respectively, are seen to be isomer mixtures. This phenomenon is explained by a rapid equilibration of the cis, trans form of the I-chloro ion through a pentacovalent species. Structures of the oxides and phosphines were assigned by ¹H and ¹³C nmr relations. The 1-phenyl-cis-2,5-dimethyl-3-phospholenium ion and related compounds were also characterized.     

Self-assembly and aggregation of ATRP prepared amphiphilic BAB tri-block copolymers contained nonionic ethylene glycol and fluorescent 9,10-di(1-naphthalenyl)-2-vinyl-anthracene/1-vinyl-pyrene segments

Two novel amphiphilic BAB-type block copolymers, ADN-PEG3400-ADN and Py-PEG3400-Py containing deep blue and bluish-green fluorescent moieties were prepared using atom transfer radical polymerization (ATRP) (where, ADN = poly(9,10-di(1-naphthalenyl)-2-vinylanthracene), Py = poly(1-vinyl pyrene) and PEG3400 = poly(ethylene glycol) with M_n = 3400 g/mol). The GPC number averaged molecular weights (MW) of the block copolymers were M_n = 9600 and 13,800 g/mol, respectively, based on polystyrene MW standards. The PEG3400 segment has a melting temperature (T_m peak) at 64–65 °C, whereas the glass transition temperatures (T_g midpoint) of the ADN and Py segments were found to be 230 °C and 193 °C, respectively, and are similar to their respective homopolymers indicating complete microphase segregration. The photoluminescence (PL) emission of the copolymers ADN-PEG3400-ADN exhibited two maxima at 423.5 nm and 441.5 nm while Py-PEG3400-Py has a maximum at 488.5 nm. Both copolymers form individual spherical micelles with diameter from 30 to 90 nm for Py-PEG3400-Py and 40–160 nm for ADN-PEG3400-ADN. The micelles, however, transform into cross-linked pearl-necklace-like aggregates at polymer concentrations above 1000 ppm, which may be attributed to the physical cross-linking between adjacent spherical micelles caused by the PEG3400 segments.     

Natural bond orbital analysis in the ONETEP code: Applications to large protein systems

First principles electronic structure calculations are typically performed in terms of molecular orbitals (or bands), providing a straightforward theoretical avenue for approximations of increasing sophistication, but do not usually provide any qualitative chemical information about the system. We can derive such information via post‐processing using natural bond orbital (NBO) analysis, which produces a chemical picture of bonding in terms of localized Lewis‐type bond and lone pair orbitals that we can use to understand molecular structure and interactions. We present NBO analysis of large‐scale calculations with the ONETEP linear‐scaling density functional theory package, which we have interfaced with the NBO 5 analysis program. In ONETEP calculations involving thousands of atoms, one is typically interested in particular regions of a nanosystem whilst accounting for long‐range electronic effects from the entire system. We show that by transforming the Non‐orthogonal Generalized Wannier Functions of ONETEP to natural atomic orbitals, NBO analysis can be performed within a localized region in such a way that ensures the results are identical to an analysis on the full system. We demonstrate the capabilities of this approach by performing illustrative studies of large proteins—namely, investigating changes in charge transfer between the heme group of myoglobin and its ligands with increasing system size and between a protein and its explicit solvent, estimating the contribution of electronic delocalization to the stabilization of hydrogen bonds in the binding pocket of a drug‐receptor complex, and observing, in situ, the n → π* hyperconjugative interactions between carbonyl groups that stabilize protein backbones. © 2012 Wiley Periodicals, Inc.     

Structure‐Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA

The galactopeptide dendrimer GalAG2 ((β‐Gal‐OC₆H₄CO‐Lys‐Pro‐Leu)₄(Lys‐Phe‐Lys‐Ile)₂Lys‐His‐Ile‐NH₂) binds strongly to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as well as disperses already established ones. By starting with the crystal structure of the terminal tripeptide moiety GalA‐KPL in complex with LecA, a computational mutagenesis study was carried out on the galactotripeptide to optimize the peptide–lectin interactions. 25 mutants were experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal titration calorimetry, and 3 by X‐ray crystallography. Two of these tripeptides, GalA‐KPY (dissociation constant (K_D)=2.7 μM ) and GalA‐KRL (K_D=2.7 μM ), are among the most potent monovalent LecA ligands reported to date. Dendrimers based on these tripeptide ligands showed improved PA biofilm inhibition and dispersal compared to those of GalAG2 , particularly G2KPY ((β‐Gal‐OC₆H₄CO‐Lys‐Pro‐Tyr)₄(Lys‐Phe‐Lys‐Ile)₂Lys‐His‐Ile‐NH₂). The possibility to retain and even improve the biofilm inhibition in several analogues of GalAG2 suggests that it should be possible to fine‐tune this dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in addition to the biofilm inhibition through amino acid substitutions.     

Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense

This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated in vitro screen. Eight compounds exhibited selective activity against T. b. rhodesiense (IC₅₀<2.2 μm ) with no detectable side activity against T. cruzi and Leishmania infantum. Compound 20 showed low nanomolar potency against T. b. rhodesiense (IC₅₀=40 nm ) and no toxicity against MRC-5 and PMM cell lines and may be regarded as a new lead template for agents against T. b. rhodesiense. The isoindolone-based compounds have the potential to progress into lead optimization in view of their highly selective in vitro potency, absence of cytotoxicity and acceptable metabolic stability. However, the solubility of the compounds represents a limiting factor that should be addressed to improve the physicochemical properties that are required to proceed further in the development of in vivo-active derivatives.     

Health Impacts in a Changing Climate – An Overview

In the past decades the topic of climate change has been subjected to intense scientific scrutiny, and since the mid-1990’s it has become an increasingly political issue. Because of increased temperatures and more frequent and intense extreme weather events, the number of direct injuries and deaths will increase, along with infectious diseases, whether food, water or vector-borne; respiratory and cardiovascular diseases are expected to rise due to worsened air pollution and extreme heat. In a context of on-going environmental degradation, local food-producing systems, both marine and terrestrial, will be affected and the risk of malnutrition, especially in children, will increase. These impacts on health and livelihood are expected to be significant factors in the spread of regional social crises, potentially leading to forced migration, conflicts and increased poverty.     

Variable electron-phonon coupling in isolated metallic carbon nanotubes observed by Raman scattering

We report the existence of broad and weakly asymmetric features in the high-energy (G) Raman modes of freely suspended metallic carbon nanotubes of defined chiral index. A significant variation in peak width (from 12 cm(-1) to 110 cm(-1)) is observed as a function of the nanotube's chiral structure. When the nanotubes are electrostatically gated, the peak widths decrease. The broadness of the Raman features is understood as the consequence of coupling of the phonon to electron-hole pairs, the strength of which varies with the nanotube chiral index and the position of the Fermi energy.     

Improved Synthesis,Structure, and Solution Characterization of the Cyclic 48-Tungsto-8-Arsenate(V), [H4As8W48O184]36−

We report on an improved synthesis and structural characterization of the cyclic 48-tungsto–8-arsenate(V) [H₄As₈W₄₈O₁₈₄]^36? (1). The mixed lithium–potassium salt of this polyanion, K_26.5Li_9.5[H₄As₈W₄₈O₁₈₄]·90H₂O (KLi-1), has been studied in the solid state by IR, single-crystal X-ray diffraction, and elemental analysis, and in solution by ¹⁸³W NMR spectroscopy.