Preparation and structure of fluorite-type (Sr,Y)Cl2.05

Anion excess colorless fluorite-type strontium-yttrium chloride has been prepared. Single crystals of the SrY compound exhibit a primitive cubic lattice with a = 6.967(1)Å. Two mutually exclusive structural models for solutions, neither of which is exact, are discussed. The first is a vacancy model in which the extra charge which results from substitution of Y³⁺ for Sr²⁺ is balanced by the simultaneous removal of a Sr²⁺Cl^? ion pair. This model requires individual ion sites to be partially occupied and nonequivalent and is strongly suggestive of vacancy ordering. Refinement in space group P1, with sites refined independenty, led to R = 0.1096. The second model describes the structure in terms of a Willis cluster of defects and includes both anion vacancies and interstitial anions. Full-matrix least squares refinement in space group Fm3m, with positions analogous to those in UO_2.12 and (Ca,Y)F_2.10, converged at R = 0.0633 for the 114 face-centered parent structure reflections whose |F|;² > σ(F²). This second model is discussed in relation to a probable true solution which involves longrange order.     

Effect of ionic strength on the self-assembly, morphology and gelation of pH responsive β-sheet tape-forming peptides

Molecular self-assembly is an intrinsic property of proteins central to their biological functionality. One important industrially interesting property is the ability to control and switch on and off self-assembly using a variety of external chemical and physical triggers. Model peptides have been developed with significantly reduced chemical and structural complexity compared to biological proteins. These are ideal systems for exposing the fundamental principles that drive protein-like self-assembly, as well as for establishing in a quantitative manner their structure-function relationship. We investigate simple, short model peptides that adopt a purely β-strand conformation, align in an antiparallel manner and self-assemble in one dimension in solution into long β-sheet nanotapes and higher order aggregates with no other conformation (i.e., helices, turns or random coils) present in the aggregates. These micrometre-long nanostructures gel in solutions at concentrations as low as 0.2% v/v. Their gel-fluid transition has been previously shown to be controlled by pH, temperature, or by mixing with complementary peptides. Here we show the dramatic effect of another chemical trigger, that of physiological-like salt concentration, on the self-assembly, morphology and gelation of a series of systematically designed charged self-assembling tape-forming peptides, each 11 amino acid residues in length, in the pH range of 2-14. This study provides a detailed understanding of the self-assembly of this class of peptides in aqueous solutions of biologically relevant pH and ionic strength. This insight has led to the development of injectable self-assembling peptide lubricants as potential therapeutics for the treatment of early stage knee joint osteoarthritis.     

Development of an in situ fiber optic Raman system to monitor hydrothermal vents

The development of a field portable fiber optic Raman system modified from commercially available components that can operate remotely on battery power and withstand the corrosive environment of the hydrothermal vents is discussed. The Raman system is designed for continuous monitoring in the deep-sea environment. A 785 nm diode laser was used in conjunction with a sapphire ball fiber optic Raman probe, single board computer, and a CCD detector. Using the system at ambient conditions the detection limits of SO(4)(2-), CO(3)(2-) and NO(3)(-) were determined to be approximately 0.11, 0.36 and 0.12 g l(-1) respectively. Mimicking the cold conditions of the sea floor by placing the equipment in a refrigerator yielded slightly worse detection limits of approximately 0.16 g l(-1) for SO(4)(-2) and 0.20 g l(-1) for NO(3)(-). Addition of minerals commonly found in vent fluid plumes also decreased the detection limits to approximately 0.33 and 0.34 g l(-1) respectively for SO(4)(-2) and NO(3)(-).     

A synthetic strategy for the preparation of cyclic peptide mimetics based on SET-promoted photocyclization processes

A novel method for the synthesis of cyclic peptide analogues has been developed. The general approach relies on the use of SET-promoted photocyclization reactions of peptides that contain N-terminal phthalimides as light absorbing electron acceptor moieties and C-terminal alpha-amidosilane or alpha-amidocarboxylate centers. Prototypical substrates are prepared by coupling preformed peptides with the acid chloride of N-phthalimidoglycine. Irradiation of these substrates results in the generation of cyclic peptide analogues in modest to good yields. The chemical efficiencies of these processes are not significantly affected by (1) the lengths of the peptide chains separating the phthalimide and alpha-amidosilane or alpha-amidocarboxylate centers and (2) the nature of the penultimate cation radical alpha-heterolytic fragmentation process (i.e., desilylation vs decarboxylation). An evaluation of the effects of N-alkyl substitution on the amide residues in the peptide chain showed that N-alkyl substitution does not have a major impact on the efficiencies of the photocyclization reactions but that it profoundly increases the stability of the cyclic peptide.     

Synthesis and Reactivity of Metallophosphanes

Abstract

Aspects of the reactivity of metallophosphanes are presented along with the synthesis and structure determinations for new aluminophosphanes.     

Solvent-Free Microwave-Assisted Organic Reactions Preparation of β-Keto Esters

Microwave technique has been utilised in the preparation of β-keto esters. Two different procedures are described: transesterification of β-keto esters and ring opening of 2,2,6-trimethyl-1,3-dioxin-4-one.     

A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice

Alcohol use disorder (AUD) affects over 18 million people in the US. Unfortunately, pharmacotherapies available for AUD have limited clinical success and are under prescribed. Previously, we established that avermectin compounds (ivermectin [IVM] and moxidectin) reduce alcohol (ethanol/EtOH) consumption in mice, but these effects are limited by P-glycoprotein (Pgp/ABCB1) efflux. The current study tested the hypothesis that dihydromyricetin (DHM), a natural product suggested to inhibit Pgp, will enhance IVM potency as measured by changes in EtOH consumption. Using a within-subjects study design and two-bottle choice study, we tested the combination of DHM (10 mg/kg; i.p.) and IVM (0.5–2.5 mg/kg; i.p.) on EtOH intake and preference in male and female C57BL/6J mice. We also conducted molecular modeling studies of DHM with the nucleotide-binding domain of human Pgp that identified key binding residues associated with Pgp inhibition. We found that DHM increased the potency of IVM in reducing EtOH consumption, resulting in significant effects at the 1.0 mg/kg dose. This combination supports our hypothesis that inhibiting Pgp improves the potency of IVM in reducing EtOH consumption. Collectively, we demonstrate the feasibility of this novel combinatorial approach in reducing EtOH consumption and illustrate the utility of DHM in a novel combinatorial approach.