Publications by authors named "Neil Wells"

Fluorine substitution can have a profound impact on molecular conformation. Here, we present a detailed conformational analysis of how the 1,3-difluoropropylene motif (-CHF-CH-CHF-) determines the conformational profiles of 1,3-difluoropropane, - and -2,4-difluoropentane, and - and -3,5-difluoroheptane. It is shown that the 1,3-difluoropropylene motif strongly influences alkane chain conformation, with a significant dependence on the polarity of the medium.

View Article and Find Full Text PDF

Due to tautomeric equilibria, NMR spectra of reducing sugars can be complex with many overlapping resonances. This hampers coupling constant determination, which is required for conformational analysis and configurational assignment of substituents. Given that mixtures of interconverting species are physically inseparable, easy-to-use techniques that enable facile full H NMR characterization of sugars are of interest.

View Article and Find Full Text PDF

Protein arylation has attracted much attention for developing new classes of bioconjugates with improved properties. Here, we have evaluated 2-sulfonylpyrimidines as covalent warheads for the mild, chemoselective, and metal free cysteine -arylation. 2-Sulfonylpyrimidines react rapidly with cysteine, resulting in stable -heteroarylated adducts at neutral pH.

View Article and Find Full Text PDF

The canonical Wingless-related integration site signaling pathway plays a critical role in human physiology, and its dysregulation can lead to an array of diseases. β-Catenin is a multifunctional protein within this pathway and an attractive yet challenging therapeutic target, most notably in oncology. This has stimulated the search for potent small-molecule inhibitors binding directly to the β-catenin surface to inhibit its protein-protein interactions and downstream signaling.

View Article and Find Full Text PDF

Protein-carbohydrate interactions are implicated in many biochemical/biological processes that are fundamental to life and to human health. Fluorinated carbohydrate analogues play an important role in the study of these interactions and find application as probes in chemical biology and as drugs/diagnostics in medicine. The availability and/or efficient synthesis of a wide variety of fluorinated carbohydrates is thus of great interest.

View Article and Find Full Text PDF

The internet is becoming a common source of health information for hand surgery patients. This study evaluates the quality of web-based resources on ganglion cysts of the hand. We completed a search for "ganglion cyst" on 3 search engines (Google, Dogpile, and Yippy).

View Article and Find Full Text PDF

Fluorination has become an effective tool to optimize physicochemical properties of bioactive compounds. One of the applications of fluorine introduction is to modulate the lipophilicity of the compound. In our group, we are interested in the study of the impact of fluorination on lipophilicity of aliphatic fluorohydrins and fluorinated carbohydrates.

View Article and Find Full Text PDF

Background: Tissue expansion in the lower extremity is controversial, with studies reporting complication rates as high as 83%. Few studies have looked at tissue expansion prior to orthopaedic correction of severe foot and ankle deformities, and those available are restricted to clubfoot in the pediatric population. Here, we report the largest case series on the use of tissue expanders for the reconstruction of severe foot and ankle deformity and the only report in adults.

View Article and Find Full Text PDF

We describe the synthesis and characterisation of open fullerene (1) and its reduced form (2) in which CH and NH are encapsulated, respectively. The H NMR resonance of endohedral NH is broadened by scalar coupling to the quadrupolar N nucleus, which relaxes rapidly. This broadening is absent for small satellite peaks, which are attributed to natural abundance N.

View Article and Find Full Text PDF

Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives.

View Article and Find Full Text PDF

A series of neutral ditopic and negatively charged, monotopic host molecules have been evaluated for their ability to bind chloride and dihydrogen phosphate anions, and neutral organophosphorus species dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PMP) and the chemical warfare agent (CWA) pinacolyl methylphosphonofluoridate (GD, soman) in organic solvent via hydrogen bonding. Urea, thiourea and boronic acid groups are shown to bind anions and neutral guests through the formation of hydrogen bonds, with the urea and thiourea groups typically exhibiting higher affinity interactions. The introduction of a negative charge on the host structure is shown to decrease anion affinity, whilst still allowing for high stability host-GD complex formation.

View Article and Find Full Text PDF

Property tuning by fluorination is very effective for a number of purposes, and currently increasingly investigated for aliphatic compounds. An important application is lipophilicity (log P) modulation. However, the determination of log P is cumbersome for non-UV-active compounds.

View Article and Find Full Text PDF

The metabolism of polyphosphate is important for the virulence of a wide range of pathogenic bacteria and the enzymes of polyphosphate metabolism have been proposed as an anti-bacterial target. In the intracellular pathogen Francisella tularensis, the product of the gene FTT1564 has been identified as a polyphosphate kinase from the polyphosphate kinase 2 (PPK2) family. The isogenic deletion mutant was defective for intracellular growth in macrophages and was attenuated in mice, indicating an important role for polyphosphate in the virulence of Francisella.

View Article and Find Full Text PDF

Fluorination is commonly exercised in compound property optimization. However, the influence of fluorination on hydrogen-bond (HB) properties of adjacent functional groups, as well as the HB-accepting capacity of fluorine itself, is still not completely understood. Although the formation of OH⋅⋅⋅F intramolecular HBs (IMHBs) has been established for conformationally restricted fluorohydrins, such interaction in flexible compounds remained questionable.

View Article and Find Full Text PDF

The bacterial stringent response is induced by nutrient deprivation and is mediated by enzymes of the RSH (RelA/SpoT homologue; RelA, (p)ppGpp synthetase I; SpoT, (p)ppGpp synthetase II) superfamily that control concentrations of the 'alarmones' (p)ppGpp (guanosine penta- or tetra-phosphate). This regulatory pathway is present in the vast majority of pathogens and has been proposed as a potential anti-bacterial target. Current understanding of RelA-mediated responses is based on biochemical studies using Escherichia coli as a model.

View Article and Find Full Text PDF

A series of supramolecular diamide organogels containing a reactive compound for the remediation of organophosphorus (OP) species, in particular OP chemical warfare agents (CWAs), has been prepared in DMSO. The organogels have been found to absorb, encapsulate and decontaminate various OP CWA simulants . At high simulant concentrations the gels also undergo a gel-sol transition releasing high local concentrations of remediation agent.

View Article and Find Full Text PDF

We report a dynamic covalent approach to transmembrane transport of amino acids by the formation of a three-component assembly. A mixture of a squaramide and a lipophilic and electrophilic aldehyde is shown to synergistically transport highly polar glycine (Gly) across vesicle membranes. The transport was investigated by a (13)C NMR assay, an osmotic response assay, a newly developed fluorescence assay suitable for measuring Gly influx, and other fluorescence assays for leakage and pH change.

View Article and Find Full Text PDF

Simple, highly fluorinated receptors are shown to function as highly effective transmembrane anion antiporters with the most active transporters rivalling the transport efficacy of natural anion transporter prodigiosin for bicarbonate.

View Article and Find Full Text PDF

A series of low molecular weight tripodal amide/histidine-containing compounds (1-2) have been synthesised and shown to increase the rate of bis-(p-nitrophenyl) phosphate (BNPP) and soman (GD) breakdown in buffered aqueous solution.

View Article and Find Full Text PDF

Small molecule synthetic anion transporters may have potential application as therapeutic agents for the treatment of diseases including cystic fibrosis and cancer. Understanding the factors that can dictate the anion transport activity of such transporters is a crucial step towards their application in biological systems. In this study a series of acylthiourea anion transporters were synthesised and their anion binding and transport properties in POPC bilayers have been investigated.

View Article and Find Full Text PDF

The formation of tren-based tris-urea supramolecular gels in organic solvents is perturbed by the presence of the nerve agent soman providing a new method of sensing the presence of organophosphorus warfare agents.

View Article and Find Full Text PDF

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18)F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18)F]-fluoride ion. Three model linker-vector molecules 7a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy.

View Article and Find Full Text PDF

Studies of sulfamide, phosphoric triamide and thiophosphoric triamide-based organocatalysts show that the phosphorus containing systems are effective new hydrogen bonding motifs for the recognition and transport of anions.

View Article and Find Full Text PDF

The influence of anions on tautomerism in benzimidazole containing anion receptors has been studied via a variety of techniques in both solution and the solid state. The results show that hydrogen bonding interactions between the receptors and guests have a significant effect of the nature of the tautomer present. The compounds show a preference for complexation of lactate over pyruvate.

View Article and Find Full Text PDF

Background: Over 70% of Canadian carpal tunnel syndrome (CTS) operations are performed outside of the main operating room (OR) with field sterility and surgeon-administered pure local anesthesia [LeBlanc et al., Hand 2(4):173-8, 14]. Is main OR sterility necessary to avoid infection for this operation? This study evaluates the infection rate in carpal tunnel release (CTR) using minor procedure room field sterility.

View Article and Find Full Text PDF