Coinage metal complexes of a boron substituted soft scorpionate ligand

An improved synthesis of lithium phenyltris(methimazolyl)borate, Li[PhTm(Me)], (methimazole = 1-methylimidazole-2-thione) is described, and the structure of the methanol-solvated [Li(OHMe)4][PhTm(Me)] has been determined. The syntheses and characterization of complexes [M(PhTm(Me))(PR3)] (M = Cu, Ag, Au; R = Et, Ph;) are reported, and the complexes [Cu(PhTm(Me))(PPh3)], [Ag(PhTm(Me))(PEt3)] and [Au(PhTm(Me))(PEt3)] are crystallographically characterized, showing a progression from pseudo-tetrahedral geometry (copper, S3P coordination) to trigonal planar geometry (silver, S2P coordination) to linear geometry (gold, SP coordination). In addition, the copper(I) and silver(I) triphenylphosphine complexes of the adventitiously formed phenylhydrobis(methimazolyl)borate ligand, [M(PhBm(Me))(PPh3)], have been crystallographically characterized, showing both species to have a trigonal planar primary coordination sphere, with a secondary M...H-B interaction. Finally, reaction of copper(II) chloride with Li[PhTm(Me)] results in formation of a compound analyzing as [Cu(II)(PhTm(Me))Cl], although its extreme insolubility and marked instability have precluded its complete characterization. Attempts to prepare this by ultra-slow diffusion of the reactants through solvent blanks has led to isolation of a mixed-valence copper(I/II) methimazolate cluster, [Cu(I)10Cu(II)2(mt)12Cl2] and a copper(I) dimeric complex [Cu2(PhTm(Me))2], indicating that copper(II) ions oxidatively decompose the phenyltris(methimazolyl)borate anion

Studies of oxidative stress in cellular systems The interaction of monocytes and erythrocytes

Abstract1H spin echo NMR spectroscopy is used to follow the interaction of intact and viable erythrocytes and monocytes obtained from different sources in mixed cultures. After a lag time (270 min) erythrocyte glutathione is observed to become more oxidised. This result is believed to occur as a consequence of monocyte activation generating hydrogen peroxide or hypochlorous acid, which is targeted at the erythrocyte. The red cell in turn employs its sulphydryl system as an anti-oxidant defence

Detection of potentially toxic metals by SERS using salen complexes

Surfaced enhanced Raman scattering (SERS) can discriminate between metal complexes due to the characteristic “spectral fingerprints” obtained. As a result, SERS has the potential to develop relatively simple and sensitive methods of detecting and quantifying a range of metal ions in solution. This could be beneficial for the environmental monitoring of potentially toxic metals (PTMs). Here, salen (C16H16N2O2) was used as a ligand to form complexes of Ni(II), Cu(II), Mn(II) and Co(II) in solution. The SERS spectra showed characteristic spectral differences specific to each metal complex, thus allowing the identification of each of these metal ions. This method allows a number of metal ions to be detected using the same ligand and an identical preparation procedure. The limit of detection (LOD) was determined for each metal ion, and it was found that Ni(II), Cu(II) and Mn(II) could be detected below the WHO’s recommended limits in drinking water at 1, 2 and 2 µg L-1, respectively. Co(II) was found to have an LOD of 20 µg L-1, however no limit has been set for this ion by the WHO as the concentration of Co(II) in drinking water is generally <1-2 μg L-1. A contaminated water sample was also analysed where Mn(II) was detected at a level of 800 µg L-1

Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG

SummaryObjectivesDespite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin.MethodsSeven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease.ResultsVaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release.ConclusionSpy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria

An Opsonophagocytic Killing Assay for the Evaluation of Group A Streptococcus Vaccine Antisera

Group A Streptococcus (GAS) is a major cause of global mortality, yet there are no licensed GAS vaccines. Vaccine progress has been hampered, in part, by a lack of standardized assays able to quantify antibody function in test antisera. The most widely used assay was developed over 50 years ago by Rebecca Lancefield and relies on human whole blood as a source of complement and neutrophils. Recently, an opsonophagocytic killing (OPK) assay has been developed for GAS by adapting the OPK methods utilized in Streptococcus pneumoniae vaccine testing. This assay uses dimethylformamide (DMF)-differentiated human promyelocytic leukemia cells (HL-60 cells) as a source of neutrophils and baby rabbit complement, thus removing the major sources of variation in the Lancefield assays. This protocol outlines methods for performing a GAS OPK assay including titering test sera to generate an opsonic index. This in vitro assay could aid in selecting vaccine candidates by demonstrating whether candidate-induced antibodies lead to complement deposition and opsonophagocytic killing

Surface science of soft scorpionates

The chemisorption of the soft scorpionate Li[PhTmMe] onto silver and gold surfaces is reported. Surface enhanced Raman spectroscopy in combination with the Raman analysis of suitable structural models, namely, [Cu(κ3-S,S,S-PhTmMe)(PCy3)], [Ag(κ3-S,S,S-PhTmMe)(PCy3)], [Ag(κ2-S,S-PhTmMe)(PEt3)], and [Au(κ1-S-PhTmMe)(PCy3)], are employed to identify the manner in which this potentially tridentate ligand binds to these surfaces. On colloidal silver surface-enhanced Raman spectroscopy (SERS) spectra are consistent with PhTmMe binding in a didentate fashion to the surface, holding the aryl group in close proximity to the surface. In contrast, on gold colloid, we observe that the species prefers a monodentate coordination in which the aryl group is not in close proximity to the surface