Metal Acetylides in Cycloaddition Reactions

This review highlights recent advances in the synthesis of (hetero)aromatic systems via cycloaddition reactions of alkynylmetals with dienes and dipoles. This methodology is advantageous when accessing complex molecules because it offers a short, atom-economic, and regioselective route to quickly access scaffolds of broad interest to the chemical sciences

Total synthesis and structure-activity-relationship of Alternaric acid delivers an herbicide vector

E.M.I and A.J.B.W. thank Syngenta and EPSRC for an iCASE PhD studentship.Global food security is one of the foremost challenges of our time and requires a multifaceted solution. Crop protection strategies are an essential part of this response; however, there is increasing resistance to known modes of action. Since its discovery in 1949, the natural product alternaric acid has been proposed as a starting point for herbicide development. However, this target is undeveloped due to its poor synthetic accessibility and a lack of knowledge of the associated pharmacology. Here we report the discovery of herbicidal compounds from alternaric acid that operate via a potentially unknown mode of action. Development of a total synthesis enabled structure–activity relationship profiling of compound libraries, which, combined with phenotypic screening and molecular modelling data, identified small-molecule lead compounds with enhanced and broader spectrum herbicidal activity than alternaric acid.PostprintPeer reviewe

Synthesis of aminopyrazoles from sydnones and ynamides.

Aminopyrazoles are prepared from readily accessible sydnones and sulfonyl ynamides using either a copper-mediated sydnone alkyne cycloaddition (CuSAC) or in situ generated strained cyclic ynamides

Fate of pharmaceuticals and their transformation products in integrated membrane systems for wastewater reclamation

The removal of pharmaceuticals (PhACs) present in urban wastewater by membrane bioreactors (MBRs) followed by reverse osmosis (RO) or nanofiltration (NF) membranes has been frequently addressed in the literature. However, data regarding the removal of their main human metabolites and transformation products (TPs) is still scarce. In this study, the presence of 13 PhACs and 20 of their metabolites and TPs was monitored during 2 consecutive years in the different treatment steps of urban raw wastewater (sewer, primary treatment, MBR and RO/NF). Rejection of the selected contaminants when using low pressure NF membranes (NF-90) or RO membranes (ESPA 2) after the MBR step was also investigated. The analgesic acetaminophen, which was found at the highest concentrations in the sewer and influent samples (18–74 µg L-1) over the two experimental periods, was fully eliminated during MBR treatment. Those PhACs that were only partially removed after the MBR, were almost completely removed (>99%) by the RO membrane working under different process conditions. At a similar average permeate fluxes (18 L m-2 h-1), the NF membrane showed high removal efficiencies (>90%) for all of the PhACs and their metabolites, though lower than those achieved by the RO membrane. When the flux of the NF90 membrane was increased to 30 L m-2 h-1 (while still operating at a feed pressure lower than the RO membrane at 18 L m-2 h-1) the performance of the membrane increased, achieving 98% rejection of PhACs.Peer ReviewedPostprint (author's final draft

A self-assembled nanostructured material with photosensitising properties

Using a combination of molecular modelling and spectroscopic experiments, the naturally-occurring pharmacologically active hypericin compound is shown to form a stable 1:1 complex with apomyoglobin that preserves its fluorescence and singlet oxygen photosensitising properties. The binding equilibrium constant has been determined as Ka = (2.4 ± 0.5) × 105 M-1, equivalent to a dissociation constant Kd =4.2±0.8 .M. The kinetic details of singlet oxygen production have been characterised and indicate that the protein scaffold protects hypericin from oxygen. The complex is active against Staphylococcus aureus bacteria and shows lower dark toxicity than free hypericin. In view of its superb biocompatibility, apomyoglobin should be considered as nanovehicle for hypericin in theranostic applications

Fate of pharmaceuticals and their transformation products in integrated membrane systems for wastewater reclamation

The removal of pharmaceuticals (PhACs) present in urban wastewater by membrane bioreactors (MBRs) followed by reverse osmosis (RO) or nanofiltration (NF) membranes has been frequently addressed in the literature. However, data regarding the removal of their main human metabolites and transformation products (TPs) is still scarce. In this study, the presence of 13 PhACs and 20 of their metabolites and TPs was monitored during 2 consecutive years in the different treatment steps of urban raw wastewater (sewer, primary treatment, MBR and RO/NF). Rejection of the selected contaminants when using low pressure NF membranes (NF-90) or RO membranes (ESPA 2) after the MBR step was also investigated. The analgesic acetaminophen, which was found at the highest concentrations in the sewer and influent samples (18–74 µg L-1) over the two experimental periods, was fully eliminated during MBR treatment. Those PhACs that were only partially removed after the MBR, were almost completely removed (>99%) by the RO membrane working under different process conditions. At a similar average permeate fluxes (18 L m-2 h-1), the NF membrane showed high removal efficiencies (>90%) for all of the PhACs and their metabolites, though lower than those achieved by the RO membrane. When the flux of the NF90 membrane was increased to 30 L m-2 h-1 (while still operating at a feed pressure lower than the RO membrane at 18 L m-2 h-1) the performance of the membrane increased, achieving 98% rejection of PhACs.Peer Reviewe

Direct Arylation of Sydnones with Aryl Chlorides toward Highly Substituted Pyrazoles

The direct arylation of the C4 position of both N-alkyl- and N-arylsydnones with aryl/heteroaryl chlorides has been realized. The reaction is quite general and allows access to a wide range of 4-substituted sydnones. Yields of more challenging substrates can be improved through the use of aryl bromides