A5090712170- Sulfur Compounds in Biology
- Catalytic C–H Functionalization Methods
- Eicosanoids and Hypertension Pharmacology
- Synthesis and Catalytic Reactions
- Photochromic and Fluorescence Chemistry
- Asymmetric Synthesis and Catalysis
- Photodynamic Therapy Research Studies
- Cancer, Hypoxia, and Metabolism
- Cyclopropane Reaction Mechanisms
- Photoreceptor and optogenetics research
- Synthetic Organic Chemistry Methods
- Asymmetric Hydrogenation and Catalysis
- Carbohydrate Chemistry and Synthesis
- Nanoplatforms for cancer theranostics
- Oxidative Organic Chemistry Reactions
- Catalytic Cross-Coupling Reactions
- Molecular Sensors and Ion Detection
- Sulfur-Based Synthesis Techniques
- Synthesis of Indole Derivatives
- Neuroscience of respiration and sleep
- Nitric Oxide and Endothelin Effects
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Metabolism and Genetic Disorders
- Chemical Synthesis and Reactions
- Chemical synthesis and alkaloids
University of Exeter
2015-2025
Royal Cornwall Hospital
2023
University of Florida
2020
Phillips Exeter Academy
2015-2020
University of York
2008-2015
University of Leeds
2004-2009
Institute of Structural and Molecular Biology
2009
Spaulding Rehabilitation Hospital
2005
University of Glasgow
2002
The preparation of 3,3-disubstituted oxindoles by a formal C−H, Ar−H coupling anilides is described. Highly efficient conditions have been identified using catalytic (5 mol %) Cu(OAc)2·H2O with atmospheric oxygen as the reoxidant; no additional base required, and reaction can be run in toluene or mesitylene. Optimization studies are reported together scope limitation investigation based on variation anilide precursors. application this methodology to prepare key intermediate for total...
A novel copper(II)-mediated route for the conversion of anilides into 3,3-disubstituted-oxindoles is described which proceeds via a formal C-H, Ar-H coupling process.
The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production endothelial cells. Hyperglycemia induces superoxide the mitochondria and initiates changes membrane potential that leads to dysfunction. Hydrogen sulfide (H2S) supplementation has been shown reduce oxidant shows efficacy against damage vivo. However, half-life H2S very short it not specific for mitochondria. We have therefore evaluated two novel...
Mitochondrial dysfunction is observed in many diseases. Targeting H<sub>2</sub>S generation to mitochondria may be cytoprotective.
Both nitric oxide (NO) and hydrogen sulfide (H2S) are two important gaseous mediators regulating heart function. The present study examined the interaction between these biological gases its role in heart. We found that l-arginine, a substrate of NO synthase, decreased amplitudes myocyte contraction electrically induced calcium transients. Sodium (an H2S donor), which alone had minor effect, reversed negative inotropic effects l-arginine. effect l-arginine + sodium was abolished by three...
The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in world and frequently detected wildlife humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic other hormonal properties, but direct causal links are unclear humans animal models. Here we simulated measured (1×) predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations metabolite MBP, using fluorescent...
A two-step hydrolytic decomposition pathway has been elucidated for the slow-release hydrogen sulfide donor GYY4137.
The diverse reactivity presented by alkyl enol ethers underpins a wide range of synthetically significant processes. Their synthesis is often achieved atom‐economical alkyne hydroalkoxylation (i.e., addition an alcohol across alkyne), either using superbasic conditions or transition metal catalysis. Unfortunately, the harsh former approach limit substrate tolerance whilst latter requires inert, anhydrous and exotic, expensive catalysts. In order to pursue more convenient, general sustainable...
Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack agreement its mechanism(s) action likely stem from comparisons between vivo and vitro test systems potential multiple effects pathways. In rodents, vivo, metabolic activation BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported be up 1000 times more potent as an estrogen than BPA. We investigated estrogenic...
Abstract A copper(II)‐catalysed approach to oxindoles, thio‐oxindoles, 3,4‐dihydro‐1 H ‐quinolin‐2‐ones, and 1,2,3,4‐tetrahydroquinolines via formal CH, ArH coupling is described. In a new variant, copper(II) 2‐ethylhexanoate has been identified as an inexpensive efficient catalyst for this transformation, which utilises atmospheric oxygen the re‐oxidant.
Abstract A novel telescoped intramolecular Michael addition/proton transfer/HWE olefination sequence has been developed to provide rapid access α‐alkylidene‐γ‐butyrolactones. This methodology applied prepare a range of tetrahydrobenzofuran‐2,5‐diones, and related systems, also utilised in an extremely short synthesis the natural product (+)‐paeonilactone B enantiomerically pure form. In addition, preliminary experiments are described that illustrate palladium‐catalysed variant proceeding by...
Abstract A telescoped sequence involving palladium‐catalysed intramolecular enolate arylation followed by an in situ HWE olefination has been developed to provide rapid access 3‐alkenyl‐oxindoles. This “one‐pot” process, which is greatly accelerated microwave irradiation, proceeds with low loadings of palladium(II) acetate (0.2–1.0 mol‐%), and used prepare a range adducts derived from aromatic, heteroaromatic aliphatic aldehydes as well formaldehyde. In addition, further elaboration the...
Photodynamic therapy (PDT) is a light activated drug that can be used to treat number of cancers and precancers. It particularly useful in its topical form dermatology but improvement efficacy required widen application. An ester between aminolaevulinic acid (ALA) CP94 was synthesised (AP2-18) experimentally evaluated determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could improved. A biological evaluation AP2-18 conducted cultured human primary cells with both PpIX...
Non-melanoma skin cancers are the most frequently occurring type of cancer worldwide. They can be effectively treated using topical dermatological photodynamic therapy (PDT) employing protoporphyrin IX (PpIX) as active photosensitising agent long disease remains superficial. Novel iron chelating agents being investigated to enhance effectiveness and extend applications this treatment modality, limiting free increases accumulation PpIX available for light activation thus cell kill.Human lung...
(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the glioma. Both processes enhanced by increasing intracellular PpIX concentrations, which can achieved through iron chelation. AP2-18 is a novel combinational drug, ester-links precursor (aminolaevulinic acid; ALA) an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG were cultured in 96-well plates for...
Stereochemical control of spiropyran ring-closure was explored through synthesis sterically-congested spiropyrans by a novel, efficient method.
Efficient syntheses are described for the new bridging bis-phosphanes DPPN (4) and DPEN (5) built around restricted rigidity of a 2,7-dialkoxynaphthalene backbone. These show marked preference pairs metal atoms (PtII, Mo0) to form metallamacrocycles or oligomers. Single-crystal X-ray structure determinations four dimeric complexes with PtII Mo0 reported. The platinum can be obtained as kinetically favoured trans,trans products, which isomerise cis,cis forms in presence free ligand....