A5060710071- Ammonia Synthesis and Nitrogen Reduction
- Asymmetric Hydrogenation and Catalysis
- Nanomaterials for catalytic reactions
- Metalloenzymes and iron-sulfur proteins
- Connective tissue disorders research
- Aortic Disease and Treatment Approaches
- Enzyme Catalysis and Immobilization
- Cyclopropane Reaction Mechanisms
- Catalysis for Biomass Conversion
- CO2 Reduction Techniques and Catalysts
- Microbial Fuel Cells and Bioremediation
- Genetic Associations and Epidemiology
- Catalytic C–H Functionalization Methods
- Cardiovascular Health and Disease Prevention
- Asymmetric Synthesis and Catalysis
- Aortic aneurysm repair treatments
- Elasticity and Material Modeling
- Synthesis and Catalytic Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Atherosclerosis and Cardiovascular Diseases
- Bone and Joint Diseases
- Natural product bioactivities and synthesis
- Biological Research and Disease Studies
- Cardiovascular Disease and Adiposity
- Nutrition, Genetics, and Disease
University of Oxford
2020-2024
University of Cambridge
2014-2022
Science Oxford
2021
University of Vermont
2017-2019
Addenbrooke's Hospital
2018
Burlington College
2017
Deletion of exon 9 from Cullin-3 (CUL3, residues 403-459: CUL3(Δ403-459)) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 various substrate adaptors to Cullin-RING-ubiquitin-ligase complexes. Bound KLHL3, CUL3-RBX1 ubiquitylates WNK kinases, promoting their ubiquitin-mediated proteasomal degradation. Since kinases activate Na/Cl co-transporters promote salt retention, regulates blood pressure....
Abstract Cleaner synthesis of amines remains a key challenge in organic chemistry because their prevalence pharmaceuticals, agrochemicals and synthetic building blocks. Here, we report different paradigm for chemoselective hydrogenation nitro compounds to amines, under mild, aqueous conditions. The hydrogenase enzyme releases electrons from H 2 carbon black support which facilitates nitro-group reduction. For 30 nitroarenes demonstrate full conversion (isolated yields 78 – 96%), with...
Vinyl cations, generated by reacting β-hydroxy-α-diazo ketones with Lewis acids, undergo a 1,2-shift and C–H insertion to give cyclopentenone products.
Abstract Stiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics complex little known about molecular drivers. We have identified first time, tagSNPs in genes extracellular matrix proteins, aggrecan fibulin-1, that modulate stiffness young healthy adults. confirmed SNP associations with ex vivo measurements expression studies human donor aortic tissues. Both fibulin-1 were found wall, but marked differences distribution...
Vinyl cations derived from diazo ketones participate in transition-metal-free C–H insertion reactions, but the corresponding amide and ester analog exhibit divergent reactivity profiles. Whereas formed undergo a rearrangement sequence, those amides do so less efficiently tend to be competitively trapped before step occurs. Diazo esters several steps fail insert. DFT calculations reveal that this disparity stems two factors: differing levels of electrostatic stabilization initially vinyl...
Abstract The enzyme CbA5H, a [FeFe]‐hydrogenase from Clostridium beijerinckii , has previously been shown to survive exposure oxygen, making it promising candidate for biotechnological applications. Thus far [NiFe]‐hydrogenases are typically considered such applications, due the superior O 2 ‐tolerance and therefore simplified handling. However, methods production of [FeFe]‐hydrogenases generally more successful than other classes hydrogenases, in this work we focus on demonstrating scalable...
Heterogeneous chemo-bio catalytic hydrogenation is an attractive strategy for clean, enantioselective CX reduction.
Age-related remodelling of the arterial wall shifts load bearing from compliant elastin network to stiffer collagen fibres. While this phenomenon has been widely investigated in animal models, human studies are lacking due shortage donors’ arteries. This work aimed characterise effect ageing on mechanical properties aortic circumferential direction. N = 127 thoracic rings (age 18–81 years) were subjected tensile testing. The tangential elastic modulus (Kθθθθ) was calculated at...
A new activity for the [NiFe] uptake hydrogenase 1 of Escherichia coli (Hyd1) is presented. Direct reduction biological flavin cofactors FMN and FAD achieved using H2 as a simple, completely atom-economical reductant. The robust nature Hyd1 exploited across broad range temperatures (25-70 °C) extended reaction times. utility this system easy to implement FMNH2 or FADH2 regenerating then demonstrated by supplying reduced Old Yellow Enzyme "ene-reductases" support asymmetric alkene reductions...
We report a new paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. Hydrogenase enzyme releases electrons from H2 carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 – 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, 4-aminophenol precursor acetaminophen (paracetamol). also showcase gram-scale synthesis 90% isolated yield....
The Lewis acid-promoted generation of destabilized vinyl cations from β-hydroxy diazo ketones leads to an energetically favorable 1,2-shift across the alkene followed by irreversible C–H insertion give cyclopentenone products. This reaction sequence overcomes typical challenges counter-ion trapping and rearrangement reversibility has been used study migratory aptitudes nonequivalent substituents in uncommon C(sp2) C(sp) cation rearrangement. aptitude trends were consistent with those...
Translation of redox biocatalysis into a commercial hydrogenation flow reactor, with in-built electrolytic H 2 generation, was achieved using immobilized enzyme systems. Carbon-supported biocatalysts were first tested in batch mode, and then transferred continuous columns for -driven, NADH-dependent asymmetric ketone reductions. The thus handled comparably to heterogeneous metal catalysts, but operated at room temperature 1–50 bar , highlighting that biocatalytic strategies enable...
Hydrogenase-mediated reduction of flavin mononucleotide by H 2 is exploited to enable cleaner application nitroreductase enzymes for aromatic nitro functional groups. This turns the overall reaction into a biocatalytic hydrogenation. Use flavin-containing nitroreductases in industrial biotechnology typically relies upon NADH or NADPH as reductant, together with glucose dehydrogenase and regeneration system reduced nicotinamide cofactor, 3 equivalents carbon-intensive required single...
Introduction: This work was carried out to understand if a heterogeneous biocatalytic hydrogenation system could be implemented in slurry mode continuous flow reactor, as “slot-in” alternative metal/carbon catalyst with minimal process or chemical engineering development. Method: Biocatalytic compared metal (Pd/C) catalysed for ketone chiral alcohol conversion both reactor (Coflore ACR, AM Technology) and analogous scaled down batch reactions. Results discussion: Initial results demonstrated...
The recent genome-wide analysis of carotid-femoral pulse wave velocity (PWV) identified a significant locus within the 14q32.2 gene desert. Gene regulatory elements for transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) are this and an attractive target association. We investigated functional impact these desert SNPs on BCL11B transcript in human aorta to characterize further its role aortic stiffness. To do this, we used large repository tissues (n = 185) from organ transplant...
<p>Robust [NiFe] hydrogenase 1 (Hyd1) from <i>Escherichia coli</i> is shown to have non-native, H<sub>2</sub>-dependent activity for FMN and FAD reduction, function as a promising recycling system FMNH<sub>2</sub> supply flavoenzymes chemical synthesis, giving total turnover number over 10 thousand when coupled with an Old Yellow Enzyme ene reductase. </p>
Background: Premature arterial stiffening is a predictor of increased cardiovascular risk. It highly heritable, but the precise molecular pathways regulating it are poorly understood. We aimed to identify genetic risk loci associated with aortic stiffness in young healthy adults (<25 years) at low Methods: Demographic, blood pressure and pulse wave velocity (aPWV) data were recorded using validated methods. Genotyping performed ACCT individuals extremes (high aPWV, n=1200) Illumina 610K Quad...
Background Arterial stiffness has emerged as an important and independent predictor of cardiovascular disease outcome in many populations. A recent GWAS meta‐analysis, the AortaGen Consortium , led by Framingham investigators identified a number loci on chromosome 14 which associated with aortic pulse wave velocity (aPWV), current gold standard measure arterial stiffness. The top signals from this meta‐ analysis lie within non‐coding regions; BCL11B is closest known gene to locus. This zinc...
Robust [NiFe] hydrogenase 1 (Hyd1) from Escherichia coli is shown to have non-native, H 2 -dependent activity for FMN and FAD reduction, function as a promising recycling system FMNH supply flavoenzymes chemical synthesis, giving total turnover number over 10 thousand when coupled with an Old Yellow Enzyme ene reductase.