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Posts by Dave Leigh

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Out-of-equilibrium sensing with a chemically fueled molecular machine Biological adaptive receptors are driven out of equilibrium to change the detectable range of analyte concentrations. Here, a chemically fueled rotaxane information ratchet couples Zn(II) binding to c...

In @cp-chem.bsky.social tinyurl.com/3vmzatbh Maria @benjaminoacid.bsky.social @stefanborsley.bsky.social Fabio & @zashbridge.bsky.social show that driving a receptor out-of-equilibrium through chem fueling allows quantification of binding at concentrations where receptor is saturated at equilibrium😃

3 weeks ago 20 4 0 1
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Sadiq Khan urges Labour to campaign on rejoining EU at next election Mayor of London says returning to EU now more desirable because of economic instability caused by Donald Trump Labour should go into the next general election promising to rejoin the EU, Sadiq Khan has said. The mayor of London has repeatedly made the case for joining the customs union and single market, but went much further on Wednesday night by suggesting the party should promise full membership at next ballot. Continue reading...

Sadiq Khan urges Labour to campaign on rejoining EU at next election

1 month ago 218 38 9 12
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Electroreductive Cleavage of C(sp3)–N Bonds in Saturated N-Carbonyl Heterocycles Ring-opening C–N bond cleavage reactions provide an effective means to convert widespread, readily accessible chiral N-heterocycles into hard-to-attain stereodefined linear amines. Current strategies either rely on the strain-induced release of small aziridine and azetidine rings or, for larger ring systems, require highly electrophilic reagents, oxidative conditions, or preinstalled reactive functionalities to enable the ring-opening event. Recently, complementary radical strategies that exploit the reactivity of α-amino-ketyl radicals, formed upon single-electron transfer (SET) reduction of common N-carbonyl protecting groups, have emerged. Nevertheless, these methods facilitate the homolytic fragmentation only of up to 5-membered azacycles. In this study, we leveraged electroreductive conditions to switch the nature of the above C–N bond cleavage manifold from radical to ionic and enable the heterolytic ring-opening of a broad array of unstrained cyclic amines (comprising pyrrolidines, piperidines, azepines, azocanes, and N-macrocycles), protected as N-(thio)amides, carbamates, or ureas. Crucially, this electrochemically enabled reactivity switch grants complementary functional group compatibility and a broader ring size and N-carbonyl group scope. Computational and experimental studies indicate that electrochemical settings are crucial for generating the Mg(II)-Lewis acid catalyst, activating the N-carbonyl moiety while prompting the so-formed oxy-iminium ion intermediates to undergo two consecutive cathodic SET reductions, generating “umpoled” α-amino-α-oxy-carbanion species. These, via irreversible E1cB fragmentation of the adjacent C–N bond, lead to the desired ring-opened products. Our electrochemical procedure can be scaled up and miniaturized (enabling its application to high-throughput experimentation screening), and its synthetic utility has been demonstrated by accessing decorated stereodefined linear amides from stereochemically rich pyrrolidine and azepane derivatives.

Excited to see our recent work on the electroreductive cleavage of C(sp³)–N bonds in saturated N-carbonyl heterocycles out in @jacs.acspublications.org 🔌Check the full study here: pubs.acs.org/doi/10.1021/...

1 month ago 9 4 2 1

😎 I knew that grade C English O level would pay off one day!

1 month ago 4 0 0 0
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No time for a marmalade sandwich! 🥪 #Paddington

1 month ago 6 0 0 0
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...and here's a version with KPop demon hunters soundtrack!😳

1 month ago 0 0 0 0
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Our new video, created by Stuart Jantzen (Biocinematics), depicts the original Maxwell’s Demon thought experiment 😈 tinyurl.com/3ja25xfz, the archetypal information ratchet that inspires how we design molecular motors & pumps: tinyurl.com/msn8c2an; tinyurl.com/yj53rfvm; tinyurl.com/557vcubt 👹

1 month ago 14 3 2 0
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El Prof. Emilio M. Pérez es nombrado nuevo director del Instituto IMDEA Nanociencia, continuando nuestra misión de impulsar la investigación de excelencia en nanociencia y nanotecnología.

+info nanociencia.imdea.org/es/imdea-nan...

2 months ago 14 5 1 1
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Our latest collaborative preprint from the group and @kilbinger-group.bsky.social is out - tinyurl.com/3bbrfyhw - we've been looking at creating stably folded, helical, and polyfluorinated transmembrane channels with rates of water transport exceeding Aquaporins. Great to see the manuscript up!

3 months ago 8 4 0 1
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Here is a full text, view only, version of the paper: shorturl.at/7ISdf

3 months ago 3 0 0 1
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Chiral catalysis-driven rotary molecular motors - Nature Chemistry The structural anisotropy necessary for the powered directional rotation of chemically fuelled molecular motors had previously been provided by chiral fuels or enzymes. Now it has been shown that asym...

Out today in @natchem.nature.com 😃 Huakui, @stefanborsley.bsky.social @benjaminoacid.bsky.social & co illustrate why catalysis-driven motors (like motor proteins) can't use designs based on light-driven motors or molecules-that-rotate-through-multi-reaction-sequences www.nature.com/articles/s41...

3 months ago 22 6 1 2
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Wow, that’s a lot of brilliance in one photo! 😍 Are you sure you’re allowed to all be in the same place at the same time? Merry Christmas all! 🎄🎅#MASC2025 #RSC_MASC

4 months ago 25 1 0 0
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UK to rejoin EU’s Erasmus student exchange programme Exclusive: British students will be able to participate in EU-wide scheme from January 2027, sources say

Brilliant news!😃🇪🇺 www.theguardian.com/world/2025/d...

4 months ago 12 0 0 0
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Unfortunate 😳

5 months ago 3 0 0 0
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Reductive radical chain initiation through the thermal generation of carbon dioxide radical anion - Nature Synthesis Radical chain initiation strategies are fundamental to the synthesis of small molecule drugs and macromolecular materials. Here a general, thermally driven and scalable method for reductive initiation...

Great to see this collaborative work out in @natureportfolio.nature.com , led by Michael James @manchester.ac.uk and James Douglas @astra-zeneca.bsky.social

Congrats to Ethan Lim and everyone involved!

www.nature.com/articles/s44...

#Chemistry #Collaboration #AcademicIndustry #compchem

5 months ago 7 3 1 0
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Acceleration of [2]Catenane Formation by One of its Rings This highlight underscores the most straightforward synthesis of [2]catenanes from readily available molecular precursors: The one-pot, two-step catenane formation from a crown ether, a linear diamin...

Jean-Claude Chambron highlights the work by @profdaveleigh.bsky.social and co-workers on the synthesis of [2]catenanes from readily available molecular precursors via a metal-free active template approach. Have a look at the article at onlinelibrary.wiley.com/doi/10.1002/... #AngewandteChemieNovit

5 months ago 7 1 0 0
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7 months ago 3 0 0 0
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Drs Clare Megarity & Jack Rowbotham😃

7 months ago 2 0 1 0

Fantastic talk from @marklautens.bsky.social, our 2025 T Y Shen Lecturer! Ably supported by…

7 months ago 4 1 2 0
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A trip “home” - back to the area my family emigrated from in 1951!

They left Oldham after WWII, when jobs were in short supply for unskilled workers.

I return a few years later to give the TY Shen Lecture University of Manchester with my kind host @profdaveleigh.bsky.social

7 months ago 7 2 0 0
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‼️ Today, we have the great pleasure to host David Leigh @profdaveleigh.bsky.social in Rennes. He is currently giving an incredible talk about "Giving chemistry direction". 👍

@iscr-rennes.bsky.social

7 months ago 17 5 0 0
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Multiple Template Site Nitrogen Atom Deletions from Rotaxanes, Catenanes, and a Molecular Knot We report the deletion of nitrogen atoms from multiple template sites in rotaxanes, catenanes, and a molecular knot. Nitrogen extrusion from secondary amines in the backbone of the interlocked structures is achieved using O-diphenylphosphinylhydroxylamine (DPPH), forming carbon–carbon bonds while largely maintaining the integrity of the original mechanical bonding. We find that DPPH gives improved yields (up to 51%) for nitrogen atom deletions from template sites in rotaxanes compared to an anomeric amide nitrogen-deletion reagent and overcomes a major substrate limitation in that, using DPPH, only one of the substituents of the secondary amine in the rotaxane axle needs to be radical-stabilizing. Multiple template site nitrogen atom deletions were accomplished from a range of mechanically interlocked architectures, despite the potential for dethreading, unlinking, and/or strand uncrossing during each successive deletion event. Highlights include the deletion of two template sites from a doubly threaded [3]rotaxane (37% yield) and [3]catenane (45%), quadruple N-deletion of amines from both rings of a [2]catenane (33%), and six N-deletions from the six amine groups in a molecular trefoil knot (7%). The combination of skeletal editing with template synthesis provides a general strategy for synthesis that significantly increases the structural diversity of interlocked molecules that are potentially accessible.

...Yet here in @jacs.acspublications.org Daniel, Qi, Jess & co show they can delete multiple template sites from rotaxanes, catenanes and a molecular knot, severing the strands multiple times, and still end up with mechanically interlocked molecules. Amazing!🤯 pubs.acs.org/doi/10.1021/...

7 months ago 27 3 0 1

Chemistry involves such large and small numbers that it’s often hard to take in just how fast some processes occur. Dethreading a ring off the open end of a chain when there are no binding interactions present, or passing the end of one strand past another, are incredibly fast processes...

7 months ago 11 1 1 0

In Macclesfield?😲

8 months ago 0 0 1 0
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An mRNA Crime
8 months ago 60 27 1 6
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An information ratchet improves selectivity in molecular recognition under non-equilibrium conditions - Nature Nanotechnology An abiotic information ratchet mechanism increases selectivity for the correct DNA duplex from 2:1 at equilibrium to 6:1 under energy-dissipating conditions.

Information ratchets drive many molecular motors, but we can also use them for other nonequilibrium processes like performing error correction in a molecular recognition process to increase selectivity. Published today in @natnano.nature.com
www.nature.com/articles/s41...

8 months ago 20 6 3 2
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In Situ Quantification of Directional Rotation by a Catalysis-Driven Azaindole-N-Oxide–Phenoic Acid Molecular Motor We report the in situ quantification of directional rotation of a new type of catalysis-driven rotary motor featuring a phenyl carboxylic acid rotor attached to a 7-azaindole-N-oxide stator through a biaryl C–N bond. Continuous directional rotation of the rotor about the stator is driven by the achiral motor’s rotary catalysis of carbodiimide hydration in the presence of a chiral pyrrolidinylpyridine-N-oxide. The catalytic cycle features an intermediate O-acyl-azaindole-N-oxide ester tether formed between the carboxylic acid of the rotor and the N-oxide of the stator. Face-selective cleavage of the tether by the chiral pyrrolidinylpyridine-N-oxide additive generates relatively long-lived diastereomeric pyridine-N-oxide esters of the phenyl carboxylic acid. These are hydrolyzed during the catalytic cycle to reform the carboxylic acid resting state of the motor, completing net directional 360° rotation. In contrast to previous catalysis-driven motor-molecules, the motor’s directionality could be determined directly from the transient concentrations of the diastereomeric intermediates formed during rotary catalysis. This avoids reliance on restricted rotation models to assess motor directionality and provides direct access to other key performance indicators such as motor speed and catalytic, coupling and fuel efficiency. The in situ-determined directionality of the motor was found to be in excellent agreement with the directionality determined from a restricted rotation model, supporting both the efficacy of the new approach and the validity of using appropriately designed restricted rotation models. The results establish a straightforward method for the in situ quantification of various aspects of motor behavior, aiding the design and optimization of artificial molecular motors.

Can you work out how fast a molecular motor rotates from in situ measurments? Turns out that yes, you can, as we show today in @jacs.acspublications.org
pubs.acs.org/doi/10.1021/...
@profdaveleigh.bsky.social @stefanborsley.bsky.social

8 months ago 19 2 1 0
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'Ullo @jacs.acspublications.org, Hua-Kui, Axel, @benjaminoacid.bsky.social & @stefanborsley.bsky.social have gotta new motor! doi.org/10.1021/jacs...

8 months ago 12 1 0 2
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Delighted to follow @mvdelius.bsky.social into the 1st issue of @angewandtechemie.bsky.social Novit! Congrats to Jiankang, Enzo, Patrick, Axel, Andrei & Dan on the spontaneous assembly of catenanes lacking strong recognition sites🔗😃 onlinelibrary.wiley.com/doi/full/10....

8 months ago 22 1 0 0
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Lovely evening at the fabulous @nationalgalleries.bsky.social in Edinburgh for the unveiling of portraits of recent Scottish chemistry Nobel laureates Sir Fraser Stoddart, Richard Henderson & Sir Dave MacMillan😃. Sir Fraser captured looking like he wanted to get back to work!😆

8 months ago 37 7 0 0