Kay Severin

I am very happy to announce that I’ve joined UVSQ @uvsq.bsky.social (Université Paris-Saclay) as a Junior Professor (Chaire de Professeur Junior).

Construction of dual-cofactor artificial metalloenzymes for synergistic and enantiodivergent catalysis of Michael addition reactions - Nature Synthesis A dual-cofactor artificial metalloenzyme is developed, incorporating a biotinylated nickel complex and a Strep-tagged peptide catalyst in adjacent streptavidin-binding sites. This synergistic artifici...

Now online:

Article by Xile Hu & co-workers @xilehu-epfl.bsky.social

Construction of dual-cofactor artificial metalloenzymes for synergistic and enantiodivergent catalysis of Michael addition reactions

www.nature.com/articles/s44... ($)
#Chemsky

A Crystalline Monomeric Diboryl Diazene Azo compounds (R─N═N─R′) are a foundational class of nitrogen-containing molecules. In contrast to the bench-stability of many azo derivatives, monomeric diboryl diazenes (R2BN═NBR2) have long eluded ...

We’ve been quiet for a while, but here’s something exciting: hot off the press: a crystalline monomeric diboryl diazene @jacs.acspublications.org pubs.acs.org/doi/10.1021/...

Jean de Montmollin (@jcedemontmollin.bsky.social ) has destroyed coordination cages to examine their thermodynamic and kinetic stability. The results are summarized in an #openaccess publication in @daltontrans.rsc.org : pubs.rsc.org/en/content/a...
#chemsky #EPFL

Phosphanides are able to capture nitrous oxide (N2O, #laughinggas). Work by Alex Genoux (@alexgenouxchem.bsky.social ), Dicky Wong (@thwongax.bsky.social ), and Farzaneh Fadaei-Tirani. Now out (#openaccess ) in @chemcomm.rsc.org : pubs.rsc.org/en/content/a...
#chemsky #EPFL

OMCOS 22 is coming to an end, and the torch is being passed to the next OMCOS meeting. OMCOS 23 will be held in Lausanne and hosted by Professor Nicolai Cramer. #omcos22

Peptide/Protein Functionalization and Macrocyclization via Alkyne Umpolung with Hypervalent Iodine Reagents ConspectusAlkynes are one of the most fundamental functional groups in organic synthesis due to the versatile chemistry of the triple bond, their unique rigid structure, and their use in bioconjugation. The introduction of alkynes onto organic molecules traditionally relies on nucleophilic activation, often requiring strong bases or metal catalysts. These conditions, however, restrict applications involving biomolecules such as peptides and proteins due to functional group incompatibility. To address this limitation, our group developed an “umpolung” approach, utilizing hypervalent iodine compounds to create electrophilic alkyne transfer reagents such as benziodoxol(on)es (Bx(X)s) and benziodazolones (BZs). The high reactivity of EBx/X/Z reagents enables efficient alkyne transfer to various nucleophilic residues in peptides and proteins under different reaction conditions, providing a versatile tool for biomolecule modification.In this Account, we highlight the residue-selective alkynylation and alkenylation of peptides enabled by the development of novel EBx/X/Z reagents with a focus on progress since 2021. This includes the following: (1) Selective residue modification: We have made significant progress in the residue-selective alkynylation and alkenylation of peptides and proteins. Building on our initial work with Cys-selective alkynylation, we enhanced reactivity and solubility by introducing a sulfonate group on the benziodoxolone arene core, facilitating lipophilic alkynylation in an aqueous environment. Furthermore, we developed perfluoroaryl-modified BZ reagents to achieve sequential Cys-Cys cross-linking and used them for antibody cross-linking with superior reactivity compared to that of conventional methods. Additionally, we expanded the reactivity beyond Cys to achieve Tyr-selective conjugation. All of these achievements underscored the tunability of EBx/X/Z reagents through strategic substituent modification on the iodine core. (2) Peptide stapling and macrocyclization: We designed EBx(X) reagents featuring an additional reactive site on the alkyne moiety, enabling Cys-Cys and Cys-Lys stapling in peptides. This approach enhanced their α-helicity and potential as PPI inhibitors with improved binding affinity to the MDM2 protein. For sequences lacking Cys, we incorporated the whole EBx(X) core onto Lys residues via an activated ester on the alkyne, forming peptide-EBx(X) conjugates. These conjugates facilitated the formation of rigid, functional peptide macrocycles using C-terminal or Trp-selective alkynylation. The utility of these macrocyclizations was demonstrated by achieving improved binding affinity to the KEAP1 protein and by generating fluorescent cyclic peptides suitable for live-cell imaging without additional fluorophores. (3) Broadening applicability with EBx-containing amino acids: We prepared EBx amino acids compatible with both solid-phase peptide synthesis (SPPS) and solution-phase synthesis (SPS), allowing us to apply our cyclization strategies to construct a diverse library of cyclic peptides.

The review of @xingyuliu9595.bsky.social on the group work on peptide/protein functionalization and macrocyclization has been published at Acc. Chem. Res.
doi.org/10.1021/acs....
What next? With all these nice tools developed, we are eager to collaborate with chemical biologists for applications!

📢pls share
We are hiring! New opening for a W2 Professor in "experimental inorganic chemistry" @unibonn.bsky.social
Deadline Oct. 10 t.co/EqMLA0fCuC

and Rosario Scopelliti (XRD)

With help of Renata Svecova (synthesis) and Farzaneh Fadaei-Tirani (XRD). Thanks a lot!!

Noga Eren has investigated the constitutional dynamic chemistry of Au3(pyrazolate)3 complexes. Just published in @daltontrans.rsc.org : pubs.rsc.org/en/Content/A...
#chemsky #EPFL

We have an opening in our institute at #EPFL for a tenure-track assistant professor position.
Please repost...
www.epfl.ch/about/workin...

At the University of Geneva, we have an opening for an associate or full professor in theoretical and/or computational chemistry! Please spread the word.

jobs.unige.ch/www/wd_porta...

The work of Xingyu Liu @xingyuliu9595.bsky.social in collaboration with Wei Cai in Beat Fierz @beatfierz.bsky.social group @lcbm-epfl.bsky.social and Anne-Sophie Chauvin on peptide-cyanoarenes used as photocatalysts is now accepted in @angewandtechemie.bsky.social !
doi.org/10.1002/anie...

Rhodium-catalysed hydrogenation of nitrous oxide We report on the discovery of “hidden” heterogeneous catalysis in the hydrogenation of nitrous oxide while assessing the catalytic activity of a rhodium(i) hydride complex supported by a nominally rob...

Rhodium-catalysed hydrogenation of nitrous oxide… a cautionary tale of “hidden” heterogeneous catalysis @catalysisscitech.rsc.org 🔑 doi.org/10.1039/D5CY...

While many collaborations never culminate in a publication, others simply require time to mature. In this case, a full decade proved to be the necessary incubation period. Finally out in Chem. Eur. J.: chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1...

@irenebenzop.bsky.social #chemsky #EPFL

Unfortunately, Figure 1 and Scheme 1 were mixed up at the proof stage...

With help from Paul Varava (synthesis), Rosario Scopelliti (XRD), and Farzaneh Fadaei-Tirani (XRD). Thanks a lot!!

Dicky Wong (@thwongax.bsky.social ) has explored the chemistry of iridium complexes with N-heterocyclic vinylidene ligands. Just published in JACS (@jacs.acspublications.org ): pubs.acs.org/doi/10.1021/...
#chemsky #EPFL

Have a look at BCP-EBXs, combining ethynylbenziodoxolones and bicyclo[1.1.1] pentanes (BCPs) to open new chemical space around BCP bioisosteres!
This work of Najung, Jonas and Elija has just been accepted in @angewandtechemie.bsky.social !

doi.org/10.1002/anie...

Great to see again EPFL Chemistry represented in the talented 12 again with @feldmannlab.bsky.social Congrats!

<italic toggle&#x3D;"yes">In Crystallo</italic> Photochemistry: Reimagining Synthetic Tractability with Transparent Single-Crystalline Flasks Expanding the boundaries of synthetic tractability ─ of what molecules can be synthesized and isolated ─ is an eternal challenge for synthetic chemists. The development of new synthetic methods and strategies enables the properties and potential functions of novel molecular targets to be experimentally evaluated. In the context of catalysis, predictable synthetic strategies are often available to access kinetically persistent intermediates such as catalyst resting states. In contrast, synthesis and characterization of the reactive intermediates are often not possible due to the fleeting lifetimes of these species. In crystallo photochemistry combines single-crystal matrix isolation with cryogenic photochemistry to enable reactive intermediates to be synthesized under conditions in which they are persistent and can be (crystallographically) characterized. This Outlook highlights key achievements of in crystallo photochemistry as well as discusses opportunities and challenges that confront realization of the potential of in crystallo synthesis to redefine the boundaries of synthetic tractability.

Our first post here! Aishanee has done a great job, taking a closer look at synthetic tractability using in crystallo photochemistry in our latest paper, now out in ACS Cent. Sci. (@pubs.acs.org).

pubs.acs.org/doi/10.1021/...

We developed an encapsulated NiCo alloy catalyst for high temp CO2 reduction in solid oxide electrochemical cells. An voltage of 1.1 V at 1 A/cm2, corresponding to 90% energy efficiency. The reactions produce CO in 100% selectively and we run it for 2000 h. www.nature.com/articles/s41... #chemsky

We're recruiting a PDRA to work with our team at Oxford Chemistry @ox.ac.uk @oxfordchemistry.bsky.social ! If you are interested in synthetic inorganic chemistry and catalysis research, Apply!

my.corehr.com/pls/uoxrecru...

Our @snf-fns-ch.bsky.social research project "Hypervalent iodine reagents for peptide and protein modification and applications in chemical biology" has been accepted! 2 PhD and one postdoc positions are now open @lcsolab.bsky.social For more details to apply, See:

www.epfl.ch/labs/lcso/gr...

Xue-Zhi Wang and Damien Chen have developed a synthetic receptor for the complexation of perfluoroalkyl carboxylates. Now out in Angewandte Chemie: onlinelibrary.wiley.com/doi/full/10....

#chemsky #EPFL 🧪

Pushing the boundaries of #organosodium reagents, we are incredibly excited to report their applications in #iron #catalysed #crosscouplings with Sobi Asako and Laurean Ilies at RIKEN 🇯🇵 @naturesynthesis.bsky.social
@unibe.ch #openaccess #TeamWorkMakestheDreamWork

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

With help from Anastasia Gitlina, Carl Thomas Bormann, Alexandre Genoux (synthesis) and Farzaneh Fadaei-Tirani (XRD). Thanks a lot!!

Bis-triazenylarenes enable vicinal Sandmeyer-type reactions. Work by @christeenamathew.bsky.social. Now out in Angewandte Chemie: onlinelibrary.wiley.com/doi/10.1002/...
#chemsky #EPFL 🧪

Pd-Catalyzed Strain-Releasing Dyotropic Rearrangement: Ring-Expanding Amidofluorination of Methylenecyclobutanes Under the Pd(II)/Pd(IV) catalytic cycle, the cyclization of pent-4-en-1-amine derivatives typically yields either pyrrolidines or piperidines depending on the N-protecting group. We report herein an unprecedented Pd(II)-catalyzed oxidative domino process that converts readily accessible N-protected 2-(2-amidoethyl)-1-methylenecyclobutane derivatives to 1-fluoro-2-azabicyclo[3.2.1]octanes. This transformation constructs three chemical bonds under mild conditions [Pd(hfacac)2 (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a domino sequence involving 5-exo-trig amidopalladation/Pd(II)–oxidation/chemoselective dyotropic rearrangement/C–F bond-forming reductive elimination. Notably, the cyclization mode remains independent of the N-protecting group under these conditions. Furthermore, diverse functional groups can be introduced at the bridgehead position of a bicyclic compound via an apparent anti-Bredt bridgehead iminium intermediate.

Nice combination of strained rings and Pd-dyotropic rearrangement by our neighbor Jieping Zhu group now in JACS!
pubs.acs.org/doi/10.1021/...