Professor in Synthetic Organic Chemistry University of California, Irvine is hiring. Apply now!

Please RT!

The Dept of Chemistry at UC Irvine invites applications for a tenured faculty position in Synthetic Organic Chemistry. Deadline: July 1, 2026.

More information about the position can be found here: recruit.ap.uci.edu/JPF10109

@uciphyssci.bsky.social

*caveat: might not count as food

New technique for synthesizing branched molecules could accelerate the development of future medicines

A new method from the @shenvi.bsky.social lab enables the construction of branched molecular frameworks from simple alkenes via controlled MHAT chemistry, resolving a longstanding selectivity challenge and accelerating access to drug-relevant structures, as reported in @science.org.

Glad to share our new work: RitS (Right into the Saddle): a generative model for direct transition state (TS) prediction.
📄 Paper: chemrxiv.org/doi/full/10.26…
🤠 Code: github.com/isayevlab/RitS
• Flow-matching model with explicit stereochemistry control
• Direct TS generation from SMILEs #compchem

Here is what that looks like:

We solve this problem by replacement of the common PhSiH3 reductant with lutidinium and Mn or Zn powder, in order to selectively form Co-H and suppress Ni-H. This unique system proves crucial for selectivity. It also appears to be generally applicable to our MHAT arylation and isomerization. 3/3

The reaction is mediated by Co/Ni co-catalysts, which we had reported to deliver branched alkanes from a single alkene substrate. When applied to three alkenes—reactant, co-reactant, product—our prior conditions reacted indiscriminately, apparently due to nonselective formation of M-H mixtures. 2/3

They report a method to cross-couple two alkenes and form a branched alkene using dual metal catalysis that selects for a single metal hydride (and therefore a single product). As an iterative reaction, the product alkene can then be cross-coupled again. 1/3

Congrats to Chunyu Li, Dr Xu-cheng Gan, Yu (Hannah) Irie and Dr Milo Smith for their paper appearing today in Science!

High-throughput ligand diversification to discover chemical inducers of proximity - Nature Chemical Biology Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into mol...

What a thrill to see this out! Our prospective, scalable, and target-centric solution for molecular glue discovery.

More thoughts and details here: www.linkedin.com/posts/activi...

Paper here: www.nature.com/articles/s41...

Thrilled to share our new paper just published in @acsjacs.bsky.social: a modular, 11‑step total synthesis of lasalocid acid A—enabled by a new Pd‑catalyzed C-glycosylation reaction to construct C(sp³)–C(sp³) attached‑rings.

Read the paper: pubs.acs.org/doi/10.1021/...

Simply outrageous!

Profiling the proteome-wide selectivity of diverse electrophiles - Nature Chemistry Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow...

How can we study target engagement and selectivity of covalent inhibitors? Which electrophilic probes are best suited to study a certain amino acid?

Our study on "Profiling the proteome-wide selectivity of diverse electrophiles" is published in Nature Chemistry.(1/7)

www.nature.com/articles/s41...

Hydrogen-Mediated Reductive Cross-Coupling of Aryl Iodides with Activated Aryl and Heteroaryl Bromides Hydrogen-mediated reductive cross-couplings of aryl iodides with activated aryl and heteroaryl bromides are described, along with related homocouplings (Ullmann reactions) and vinylic reductive couplings that occur with cine-substitution. To corroborate key events in the catalytic cycle, Pd-to-Pd transmetalation and cross-selective reductive elimination, dianionic diarylpalladate complexes [Pd(Aryl)(μ-Br)Br]2[NPr4]2 bearing p-fluorophenyl, p-methoxyphenyl and p-nitrophenyl moieties were prepared. Stoichiometric reactions of these complexes in the presence of iodide demonstrate that Pd-to-Pd transmetalation by way of monomeric arylpalladates occurs at a greater rate than reductive elimination and that cross-selective C–C reductive elimination is favored for electronically distinct aryl partners. Hydrogen-mediated reductive cross-coupling of aryl iodides with α-bromostyrene occurs with cine-substitution (as observed in related formate-mediated processes), consistent with carbopalladation of α-bromostyrene by monomeric arylpalladates Pd(Aryl)I2[NBu4] that arise upon dissociation of [Pd(Aryl)(μ-I)I]2[NBu4]2.

Amazing paper from Krische, Carrow, White and Dotson out today in JACS. Cross-electrophile coupling to form biaryls using H2 as reductant. Wow.
Check it out: pubs.acs.org/doi/pdf/10.1...

Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...

Happy to share the final version of this work out in ACS CS. Inspired by ‘binding-focused’ chemoproteomic methods, we developed a ‘function-focused’ strategy to agnostically identify degradable proteins.
This was a big team effort led by
@inesforrest.bsky.social
and in collaboration with AbbVie.

During these uncertain times, I’m very happy to see that my institution, @scripps.edu has an open tenure-track Assistant Professor position. Any field in Chemistry or Biology is welcome. I’d especially love to see fellow neuroscientists apply. Please repost!

apply.interfolio.com/174756

Here we transform the natural product into a series of partial, full and G protein biased KOR-selective agonists, which appear centrally active in vivo. Core diversification was aided by mutually chemoselective sp3-sp2 and sp2-sp2 cross-couplings.

Congrats to Florian, Stone and Sam for publication of Part 1 in our collaboration with Laura Bohn's lab to explore the pharmacology of GB18, a Galbulimima alkaloid that we identified as a novel opioid in 2022.
pubs.acs.org/doi/10.1021/acscentsci.5c00573

“…deaths of such children but also to deny these deaths and call them lies. The denials erase these children and dodge all responsibility.”

“If Rubio needs further reminder of the human toll, this little girl is Achol Deng, 8, who likewise died when she lost access to antiretrovirals because of the U.S.A.I.D. freeze.”
“I share these photos of Evan and Achol because it strikes me as doubly offensive not only to cause unnecessary..”

…and it turned the tide of AIDS around the world and built enormous good will toward the US.”
“Then along came President Trump and his freeze on most humanitarian aid in January. How could a 5-year-old orphan obtain medicine on his own? Evan weakened and soon died of an opportunistic infection.”

“… five years America kept him alive with antiretroviral medicines costing less than 12 cents a day, through the President’s Emergency Plan for AIDS Relief, or PEPFAR. This was a program started by President George W. Bush that has saved more than 26 million lives so far…”

““That’s a lie,” Rubio said. “False.”

So let me help Rubio with the truth. Meet Evan Anzoo, a 5-year-old boy who was born with H.I.V. in South Sudan.”

“I mentioned Evan in a column in March from South Sudan. This was a child as precious as yours or mine.”

“Evan’s life was in our hands, and for…”

“… is whether to measure the dead in the thousands, tens of thousands or hundreds of thousands.”
“So Representative Brad Sherman, a California Democrat, challenged Rubio, citing reporting overseas by me and by Reuters of individuals who died as a result of the shutdown of American humanitarian aid.”

Opinion | Really, Secretary Rubio? I’m Lying About the Kids Dying Under Trump?

www.nytimes.com/2025/05/31/o...

“It was Elon Musk who first insisted that ‘no one has died.’ Now Rubio has doubled down.”

“While testifying before Congress, Rubio claimed that the Trump administration’s dismantling of USAID had not cost any lives. This is ludicrous. The only debate..”

Excited to present our newest preprint on the structure-function relationship of anaphylatoxin complement receptors. A casual number of 19 structures deciphering ligand recognition mechanisms, G protein/arrestin and species specific signaling. Please check it out! 🧪💊 www.biorxiv.org/content/bior...

Synthesis and target annotation of the alkaloid GB18 - Nature A synthetic route to GB18, an alkaloid from the bark of hallucinogenic Galbulimima sp., is developed, enabling its identification as an antagonist of κ- and μ-opioid receptors.

Here are some published studies, more en route. The pharmacology is ongoing, hence the need for continued support.
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
pubs.acs.org/doi/10.1021/...
www.science.org/doi/pdf/10.1...
www.nature.com/articles/s41...

The salvinorins and GB alkaloids are poised to become next generation medicines to treat pain and pruritis, as well as substance use disorders (SUDs) and mood disorders.

I can’t imagine a better investment of federal funds.

Or a bigger waste if the devastating cuts to NSF and NIH proceed.

Bittersweet graduation this year.

These two earned their PhDs working to understand components of traditional medicine (Salvinorin A and the GB alkaloids), each earned a Science paper and graduated in 4y.

Now they are highly skilled scientists with Merck and Janssen, trained with federal funds.