Evidence map›Paper›PMID 38994402›Full record

ArticleChemical science2024

Controlling rates and reversibilities of elimination reactions of hydroxybenzylammoniums by tuning dearomatization energies.

Zihuan Fu, Joseph W Treacy, Brock M Hosier, K N Houk, Heather D Maynard

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Selective Iridium-Catalyzed Reductive Amination Inside Living Cells.Journal of the American Chemical Society · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Zihuan FuDepartment of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles California 90095-1569 USA maynard@chem.ucla.edu.ORCID https://orcid.org/0000-0002-6559-0449
Joseph W TreacyDepartment of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles California 90095-1569 USA maynard@chem.ucla.edu.ORCID https://orcid.org/0000-0002-8597-0246
Brock M HosierDepartment of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles California 90095-1569 USA maynard@chem.ucla.edu.
K N HoukDepartment of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles California 90095-1569 USA maynard@chem.ucla.edu.ORCID https://orcid.org/0000-0002-8387-5261
Heather D MaynardDepartment of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles California 90095-1569 USA maynard@chem.ucla.edu.ORCID https://orcid.org/0000-0003-3692-6289

Funding

Chemistry Biology Interface Training ProgramT32GM136614 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Patrick G. Harran · 2020 to 2026
$2.8M
Stabilization of Glucagon by Trehalose Gylcopolymer NanogelsR01DK127908 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 2021 to 2023
$1.1M
NIDDK NIH HHS R01 DK127908NIGMS NIH HHS T32 GM136614
6 · The paper itself

Abstract

Hydroxybenzylammonium compounds can undergo a reversible 1,4- or 1,6-elimination to afford quinone methide intermediates after release of the amine. These molecules are useful for the reversible conjugation of payloads to amines. We hypothesized that aromaticity could be used to alter the rate of reversibility as a distinct thermodynamic driving force. We describe the use of density functional theory (DFT) calculations to determine the effect of aromaticity on the rate of release of the amine from hydroxybenzylammonium compounds. Namely, the aromatic scaffold affects the dearomatization reaction to reduce the kinetic barrier and prevent the reversibility of the amine elimination. We consequently synthesized a small library of polycyclic hydroxybenzylammoniums, which resulted in a range of release half-lives from 18 minutes to 350 hours. The novel mechanistic insight provided herein significantly expands the range of release rates amenable to hydroxybenzylammonium-containing compounds. This work provides another way to affect the rate of payload release in hydroxybenzylammoniums.

Identifiers

PMID38994402
PMCPMC11234877

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.