Organometallic Chemistry Tools for Building Biologically Relevant Nanoscale Systems DOI
James A. R. Tilden, Evan A. Doud, Hayden R. Montgomery

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

The recent emergence of organometallic chemistry for modification biomolecular nanostructures has begun to rewrite the long-standing assumption among practitioners that small-molecule organometallics are fundamentally incompatible with biological systems. This Perspective sets out clarify some existing misconceptions by focusing on growing toolbox modification. Specifically, we highlight key transformations in constructing complex biologically relevant systems nanomolecular scale, and synthesis hybrid nanomaterials composed classical nanomaterial components combined species. As research progresses, many challenges associated applying this context rapidly being reassessed. Looking future, utility will likely make them more ubiquitous construction nanostructures.

Language: Английский

In Silico Screening of P,N-Ligands Facilitates Optimization of Au(III)-Mediated S-Arylation DOI Creative Commons
Joseph W. Treacy, James A. R. Tilden, Elaine Y. Chao

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In silico examination of 13 P , N -ligated Au( iii ) OACs determined the key mechanistic factors governing )-mediated S -arylation. Three complexes were synthesized which exhibited bimolecular coordination rate constants as high 20 200 M −1 s .

Language: Английский

Citations

2
Exploring the Electronic and Steric Effects of Hemilabile (P^N) Ligands in Redox Gold Catalysis: Application to the Cross-Coupling Reaction of Aliphatic Amines with Aryl Iodides DOI

Urvashi Urvashi,

Saurabh Rai, Gaurav Shukla

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Herein, we report 17 new (P^N) ligands for redox gold catalysis, featuring various substituents at -C4, -C5, and -C6 of the aryl ring nitrogen handle. Rate kinetics experiments revealed that electron-rich -C4 -C5 positions enhanced rate oxidative addition Au(I) with C(sp2)-Br bonds compared to electron-poor substituents. Further, an unprecedented gold-catalyzed arylation aliphatic amines using electronically rich ligand (L6) -OMe group position.

Language: Английский

Citations

1
Organometallic Oxidative Addition Complexes for S-Arylation of Free Cysteines DOI
Hayden R. Montgomery, Alexander M. Spokoyny, Heather D. Maynard

et al.

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: 35(7), P. 883 - 889

Published: June 24, 2024

Development of bioconjugation strategies to efficiently modify biomolecules is key importance for fundamental and translational scientific studies. Cysteine

Language: Английский

Citations

5
Electronic Effects of Bidentate P,N-Ligands on the Elementary Steps of Au(I)/Au(III) Reactions Relevant to Cross-Coupling Chemistry DOI Creative Commons
Joseph W. Treacy, Elaine Y. Chao, Grace E. Kunkel

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Oxidant-free Au(I)/Au(III)-catalyzed cross-coupling has been recently enabled by the use of bidentate

Language: Английский

Citations

5
A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins DOI Creative Commons

Xiaoxi Lin,

Shaswati Mandal, Raj V. Nithun

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(37), P. 25788 - 25798

Published: Sept. 3, 2024

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is aromatic side chain Tyr, which undergoes such as phosphorylation nitration. Despite biological physiological importance Tyr-PTMs, our current understanding mechanisms by these contribute to human health disease remains incomplete. This knowledge gap arises from absence natural amino acids that can mimic PTMs lack synthetic tools for site-specific introduction into proteins. Herein, we describe a facile method chemical installation through palladium-mediated S-C(sp

Language: Английский

Citations

4
Gold-Catalyzed Cross-Coupling Reactions of Organoiodides with Disulfides: Access to Aryl Sulfides and Vinyl Sulfide Derivatives DOI

Lizhu Zhang,

Yan-Fei Hu, Fen Zhao

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Thioethers and their derivatives play important roles in synthetic chemistry, medicinal materials science. Herein, we report a hemilabile P,N-ligand-assisted gold-catalyzed C-S cross-coupling reaction of organoiodides with disulfides. In this reaction, alkyl or aryl disulfides react smoothly vinyl iodides to afford series sulfide good excellent yields. The robust capabilities thioether synthesis are exemplified by the readily available easily handled reagents as well compatibility wide range functional groups.

Language: Английский

Citations

0
Phosphine-promoted Thiol-Specific Bioconjugation with Allylic Acetates DOI Creative Commons
Teck‐Peng Loh, Xiaohong Li, Tao Xu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Thiol-specific modification of proteins through conjugation with small molecules represents a critical advancement in biological research and therapeutic development, particularly the context antibody-drug conjugates (ADCs) for targeted cancer therapy. Despite widespread use maleimide-based linkers, their stability under physiological conditions remains major limitation, often compromising efficacy. In this investigation, we developed novel efficient thiol-specific bioconjugation strategy that employs allylic acetate, activated by recyclable solid phosphine catalyst. This approach achieves high yields demonstrates robust bio-compatible, room-temperature conditions. Notably, it sets new record fastest cysteine-conjugation reaction rate reported to date, constant k2 = 1.49 × 106 M− 1s− 1. The method expands substrate scope introduces sustainable, environmentally friendly ADC linker design, offering significant creation stable, biocompatible, therapeutically effective compounds.

Language: Английский

Citations

0
A systematic kinetic assay of phenylsulfonyl pyridine derivatives with free thiol for site-specific modification of proteins DOI

Xing Zhang,

Mohan Li,

Ben‐Guang Chen

et al.

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This study examined the kinetics of phenylsulfonyl pyridines to free thiol, with reactivity that can be tuned by an order magnitude 1–5. The pyridine derivatives provide a powerful tool for precise protein modifications under mild conditions.

Language: Английский

Citations

0
Gold-Catalyzed Deallylative C–S Cross-Coupling Reactions DOI

Prafulla Bera,

Tanmayee Nanda,

Nivrutti B. Barhate

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Herein, we report the gold-catalyzed deallylative C-S cross-coupling reaction through ligand-enabled Au(I)/Au(III) redox catalysis. One of major challenges in reactions is to prevent catalyst deactivation caused by formation a strong gold-sulfur bond. We discovered that use allyl phenyl sulfide as sulfur surrogate facilitates dynamic equilibrium between cationic Au(I) and Au(I)-sulfide complexes, overcoming gold quenching problem. A detailed mechanistic investigation, including 31P NMR studies, mass analysis, stoichiometric experiments, provided valuable insights into mechanism, which further supported computational studies.

Language: Английский

Citations

0
Comparison of Cyclic and Linear PEG Conjugates DOI Creative Commons
Grace E. Kunkel, Qingyang Zhou, Joseph W. Treacy

et al.

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: 35(6), P. 744 - 749

Published: May 29, 2024

Bioconjugation of polymers to proteins is a method impart improved stability and pharmacokinetic properties biologic systems. However, the precise effects polymer architecture on resulting bioconjugates are not well understood. Particularly, cyclic known possess unique features such as decreased hydrodynamic radius when compared their linear counterparts same molecular weight, but have yet been studied. Here, we report first bioconjugation polymer, poly(ethylene glycol) (PEG), model protein, T4 lysozyme, containing single engineered cysteine residue (V131C). We compare activity this conjugate with those PEG-T4 lysozyme analogue similar weight. Furthermore, used dynamics (MD) simulations determine behavior polymer–protein conjugates in solution. introduce potential candidates for improvement therapeutics.

Language: Английский

Citations

2