Cyclometalated AuIII Complexes for Cysteine Arylation in Zinc Finger Protein Domains: towards Controlled Reductive Elimination

Giampaolo Barone, Riccardo Bonsignore, Margot N. Wenzel, Sophie R. Thomas, Didier Bourissou, Angela Casini

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C-atom transfer, the gold-mediated cysteine arylation through a reductive elimination process occurring from the reaction of cyclometalated AuIII C^N complexes with a zinc finger peptide (Cys2His2 type) is here reported. Among the four selected AuIII cyclometalated compounds, the [Au(CCON)Cl2] complex featuring the 2-benzoylpyridine (CCON) scaffold was identified as the most prone to reductive elimination and Cys arylation in buffered aqueous solution (pH 7.4) at 37 °C by high-resolution LC electrospray ionization mass spectrometry. DFT and quantum mechanics/molecular mechanics (QM/MM) studies permitted to propose a mechanism for the title reaction that is in line with the experimental results. Overall, the results provide new insights into the reactivity of cytotoxic organogold compounds with biologically important zinc finger domains and identify initial structure–activity relationships to enable AuIII-catalyzed reductive elimination in aqueous media.
Original languageEnglish
Pages (from-to)7628-7634
Number of pages7
JournalCHEMISTRY-A EUROPEAN JOURNAL
Volume25
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

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