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Cyclometalated Au III Complexes for Cysteine Arylation in Zinc Finger Protein Domains: towards Controlled Reductive Elimination
Author(s) -
Wenzel Margot N.,
Bonsignore Riccardo,
Thomas Sophie R.,
Bourissou Didier,
Barone Giampaolo,
Casini Angela
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901535
Subject(s) - chemistry , zinc finger , reductive elimination , zinc , combinatorial chemistry , electrospray ionization , aqueous solution , cysteine , reactivity (psychology) , mass spectrometry , catalysis , medicinal chemistry , stereochemistry , computational chemistry , organic chemistry , enzyme , medicine , biochemistry , alternative medicine , pathology , transcription factor , gene , chromatography
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 Au III C^N complexes with a zinc finger peptide (Cys 2 His 2 type) is here reported. Among the four selected Au III cyclometalated compounds, the [Au(C CO N)Cl 2 ] complex featuring the 2‐benzoylpyridine (C CO N) 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 Au III ‐catalyzed reductive elimination in aqueous media.