title: Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis.
abstract: Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chemistry. Here we report a new series of water-soluble catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are additionally functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the production of triazoles with different substitution patterns. Additionally, successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calculations.
authors.affiliation: Laboratory of Organometallics, Catalysis and Ordered Materials, State Key Laboratory of Advanced Technology for Materials Synthesis and Processing; Center for Chemical and Material Engineering, Wuhan University of Technology; Department of Applied Chemistry, Faculty of Sciences, Wuhan University of Technology, Wuhan 430070, P.R. China. francis.verpoort@ghent.ac.kr.
authors.forename: Heriberto
authors.initials: H
authors.lastname: Díaz Velázquez
authors.forename: Yara
authors.initials: Y
authors.lastname: Ruiz García
authors.forename: Matthias
authors.initials: M
authors.lastname: Vandichel
authors.forename: Annemieke
authors.initials: A
authors.lastname: Madder
authors.forename: Francis
authors.initials: F
authors.lastname: Verpoort
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry; D002384:Catalysis; D057930:Click Chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D061565:Cycloaddition Reaction; D004247:DNA / Q000737:chemistry; D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D012995:Solubility; D013816:Thermodynamics; D014230:Triazoles / Q000138:chemical synthesis; D014867:Water
chemical_list: D000480:Alkynes; D001386:Azides; D050976:Basic-Leucine Zipper Transcription Factors; D056831:Coordination Complexes; C501391:GCN4 protein, S cerevisiae; D006571:Heterocyclic Compounds; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D014230:Triazoles; D014867:Water; C030011:carbene; D003300:Copper; D004247:DNA; D008697:Methane