title: Synthesis of N,N-Dialkylamino-nor-Dihydroxanthene-Hemicyanine Fused Near-Infrared Fluorophores and Their First Water-Soluble and/or Bioconjugatable Analogues.
abstract: The effective synthesis of extended conjugated N,N-dialkylamino-nor-dihydroxanthene-based fluorophores is described from diversely functionalized salicylic aldehydes. The access to these original fluorescent derivatives proceeded in two steps through a one-pot construction of the unusual nor-dihydroxanthene (nor-DHX) scaffold followed by a diversification step providing a wide variety of nor-DHX-hemicyanine fused dyes emitting in the range of 730-790 nm. The versatility of our approach has enabled a further extension to the late-stage introduction of negatively/positively charged polar groups onto their terminal nitrogen heterocyclic subunit, thereby giving access to the first water-soluble and/or bioconjugatable members of this emerging class of NIR fluorophores. Our water-solubilizing method is easily implementable, and the nor-DHX-hemicyanine skeleton maintains satisfying fluorescence quantum yields (5-20 %) under physiological conditions. Finally, the bioconjugation ability of fluorescent derivatives bearing a free carboxylic acid was demonstrated through the covalent labeling of a model protein, namely, bovine serum albumin.
authors.affiliation: Organic Chemistry, Institute of Chemical and Engineering Sciences, ICES, Agency for Science, Technology and Research, A*STAR, 8 Biomedical Grove, Neuros, #07-01, Singapore, 138665, Singapore.
authors.forename: Michelle Jui Hsien
authors.initials: MJH
authors.lastname: Ong
authors.affiliation: ICMUB, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21078, Dijon cedex, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Debieu
authors.affiliation: ICMUB, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21078, Dijon cedex, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Moreau
authors.affiliation: ICMUB, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21078, Dijon cedex, France.|Institut Universitaire de France, 103, Boulevard Saint-Michel, 75005, Paris, France.
authors.forename: Anthony
authors.identifier: http://orcid.org/0000-0002-2300-4499
authors.initials: A
authors.lastname: Romieu
authors.affiliation: Organic Chemistry, Institute of Chemical and Engineering Sciences, ICES, Agency for Science, Technology and Research, A*STAR, 8 Biomedical Grove, Neuros, #07-01, Singapore, 138665, Singapore.
authors.forename: Jean-Alexandre
authors.initials: JA
authors.lastname: Richard
mesh_terms: D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D007259:Infrared Rays; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry*; D014966:Xanthenes / Q000737:chemistry*
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D014966:Xanthenes; C000601156:tetramethylene hemicyanine; D014867:Water; D012710:Serum Albumin, Bovine
keywords: NIR dyes; fluorescence; nor-dihydroxanthene; protein labeling; water solubility