title: Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications.
abstract: The syntheses and photophysical characterization of ZP9, 2-{2-chloro-6-hydroxy-3-oxo-5-[(2-{[pyridin-2-ylmethyl-(1H-pyrrol-2-ylmethyl)amino]methyl}phenylamino)methyl]-3H-xanthen-9-yl}benzoic acid, and ZP10, 2-{2-chloro-6-hydroxy-5-[(2-{[(1-methyl-1H-pyrrol-2-ylmethyl)pyridin-2-ylmethylamino]methyl}phenylamino)methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid, two asymmetrically derivatized fluorescein-based dyes, are described. These sensors each contain an aniline-based ligand moiety functionalized with a pyridyl-amine-pyrrole group and have dissociation constants for Zn(II) in the sub-micromolar (ZP9) and low-micromolar (ZP10) range, which we define as "midrange". They give approximately 12- (ZP9) and approximately 7-fold (ZP10) fluorescence turn-on immediately following Zn(II) addition at neutral pH and exhibit improved selectivity for Zn(II) compared to the di-(2-picolyl)amine-based Zinpyr (ZP) sensors. Confocal microscopy studies indicate that such asymmetrical fluorescein-based probes are cell permeable and Zn(II) responsive in vivo.
authors.affiliation: Department of Chemistry, Picower Institute of Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Nolan
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Maryann E
authors.initials: ME
authors.lastname: Racine
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000814:Aniline Compounds / Q000032:analysis / Q000737:chemistry; D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D002478:Cells, Cultured; D015392:Chemistry, Inorganic / Q000379:methods*; D005260:Female; D005453:Fluorescence; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008967:Molecular Biology / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D015032:Zinc / Q000032:analysis / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D015032:Zinc; C023650:aniline