The rhodafluor family. An initial study of potential ratiometric fluorescent sensors for Zn2+.
A new class of ratiometric Zn(2+) sensors that employ a hybrid fluorescein and rhodamine fluorophore has been designed, and two members of the rhodafluor family of sensors, RF1 and RF2, have been synthesized. The preparation of RF1 (9-(o-carboxyphenyl)-2-chloro-6-[bis(2-pyridylmethyl)amino]-3-xanthanone, Rhodafluor-1), uses conventional synthetic methods. Elaboration of the RF1 synthesis in an effort to enhance the Zn(2+) affinity was unsuccessful, so palladium-catalyzed aryl amination was applied to prepare RF2 (1-[9'-(o-carboxyphenyl)-6'-amino-2'-chloro-3'-xanthanone]-4,10-(diethyl)-7-(2-pyridylmethyl)-1,4,7,10-tetraazacyclododecane, Rhodafluor-2). The key step in the synthesis of RF2 is coupling of a triprotected tetraazamacrocycle (cyclen) to 3-bromoanisidine. RF2 binds Zn(2+) with a dissociation constant of 13.5 microM accompanied by an approximately 50% increase in quantum yield. Although only small shifts in absorption wavelength were observed, because protonation of the amino nitrogen atoms of the macrocycle prevents the uncomplexed sensor from adopting the desired mesomer, the intensity doubling makes the probe of value for immediate application in situations where our previous tight binding (<1 nM) sensors are inadequate.
Burdette
Shawn C
SC
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Lippard
Stephen J
SJ
D002384:Catalysis; D018360:Crystallography, X-Ray; D005452:Fluoresceins / Q000138:chemical synthesis* / Q000737:chemistry; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000138:chemical synthesis*; D015032:Zinc / Q000032:analysis* / Q000737:chemistry*
C473809:1-(9'-(o-carboxyphenyl)-6'-amino-2'-chloro-3'-xanthanone)-4,10-(diethyl)-7-(2-pyridylmethyl)-1,4,7,10-tetraazacyclododecane; C473808:9-(o-carboxyphenyl)-2-chloro-6-(bis(2-pyridylmethyl)amino)-3-xanthanone; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012235:Rhodamines; D014966:Xanthenes; D010165:Palladium; D015032:Zinc