title: A new fluorescent probe for zinc(II): an 8-hydroxy-5-N,N-dimethylaminosulfonylquinoline-pendant 1,4,7,10-tetraazacyclododecane.
abstract: A new fluorescent probe for Zn2+, namely, 8-hydroxy-5-N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant cyclen (L8), was designed and synthesized (cyclen=1,4,7,10-tetraazacyclododecane). By potentiometric pH, 1H NMR, and UV spectroscopic titrations, the deprotonation constants pKa1-pKa6 of L(8)4 HCl were determined to be <2, <2, <2 (for amino groups of the cyclen and quinoline moieties), 7.19+/-0.05 (for 8-OH of the quinoline moiety), 10.10+/-0.05, and 11.49+/-0.05, respectively, at 25 degrees C with I=0.1 (NaNO3). The results of 1H NMR, potentiometric pH, and UV titrations, as well as single-crystal X-ray diffraction analysis, showed that L8 and Zn2+ form a 1:1 complex [Zn(H-1L8)], in which the 8-OH group of the quinoline ring of L8 is deprotonated and coordinates to Zn2+, in aqueous solution at neutral pH. On addition of one equivalent of Zn2+ and Cd2+, the fluorescence emission of L8 (5 microM) at 512 nm in aqueous solution at pH 7.4 [10 mM HEPES with I=0.1 (NaNO3)] and 25 degrees C increased by factors of 17 and 43, respectively. We found that the cyclen moiety has the unique property of quenching the fluorescence emission of the quinolinol moiety when not complexed with metal cations, but enhancing emission when complexed with Zn2+ or Cd2+. In addition, the Zn2+-L8 complex [Zn(H-1L8)] is much more thermodynamically and kinetically stable (Kd{Zn(H-1L8)}=[Zn2+]free[L8]free/[Zn(H-1L8)]=8 fM at pH 7.4) than the Zn2+ complexes of our previous Zn2+ fluorophores ([Zn(H-1L2)] and [Zn(L3)]). Furthermore, formation of [Zn(H-1L8)] is much faster than those of [Zn(H-1L2)] and [Zn(L3)]. The staining of early-stage apoptotic cells with L8 is also described.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan. shinaoki@rs.noda.tus.ac.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Aoki
authors.forename: Kazusa
authors.initials: K
authors.lastname: Sakurama
authors.forename: Nanako
authors.initials: N
authors.lastname: Matsuo
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takasawa
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Kei
authors.initials: K
authors.lastname: Takeda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kimura
mesh_terms: D000588:Amines / Q000737:chemistry*; D002104:Cadmium / Q000737:chemistry; D002413:Cations, Divalent; D000080027:Cyclams; D004563:Electrochemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry*; D013057:Spectrum Analysis; D013816:Thermodynamics; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry*
chemical_list: D000588:Amines; D002413:Cations, Divalent; D000080027:Cyclams; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; D011804:Quinolines; D002104:Cadmium; C038072:cyclen; C037219:quinoline; D015032:Zinc