Design and synthesis of a caged Zn2+ probe, 8-benzenesulfonyloxy-5-N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant 1,4,7,10-tetraazacyclododecane, and its hydrolytic uncaging upon complexation with Zn2+.
8-Benzenesulfonyloxy-5- N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant cyclen (BS-caged-L(4), BS = benzenesulfonyl) was designed and synthesized as a "caged" derivative of a previously described Zn(2+) fluorophore, 8-hydroxy-5- N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant cyclen (L(4)) (cyclen = 1,4,7,10-tetraazacyclododecane). In the absence of metal ions and in the dark, BS-caged-L(4) (10 microM) showed negligible fluorescence emission at pH 7.4 (10 mM HEPES with I = 0.1 (NaNO3)) and 25 degrees C (excitation at 328 nm). Addition of Zn(2+) induced an increase in the UV/vis absorption of BS-caged-L(4) (10 microM) at 258 nm and a significant increase in fluorescence emission at 512 nm. These responses are results from the formation of Zn(H-1L(4)) by the hydrolysis of the sulfonyl ester at the 8-position of the quinoline unit promoted by the Zn(2+)-bound HO(-). Improvement of cell membrane permeation in comparison with L(4) is also described.
Aoki
Shin
S
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510 Japan. shinaoki@rs.noda.tus.ac.jp
Sakurama
Kazusa
K
Ohshima
Ryosuke
R
Matsuo
Nanako
N
Yamada
Yasuyuki
Y
Takasawa
Ryoko
R
Tanuma
Sei-ichi
S
Takeda
Kei
K
Kimura
Eiichi
E
D002104:Cadmium / Q000737:chemistry; D002413:Cations, Divalent / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013053:Spectrophotometry; D013457:Sulfur Compounds / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
C529199:8-benzenesulfonyloxy-5-N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant 1,4,7,10-tetraazacyclododecane; D002413:Cations, Divalent; D005456:Fluorescent Dyes; D006573:Heterocyclic Compounds, 1-Ring; D013457:Sulfur Compounds; D002104:Cadmium; D006859:Hydrogen; D015032:Zinc