Quinoline-based, glucose-pendant fluorescent zinc probes.

Quinoline-based tetradentate ligands with glucose pendants, N,N'-bis[2-(β-d-glucopyranosyloxy)ethyl]-N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine (N,N'-6-MeOBQBGEN) and its N,N-counterpart, N,N-6-MeOBQBGEN, have been prepared, and their fluorescence-spectral changes upon Zn binding were investigated. Upon excitation at 336 nm, N,N'-6-MeOBQBGEN showed weak fluorescence (ϕ ≈ 0.016) in HEPES buffer (HEPES 50 mM, KCl 100 mM, pH 7.5). In the presence of Zn, N,N'-6-MeOBQBGEN exhibited a significant increase in fluorescence (ϕ = 0.096) at 414 nm. The fluorescence enhancement is specific for Zn and Cd (I(Cd) /I(Zn) of 50% at 414 nm). On the other hand, N,N-6-MeOBQBGEN exhibited a smaller fluorescence enhancement upon Zn complexation (ϕ = 0.043, λ(ex) = 334 nm, λ(em) = 407 nm) compared with N,N'-6-MeOBQBGEN. Fluorescence microscopic analysis using PC-12 rat adrenal cells revealed that N,N'-6-MeOBQBGEN exhibits a 1.8-fold higher fluorescence-signal response to Zn ion concentration compared with sugar-depleted compound 2 (N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine), due to its enhanced uptake into cells due to the targeting ability of the attached carbohydrates.