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.

Potent inhibition of dinuclear zinc(II) peptidase, an aminopeptidase from Aeromonas proteolytica, by 8-quinolinol derivatives: inhibitor design based on Zn2+ fluorophores, kinetic, and X-ray crystallographic study

“…The mode of inhibition of AAP by 8-HQ derivatives [28,29]. In addition, the findings indicate that the 8-HQ derivatives are competitive inhibitors of AAP, as described earlier.…”

“…fluorophores L 2 and L 3 that contain 8-quinolinol (8-hydroxyquinoline, 8-HQ, or oxine) groups on the side chains also form 1:1 Zn 2? complexes 2 [Zn(H -1 L 2 )] and 3 [Zn(H -1 L 3 )] [28,29], resulting in a substantial increase in fluorescence by a factor of 17 and 32 (the quantum yields for the emission of 2 and 3 are 4.4 9 10 -2 and 4.1 9 10 -1 ). The dissociation constants, K d , of 2 and 3 were determined to be of femtomolar order at pH 7.4, and the formation of 2 and 3 is complete in milliseconds, implying that 2 and 3 are very stable, not only thermodynamically but also kinetically owing to bidentate chelation via the phenolate oxygen and the quinoline nitrogen of the 8-quinolinolate group, as confirmed by X-ray crystal structure analysis and spectroscopic data [28,29].…”

Metal‐Catalysed Oxidation Processes in Thiosemicarbazones: New Complexes with the Ligand N‐{2‐([4‐N‐Ethylthiosemicarbazone]methyl)phenyl}‐p‐toluenesulfonamide

“…[19,20] Therefore, the different emission intensities depend on the delocalization of charge through the vacant orbitals of each metal centre. [21] The emission spectra of the complexes [Zn(L (14) each show a single broad band, with the maxima at 490 nm (Zn and Pb) and 486 nm (Cd). The spectra are independent of the excitation monitoring wavelength, suggesting the presence of a single emissive species in the excited state.…”

Photochemical Cleavage Reactions of 8-Quinolinyl Sulfonates in Aqueous Solution

“…38,40) 8-Benzenesulfonyloxy-5-N,N-dimethylaminosulfonylquinaldine (5a) 38) A solution of benzenesulfonyl chloride (164 ml, 1.28 mmol) in THF (10 ml) was added dropwise to a solution of 5-N,N-dimethylaminosulfonyl-8-hydroxy-quinaldine (9) (256 mg, 1.00 mmol) and Et 3 N (210 ml, 1.5 mmol) in …”