A Novel Biomimetic Zinc(II)−Fluorophore, Dansylamidoethyl−Pendant Macrocyclic Tetraamine 1,4,7,10-Tetraazacyclododecane (Cyclen)

• Published in: Journal of the American Chemical Society Vol. 118; no. 50; pp. 12696 - 12703
• Main Authors: Koike, Tohru, Watanabe, Tomohiko, Aoki, Shin, Kimura, Eiichi, Shiro, Motoo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.12.1996; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; CARBONIC-ANHYDRASE; TRIAMINE; ALCOHOL-PENDANT; PHENOL-PENDANT; ZINC(II) COMPLEX; MODEL; POLYAMINE COMPLEXES; FLUORESCENT-PROBE; CARBOXYESTER HYDROLYSIS; AQUEOUS-SOLUTION
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja962527a

On the basis of the chemical principle of carbonic anhydrase (CA)−aromatic sulfonamide inhibitor interaction, a dansylamidoethyl−pendant cyclen (1-(2-(5-(dimethylamino)-1-naphthalenesulfonamido)ethyl)-1,4,7,10-tetraazacyclododecane, HL) has been synthesized as a novel type of zinc(II)−fluorophore. The new ligand HL forms very stable complexes (ML) with zinc(II), cadmium(II), and copper(II) at physiological pH. The potentiometric and spectrophotometric pH-titration study disclosed the 1:1 metal(II) complexes stability constants log K(ML) (= log([ML]/[M][L])) to be 20.8 ± 0.1 for ZnL, 19.1 ± 0.1 for CdL, and >30 for CuL. The crystalline zinc(II) complex ZnL was isolated from aqueous solution at pH 7. The X-ray crystal study of ZnL disclosed a five-coordinate, distorted square-pyramidal structure with the deprotonated dansylamide N- coordinating at the apical site. Crystals of the monoperchlorate salt of ZnL (C22H35N6O6SClZn) are orthorhombic, space group Pna21 (no. 33) with a = 23.777(3) Å, b = 12.744(5) Å, c = 9.092(3) Å, V = 2755(2) Å3, Z = 4, R = 0.032, and R w = 0.047. The zinc(II) complex shows a maximum UV absorption band (λmax) at 323 nm (ε 5360) at 25 °C in aqueous solution. The fluorescent maximum and the quantum yield (Φ) of ZnL vary with the solvent:  at 528 nm (Φ = 0.11) in H2O, 496 nm (0.53) in MeOH, 489 nm (0.60) in EtOH, and 484 nm (0.44) in CH3CN. Demetalation of ZnL with excess amount of EDTA yielded the metal-free ligand HL, which in pH 7.3 aqueous solution has an excitation and a weak emission fluorescence at 330 nm (ε 4950) and 555 nm (Φ = 0.03), respectively. The copper(II) ion, to the contrary, completely quenches the fluorescence. The crystalline copper(II) complex CuL (λmax 306 nm, ε 7630 in H2O) was isolated as its monoperchlorate salt. The zinc(II)-dependent fluorescence with 5 μM HL at pH 7.3 is quantitatively responsive to 0.1−5 μM concentration of zinc(II), which is unaffected by the presence of mM concentration of biologically important metal ions such as Na+, K+, Ca2+, and Mg2+. The new ligand HL forms a far more stable 1:1 zinc(II) complex than any previous zinc(II)-fluorophore and is evaluated as a new zinc(II)-fluorophore.