|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1998 : ¥1,600,000 (Direct Cost : ¥1,600,000)
In order to determine the zinc(II) acidity in macrocyclic polyamine, a new carbonyl-bound zinc(II) complex was demonstrated to be a good model that serves to elucidate the role of zinc(II) in the class II aldolases and proteases. The deprotonation of the zinc(II)-bound carbonyl occurred with a pKィイD2aィエD2 of 8.41 and one of the resulting products, an enolate-bound complex 12 was separately isolated. Thus, zinc(II) ion demonstrated a thermodynamic effect to raise the acidity of the carbonyl methylene (ordinary pKィイD2aィエD2, ca. 19) by orders of 10. The deprotonation from the zinc(II) complex competitively yielded an isomeric zinc hydroxide complex in the equilibrium (ratio = 1 : 3) regardless of the aqueous solution at 25°C. In more anhydrous conditions, the equilibrium shifted to the enolate-bound complex and in pure MeCN solution only enolate-bound complex was formed. The present discovery that in the presence of zinc enolates can be generated near neutral pH would be useful informatio
n in exploring more refined Zn-cataiytic aldol reactions and amide-hydrolysis reactions in aqueous solution.
Moreover, a lipophilic zinc(II) complex has been synthesized and fully characterized. It was demonstrated that in co-micellar solution , the zinc complex forms Zn-hydroxideat alkaline pH. The Zn-hydroxide is the nucleophilic catalyst in the co-micelle for hydrolysis of 4-nitrophenyl acetate, phosphotriester and phosphodiester monoanion. This study suggests that the lipophilic zinc complex in the presence of the surfactant may be an extremely promising candidate for disposal of nerve gases. Using amido substrates (e.g., acetoanilide, 4-nitroacetoanilide, glycylgricine), however, we could not observe the amide hydrolysis by the zinc complex.
Furthermore, we have demonstrated that bis(Zn-cyclen) and tris(Zn-cyclen) are novel types of DNA sequence-selective ligands, which are extremely efficient in bnding to poly-thymine group (e.g., TpT and TpTpT) at μM concentrations. These zinc(II)-polymacrocyclic complexes and their modifications would find wide biochemical and medicinal applications by a mechanism entirely different from those of conventional DNA-motif recognizing drugs. Less