A new benzyl alcohol-pendant 1,4,7,10-tetraazacyclododecane (cyclen) ligand, (S)-1-(2-hydroxy-2-phenylethyl)-1,4,7,10-tetraazacyclododecane (L) (11), has been synthesized. The complexation of 11 with Zn-II yielded 1:1 five-coordinate complexes (isolated as its perchlorate salts with the pendant alcohol either undissociated (ZnL, 14a) or dissociated (ZnH(-1)L, 14b) from acidic (pH 6.0) or basic (pH 9.5) aqueous solution, respectively). The pK(a) value for the pendant alcohol (14a reversible arrow 14b + H+) was determined by potentiometric pH titration to be 7.30 +/- 0.02 at 35 degrees C with I = 0.10 (NaNO3). The X-ray crystal study of 14b has shown two crystallographically distinct structures with the alkoxide closely coordinated at the fifth coordination site, where an average distance of Zn-O- is 1.91 Angstrom. Crystals of 14b . ClO4 (C16H27N4O5ClZn) are orthorhombic, space group P2(1)2(1)2(1) (no. 19) with a = 16.977 (4) Angstrom, b = 18.135 (4) Angstrom, c = 13.173 (3) Angstrom, V = 4055 (1) Angstrom(3), Z = 8, R = 0.050, and R(w) = 0.077. The Zn-II-bound alkoxide anion in 14b is a more reactive nucleophile than N-methylcyclen-Zn-II-OH- species 15b. In the kinetic study using 14 in aqueous solution (pH 6.0-10.3) at 35 degrees C with I = 0.10 (NaN03), the rate-pH profile for a phosphoryl transfer reaction from bis(4-nitrophenyl) phosphate (BNP-) to 14b gave a sigmoidal curve with an inflection point at pH 7.4, which corresponds to the pK(a) value for 14a reversible arrow 14b + H+. The second-order rate constant k(BNP) of (6.5 +/- 0.1) x 10(-4) M(-1) s(-1) is 125 times greater than the corresponding value of (5.2 +/- 0.2) x 10(-6) M(-1) s(-1) for BNP- hydrolysis catalyzed by 15b. The product of the phosphoryl transfer reaction from BNP- to 14b is the pendant alcohol-phosphorylated 16, which was isolated as its perchlorate salt 16a by reacting 14b with BNP- in DMF. In anhydrous DMF solution, the phosphoryl transfer (k(BNP) of 1.1 +/- 0.1 M(-1) s(-1) at 35 degrees C) is 1700 times faster than that in aqueous solution. In the subsequent reaction of 16, the pendant phosphodiester undergoes an intramolecular nucleophilic attack by the Zn-II-bound OH- of 16b to yield a phosphomonoester product 17. From the sigmoidal rate-pH relationship (pH 7.4-10.5), the kinetic pK(a) value of 9.0 was estimated for 16a reversible arrow 16b + H+, which is almost the same value (pK(a) = 9.10 +/- 0.05) determined by potentiometric pH titration at 35 degrees C. The first-order rate constant for the reaction 16b --> 17 is (3.5 +/- 0.1) x 10(-5) s(-1) at 35 degrees C with I = 0.10 (NaNO3). As a reference to this intramolecular phosphodiester hydrolysis, ethyl (4-nitrophenyl) phosphate (NEP(-)) was hydrolyzed by 15b; The second-order rate constant k(NEP) was (7.9 +/- 0.3) x 10(-7) M(-1) s(-1) at 35 degrees C with I = 0.10 (NaNO3). Thus, the intramolecular hydrolysis is 45 000 times faster than the intermolecular NEP(-) hydrolysis with 1 mM 15h. The present findings that demonstrate the potential of the proximate alcohol by Zn-II in the initial phosphoryl transfer and the potential of the Zn-II-bound water in the intramolecular phosphate hydrolysis may well serve to elucidate the collaborative functions of Ser-102 and Zn-II ions in alkaline phosphatase.옆