A Simple DNase Model System Comprising a Dinuclear Zn(II) Complex in Methanol Accelerates the Cleavage of a Series of Methyl Aryl Phosphate Diesters by 10 super(11)-10 super(13)

The di-Zn(II) complex of 1,3-bis[N sub(1),N sub(1)'-(1,5,9- triazacyclododecyl)]propane with an associated methoxide (3:Zn(II) sub(2): super(- )OCH sub(3)) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters (6) was studied at sub(s) super(s)pH 9.8 in methanol at 25.0 +/- 0.1 degree C. Plots of k sub(obs) vs [3:Zn(II) sub(2): super(-) OCH sub(3)] sub(free) for all members of 6 show saturation behavior from which K sub(M) and k sub(cat) super(max) were determined. The second order rate constants for the catalyzed reactions (k sub(cat) super(max)/K sub(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k sub(2) super(-OMe)) by 1.4 x 10 super(8) to 3 x 10 super(9)-fold. The values of k sub(cat) super(max) for all members of 6 are between 4 x 10 super(11) and 3 x 10 super(13) times larger than the solution reaction at sub(s) super(s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO sub(2) or C(O)OCH sub(3) groups. Based on the linear Broensted plots of k sub(cat) super(max) vs sub(s) super(s) pK sub(a) of the phenol, beta sub(lg) values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO sub(2) or C(O)OCH sub(3) groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH sub(3)O super(-):6] super(d), giving a hypothetical [3:Zn(II) sub(2):CH sub(3)O super(- ):6] super(d) complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO sub(2) or C(O)OCH sub(3) groups.