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 1011−1013
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- 作者：Alexei A. Neverov ; C. Tony Liu ; Shannon E. Bunn ; David Edwards ; Christopher J. White ; Stephanie A. Melnychuk ; R. Stan Brown
- 刊名：Journal of the American Chemical Society
- 出版年：2008
- 出版时间：May 21, 2008
- 年：2008
- 卷：130
- 期：20
- 页码：6639 - 6649
- 全文大小：256K
- 年卷期：v.130,no.20(May 21, 2008)
- ISSN：1520-5126
文摘
The di-Zn(II) complex of 1,3-bis[N1,N1′-(1,5,9-triazacyclododecyl)]propane with an associated methoxide (3:Zn(II)2:−OCH3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters (6) was studied at sspH 9.8 in methanol at 25.0 
0.1 °C. Plots of kobs vs [3:Zn(II)2:−OCH3]free for all members of 6 show saturation behavior from which KM and kcatmax were determined. The second order rate constants for the catalyzed reactions (kcatmax/KM) for each substrate are larger than the corresponding methoxide catalyzed reaction (k2–OMe) by 1.4 × 108 to 3 × 109-fold. The values of kcatmax for all members of 6 are between 4 × 1011 and 3 × 1013 times larger than the solution reaction at sspH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO2 or C(
O)OCH3 groups. Based on the linear Brønsted plots of kcatmax vs sspKaof the phenol, βlg values of −0.57 and −0.34 are determined respectively for the catalyzed methanolysis of “regular” substrates that do not contain the ortho-NO2 or C(O)OCH3 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 [CH3O−:6]
, giving a hypothetical [3:Zn(II)2:CH3O−:6] complex, by −21.4 to −24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO2 or C(O)OCH3 groups.
0.1 °C. Plots of kobs vs [3:Zn(II)2:−OCH3]free for all members of 6 show saturation behavior from which KM and kcatmax were determined. The second order rate constants for the catalyzed reactions (kcatmax/KM) for each substrate are larger than the corresponding methoxide catalyzed reaction (k2–OMe) by 1.4 × 108 to 3 × 109-fold. The values of kcatmax for all members of 6 are between 4 × 1011 and 3 × 1013 times larger than the solution reaction at sspH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO2 or C(O)OCH3 groups. Based on the linear Brønsted plots of kcatmax vs sspKaof the phenol, βlg values of −0.57 and −0.34 are determined respectively for the catalyzed methanolysis of “regular” substrates that do not contain the ortho-NO2 or C(O)OCH3 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 [CH3O−:6], giving a hypothetical [3:Zn(II)2:CH3O−:6] complex, by −21.4 to −24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO2 or C(O)OCH3 groups.