Weinert Emily E, Dondi Ruggero, Colloredo-Melz Stefano, Frankenfield Kristen N, Mitchell Charles H, Freccero Mauro, Rokita Steven E
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
J Am Chem Soc. 2006 Sep 13;128(36):11940-7. doi: 10.1021/ja062948k.
Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron-deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron-donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 h. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span 5 orders of magnitude with electron-rich species reacting most slowly and electron-deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application.
醌甲基化物（QM）的电子扰动极大地影响其稳定性，进而改变QM与脱氧核苷反应的动力学和产物分布。与这种反应性中间体的缺电子性质一致，供电子取代基具有稳定作用，而吸电子取代基则具有去稳定作用。例如，在观察过程中（7天），由于存在抑制QM再生的吸电子酯基，dC N3-QM加合物变得稳定。相反，具有供电子甲基的相关加合物非常不稳定，其QM的再生半衰期约为5小时。通过一系列含有相对于环外亚甲基在不同位置连接的各种取代基的替代醌甲基化物前体（QMP）证明了这些效应的普遍性。通过激光闪光光解测量的对取代QM的亲核加成速率同样跨越5个数量级，富电子物种反应最慢，缺电子物种反应最快。现在可以针对任何所需应用可预测地调整QM反应的可逆性。
