Wu R R, Chen Yu, Rodgers M T
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.
Phys Chem Chem Phys. 2016 Jan 28;18(4):2968-80. doi: 10.1039/c5cp05738h.
Experimental and theoretical investigations suggest that hydrolysis of N-glycosidic bonds generally involves a concerted SN2 or a stepwise SN1 mechanism. While theoretical investigations have provided estimates for the intrinsic activation energies associated with N-glycosidic bond cleavage reactions, experimental measurements to validate the theoretical studies remain elusive. Here we report experimental investigations for N-glycosidic bond cleavage of the protonated guanine nucleosides, dGuo+H and Guo+H, using threshold collision-induced dissociation (TCID) techniques. Two major dissociation pathways involving N-glycosidic bond cleavage, resulting in production of protonated guanine or the elimination of neutral guanine are observed in competition for both dGuo+H and Guo+H. The detailed mechanistic pathways for the N-glycosidic bond cleavage reactions observed are mapped via electronic structure calculations. Excellent agreement between the measured and B3LYP calculated activation energies and reaction enthalpies for N-glycosidic bond cleavage of dGuo+H and Guo+H in the gas phase is found indicating that these dissociation pathways involve stepwise E1 mechanisms in analogy to the SN1 mechanisms that occur in the condensed phase. In contrast, MP2 is found to significantly overestimate the activation energies and slightly overestimate the reaction enthalpies. The 2'-hydroxyl substituent is found to stabilize the N-glycosidic bond such that Guo+H requires ∼25 kJ mol(-1) more than dGuo+H to activate the glycosidic bond.
实验和理论研究表明，N-糖苷键的水解通常涉及协同的SN2或逐步的SN1机制。虽然理论研究已经给出了与N-糖苷键裂解反应相关的固有活化能的估计值，但用于验证理论研究的实验测量仍然难以实现。在此，我们报告了使用阈值碰撞诱导解离（TCID）技术对质子化鸟嘌呤核苷dGuo+H和Guo+H的N-糖苷键裂解进行的实验研究。在dGuo+H和Guo+H的竞争反应中，观察到了两条涉及N-糖苷键裂解的主要解离途径，分别导致质子化鸟嘌呤的产生或中性鸟嘌呤的消除。通过电子结构计算绘制了所观察到的N-糖苷键裂解反应的详细机理途径。发现气相中dGuo+H和Guo+H的N-糖苷键裂解的测量活化能和反应焓与B3LYP计算值之间具有极好的一致性，这表明这些解离途径涉及类似于凝聚相中发生的SN1机制的逐步E1机制。相比之下，发现MP2显著高估了活化能，并略微高估了反应焓。发现2'-羟基取代基可稳定N-糖苷键，使得Guo+H比dGuo+H激活糖苷键所需的能量多约25 kJ mol(-1)。
