Dipartimento di Chimica and IMC - CNR Sezione Meccanismi di Reazione, Università La Sapienza , 00185 Roma, Italy.
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università degli Studi di Parma , Viale delle Scienze 17/A, 43124 Parma, Italy.
J Org Chem. 2017 Oct 6;82(19):10461-10469. doi: 10.1021/acs.joc.7b01925. Epub 2017 Sep 19.
The catalytic activity of the guanidinium units toward the cleavage of phosphoric diesters is deeply investigated both with kinetic experiments and DFT calculations. The first part of the investigation aims to determine how the structure of the substrate (phenyl or alkyl esters) is able to influence the guanidinium-catalyzed hydrolysis changing the mechanism from AD to A+D. In the cleavage of the DNA model bis(4-nitrophenyl)phospate (BNPP), experimental kinetic data highlight the operation of a guanidine-guanidinium catalytic dyad that can act both intermolecularly and intramolecularly on different molecular scaffolds exhibiting notable values of effective molarity. P NMR spectra and DFT investigation provide indication that the deprotonated guanidine involved in such a catalysis acts as a general base in the deprotonation of a water molecule involved in the cleavage, and not as nucleophilic unit. Moreover, DFT calculations were carried out to determine the guanidinium promoted activation energy of pseudorotation. The results indicate a remarkable drop in the activation energy of this process for dialkylphosphate esters explaining, in part, the higher sensitivity of diribonucleoside to the presence of guanidinium-based catalysts compared to the more activated RNA model HPNP.
胍基单元对磷酸二酯键的催化活性通过动力学实验和 DFT 计算进行了深入研究。研究的第一部分旨在确定底物（苯基或烷基酯）的结构如何能够影响胍催化水解，从而改变从 AD 到 A+D 的机制。在 DNA 模型双（4-硝基苯基）磷酸酯（BNPP）的断裂中，实验动力学数据突出了胍-胍双催化偶的作用，该偶可以在不同的分子支架上进行分子间和分子内相互作用，表现出显著的有效摩尔浓度值。31P NMR 谱和 DFT 研究表明，参与这种催化的去质子胍作为参与断裂的水分子去质子化的通用碱，而不是亲核单元。此外，还进行了 DFT 计算以确定胍促进的假旋转活化能。结果表明，二烷基磷酸酯的这一过程的活化能显著降低，这部分解释了与更活跃的 RNA 模型 HPNP 相比，二核苷酸对胍基催化剂的存在更敏感的原因。
