The knowledge of the mechanism of reactions occurring in solution is a primary research line both in the context of theoretical‐computational chemistry and in the field of organic and bio‐organic chemistry. Given the importance of the hydrolysis of nucleic acids in life‐related phenomena, here we present a combined experimental and computational study on the cleavage of an RNA model compound. This phosphodiester features a cleavage rate strictly dependent on the pH with three different dependence domains. Such experimental evidence, highlighted by an in‐depth kinetic investigation, unequivocally suggests a change in the reaction mechanism along the pH scale. In order to interpret the data and to explain the experimental behavior, we have applied a theoretical‐computational procedure, involving a hybrid quantum/classical approach, able to model chemical reactions in complex environments, i.e. in solution. This study turns out to quantitatively reproduce the experimental data with accuracy and, in addition, provides useful mechanistic insight into the transesterification process of the investigated compound. The study indicates that the cleavage can occur through an ANDN, an AN+DN, and a DNAN mechanism depending on the pH values.

中文翻译：

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揭示 RNA 模型化合物在整个 pH 范围内的裂解机制：计算与实验相结合，确定反应速率

溶液中发生的反应机理的知识是理论计算化学以及有机和生物有机化学领域的主要研究方向。鉴于核酸水解在生命相关现象中的重要性，我们在此提出了一项关于 RNA 模型化合物裂解的实验和计算相结合的研究。该磷酸二酯的裂解率严格依赖于 pH 值，具有三个不同的依赖域。深入的动力学研究强调了此类实验证据，明确表明反应机制沿 pH 范围发生变化。为了解释数据并解释实验行为，我们应用了理论计算程序，涉及混合量子/经典方法，能够模拟复杂环境（即溶液中）的化学反应。这项研究结果准确地定量重现了实验数据，此外，还为所研究化合物的酯交换过程提供了有用的机制见解。研究表明，根据 pH 值，裂解可以通过 ANDN、AN+DN 和 DNAN 机制发生。