Pabis Anna, Williams Nicholas H, Kamerlin Shina C L
Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden.
Org Biomol Chem. 2017 Sep 13;15(35):7308-7316. doi: 10.1039/c7ob01734k.
Phosphoryl transfer reactions can proceed through several plausible mechanisms, and the potential for both solvent and substrate-assisted pathways (involving proton transfer to the phosphoryl oxygens) complicates both experimental and computational interpretations. To avoid this problem, we have used electronic structure calculations to probe the mechanisms of the reactions of pyridinio-N-phosphonates with pyridine. These compounds avoid the additional complexity introduced by proton transfer between the nucleophile and the leaving group, while also serving as a valuable model for biological P-N cleavage. Through a comparative study of a range of substrates of varying basicity, we demonstrate a unified concerted mechanism for the phosphoryl transfer reactions of these model compounds, proceeding through a dissociative transition state. Finally, a comparison of these transition states with previously characterized transition states for related compounds provides a more complete model for non-enzymatic phosphoryl transfer, which is a critical stepping stone to being able to fully understand phosphoryl transfer in biology.
磷酰基转移反应可以通过几种合理的机制进行，溶剂和底物辅助途径（涉及质子转移到磷酰基氧原子）的可能性使得实验和计算解释都变得复杂。为了避免这个问题，我们使用电子结构计算来探究吡啶鎓 - N - 膦酸酯与吡啶反应的机制。这些化合物避免了亲核试剂和离去基团之间质子转移引入的额外复杂性，同时也作为生物P - N裂解的有价值模型。通过对一系列不同碱性底物的比较研究，我们证明了这些模型化合物磷酰基转移反应的统一协同机制，该机制通过解离过渡态进行。最后，将这些过渡态与相关化合物先前表征的过渡态进行比较，为非酶促磷酰基转移提供了更完整的模型，这是能够完全理解生物学中磷酰基转移的关键垫脚石。
