Faculty of Science and Technology, Jan Dlugosz University in Czestochowa, Al. Armii Krajowej 13/15, 42-200 Czestochowa, Poland.
Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland.
Molecules. 2023 Mar 27;28(7):2993. doi: 10.3390/molecules28072993.
Amino derivatives of purine (2-, 6-, 8-, and N-NH) have found many applications in biochemistry. This paper presents the results of a systematic computational study of the substituent and solvent effects in these systems. The issues considered are the electron-donating properties of NH, its geometry, π-electron delocalization in purine rings and tautomeric stability. Calculations were performed in ten environments, with 1 < ε < 109, using the polarizable continuum model of solvation. Electron-donating properties were quantitatively described by cSAR (charge of the substituent active region) parameter and π-electron delocalization by using the HOMA (harmonic oscillator model of aromaticity) index. In aminopurines, NH proximity interactions depend on its position and the tautomer. The results show that they are the main factor determining how solvation affects the electron-donating strength and geometry of NH. Proximity with the NH∙∙∙HN repulsive interaction between the NH and endocyclic NH group results in stronger solvent effects than the proximity with two attractive NH∙∙∙N interactions. The effect of amino and nitro (previously studied) substitution on aromaticity was compared; these two groups have, in most cases, the opposite effect, with the largest being in N1H and N3H purine tautomers. The amino group has a smaller effect on the tautomeric preferences of purine than the nitro group. Only in 8-aminopurine do tautomeric preferences change: N7H is more stable than N9H in HO.
嘌呤（2-、6-、8- 和 N-NH）的氨基衍生物在生物化学中有着广泛的应用。本文介绍了对这些体系中取代基和溶剂效应的系统计算研究结果。所考虑的问题是 NH 的供电子性质、其几何形状、嘌呤环中的π电子离域和互变异构稳定性。在 1 < ε < 109 的十个环境中使用极化连续体模型进行了计算。供电子性质由 cSAR（取代基活性区电荷）参数定量描述，π电子离域用 HOMA（芳香性谐波振荡器模型）指数表示。在氨基嘌呤中，NH 近邻相互作用取决于其位置和互变异构体。结果表明，它们是决定溶剂如何影响 NH 的供电子强度和几何形状的主要因素。与两个吸引力 NH∙∙∙N 相互作用相比，与 NH∙∙∙HN 排斥相互作用的 NH 近邻相互作用导致更强的溶剂效应。比较了氨基和硝基（以前研究过）取代对芳香性的影响；在大多数情况下，这两个基团的影响相反，最大的影响是在 N1H 和 N3H 嘌呤互变异构体中。与硝基基团相比，氨基基团对嘌呤互变异构体的偏好影响较小。只有在 8-氨基嘌呤中，互变异构体的偏好才会发生变化：在 HO 中，N7H 比 N9H 更稳定。
