Department of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719, Olsztyn, Poland.
Eur Biophys J. 2023 Oct;52(6-7):545-557. doi: 10.1007/s00249-023-01672-x. Epub 2023 Jul 28.
8-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer and malaria therapy. Its intrinsic fluorescence properties can be utilized for monitoring its interactions with biological polymers like proteins or nucleic acids. In order to better understand these interactions, it is important to know the tautomeric equilibrium of this compound. In this work, the tautomeric equilibrium of all natural neutral and anionic compound forms (except highly improbable imino-enol tautomers) as well as their methyl derivatives and ribosides was revealed by quantum chemistry methods. It was shown that, as expected, tautomers protonated at positions 1 and 9 dominate neutral forms both in gas phase and in aqueous solution. 8-azaguanines methylated at any position of the triazole ring are protonated at position 1. The computed vertical absorption and emission energies are in very good agreement with the experimental data. They confirm the validity of the assumption that replacing the proton with the methyl group does not significantly change the positions of absorption and fluorescence peaks.
8-氮杂鸟嘌呤是一种三唑并嘧啶核苷类似物，具有很强的抗菌和抗肿瘤活性，被认为是癌症和疟疾治疗的先导分子。其固有荧光性质可用于监测其与生物聚合物（如蛋白质或核酸）的相互作用。为了更好地理解这些相互作用，了解该化合物的互变异构平衡是很重要的。在这项工作中，通过量子化学方法揭示了所有天然中性和阴离子化合物形式（除了极不可能的亚氨基-烯醇互变异构体）及其甲基衍生物和核苷的互变异构平衡。结果表明，正如预期的那样，在气相和水溶液中，位于 1 位和 9 位的质子化互变异构体都主导中性形式。三唑环上任何位置甲基化的 8-氮杂鸟嘌呤都在 1 位质子化。计算得到的垂直吸收和发射能与实验数据非常吻合。它们证实了这样一个假设的有效性，即用甲基取代质子不会显著改变吸收和荧光峰的位置。
