Hypochlorous acid (HOCl) released from activated leukocytes plays a significant role in the human immune system, but is also implicated in numerous diseases due to its inappropriate production. Chlorinated nucleobases induce genetic changes that potentially enable and stimulate carcinogenesis, and thus have attracted considerable attention. However, their multiple halogenation sites pose challenges to identify them. As a good complement to experiments, quantum chemical computation was used to uncover chlorination sites and chlorinated products in this study. The results indicate that anion salt forms of all purine compounds play significant roles in chlorination except for adenosine. The kinetic reactivity order of all reaction sites in terms of the estimated apparent rate constant k_obs-est (in M⁻¹ s⁻¹) is heterocyclic NH/N (10²–10⁷) > exocyclic NH₂ (10⁻²–10) > heterocyclic C8 (10⁻⁵–10⁻¹), but the order is reversed for thermodynamics. Combining kinetics and thermodynamics, the numerical simulation results show that N9 is the most reactive site for purine bases to form the main initial chlorinated product, while for purine nucleosides N1 and exocyclic N²/N⁶ are the most reactive sites to produce the main products controlled by kinetics and thermodynamics, respectively, and C8 is a possible site to generate the minor product. The formation mechanisms of biomarker 8-Cl- and 8-oxo-purine derivatives were also investigated. Additionally, the structure–kinetic reactivity relationship study reveals a good correlation between lg k_obs-est and APT charge in all purine compounds compared to FED² (HOMO), which proves again that the electrostatic interaction plays a key role. The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

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氯化过程中嘌呤碱基和核苷的反应位点和氯化产物的鉴定：计算研究

活化的白细胞释放的次氯酸 (HOCl) 在人体免疫系统中发挥着重要作用，但由于其产生不当，也与多种疾病有关。氯化核碱基可诱导遗传变化，从而可能促进和刺激致癌作用，因此引起了相当大的关注。然而，它们的多个卤化位点给识别它们带来了挑战。作为对实验的良好补充，本研究中使用量子化学计算来揭示氯化位点和氯化产物。结果表明，除腺苷外，所有嘌呤化合物的阴离子盐形式在氯化中均发挥重要作用。根据估计的表观速率常数k _obs-est（以 M ^-1 s ^-1为单位），所有反应位点的动力学反应顺序为杂环 NH/N (10 ² –10 ⁷ ) > 外环 NH ₂ (10 ^-2 – 10) > 杂环C8 (10 ^-5 –10 ^-1 )，但热力学顺序相反。结合动力学和热力学，数值模拟结果表明，N9是嘌呤碱基形成主要初始氯化产物最活跃的位点，而嘌呤核苷N1和外环N ² / N ⁶是产生主要产物的最活跃位点分别受动力学和热力学控制，C8 是生成次要产物的可能位点。还研究了生物标志物 8-Cl- 和 8-氧代-嘌呤衍生物的形成机制。此外，结构-动力学反应性关系研究表明， 与 FED ² (HOMO)相比，所有嘌呤化合物中lg k _obs-est和 APT 电荷之间存在良好的相关性，这再次证明静电相互作用起着关键作用。研究结果有助于进一步了解芳香族化合物在氯化过程中各个反应位点的反应活性。