The discovery that β-propiolactone (BPL), once a commercially important chemical, causes various tumors in experimental animals has led to a significant decrease in its use. However, owing to its efficacy this possible human carcinogen remains to be utilized in vaccines for inactivation of viruses. The focus of the current study was to uncover the mechanisms of β-propiolactone reactions with both nucleobases and glutathione (GSH) through computer simulations based on quantum chemical methods. Our results, in accordance with in vitro studies, show that among all nucleobases guanine most readily forms adducts with BPL through SN2 reaction mechanism. Acquired activation energies with incorporated solvent effects reveal that alkylation represents an energetically more favorable reaction than acylation for all nucleobases. Comparison of activation free energies of glutathione and guanine reactions with BPL suggest that glutathione may represent an efficient natural scavenger of BPL. Therefore, glutathione present in the organism may provide protection to the DNA and thus prevent BPL's genotoxicity, mutagenicity, and possibly even carcinogenicity.

中文翻译：

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β-丙内酯致癌作用：一项计算研究。

β-丙内酯（BPL）曾经是一种商业上重要的化学物质，会引起实验动物的各种肿瘤，这一发现导致其使用量大大减少。然而，由于其功效，这种可能的人类致癌物仍有待用于疫苗中以灭活病毒。本研究的重点是通过基于量子化学方法的计算机模拟来揭示β-丙内酯与核碱基和谷胱甘肽（GSH）的反应机理。根据体外研究，我们的结果表明，在所有核碱基中，鸟嘌呤最容易通过SN2反应机理与BPL形成加合物。获得的活化能与溶剂效应的结合表明，对于所有核碱基，烷基化比酰化在能量上代表了更有利的反应。谷胱甘肽和鸟嘌呤反应与BPL的活化自由能的比较表明，谷胱甘肽可能代表BPL的有效天然清除剂。因此，生物体中存在的谷胱甘肽可以为DNA提供保护，从而防止BPL的遗传毒性，诱变性甚至可能致癌。