H2O˙+ 和 OH+ 对呋喃的活性反应:研究辐射损伤建模中的实验低能绝对截面。
H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage.
发表日期:2023 Sep 04
作者:
Daniela Ascenzi, Ewa Erdmann, Paola Bolognesi, Lorenzo Avaldi, Mattea Carmen Castrovilli, Roland Thissen, Claire Romanzin, Christian Alcaraz, Ismanuel Rabadan, Luis Mendez, Sergio Díaz-Tendero, Antonella Cartoni
来源:
MOLECULAR & CELLULAR PROTEOMICS
摘要:
放射疗法是一种广泛且有效的抗击恶性肿瘤的策略之一。尽管其应用广泛,但辐射与DNA相互作用的机制仍在研究之中。由于模拟真实细胞环境的困难以及包括大量次级过程的存在,预测特定剂量效应的理论模型仍处于初级阶段。本研究报道了利用同步辐射光电离产生的H2O˙+和OH+离子与呋喃(DNA中脱氧核糖糖模板)分子的离子-分子反应的第一项实验研究。该实验以离子的碰撞能量和可调节的光电离能作为变量,提供了辐射剂量效应的关键参数,如产生质子化呋喃(furanH+)和自由基阳离子(furan˙+)的绝对亚段面积为关键产品,亚段面积在非常低的碰撞能量(<1.0 eV)下可达到200 Å2。实验结果表明,furanH+更加脆弱,这表明DNA的糖组分的质子化可能有利于其解离,具有可能导致重大放射增敏效应的潜力。此外,本研究还通过分子动力学模拟和量子化学计算探索了furanH+异构体的环开放以及最重要的裂解通道的势能面。结果表明,在furanH+最稳定的异构体中,环开放通过碳氧键断裂的低能路径发生,然后失去中性的一氧化碳,并形成烯丙基阳离子CH2CHCH2+,而在furan˙+的裂解中未观察到烯丙基阳离子的形成。在较高能量下,通过碳碳键的环开放伴随着甲醛的失去,生成HCCCH2+,这是实验中检测到的最强剖面离子。本研究强调了次级过程的重要性,例如低能区域的离子-分子反应在辐射损伤中具有非常大的亚段面积,本研究旨在为开发适用于此低碰撞能量范围的合适模型提供基准数据。
Radiotherapy is one of the most widespread and efficient strategies to fight malignant tumors. Despite its broad application, the mechanisms of radiation-DNA interaction are still under investigation. Theoretical models to predict the effects of a particular delivered dose are still in their infancy due to the difficulty of simulating a real cell environment, as well as the inclusion of a large variety of secondary processes. This work reports the first experimental study of the ion-molecule reactions of the H2O˙+ and OH+ ions, produced by photoionization with synchrotron radiation, with a furan (c-C4H4O) molecule, a template for deoxyribose sugar in DNA. The present experiments, performed as a function of the collision energy of the ions and the tunable photoionization energy, provide key parameters for the theoretical modelling of the effect of radiation dose, like the absolute cross sections for producing protonated furan (furanH+) and a radical cation (furan˙+), the most abundant products, which can amount up to 200 Å2 at very low collision energies (<1.0 eV). The experimental results show that furanH+ is more fragile, indicating how the protonation of the sugar component of the DNA may favor its dissociation with possible major radiosensitizing effects. Moreover, the ring opening of furanH+ isomers and the potential energy surface of the most important fragmentation channels have been explored by molecular dynamics simulations and quantum chemistry calculations. The results show that, in the most stable isomer of furanH+, the ring opening occurs via a low energy pathway with carbon-oxygen bond cleavage, followed by the loss of neutral carbon monoxide and the formation of the allyl cation CH2CHCH2+, which instead is not observed in the fragmentation of furan˙+. At higher energies the ring opening through the carbon-carbon bond is accompanied by the loss of formaldehyde, producing HCCCH2+, the most intense fragment ion detected in the experiments. This work highlights the importance of the secondary processes, like the ion-molecule reactions at low energies in the radiation damage due to their very large cross sections, and it aims to provide benchmark data for the development of suitable models to approach this low collision energy range.