Ascenzi Daniela, Erdmann Ewa, Bolognesi Paola, Avaldi Lorenzo, Castrovilli Mattea Carmen, Thissen Roland, Romanzin Claire, Alcaraz Christian, Rabadan Ismanuel, Mendez Luis, Díaz-Tendero Sergio, Cartoni Antonella
Department of Physics, University of Trento, Via Sommarive 14, 38123 Trento, Italy.
Faculty of Applied Physics and Mathematics, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland.
Phys Chem Chem Phys. 2023 Sep 20;25(36):24643-24656. doi: 10.1039/d3cp02772d.
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 HO˙ and OH ions, produced by photoionization with synchrotron radiation, with a furan (c-CHO) 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 Å at very low collision energies (<1.0 eV). The experimental results show that furanH is more , 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 a low energy pathway with carbon-oxygen bond cleavage, followed by the loss of neutral carbon monoxide and the formation of the allyl cation CHCHCH, 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 HCCCH, 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.
放射疗法是对抗恶性肿瘤最广泛且有效的策略之一。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。由于难以模拟真实的细胞环境以及包含大量的次级过程，预测特定剂量辐射效果的理论模型仍处于起步阶段。这项工作报道了首次关于由同步辐射光致电离产生的HO˙和OH离子与呋喃（c-CHO）分子（DNA中脱氧核糖的模板）的离子-分子反应的实验研究。本实验作为离子碰撞能量和可调谐光致电离能量的函数进行，为辐射剂量效应的理论建模提供了关键参数，例如产生质子化呋喃（furanH）和最丰富产物之一的自由基阳离子（furan˙）的绝对截面，在非常低的碰撞能量（<1.0 eV）下，这些截面可达200 Å。实验结果表明furanH更多，这表明DNA糖成分的质子化可能如何有利于其解离并可能产生主要的放射增敏作用。此外，通过分子动力学模拟和量子化学计算探索了furanH异构体的开环以及最重要碎片通道的势能面。结果表明，在furanH最稳定的异构体中，开环通过碳-氧键断裂的低能量途径发生，随后中性一氧化碳损失并形成烯丙基阳离子CHCHCH，而在furan˙的碎片中未观察到这种情况。在较高能量下，通过碳-碳键的开环伴随着甲醛的损失，产生HCCCH，这是实验中检测到的最强碎片离子。这项工作强调了次级过程的重要性，例如低能量下的离子-分子反应在辐射损伤中的重要性，因为它们具有非常大的截面，并且旨在为开发适用于该低碰撞能量范围的模型提供基准数据。
