Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada.
Chem Res Toxicol. 2024 Feb 19;37(2):419-428. doi: 10.1021/acs.chemrestox.3c00370. Epub 2024 Feb 5.
Photolysis of DNA attached to gold nanoparticles (AuNPs) with ultraviolet (UV) photons induces DNA damage. The release of nucleobases (Cyt, Gua, Ade, and Thy) from DNA was the major reaction (99%) with an approximately equal release of pyrimidines and purines. This reaction contributes to the formation of abasic sites in DNA. In addition, liquid chromatography-mass spectrometry/MS (LC-MS/MS) analysis revealed the formation of reduction products of pyrimidines (5,6-dihydrothymidine and 5,6-dihydro-2'-deoxyuridine) and eight 2',3'- and 2',5'-dideoxynucleosides. In contrast, there was no evidence of the formation of 5-hydroxymethyluracil and 8-oxo-7,8-dihydroguanine, which are common oxidation products of thymine and guanine, respectively. Using appropriate filters, the main photochemical reactions were found to involve photoelectrons ejected from AuNPs by UV photons. The contribution of "hot" conduction band electrons with energies below the photoemission threshold was minor. The mechanism for the release of free nucleobases by photoelectrons is proposed to take place by the initial formation of transient molecular anions of the nucleobases, followed by dissociative electron attachment at the C1'-N glycosidic bond connecting the nucleobase to the sugar-phosphate backbone. This mechanism is consistent with the reactivity of secondary electrons ejected by X-ray irradiation of AuNPs attached to DNA, as well as the reactions of various nucleic acid derivatives irradiated with monoenergetic very-low-energy electrons (∼2 eV). These studies should help us to understand the chemistry of nanoparticles that are exposed to UV light and that are used as scaffolds and catalysts in molecular biology, curative agents in photodynamic therapy, and components of sunscreens and cosmetics.
金纳米粒子（AuNPs）上附着的 DNA 经紫外（UV）光子光解后会诱导 DNA 损伤。从 DNA 释放出的核苷碱基（Cyt、Gua、Ade 和 Thy）是主要反应（99%），嘧啶和嘌呤的释放大致相等。该反应导致 DNA 中形成无碱基位点。此外，液相色谱-质谱/质谱（LC-MS/MS）分析显示嘧啶的还原产物（5,6-二氢胸腺嘧啶和 5,6-二氢-2'-脱氧尿嘧啶）和 8 种 2',3'-和 2',5'-脱氧核苷的形成。相比之下，没有证据表明 5-羟甲基尿嘧啶和 8-氧代-7,8-二氢鸟嘌呤的形成，它们分别是胸腺嘧啶和鸟嘌呤的常见氧化产物。使用适当的滤光片，发现主要的光化学反应涉及被 UV 光子从 AuNPs 中逐出的光电子。能量低于光发射阈值的“热”导带电子的贡献较小。光电子释放游离核苷碱基的机制被提出为通过碱基的瞬态分子阴离子的初始形成来发生，随后在将碱基连接到糖-磷酸主链的 C1'-N 糖苷键处进行离解电子附着。该机制与附着在 DNA 上的 AuNPs 经 X 射线照射时逐出的次级电子的反应以及用单能极低能电子（约 2 eV）照射各种核酸衍生物的反应一致。这些研究应有助于我们理解暴露于紫外光的纳米粒子的化学性质，这些纳米粒子可用作分子生物学中的支架和催化剂、光动力治疗中的治疗剂以及防晒霜和化妆品的成分。
