Laboratory of Biological Sensitizers, Department of Physical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Department of Organic Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland.
J Am Chem Soc. 2023 Apr 26;145(16):9059-9071. doi: 10.1021/jacs.3c00591. Epub 2023 Apr 11.
Single-strand breaks (SSBs) induced via electron attachment were previously observed in dry DNA under ultrahigh vacuum (UHV), while hydrated electrons were found not able to induce this DNA damage in an aqueous solution. To explain these findings, crossed electron-molecular beam (CEMB) and anion photoelectron spectroscopy (aPES) experiments coupled to density functional theory (DFT) modeling were used to demonstrate the fundamental importance of proton transfer (PT) in radical anions formed via electron attachment. Three molecular systems were investigated: 5'-monophosphate of 2'-deoxycytidine (dCMPH), where PT in the electron adduct is feasible, and two ethylated derivatives, 5'-diethylphosphate and 3',5'-tetraethyldiphosphate of 2'-deoxycytidine, where PT is blocked due to substitution of labile protons with the ethyl residues. CEMB and aPES experiments confirmed the cleavage of the C3'/C5'-O bond as the main dissociation channel related to electron attachment in the ethylated derivatives. In the case of dCMPH, however, electron attachment (in the aPES experiments) yielded its parent (intact) radical anion, dCMPH, suggesting that its dissociation was inhibited. The aPES-measured vertical detachment energy of the dCMPH was found to be 3.27 eV, which agreed with its B3LYP/6-31++G(d,p)-calculated value and implied that electron-induced proton transfer (EIPT) had occurred during electron attachment to the dCMPH model nucleotide. In other words, EIPT, subduing dissociation, appeared to be somewhat protective against SSB. While EIPT is facilitated in solution compared to the dry environment, the above findings are consistent with the stability of DNA against hydrated electron-induced SSB in solution versus free electron-induced SSB formation in dry DNA.
单链断裂（SSBs）通过电子附加物在超高真空（UHV）下的干燥 DNA 中被观察到，而在水溶液中未发现水合电子能够诱导这种 DNA 损伤。为了解释这些发现，使用交叉电子-分子束（CEMB）和阴离子光电电子能谱（aPES）实验结合密度泛函理论（DFT）建模来证明通过电子附加物形成的自由基阴离子中质子转移（PT）的基本重要性。研究了三个分子系统：2'-脱氧胞苷 5'-单磷酸（dCMPH），其中电子加合物中的 PT 是可行的，以及两个乙基化衍生物，2'-脱氧胞苷的 5'-二乙基磷酸盐和 3'，5'-四乙基二磷酸，其中由于用乙基残基取代易失质子，PT 被阻断。CEMB 和 aPES 实验证实，在乙基化衍生物中，C3'/C5'-O 键的断裂是与电子附加相关的主要离解通道。然而，在 dCMPH 的情况下，电子附加（在 aPES 实验中）产生了其母体（完整）自由基阴离子 dCMPH，这表明其离解受到抑制。通过 aPES 测量的 dCMPH 的垂直离解能为 3.27 eV，与 B3LYP/6-31++G（d，p）-计算值一致，这意味着在 dCMPH 模型核苷酸中电子附加时发生了电子诱导质子转移（EIPT）。换句话说，EIPT 抑制了离解，似乎对 SSB 具有一定的保护作用。虽然与干燥环境相比，EIPT 在溶液中更容易发生，但上述发现与 DNA 在溶液中对水合电子诱导的 SSB 的稳定性一致，而不是在干燥 DNA 中对自由电子诱导的 SSB 形成的稳定性。
