Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
J Phys Chem B. 2013 Jul 25;117(29):8681-8. doi: 10.1021/jp4022689. Epub 2013 Jul 10.
The phosphodiester bond cleavage in 8-bromo-2'-deoxyadenosine 3',5'-diphosphate (BrdADP), as a model of electron induced single strand break (SSB) in labeled DNA, was investigated at the B3LYP/6-31++G(d,p) level of theory both in the gas phase and in water solution. Barrier-free and highly exergonic, especially in water solution (-2.83 eV), release of the bromide anion due to electron attachment confirms radiosensitizing properties of 8-bromoadenine. Thermodynamically (-19 kcal/mol) and kinetically (barrier of 10-13 kcal/mol) feasible hydrogen atom transfer from the C3' or C5' sites of the deoxyribose moiety to the C8 center of adenine radical is followed by a relatively low (14-18 kcal/mol) activation barrier O-P bond cleavage at either the 3'- or the 5'-site. The C5' radical may also stabilize via the formation of 5',8-cycloadenosine. The latter process has favorable thermodynamic and kinetic characteristics, which makes the O-P bond breakage at the 5'-site highly unlikely. Thus, the O-P cleavage reaction, being an equivalent of SSB in DNA labeled with 8-bromoadenine, should lead to the formation of cyclic ketone, which if identified in a radiolytic experiment, would confirm the mechanism proposed in the current study.
在气相和水溶液中，我们在 B3LYP/6-31++G(d,p)理论水平上研究了 8-溴-2'-脱氧腺苷 3'，5'-二磷酸（BrdADP）中的磷酸二酯键断裂，作为标记 DNA 中电子诱导单链断裂（SSB）的模型。溴阴离子由于电子附加而无势垒且高度放能（特别是在水溶液中为-2.83 eV），证实了 8-溴腺嘌呤的放射增敏特性。从热力学（-19 千卡/摩尔）和动力学（10-13 千卡/摩尔的势垒）角度来看，脱氧核糖部分的 C3'或 C5'位点的氢原子转移到腺嘌呤自由基的 C8 中心是可行的，随后是相对较低的（14-18 千卡/摩尔）O-P 键断裂活化能，无论是在 3'-还是 5'-位点。C5'自由基也可以通过形成 5'，8-环腺嘌呤来稳定。后一种过程具有有利的热力学和动力学特性，这使得 5'-位点的 O-P 键断裂极不可能发生。因此，O-P 断裂反应作为标记有 8-溴腺嘌呤的 DNA 中的 SSB 等效物，应导致环状酮的形成，如果在辐射分解实验中鉴定出该环状酮，则将证实当前研究中提出的机制。
