Schyman Patric, Zhang Ru Bo, Eriksson Leif A, Laaksonen Aatto
Division of Physical Chemistry, Arrhenius Laboratory, Stockholm University, 106 91, Stockholm, Sweden.
Phys Chem Chem Phys. 2007 Dec 7;9(45):5975-9. doi: 10.1039/b711083a. Epub 2007 Sep 27.
Hydrogen abstraction from the C1' and C2' positions of deoxyadenosine by a neighbouring uracil-5-yl radical in the 5'-AU*-3' DNA sequence is explored using DFT. This hydrogen abstraction is the first step in a sequence leading to single or double strand break in DNA. The uracil-5-yl radical can be the result of photolysis or low-energy electron (LEE) attachment. If the radical is produced by photolysis the neighbouring adenine will become a cation radical and if it is produced by LEE the adenine will remain neutral. The hydrogen abstraction reactions for both cases were investigated. It is concluded that it is possible for the uracil-5-yl to abstract hydrogen from C1' and C2'. When adenine is neutral there is a preference for the C1' site and when the adenine is a radical cation the C2' site is the preferred. If adenine is positively charged, the rate-limiting step when abstracting hydrogen from C1' is the formation of an intermediate crosslink between uracil and adenine. This crosslink might be avoided in dsDNA, making C1' the preferred site for abstraction.
利用密度泛函理论（DFT）研究了在5'-AU*-3' DNA序列中，相邻的尿嘧啶-5-基自由基从脱氧腺苷的C1'和C2'位置夺取氢的情况。这种氢夺取是导致DNA单链或双链断裂序列中的第一步。尿嘧啶-5-基自由基可能是光解或低能电子（LEE）附着的结果。如果自由基是由光解产生的，相邻的腺嘌呤将成为阳离子自由基；如果是由LEE产生的，腺嘌呤将保持中性。对这两种情况的氢夺取反应都进行了研究。得出的结论是，尿嘧啶-5-基有可能从C1'和C2'夺取氢。当腺嘌呤呈中性时，C1'位点是优先选择；当腺嘌呤是自由基阳离子时，C2'位点是优先选择。如果腺嘌呤带正电荷，从C1'夺取氢时的限速步骤是尿嘧啶和腺嘌呤之间形成中间交联。在双链DNA中可能避免这种交联，使C1'成为夺取氢的优先位点。
