分子反應動力學的研究從氣相小分子體系擴展到更為複雜的凝聚相生物分子體系、與分子生物學等領域形成交叉，是化學動力學研究領域蘊含機會和富有挑戰的方向之一。在基金委、科技部、中科院支持下，化學研究所分子反應動力學實驗室的科研人員，致力於發展時間分辨紅外等光譜方法，深入研究導致DNA光損傷的激發態及自由基反應的複雜過程，取得了系列進展，發現並提出分子和量子態層次上認識DNA光損傷的多種化學反應新機理。
DNA光損傷的本質是生色團鹼基分子吸收紫外光發生光化學反應。反應涉及到1ππ*、1nπ*、3ππ*激發態以及基電子態等多個電子態的參與及電子非絕熱效應，探測反應發生的非絕熱途徑是認識DNA激發態複雜反應衰變過程的關鍵。對導致交聯損傷的CPD反應，即嘧啶鹼基雙鍵的[2+2]環加成、生成環丁烷嘧啶二聚體(CPD)的反應，研究人員成功探測到CPD生成動力學，揭示了反應的激發三重態機理及T1/S0勢能面交叉的存在和反應發生的非絕熱反應途徑（J. Phys. Chem. A. 2011， 115，5335-5345）。對SP損傷反應，即胸腺嘧啶T鹼基的CH3基團與相鄰T鹼基的C=C雙鍵發生加成反應生成SP交聯產物，研究人員揭示了反應的雙自由基分步機理和非絕熱反應途徑，解決了生物化學上對該反應是協同機理還是分步機理的長期困惑（J. Phys. Chem. B. 2012， 116，11117-11123）。
在DNA光損傷反應中，還存在一類危害更大的UVA波段的紫外光引發的損傷，主要是機體組織的內源性或外源性光敏劑分子吸收UVA、產生活性氧ROS、引發一系列ROS氧化性損傷反應。深入認識UVA光損傷發生的分子反應機制，需要從物理化學上研究這些反應發生的動力學機理。以化學、生物、醫藥等多個領域普遍關注的6-硫代鳥嘌呤(6-TG)分子為例，研究人員闡明了6-TG吸收UVA光敏產生單態氧(1O2)、1O2氧化6-TG生成致癌產物GSO3的基元反應途徑和關鍵反應中間體(如圖)，發現並提出新的反應機理（GSOOH→GSO2→GSO4→GSO3），揭示了生物分子水環境下水分子協助調控反應的重要作用（J. Am. Chem. Soc. 2013， 135，4509-4515）。（生物谷Bioon.com）
Formation of Guanine-6-sulfonate from 6-Thioguanine and Singlet Oxygen: A Combined Theoretical and Experimental Study.
Xiaoran Zou , Hongmei Zhao , Youqing Yu , and Hongmei Su *
As an end metabolism product of the widely used thiopurine drugs, 6-thioguanine (6-TG) absorbs UVA and produces 1O2 by photosensitization. This unusual photochemical property triggers a variety of DNA damage, among which the oxidation of 6-TG itself by 1O2 to the promutagenic product guanine-6-sulfonate (GSO3) represents one of the major forms. It has been suspected that there exists an initial intermediate, GSO, prior to its further oxidation to GSO2 and GSO3, but GSO has never been observed. Using density functional theory, we have explored the energetics and intermediates of 6-TG and 1O2. A new mechanism via GSOOH → GSO2 → GSO4 → GSO3 has been discovered to be the most feasible energetically, whereas the anticipated GSO mechanism is found to encounter an inaccessibly high barrier and thus is prevented. The mechanism through the GSOOH and GSO4 intermediates can be validated further by joint experimental measurements, where the fast rate constant of 4.9 × 109 M–1 s–1 and the reaction stoichiometry of 0.58 supports this low-barrier new mechanism. In addition to the dominant pathway of GSOOH → GSO2 → GSO4 → GSO3, a side pathway with higher barrier, GSOOH → G, has also been located, providing a rationalization for the observed product distributions of GSO2 and GSO3 as major products and G as minor product. From mechanistic and kinetics points of view, the present findings provide new chemical insights to understand the high phototoxicity of 6-TG in DNA and point to methods of using 6-TG as a sensitive fluorescence probe for the quantitative detection of 1O2, which holds particular promise for detecting 1O2 in DNA-related biological surroundings.