Photosensitized Splitting Of Thymine Dimer By An Attached Chromophorc

A type of major damage to DNA caused by UV irradiation is the formation ofcyclobutane pyrimidine dimmers (CPDs), which will lead to form skin cancer. So,studies of DNA photolesions in photorepair process helps to reveal the repairmechanisms of CPD photolyases.Several model compounds that mimic the action of photolyase have beendesigned. Such as a chromophore attached to a pyrimidine dimer, which were used tomimic the virtually intramolecular electron transfer from the chromophore to dimer.These model systems can help us study the repair mechanisms and the influencefactors during the repair process. In the systems, the splitting efficiency of the dimerunits exhibit two reverse solvent effects. What is the origin of these two reversesolvent effects and what are the factors influence the two solvent effects? Therefore,we have synthesized two model systems, such as phenothiazine/indole attached to apyrimidine dimer unit. Studies performed with these compounds have offered usefulinsights into the electron transfer and the two reverse solvent effects involved inphotosensitized splitting.1. Solvent Effects on Photosensitized Splitting of Thymine Dimer by an AttachedPhenothiazine In two kinds of model compounds, the splitting quantum yields of dimer oroxetane unit by a covalently linked carbazole exhibited two reverse solvent effects,which derive from back electron transfer in the splitting process lying in the differentMarcus regions induced by the difference in values of Eredof an acceptor. To furtherexplore mechanism of two reverse solvent effects on dimer-splitting efficiency, threecovalently linked phenothiazine-dimer model compounds with a short linker,1a–1c,were prepared. It was observed that solvent effect on dimer-splitting efficiency forphenothiazine-dimer systems is contrary to that of the other chromophore-dimersystems. Caculated results based on the Marcus theory showed that phenothiazinesystems with a lower driving force induced by a lower value of Eoxhave a longerdonor-acceptor distance between phenothiazine moiety and dimer unit, then gives ahigher λs. Thus, back electron transfer would lie in the Marcus normal region forphenothiazine-dimer models, in which dimer splitting is more efficient in higherpolarity solvents. The value of redox potential between a donor and an acceptorshould be a key leading to back electron transfer lying in the different Marcus regionsand following two reverse solvent effects. Moreover,1H NMR spectra andfluorescence spectra showed that the conformational changes should be a factorleading to the above solvent effect and the planar conformation of the excited donorwould be favorable for the dimer splitting. However, some new insights intomechanisms of DNA photoreactivation mediated by photolyases were gained.2. Substituent Effects on Photosensitized Splitting of Thymine Dimer by an AttachedIndoleIn the chromophore–containing dimer/oxetane model systems, solvent effects onthe splitting efficiency may depend on the length of the linker, the molecularconformation and the oxidation potential of donor. To further explore the relationshipbetween the chromophore structure and the splitting efficiency, we have prepared aseries of substituted indole–dimer model compounds2a–2g and measured theirsplitting quantum yields in various solvents. Two reverse solvent effects were observed, i.e., one is an increase in the splitting efficiency in solvents of lowerpolarity for models2a–2d with an electron-donating group (EDG), and the other isjust contrary for models2e–2g with an electron-withdrawing group (EWG).According to the Hammett equation, the negative value of the slope of the Hammettplot indicates that the indole moiety during the dimer-splitting reaction loses negativecharge, and the larger negative value implies that the repair reaction is more sensitiveto substituent effects in low polarity solvents. EDGs of the models2a2d candelocalize the charge-separated state and low-polarity solvents make it more stable,which leads to higher splitting efficiency in low polarity solvents. Reversely, EWGsof the models2e2g favor the destabilization of the charge-separated state and highpolarity solvents decrease the destabilization and hence leads to more efficientsplitting in high-polarity solvents.