Triplet-sensitized cyclobutane pyrimidine dimer damage and crosslinks in DNA: filling the triplet energy gap between xanthone and thioxanthone

Abstract

Thioxanthones are tunable photosensitizers used for studying the formation of triplet-induced cyclobutane pyrimidine dimer (CPD) damage in DNA. To probe the gap between the triplet energy of xanthone (310 kJ mol⁻¹) and of thioxanthone (265 kJ mol⁻¹), we synthesized two new C-nucleosides with two differently modified thioxanthones. Ternary and photoactive DNA architectures were prepared with these C-nucleosides to analyze the CPD formation quantitatively. The dimethoxy-substituted thioxanthone as a photosensitizer has a high triplet energy (288 kJ mol⁻¹). We observed the CPD formation over up to 6 A–T pairs in DNA, and the distance dependence is characterized by a low β-value of 0.02 Å⁻¹, indicating energy hopping over the A–T pairs. The triplet energy of the chloro-and methoxy-modified photosensitizer is low (273 kJ mol⁻¹) and only slightly above the threshold for DNA photosensitization set by the triplet energy of T in DNA (267 kJ mol⁻¹). Here, only low amounts of CPDs were obtained because the energy difference compared to T is very small. These results show clearly that the triplet energy of the photosensitizer incorporated into the DNA is decisive for not only whether CPDs can be induced at all but also how much CPDs are formed; the higher the triplet energy of the photosensitizer, the more CPDs are formed.