Absorption Characteristics and Quantum Yields of Singlet Oxygen Generation of Thioguanosine Derivatives

6–Thioguanine (1a) is considered to be photochemotherapeutic agents due to its specific characteristics of photosensitivity to UVA light and singlet molecular oxygen generation. To extend its phototherapeutic ability, two related thioguanines, 8–thioguanine (2a) and 6,8–dithioguanine (3a), have been designed and explored. Since the solubility of these thioguanines in dehydrated organic solvents is too poor to study, their tri–acetyl–protected ribonucleosides, i.e. 2’,3’,5’–tri–O–acetyl–6–thioguanosine (1c), 2’,3’,5’–tri–O–acetyl–8–thioguanosine (2c) and 2’,3’,5’–tri–O–acetyl–6,8–dithioguanosine (3c) were prepared and investigated. The absorption maxima of 1c, 2c and 3c in acetonitrile were found at longer wavelengths than that of un–thiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thio–nucleobases and thio–nucleosides reported. These absorption properties were also well reproduced by quantum chemical calculations. Quantum yields of singlet oxygen generation of 2c and 3c were determined by near–infrared emission measurements to be as large as that of 1c. These results suggest that the newly synthesized thioguanosines, in particular 3c, can be further developed as a potential photosensitive agent for light–induced therapies.