6-Thioguanine (1a) is considered to be photochemotherapeutic 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 triacetyl-protected ribonucleosides, that is, 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 unthiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thionucleobases and thionucleosides 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.

2',3',5'-Tri- O-acetyl-6,8-dithioguanosine (taDTGuo) is a nucleoside derivative of drug 6-thioguanine and under further development as a potential photochemotherapeutic agent due to its desirable properties of photosensitivity to UVA light and singlet molecular oxygen generation. The photochemical characteristics of taDTGuo under biological conditions (namely in aqueous solution) were intensively investigated by the steady-state absorption and emission, time-resolved near-infrared emission measurements, and quantum chemical calculations. taDTGuo was found to be held in sequential acid dissociation equilibria within pH 3.79-11.93. With the global fitting analysis of the absorption spectra at various pHs, two p K values of the equilibria were determined to be 7.02 ± 0.01 and 9.79 ± 0.01. Quantum chemical calculations suggested that its mono- and dianionic species in the ground state should be 1-imide anionic form (N-taDTGuo) and 1,7-di-imide anionic form (taDTGuo). taDTGuo generates a singlet molecular oxygen effectively and has pH-dependent quantum yields. In conclusion, taDTGuo would be very useful as a potent agent for photochemotherapy under certain carcinomatous pH conditions.

The long intrinsic lifetime and low self-quenching rate constant of the triplet 6,8-dithioguanosine lead to efficient singlet molecular oxygen generation under carcinomatous oxygen conditions.

Relaxation of excited states and reactivity of ketoprofen (KP), one of the most popular nonsteroidal antiinflammatory drugs, with indole and methylindoles have been studied with transient absorption and quantum chemical calculations. KP in the excited triplet state, 3 KP*, abstracted a hydrogen atom from indole and methylindoles to afford a ketyl radical and a counter radical. The bimolecular quenching rate constants of 3 KP* by indole and methylindoles, k q , and the hydrogen atom abstraction rate constants, k r , were obtained. The k r values for methylindoles were larger than that for indole; in addition, transient spectra at around 350 nm, assigned to the corresponding C-centered radical, was observed. These results indicate that 3 KP* abstracts a hydrogen atom of the methyl group as well as that of N−H in the indole frame. These findings give us information on the reactivity of excited KP in the vicinity of tryptophan in a KP−protein complex, which will ultimately cause photosensitization on human skin.