7 research outputs found
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Characteristics of the Excited Triplet States of Thiolated Guanosine Derivatives and Singlet Oxygen Generation
Thioguanine is sensitive to UVA light and generates singlet molecular oxygen (1O2*) when exposed to UVA. Three thioguanosine derivatives, 2’,3’,5’–tri–O–acetyl–6–thioguanosine (ta6TGuo), 2’,3’,5’–tri–O–acetyl–8–thioguanosine (ta8TGuo), and 2’,3’,5’–tri–O–acetyl–6,8–dithioguanosine (taDTGuo) were explored photophysically and photochemically. The nanosecond transient absorption and time–resolved near–infrared emission measurements were carried out to investigate the characteristics of their excited triplet states in acetonitrile solution. The quantum yield of intersystem crossing (∅ISC), the intrinsic decay rate constant (k0), the quenching rate constant by 3O2 (kq) and the self–quenching rate constant (kSQ) of their triplet states were all determined. From precise analysis of the quantum yield of 1O2* generation (∅Δ) against the concentration of dissolved molecular oxygen, the fraction of the triplet states quenched by dissolved oxygen which gives rise to 1O2* formation (SΔ) was successfully obtained with high accuracy. The ∅Δ values at low oxygen concentrations reveal these thioguanosines, particularly taDTGuo, can still effectively generate 1O2* under low molecular oxygen concentration like carcinomatous microenvironments. These findings indicate that taDTGuo would perform well as a potential agent for photo–induced cancer therapies
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Formation of oxidative photoproduct of tri-acetyl-modified 6-thioguanosine by UVA irradiation
Thio-substituted nucleobases such as 6-thioguanine are known to be photosensitive to UVA light and capable of generating singlet molecular oxygen (1O2*). 2’,3 ’,5 ’- Tri-O-acetyl-6-thioguanosine (ta6TGuo) was prepared and its photochemistry was investigated. ta6TGuo in the aerated acetonitrile solution under UVA irradiation generates 1O2* that can also oxidize ta6TGuo itself and finally convert into tri-acetylated guanosine sulfonate (taGuoSO3). The decay rate constant of ta6TGuo was found to be in good agreement with the formation rate constant of taGuoSO3, revealing that the first step in the reaction of ta6TGuo with 1O2* would be the rate-determining step in forming taGuoSO3 as the final product. Thiolated nucleosides such as 6-thioguanosine could be used as a photosensitive agent for light-induced therapies. The key feature in the UVA irradiation of the thionucleosideis to produce 1O2*, but the resultant oxidative products would also contribute to the effect on therapies
Simultaneous Two-Photon Absorption of the Thioguanosine Analogue 2′,3′,5′-Tri‑<i>O</i>‑acetyl-6,8-dithioguanosine with Its Potential Application to Photodynamic Therapy
2',3',5'-Tri-O-acetyl-6,8-dithioguanosine (taDTGuo) is an analogue of nucleosides and currently under investigation as a potential agent for photodynamic therapy (PDT). Excitation by simultaneous two-photon absorption of visible or near-infrared light would provide an efficient PDT for deep-seated tumors. The two-photon absorption spectrum of taDTGuo was obtained by optical-probing photoacoustic spectroscopy (OPPAS). A two-photon absorption band corresponding to the S5 ← S0 transition was observed at 556 nm, and the two-photon absorption cross-section σ(2) was determined to be 26 ± 3 GM, which was much larger than that of other nucleobases and nucleosides. Quantum chemical calculations suggested that the large σ(2) value of taDTGuo was responsible for large transition dipole moments and small detuning energy resulting from the thiocarbonyl group at 6- and 8-positions. This is the first report on two-photon absorption spectra and cross-sections of thionucleoside analogues, which could be used to develop a more specific PDT for cancers in deep regions
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Excited States of Thio-2′-deoxyuridine Bearing an Extended π-Conjugated System: 3′,5′-Di-O-acetyl-5-phenylethynyl-4-thio-2′-deoxyuridine
A new thio-2′-deoxyuridine with an extended π-conjugated group was successfully synthesized: 3′,5′-di-O-acetyl-5-phenylethynyl-4-thio-2′-deoxyuridine. The thio-2′-deoxyuridine derivative has a large red-shifted absorption band in the UVA region and also shows fluorescence, a rare photo-property among thionucleobases/thionucleosides. The triplet–triplet absorption spectrum and the rate constants (the intrinsic decay rate constant of the triplet state, the self-quenching rate constant, and the quenching rate constant of the triplet state by an oxygen molecule) of the thio-2′-deoxyuridine were obtained by transient absorption spectroscopy. The quantum yield of intersystem crossing and the quantum yield of singlet molecular oxygen formation (ϕΔ) under an oxygen atmosphere were also determined. The ϕΔ value of the new thio-2′-deoxyuridine was found to be substantially higher than all reported values of other thio-2′-deoxyribonucleosides in low oxygen concentrations similar to cancer cell environments. The fluorescence quantum yield depended on the excitation wavelength, revealing certain photochemical reactions in the higher excited singlet states. However, when excited into the higher excited state with non-resonant two-photon absorption, the ϕΔ of the thio-2′-deoxyuridine derivative was found to remain sufficiently large. These findings should be very useful for the development of thio-2′-deoxyribonucleoside-based pharmaceuticals as DNA-specific photosensitizers for photochemotherapy