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Excited-state dynamics of 6-azauracil (6-AU) and sensitized singlet oxygen formation in acetonitrile solution with UV irradiation were investigated for the first time. In the transient absorption measurement, the 248 nm laser photolysis gave a relatively intense absorption band at 320 nm (= 1100 +/- 100 dm(3) mol(-1) cm(-1)) and a broadband in the 500-700 nm region due to triplet 6-AU. The triplet 6-AU, decaying with the rate constant of (5.3 +/- 0.2) x 10(6) s(-1) in Ar saturated acetonitrile, was quenched by molecular oxygen with the rate constant of (2.5 +/- 0.1) x 10(9) dm(3) mol(-1) s(-1). The formation quantum yield of excited triplet 6-AU was estimated to be unity by acetone triplet sensitization and actinometry with benzophenone. The time-resolved thermal lensing signal of 6-AU was also observed by 248 nm laser excitation. In the presence of molecular oxygen, the sensitization from triplet 6-AU gave rise to formation of singlet oxygen O(2) ((1)Delta(g)) with a quantum yield of 0.63 +/- 0.03. Drastically different excited-state dynamics of aza-substituted uracil from normal uracil were clarified, and the mechanism for the enhancement of intersystem crossing by aza-substitution is discussed.

Significant influences of sulfur and aza substitution on excited-state dynamics in thymine analogues, 6-aza-2-thiothymine (ATT) and 2-thiothymine (2TT), were intensively studied by means of nanosecond transient absorption and time-resolved luminescence spectroscopy. Transient absorption spectral measurements gave distinct spectral features and sufficiently longer lifetimes for both molecules attributable to the T(1) (pi pi*) state under Ar-saturated condition. Additionally, another long-lived subsequent transient was also observed for ATT, which suggests hydrogen abstraction from a ground-state molecule itself takes place only for triplet ATT. Quantum yields for intersystem crossing (Phi(ISC)) were determined to be unity as well as other pyrimidine analogues we reported previously, and efficient photosensitized singlet oxygen O(2)* ((1)Delta(g)) formation was also observed in the presence of dissolved molecular oxygen with a quantum yield (Phi(Delta)) of 0.69 +/- 0.02 for ATT whereas it almost halved for 2TT. These findings have shown the combination of subtle substitutions can possibly control photophysical or photochemical properties such as O(2)* ((1)Delta(g)) formation or reactivity in excited states in addition to the substantial intersystem crossing caused by replacing oxygen O2 in thymine by sulfur (referred to S2 substitution henceforward). The experimental results were corroborated by quantum chemical calculation at the B3LYP/6-31+G(d,p)/PCM level.

Excited state characteristics of aza analogues of nucleic acid bases, 8-azaadenine (8AA), 5-azacytosine (5AC), 8-azaguanine (8AG), and 6-azauracil (6AU), in acetonitrile solution were comprehensively investigated with steady state absorption and emission spectra, transient absorption measurements, emission measurements for the singlet oxygen molecule, and time-dependent density functional theory (TD-DFT) calculations. The triplet-triplet absorption spectrum of 8AA whose peak was 455 nm was observed for the first time. Sensitized singlet oxygen formation of 8AA was also observed in O(2)-saturated acetonitrile with quantum yields of 0.15 +/- 0.02. It was concluded that there were two kinds of aza analogues of nucleic acid bases: type A had substantial quantum yield for the intersystem crossing and potential of O2 (1Delta(g)) formation (8AA and 6AU), and type B did not (5AC and 8AG). TD-DFT calculations indicated that type A molecules had a dark 1npi* state below the first allowed 1pipi* state, while both S1 and S2 states for type B molecules had a pipi* character. It strongly suggested that the dark 1npi* state below the 1pipi* state would play an important role in the ISC process of aza analogues of nucleic acid bases.

Excited-state dynamics of 4-thiothymidine (S4-TdR) and its photosensitization to molecular oxygen in solution with UVA irradiation were investigated. Absorption and emission spectra measurements revealed that UVA photolysis of S4-TdR gives rise to a population of T1(pipi*), following S2(pipi*) --> S1(npi*) internal conversion. In transient absorption measurement, the 355 nm laser photolysis gave broad absorption (380-600 nm) bands of triplet S4-TdR. The time-resolved thermal lensing (TRTL) signal of S4-TdR containing the thermal component due to decay of triplet S4-TdR was clearly observed by the 355 nm laser excitation. The quantum yield for S1 --> T1 intersystem crossing was estimated to be unity by a triplet quenching experiment with potassium iodide. In the presence of molecular oxygen, the photosensitization from triplet S4-TdR gave rise to singlet oxygen O2 (1Deltag) with a quantum yield of 0.50. Therapeutic implications of such singlet oxygen formation are discussed.