Singlet Oxygen Production From Photodynamic Sensitizers

The quantum yield of triplet formation, phi T, and that of the photosensitized formation of singlet molecular oxygen, phi delta, were determined for a rare nucleoside, 4-thiouridine (4t-Urd), in water and in acetonitrile, using singlet molecular oxygen phosphorescence, laser-induced optoacoustics and time-resolved thermal lensing. These yields, phi T and phi delta, the latter in aerated solutions, were found to be, respectively, in water: 0.67 +/- 0.17 and 0.18 +/- 0.04 and in acetonitrile: 0.61 +/- 0.15 and 0.50 +/- 0.20. The fraction of the 4t-Urd triplet molecules quenched by oxygen leading to singlet molecular oxygen, S delta, was calculated to be between 0.7 and unity in both solvents, this value being indicative of a pi pi*character for the lowest triplet state of 4t-Urd.

Section: Acetonitrilesupporting

confidence: 86%

“…From these rate constants, S 0 = 0.92 results for aerated solutions (Table 1} and S 0 > 0.98 for oxygenated solutions. 1 1 ) phosphorescence (Foote and Dobrowolski, 1984).…”

Section: Acetonitrilementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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QUANTUM YIELDS OF TRIPLET AND O₂(¹∆_g) FORMATION OF 4‐THIOURIDINE IN WATER AND ACETONITRILE

Heihoff

Redmond

Braslavsky

et al. 1990

“…A photosensitizer can initiate these reactions primarily in three ways. The excited photosensitizer reacts directly by Type I photosensitization or photocycloaddition reactions, or it can transfer its energy to 3 O 2 through a Type II photosensitization mechanism . These reactions can generate highly reactive oxygen species such as singlet oxygen, superoxide and hydrogen peroxide, which then go on to damage biomolecules .…”

Section: Clinical Relevance and Applications Of Thiobasesmentioning

confidence: 99%

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Ashwood

Pollum

Crespo‐Hernández

2018

105

132

Sulfur-substituted nucleobases (a.k.a., thiobases) are among the world's leading prescriptions for chemotherapy and immunosuppression. Long-term treatment with azathioprine, 6-mercaptopurine and 6-thioguanine has been correlated with the photoinduced formation of carcinomas. Establishing an in-depth understanding of the photochemical properties of these prodrugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, a basis for developing effective compounds for targeted phototherapy. In this review, a broad examination is undertaken, surveying the basic photochemical properties and excited-state dynamics of sulfur-substituted analogs of the canonical DNA and RNA nucleobases. A molecular-level understanding of how sulfur substitution so remarkably perturbs the photochemical properties of the nucleobases is presented by combining experimental results with quantum-chemical calculations. Structure-property relationships demonstrate the impact of site-specific sulfur substitution on the photochemical properties, particularly on the population of the reactive triplet state. The value of fundamental photochemical investigations for driving the development of ultraviolet-A chemotherapeutics is showcased. The most promising photodynamic agents identified thus far have been investigated in various carcinoma cell lines and shown to decrease cell proliferation upon exposure to ultraviolet-A radiation. Overarching principles have been elucidated for the impact that sulfur substitution of the carbonyl oxygen has on the photochemical properties of the nucleobases.

“…Both '02 and 0, are probably formed in the system s2Ura/02/light. The formation of '02 from the closely-related s4U was demonstrated by the characteristic emission of 1.27 p in the infrared (Foote and Dobrowolski, 1984), and 0, was shown to be formed from s2Ura/02/light by the SOD-inhibitable reduction of cytochrome c (Cunningham er af., 1986). Both species are therefore prime candidates for the causative agent that breaks the DNA.…”

Section: Discussionmentioning

confidence: 99%

OBSERVATIONS ON THE PHOTOSENSITIZED BREAKAGE OF DNA BY 2‐THIOURACIL AND 334‐nm ULTRAVIOLET RADIATION

Peak

Foote

1986

Abstract— Breaks induced in purified DNA by 334‐nm ultraviolet (UV) radiation are enhanced 30 times when 2‐thiouracil (s2Ura) is present during aerobic irradiation. This enhancement by s2Ura is maximally effective at a concentration of about 1 mM. Anoxic irradiation reduces the s2Ura‐enhanced breakage by 90%, indicating a Type II photosensitization. Benzoate, glycerol, diazabicyclo[2.2.2.]octane (DABCO) and histidine all inhibit formation of s2Ura photosensitized breaks, unlike diethylenetriaminepenta‐acetic acid (DETAPAC) and catalase, which do not. The relationships between the concentration of DABCO. benzoate and histidine and their protection against induction of single strand breaks (SSBs) were similar, with little inhibition below 10 mM and maximal inhibition near 0.1 M for all compounds. Irradiation of the DNA‐s2Ura mixture dissolved in D2O instead of H2O enhanced the rate of induction of SSBs in DNA by 334‐nm light almost five times. Addition of superoxide dismutase (40, 80 and 200 μg/ml) decreased the rate of induction of breaks in DNA by 334‐nm radiation plus s2Ura (in H2O) by about 40%. Boiled superoxide dismutase had no effect.