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

Abstract

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.

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

“…The singlet oxygen quantum yield of these thiopurine derivatives ranges from 24% for 6-thio-2 0 -deoxyguanosine for 16% for 6-thiopurine in aqueous solution at pH 7.4 under 3 O 2 -saturated conditions (42,58,61), which is more than 50% smaller than the values reported in early investigations using indirect methods (63,64). Recent experimental results for 2 0 ,3 0 ,5 0 -Tri-O-acetyl-6,8-dithioguanosine (66), and other 6-thioguanine derivatives (82), lend support to the observation that the singlet oxygen yields in these thiopurine derivatives are not larger than ca. 30% in aqueous solutions ( Table 3).…”

“…Importantly, however, the redshift of the absorption maximum depends sensitively on the degree of thionation. Dithionation of both purine and 2′‐deoxyguanosine results in the greatest redshift of the absorption maximum of all the selected thiopurine derivatives reported in Table , with 2′,3′,5′‐tri‐ O ‐acetyl‐6,8‐dithioguanosine exhibiting the greatest redshift and the largest molar absorptivity coefficient . In general, it is unclear from the data shown in Table whether glycosylation shifts the absorption maximum within the experimental uncertainties.…”

“…Suzuki and co‐workers have also recently reported the synthesis and photophysical characterization of a series of thioguanine derivatives for potential use in photodynamic therapy . In particular, the authors demonstrated that a 6,8‐dithionated nucleoside derivative, 2′,3′,5′‐tri‐ O ‐acetyl‐6,8‐dithioguanosine, has the red‐most absorption band of all the thiopurine derivatives investigated thus far, with a maximum at 381 nm and a molar absorption coefficient of 3.76 × 10 4 M −1 cm −1 in acetonitrile . It was further shown that 2′,3′,5′‐tri‐ O ‐acetyl‐6,8‐dithioguanosine generates singlet oxygen effectively in aqueous solution, featuring a yield that varies from 32% at pH 4 to 25% at pH 12 .…”

“… and Miyata et al . are promising, the next frontier in this quest should be to investigate the mechanisms of action of these sensitizers when incubated in a variety of cell lines, as well as to investigate their photochemical properties when they are incorporated in DNA or RNA polymers. These investigations are clearly essential to further scrutinize their photodynamic potential.…”

“…Suzuki and co-workers have also recently reported the synthesis and photophysical characterization of a series of thioguanine derivatives for potential use in photodynamic therapy (66,82).…”