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Hydrated Electrons (hydrated + electron)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

A Novel Class of Antitumor Prodrug, 1-(2,-Oxopropyl)-5-fluorouracil (OFU001), That Releases 5-Fluorouracil upon Hypoxic Irradiation

CANCER SCIENCE, Issue 4 2000
Yuta Shibamoto
We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2,-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding ,* orbital of the C(1,)-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O2 into superoxide anion radicals () under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G -value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9×10,7 mol/ J following hypoxic irradiation, while the G -value for 5-FU release was 1.0×10,8 mol/J following aerobic irradiation. However, the G -values for decomposition of OFU001 were almost the same, i.e., 3.4×10,7 mol/J following hypoxic irradiation and 2.5×10,7 mol/J following aerobic irradiation. When hypoxically irradiated (7.5,30 Gy) OFU001 was added to murine SCCVII cells for 1,24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents. [source]

Spectral, kinetic, and redox properties of basic fuchsin in homogeneous aqueous and sodium dodecyl sulfate micellar media

INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 12 2003
N. Ramanathan
Effect of anionic surfactant on the optical absorption spectra and redox reaction of basic fuchsin, a cationic dye, has been studied. Increase in the absorbance of the dye band at 546 nm with sodium dodecyl sulfate (SDS) is assigned to the incorporation of the dye in the surfactant micelles with critical micellar concentration (CMC) of 7.3 × 10,3 mol dm,3. At low surfactant concentration (<5 × 10,3 mol dm,3) decrease in the absorbance of the dye band at 546 nm is attributed to the formation of a dye,surfactant complex (1:1). The environment, in terms of dielectric constant, experienced by basic fuchsin inside the surfactant micelles has been estimated. The association constant (KA) for the formation of dye,SDS complex and the binding constant (KB) for the micellization of dye are determined. Stopped-flow studies, in the premicellar region, indicated simultaneous depletion of dye absorption and formation of new band at 490 nm with a distinct isosbestic point at 520 nm and the rate constant for this region increased with increasing SDS concentration. The reaction of hydrated electron with the dye and the decay of the semireduced dye are observed to be slowed down in the presence of SDS. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 629,636, 2003 [source]

Primary Photophysical Properties of Moxifloxacin, A Fluoroquinolone Antibiotic

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2008
Fernando Lorenzo
The photophysical properties of the fluoroquinolone antibiotic moxifloxacin (MOX) were investigated in aqueous media. MOX in water, at pH 7.4, shows two intense absorption bands at 287 and 338 nm (, = 44 000 and 17 000 dm3 mol,1 cm,1, respectively). The absorption and emission properties of MOX are pH-dependent, pKa values for the protonation equilibria of both the ground (6.1 and 9.6) and excited singlet states (6.8 and 9.1) of MOX were determined spectroscopically. MOX fluoresces weakly, the quantum yield for fluorescence emission being maximum (0.07) at pH 8. Phosphorescence from the excited triplet state in frozen ethanol solution has a quantum yield of 0.046. Laser flash photolysis and pulse radiolysis studies have been carried out to characterize the transient species of MOX in aqueous solution. On laser excitation, MOX undergoes monophotonic photoionization with a quantum yield of 0.14. This leads to the formation of a long-lived cation radical whose absorption is maximum at 470 nm (,470 = 3400 dm3 mol,1 cm,1). The photoionization process releases hydrated electron which rapidly reacts (k = 2.8 × 1010 dm3 mol,1 s,1) with ground state MOX, yielding a long-lived anion radical with maximum absorption at 390 nm (,390 = 2400 dm3 mol,1 cm,1). The cation radical of MOX is able to oxidize protein components tryptophan and tyrosine. The bimolecular rate constants for these reactions are 2.3 × 108 dm3 mol,1 s,1 and 1.3 × 108 dm3 mol,1 s,1, respectively. Singlet oxygen sensitized by the MOX triplet state was also detected only in oxygen-saturated D2O solutions, with a quantum yield of 0.075. [source]

A Novel Class of Antitumor Prodrug, 1-(2,-Oxopropyl)-5-fluorouracil (OFU001), That Releases 5-Fluorouracil upon Hypoxic Irradiation

The Role of One-Electron Reduction of Lipid Hydroperoxides in Causing DNA Damage

CHEMISTRY - A EUROPEAN JOURNAL, Issue 40 2009
Conor Crean Dr.
Abstract The in vivo metabolism of plasma lipids generates lipid hydroperoxides that, upon one-electron reduction, give rise to a wide spectrum of genotoxic unsaturated aldehydes and epoxides. These metabolites react with cellular DNA to form a variety of pre-mutagenic DNA lesions. The mechanisms of action of the radical precursors of these genotoxic electrophiles are poorly understood. In this work we investigated the nature of DNA products formed by a one-electron reduction of (13S)-hydroperoxy-(9Z,11E)-octadecadienoic acid (13S -HPODE), a typical lipid molecule, and the reactions of the free radicals thus generated with neutral guanine radicals, G(,H).. A novel approach was devised to generate these intermediates in solution. The two-photon-induced ionization of 2-aminopurine (2AP) within the 2,-deoxyoligonucleotide 5,-d(CC[2AP]TCGCTACC) by intense nanosecond 308,nm excimer laser pulses was employed to simultaneously generate hydrated electrons and radical cations 2AP.+. The latter radicals either in cationic or neutral forms, rapidly oxidize the nearby G base to form G(,H).. In deoxygenated buffer solutions (pH,7.5), the hydrated electrons rapidly reduce 13S -HPODE and the highly unstable alkoxyl radicals formed undergo a prompt ,-scission to pentyl radicals that readily combine with G(,H).. Two novel guanine products in these oligonucleotides, 8-pentyl- and N2 -pentylguanine, were identified. It is shown that the DNA secondary structure significantly affects the ratio of 8-pentyl- and N2 -pentylguanine lesions that changes from 0.9:1 in single-stranded, to 1:0.2 in double-stranded oligonucleotides. The alkylation of guanine by alkyl radicals derived from lipid hydroperoxides might contribute to the genotoxic modification of cellular DNA under hypoxic conditions. Thus, further research is warranted on the detection of pentylguanine lesions and other alkylguanines in vivo. [source]

Ring Opening of the Cyclobutane in a Thymine Dimer Radical Anion

CHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2007
Chryssostomos Chatgilialoglu Dr.
Abstract The reactions of hydrated electrons (eaq,) with thymine dimer 2 and thymidine have been investigated by radiolytic methods coupled with product studies, and addressed computationally by means of BB1K-HMDFT calculations. Pulse radiolysis revealed that one-electron reduction of the thymine dimer 2 affords the radical anion of thymidine (5) with t1/2<35,ns. Indeed, the theoretical study suggests that radical anion 3, in which the spin density and charge distribution are located in both thymine rings, undergoes a fast partially ionic splitting of the cyclobutane with a half-life of a few ps. This model fits with the in vivo observation of thymine dimer repair in DNA by photolyase. ,-Radiolysis of thymine dimer 2 demonstrates that the one-electron reduction and the subsequent cleavage of the cyclobutane ring does not proceed by means of a radical chain mechanism, that is, in this model reaction the T,. is unable to transfer an electron to the thymine dimer 2. [source]