Dewar valence isomer

The HPLC-MS/MS assay was also successfully applied to the measurement of UV-induced dimeric pyrimidine photoproducts [123, 124]. The latter lesions were released from DNA as modified dinucleoside monophosphates due to resistance of the intra-dimer phosphodiester group to the exonuclease activity during the hydrolysis step [125, 126]. The hydrolyzed photoproducts exhibit mass spectrometry and chromatographic features that allow simultaneous quantification of the three main classes of photolesions, namely cyclobutane dimers, (6-4) photoproducts, and Dewar valence isomers, for each of the four possible bipyrimidine sequences. It may be added that these analyses are coupled to UV detection of normal nucleosides in order to correct for the amount of DNA in the sample and obtain a precise ratio of oxidized bases or dimeric photoproducts to normal nucleosides. 

Evidence for the formation of 34 (R = Ph) was provided by neutralization reionization mass spectrometry and more directly by the matrix isolation and spectroscopic investigations on 34 (R = Ph) in an argon matrix at 12 K. The UV spectrum of 34 (R = Ph) exhibits characteristic bands at X = 364, 386, 404, 420, 440, 470 and 502 nm, resembling those of the electronic spectrum of anthracene, but with the expected bathochromic shifts. If one irradiates into the maximum at X = 502 nm, all bands shown in the spectrum disappear completely within 5 minutes. The vanishing of these characteristic bands can again be explained by the photoisomerization of silaanthracene 34 (R = Ph) to the corresponding Dewar valence isomer. 

Clingen, P. H., Arlett, C. F., Roza, L., Mori, T. Nikaido, O., Green, M. H. L. 1995. Induction of cyclobutane pyrimidine imers, pyrimidine(6-4)pyrimidone photoproducts and Dewar valence isomers by natural sunlight in normal human mononuclear cells. Cancer Res. 

Photochemical isomerisation of [6](l,4)naphthalenophane (33) and [6](l,4)an-thracenophane (34) produces the corresponding Dewar valence isomers (35) and (36) respectively, and the efficiency of excited product formation in the adiabatic photocycloreversion of the bridged biplanemer (37) has been determined by the size of its side-chain substituents which influence the interchromo-phore distance in photoproduct (38). ... 

Clearly, all indications are that (6—4) photolyase binds DNA and repairs its substrate by a mechanism quite similar to that of classical photolyase. However, there appears to be a fundamental difference in the photochemical reaction catalyzed by the two enzymes. The quantum yield of repair by excited singlet-state flavin by classical photolyase is near unity, whereas the quantum yield of repair by excited flavin in (6-4) photolyase is 0.05-0.10. Whether this low quantum yield of repair by (6—4) photolyase is a result of the low efficiency of formation of the oxetane intermediate thermally, low efficiency of electron transfer from the flavin to the photoproduct, or low efficiency splitting of the oxetane anion coupled with high rate of back electron transfer is not known at present. Furthermore, it was found that (6-4) photolyase can photorepair the Dewar valence isomer of the (6-4) photoproduct (Taylor, 1994) that cannot form an oxetane intermediate, casting some doubt about the basic premise of the retro [2+2] reaction. However, the Dewar isomer is repaired with 300-400 lower quantum yield than the (6-4) photoproduct, and it has been proposed (Zhao et ai, 1997) that the Dewar isomer may be repaired by the enzyme through a two-photon reaction in which the first photon converts the Dewar isomer to the Kekule form and a second electron transfer reaction initiated by the second photon promotes the retro [2+2] reaction. 

CMe CF CF-CFs + EtaN-CiCMe-CFa-CF-CFs ss] can be found in Chapter 2 (pp. 62,72) and production of the Dewar valence-isomer of pentakis(pentafluoro-ethyl)pyridine (53) is also discussed elsewhere (p. 93). An interesting synthesis of the fluoroenamine (54 X = CF CF2) has emerged from studies on aza[I3]-... 

A second photoproduct is the (6-4) photoproduct (53a). This photoproduct undergoes further rearrangement at 313 nm irradiation to give the Dewar valence isomer (53b). A method for s5mthesis of the Dewar isomer in duplex DNA has been... 

FIGURE 2.13. Photoproducts (6-4PPs) artd their Dewar valence isomers. 

Chvio, P. and Fourrey, J.-L., Photochemistry of the thio anaJog of the DNA (6- ) photoproduct Dewar valence isomer structure of a new photoproduct. Tetrahedron Lett., 39, 275, 1998. 

The Chemistry of Lesion Formation Cyclobutane Pyrimidine Dimers (6- ) Photolesions The Dewar Valence Isomer The Spore Photoproduct Other DNA Photoproducts. 141 2... 

Irradiation of DNA containing the (6—4) photoadduct with wavelength above 300 nm induces a rearrangement of this (6—4) lesion into a Dewar valence isomer (Scheme 4). ... 

SCHEME 4 Rearrangement of the (6-4) photoproduct to the Dewar valence isomer upon irradiation with light >300 nm (UV-B). 

Semiempirical AMI and PM3 calculations suggest that a hypothetical oxetan intermediate would ef ciently spHt after single-electron reduction or oxidation.The reductive pathway was found to be more exothermic and should proceed over lower rate-determining barriers, which supports the assumption that the (6—4) repair is based on a reductive electron transfer from the FADH" to the lesion. It was also calculated that the Dewar valence isomer could be transformed into the (6 ) lesion by a singleelectron reduction, which could explain the ability of (6 ) photolyases to repair this lesion as well, although with much lower efficiency. ... 

Douki, T, Voituriez, L., and Cadet, J., Characterization of the (6-4) photoproduct of 2 -deoxycyti-dylyl-(3 — 5 )-thymidine and of its Dewar valence isomer, Photochem. Photobiol, 53, 293,1991. Hwang, G.S., Kim, J.-K., and Choi, B.S., NMR structural studies of DNA decamer duplex containing the Dewar photoproduct of thymidylyl(3 —> 5 )thymidine. Conformational changes of the oHgonucleotide duplex by photoconversion of a (6-4) adduct to its Dewar valence isomer, Eur. J. Biochem., 235, 359,1996. 

Taylor, J.-S., Lu, H.-F., and Kotyk, J.J., Quantitative conversion of the (6—4) photoproduct of TpdC to its Dewar valence isomer upon exposure to simulated sunKght, Photochem. PhotobioL, 51,161, 1990. 

Kan, L.-S., Voituriez, L., and Cadet, J., The Dewar valence isomer of the (6-4) photoadduct of thymidylyl-(3 -5 )-thymidine monophosphate formation, alkaline lability and conformational properties, J. Photochem. PhotobioL B Biol., 12, 339, 1992. 

---