A systematic study of a 15-member group of purine molecular systems is proposed.
The aims are to characterize the direct-ionization products of purines. Rationale for the project comes from the probability that the behavior of purines, as consitituents of DNA, is central to the response of DNA to ionizing radiation. The overall objective, therefore, is to identify and characterize the direct-ionization products of purines, and their reactions, which may provide insight into the radiation response of DNA. For that reason, four of the molecular systems contain adenine, while seven of them contain guanine. Of particular interest will be the molecular cations and their subsequent products. One reason is that the guanine cation or G+, is thought to be a primary radiation product of DNA. Full characterization of this product, to the extent possible by the crystallographic method, has not yet been achieved, although progress toward this aim has recently been reported. Also, the subsequent products, or fate, of G+ are unknown. As a result, the true importance of G+ is also unknown. Therefore it is possible that a full understanding of purine radiochemistry may be necessary in order to understand the significance of G+ DNA. Also proposed is a set of preliminary studies aimed at developing methods to use dinucleoside phosphates (DNP's) in similar studies. The rational for doing so is that DNP's which crystallize as helical fragments, will more faithfully model DNA.
The aims of the preliminary studies are to prepare suitable samples of DNP's. The proposed experimental approach is to use the methods of magnetic resonance crystallography (ESR and ENDOR). In addition, low temperature methods will be used to stabilize normally unstable products. Finally, controlled warming studies will be performed in order to identify product transformations whenever possible.
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