Subject(s)
Crohn Disease/drug therapy , DNA, Viral/blood , Diagnostic Errors , Herpesvirus 6, Human , Roseolovirus Infections/diagnosis , Virus Integration , Adolescent , Antiviral Agents/therapeutic use , Child , Crohn Disease/complications , Female , Humans , Immunosuppressive Agents/therapeutic use , Roseolovirus Infections/complications , Roseolovirus Infections/drug therapyABSTRACT
Here, we show that two tautomers are produced by the protonation of the guanine-electron adduct. The fate of electron adducts of a variety of substituted guanosines was investigated by radiolytic methods and addressed computationally by means of time-dependent DFT (TD-B3LYP/6-311G**//B1B95/6-31+G**) calculations. The reaction of e(aq-) with guanosine and 1-methylguanosine produces two transient species, whereas the reaction with N2-ethylguanosine and N2,N2-diethylguanosine produces only one. The two short-lived intermediates, which show a substantial difference in their UV-visible spectra, are recognized to be two purine tautomers (i.e., iminic 18 and aminic 19 forms). The tautomerization 18 --> 19 occurs with a rate constant of ca. 1.5 x 106 s(-1) , and theory suggests that it is a water-assisted process.
Subject(s)
Electrons , Guanine/analogs & derivatives , Guanine/chemistry , Water/chemistry , Computer Simulation , Free Radicals/chemistry , Models, Chemical , Stereoisomerism , Time FactorsABSTRACT
The reactions of hydrated electrons (e(aq) (-)) with 8-bromo-2'-deoxyinosine (8) and 8-bromoinosine (12) have been investigated by radiolytic methods coupled with product studies and have been addressed computationally by means of BB1K-HMDFT calculations. Pulse radiolysis revealed that one-electron reductive cleavage of the C--Br bond gives the C8 radical 9 or 13 followed by a fast radical translocation to the sugar moiety. Selective generation of a C5' radical occurs in the 2'-deoxyribo derivative, whereas in the ribo analogue the reaction is partitioned between the C5' and C2' positions with similar rates. Both C5' radicals undergo cyclizations, 10-->11 and 14-->15, with rate constants of 1.4 x 10(5) and of 1.3 x 10(4) s(-1), respectively. The redox properties of radicals 10 and 11 have also been investigated. A synthetically useful photoreaction has also been developed as a one-pot procedure that allows the conversion of 8 to 5',8-cyclo-2'-deoxyinosine in a high yield and a diastereoisomeric ratio (5'R)/(5'S) of 4:1. The present results are compared with data previously obtained for 8-bromoadenine and 8-bromoguanine nucleosides. Theory suggests that the behavior of 8-bromopurine derivatives with respect to solvated electrons can be attributed to differences in the energy gap between the pi*- and sigma*-radical anions.