| Abstract
| - Hydrolytic reactions of the structural analogue of guanylyl-(3‘,3‘)-uridine, guanylyl-(3‘,3‘)-(2‘-amino-2‘-deoxyuridine), having one of the 2‘-hydroxyl groups replaced with an amino function, have been followedby RP HPLC in the pH range 0−13 at 90 °C. The results are compared to those obtained earlier withguanylyl-(3‘,3‘)-uridine, guanylyl-(3‘,3‘)-(2‘,5‘-di-O-methyluridine), and uridylyl-(3‘,5‘)-uridine. Under basicconditions (pH > 8), the hydroxide ion-catalyzed cleavage of the P−O3‘ bond (first-order in [OH-]) yieldsa mixture of 2‘-amino-2‘-deoxyuridine and guanosine 2‘,3‘-cyclic phosphate which is hydrolyzed to guanosine2‘- and 3‘-phosphates. Under these conditions, guanylyl-(3‘,3‘)-(2‘-amino-2‘-deoxyuridine) is 10 times lessreactive than guanylyl-(3‘,3‘)-uridine. Under acidic and neutral conditions (pH 3−8), where the pH−rateprofile for the cleavage consists of two pH-independent regions (from pH 3 to pH 4 and from 6 to 8),guanylyl-(3‘,3‘)-(2‘-amino-2‘-deoxyuridine) is considerably reactive. For example, in the latter pH range,guanylyl-(3‘,3‘)-(2‘-amino-2‘-deoxyuridine) is more than 2 orders of magnitude more labile than guanylyl-(3‘,3‘)-(2‘,5‘-di-O-methyluridine), while in the former pH range the reactivity difference is 1 order of magnitude.Under very acidic conditions (pH < 3), the isomerization giving guanylyl-(2‘,3‘)-(2‘-amino-2‘-deoxyuridine)and depurination yielding guanine (both first-order in [H+]) compete with the cleavage. The Zn2+-promotedcleavage ([Zn2+] = 5 mmol L-1) is 15 times faster than the uncatalyzed reaction at pH 5.6. The mechanismsof the reactions of guanylyl-(3‘,3‘)-(2‘-amino-2‘-deoxyuridine) are discussed, particularly focusing on thepossible stabilization of phosphorane intermediate and/or transition state via an intramolecular hydrogenbonding by the 2‘-amino group.
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