115142-06-8Relevant academic research and scientific papers
Kinetic isotope effects and stereochemical studies on a ribonuclease model: Hydrolysis reactions of uridine 3'-nitrophenyl phosphate
Hengge,Bruzik,Tobin,Cleland,Tsai
, p. 119 - 133 (2000)
The reactions of a ribonuclease model substrate, the compound uridine-3'-p-nitrophenyl phosphate, have been examined using heavy-atom isotope effects and stereochemical analysis. The cyclization of this compound is subject to catalysis by general base (by imidazole buffer), specific base (by carbonate buffer), and by acid. All three reactions proceed by the same mechanistic sequence, via cyclization to cUMP, which is stable under basic conditions but which is rapidly hydrolyzed to a mixture of 2'- and 3'-UMP under acid conditions. The isotope effects indicate that the specific base-catalyzed reaction exhibits an earlier transition state with respect to bond cleavage to the leaving group compared to the general base-catalyzed reaction. Stereochemical analysis indicates that both of the base-catalyzed reactions proceed with the same stereochemical outcome. It is concluded that the difference in the nucleophile in the two base-catalyzed reactions results in a difference in the transition state structure but both reactions are most likely concerted, with no phosphorane intermediate. The 15N isotope effects were also measured for the reaction of the substrate with ribonuclease A. The results indicate that considerably less negative charge develops on the leaving group in the transition state than for the general base-catalyzed reaction in solution. (C) 2000 Academic Press.
Lanthanide catalyzed cyclization of uridine 3′-p-nitrophenyl phosphate
Rishavy, Mark A.,Hengge, Alvan C.,Cleland
, p. 283 - 292 (2007/10/03)
Steady state kinetics and 15N isotope effects have been used to study the cyclization reaction of uridine 3′-p-nitrophenyl phosphate. The cyclization reaction is catalyzed by transition metal ions and lanthanides, as are substitution reactions of many phosphate esters. Kinetic analysis reveals that the erbium-catalyzed cyclization reaction involves the concerted deprotonation of the 2′-OH group and departure of the leaving group. The transition state is very late, with a very large degree of bond cleavage to the leaving group, which could be due to a large degree of polarization of the P-O bonds by erbium.
The mechanism of the metal ion promoted cleavage of RNa phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group
Mikkola, Satu,Stenman, Eeva,Nurmi, Kirsi,Yousefi-Salakdeh, Esmail,Stroemberg, Roger,Loennberg, Harri
, p. 1619 - 1625 (2007/10/03)
A series of uridine 3′-alkyl phosphates and 3′-aryl phosphates were synthesised and their cleavage was studied in the presence of Zn2+ aquo ions. A βlg value was determined for the Zn2+ promoted cleavage of both types of compounds. Comparison of the results obtained to those reported previously for the cleavage of the same substrates in the absence of metal ion catalysts suggests that the alkyl leaving group departs as an alcohol in the presence of metal ion catalysts. Furthermore, metal ion catalysts seem to enhance the departure. The aryl leaving group, in contrast, departs as an oxyanion.
