The RNA dimer ApA is rapidly cleaved in the presence of lanthanum(III) chloride yielding the products of transesterification and hydrolysis, 2 '-AMP, 3'-AMEP and adenosine. The intermediate 2,3'-cAMP does not accumulate. Under pseudo-first-order conditions (approximately 100-fold excess lanthanum(III) chloride) the half-life for ApA cleavage is only 13 seconds. / The potentiometric titration, pH-rate profile and dependence upon lanthanum(IIII) chloride concentration support a penta-mu-hydroxo dilanthanum species as the active species. The kinetic isotope effect of 1.9 and a one-proton inventory indicate that the 2'-hydroxyl deprotonation is not concerted with the nucleophilic attack. It is proposed that a rapid equilibrium proton transfer occurs between the 2'-hydroxyl and a bridging hydroxo prior to the nucleophilic attack and rate-determining intramolecular general acid catalyzed breakdown of the phosphorane to products. It is proposed that the general acid is a bound water, formed from the protonation of the bridging hydroxo. / Lanthanum(III) ion was found to be among the best of the trivalent lanthanides for promoting ApA cleavage, contrary to literature reports. The proposed lanthanide dimer mechanism, which is consistent with the behavior of the other lanthanides, easily explains this. / The lanthanum(III) dimer was also found to be highly reactive towards the DNA model compound bis(p-nitrophenyl) phosphate and the cyclic nucleotides 3',5'-cAMP and 2',3'-cAMP, providing half-lives of 12s, 9min and 340ms respectively. The results were consistent with a bound mu-hydroxo as the nucleophile. / The results for the ApA and cyclic nucleotides reactions are faster than any reported for synthetic catalysts.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34740 |
| Date | January 1997 |
| Creators | Hurst, Phillip C. |
| Contributors | Chin, Jik (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001618454, proquestno: NQ44460, Theses scanned by UMI/ProQuest. |
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