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Paper
Org. Biomol. Chem., 2010, 8, 349 - 356, DOI: 10.1039/b912042d
Phosphorane intermediate vs. leaving group stabilization by intramolecular hydrogen bonding in the cleavage of trinucleoside monophosphates: implications for understanding catalysis by the large ribozymes
Tuomas Lönnberg and Maarit Laine
Hydrolysis of 2
,3-O-methyleneadenosin-5-yl 5-O-methyluridin-2-yl 5-O-methyl-2-trifluoroacetamido-2-deoxyuridin-3-yl phosphate ( 1b) has been followed by HPLC over a wide pH range to study the effects of potential hydrogen bonding interactions of the 2-trifluoroacetamido function on the rate and product distribution of the reaction. At pH < 2, decomposition of 1b (and its 3,3,5-isomer 1a) is first-order in hydronium-ion concentration and cleavage of the P–O3 bond of the 2-trifluoroacetamido-modified nucleoside is slightly favored over cleavage of the P–O5 bond. Between pH 2 and 4, the overall hydrolysis is pH-independent and the P–O3 and P–O5 bonds are cleaved at comparable rates. At pH 5, the reaction becomes first-order in hydroxide-ion concentration, with P–O3 bond cleavage predominating. At 10 mmol L-1 aqueous sodium hydroxide, no P–O5 bond cleavage is observed. Compared to the 2-OH counterpart 2, a modest rate enhancement is observed over the entire pH range studied. The absence of P–O5 fission under alkaline conditions suggests hydrogen bond stabilization of the departing 3-oxyanion by the neighboring 2-trifluoroacetamido function.
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