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Updated: Apr 15, 2026

A Novel Saturation Mutagenesis Approach: Single Step Characterization of Regulatory Protein Binding Sites in RNA Using Phosphorothioates
Published on: August 21, 2018
Understanding thio-effects in simple phosphoryl systems: role of solvent effects and nucleophile charge
Alexandra T P Carvalho1, AnnMarie C O'Donoghue, David R W Hodgson
1Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, SE-751 24, Uppsala, Sweden. kamerlin@icm.uu.se.
Abstract:
Recent experimental work (J. Org. Chem., 2012, 77, 5829) demonstrated pronounced differences in measured thio-effects for the hydrolysis of (thio)phosphodichloridates by water and hydroxide nucleophiles. In the present work, we have performed detailed quantum chemical calculations of these reactions, with the aim of rationalizing the molecular bases for this discrimination. The calculations highlight the interplay between nucleophile charge and transition state solvation in SN2(P) mechanisms as the basis of these differences, rather than a change in mechanism.
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