Reliable NMR chemical shifts for molecules in solution by methods rooted in density functional theory.

The conceptual and numerical problems involved in the computation of reliable NMR chemical shifts for molecules in condensed phases are analyzed with reference to a number of case studies ranging from aromatic compounds in low-polarity solvents to carbonyl and amidic models in aqueous solution and to large polypeptides. The results show that an integrated tool including the most recent density functionals, mixed discrete-continuum solvent models, hybrid QM/MM approaches and, when needed, averaging from molecular dynamics simulations are becoming an invaluable complement to experimental results. Copyright 2004 John Wiley & Sons, Ltd.