Rationalizing nuclear overhauser effect data for compounds adopting multiple‐solution conformations

Abstract

AbstractAn algorithm is described for refining the populations of a set of multiple‐solution conformers using experimental nuclear Overhauser effects (nOes). The method is based upon representing the effective relaxation matrix for the set of interconverting proposed conformers as a linear combination of relaxation matrices (LCORMs) due to each conformer. The conformer population derivative of the nOe is derived from a Taylor series expression for the calculated nOe. This derivative may then be used in a standard nonlinear least‐squares refinement procedure. The LCORM nOe procedure is tested using a monosaccharide system, 1‐O‐methyl‐α‐L‐iduronate, that is known to exhibit conformational variability. The measured nOes for this system are used to refine the populations of a set of three static conformers, namely, the 1C4, 4C1, and 2S0 ring conformers. The populations thus derived are compared to those previously obtained using nuclear magnetic resonance proton‐proton coupling constant information. Two possible extensions to the method are discussed: The first uses combined nOe and coupling constant data while the second removes the restrictions that the conformers used for fitting be rigid entities. © 1994 by John Wiley & Sons, Inc.