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

An 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.