Accurate NOE-Distance Relationships

We recently reported the remarkably high accuracy which can be achieved in measurements of proton-proton distances in both rigid [59] and flexible [60] small molecules. Essentially, a plot of NOE-determined distances against those expected from either high level calculation or X-ray crystallography showed a linear relationship with average errors of <5%. With a little care and attention to detail (for example using non-viscous solvents, short mixing times and low concentrations), these average errors can be reduced to <3% (Figure below, left). Effectively, this means that we can determine interproton distances to within +/- 0.1 Angstroms.

 
 
 
 
 
 
 
 
 
 
 
If one now assumes this level of accuracy some quite astounding results can be achieved, for example:
– A combination of NOE-distances, nJCH, nJHH and Density Functional Theory calculations enabled us to elucidate the conformational space of acyclic C10-chain diastereomers (with 10 chiral centres) in our recent Nature paper [86]

 
 
 
 
 
 
 
– To differentiate between the diastereomers of a steroidal epoxide which has no protons on the stereocentres! [68](Figure above)

– To identify a vanishingly small (~2.5%) second conformer of the ‘rigid’ molecule strychnine [61] (Figure above).