The solution structure of lidocaine: Conformational analysis and NMR lanthanide‐induced shifts

Proton lanthanide‐induced shifts (LIS) were measured for Yb(fod)3—lidocaine complexes in CCl4 solution. The data were used in conjunction with empirical conformational energy calculations to determine the preferred conformations of lidocaine in complex with the lanthanide shift reagent. Energy calculations gave two pairs of symmetry‐related low‐energy conformations for lidocaine. The LIS analysis ruled out, on the basis of poor agreement factors, both members from one possible pair. This combination of methods therefore yielded two low‐energy, good agreement factor, symmetry‐related conformations for lidocaine in solution. These two conformations differ significantly from the reported crystal structure of lidocaine hydrochloride in the value of the NCOCH2N dihedral angle.