The use of complexation induced proton NMR chemical shifts for structural analysis of host-guest complexes in solution

Proton shielding variations in supramolecular complexes contain a wealth of information on complex geometries in solution that has been until now mostly neglected. We describe herein ways for such analyses with five cyclophane and two cyclodextrin complexes in water, by using a program SHIFT which is based on and parametrized with the analyses of over 300 intramolecular proton shift variations in well defined molecular frameworks such as steroids or cyclophanes. The intermolecular shift changes in the host-guest complexes at 100% complexation (CIS values) are calculated as sum of anisotropy effects deltachi from aromatic ring currents and linear electric field effects LEF, based on force field generated geometries. The conformations with the best agreement between calculated and observed CIS values are at least for noncharged guest compounds close to those obtained from molecular mechanics and/or MD calculations and intermolecular NOEs (where available), noticeably without adjusting the complex geometries to the experimental CIS. Through-space electrostatic field effects LEF, which have been until now often neglected, can be sizeable also for noncharged systems; best agreement between experiment and calculation is observed with Gasteiger atomic charges.