Substituent effects on axle binding in amide pseudorotaxanes: comparison of NMR titration and ITC data with DFT calculationsThis article is part of the Organic & Biomolecular Chemistry 10th Anniversary issue.Electronic supplementary information (ESI) available: Results from NMR titrations and ITC measurements, crystallographic data, and theoretical calculations. CCDC 853879 and 853880. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2ob25196e

The binding behaviour of differently substituted diamide axle molecules to Hunter/Vögtle tetralactam macrocycles was studied with a combination of NMR titration, isothermal titration calorimetry (ITC) experiments and calculations employing density functional theory (DFT), along with dispersion-corrected exchange-correlation functionals. Guests with alkyl or alkenyl chains attached to the diamide carbonyl groups have a significantly higher binding affinity to the macrocycle than guests with benzoyl amides and their substituted analogues. While the binding of the benzoyl and alkenyl substituted axles is enthalpically driven, the alkyl-substituted guest binds mainly because of a positive binding entropy. The electronic effects of para -substituents at the benzoyl moieties have an influence on the binding affinities. Electron donating substituents increase, while electron-withdrawing substituents decrease the binding energies. The binding affinities obtained from both NMR titration and ITC experiments correlate well with each other. The substituent effects observed in the experimental data are reflected in adiabatic interaction energies calculated with density functional methods. The calculated structures also agree well with pseudorotaxane crystal structures. Guest discrimination : NMR titration and ITC experiments were used to examine the binding behavior of differently disubstituted diamide guests to a tetralactam macrocycle.