Unexpected roles of guest polarizability and maximum hardness, and of host solvation in supramolecular inclusion complexes: A dual theoretical and experimental study

The origin of differential binding affinity and structural recognition between the inclusion complexes of cyclobis(paraquat-p-phenylene), I4+, and 1,4-substituted phenyl or 4,4'-substituted biphenyl derivatives has been jointly determined by spectrometric techniques and ab initio and semiempirical molecular orbital methods. The unusual boxed geometry and tetracationic charge distribution in 1(4+) are key molecular features which produce strong intermolecular interactions with guest and solvent molecules. Solvation was addressed by including up to 12 acetonitrile molecules in the theoretical model which realigned the predicted gas-phase supramolecular structures and energies into excellent agreement with experiment. The computed complexation enthalpies, Delta H-bind, from the semiempirical molecular orbital PM3 method are on average within 1 kcal/mol of the experimental free energy binding data collected from absorption spectroscopy in acetonitrile. In addition, the computed geometric penetration and positioning of 1(4+)/benzidine and 1(4+)/4,4'-biphenol complexes are consistent with that reported from NMR NOE data. The partitioning of self-consistent field complexation energies from both classical and quantum forces has been determined by using Morokuma's variational energy decomposition technique. It was determined that the primary basis for the molecular recognition between 1,4-substituted phenyl guests and 1(4+) is short-range stabilizing electrostatic forces complemented by small amounts of polarizability and charge-transfer. In contrast, the recognition force between 4,4'-substituted biphenyl guests and 1(4+) is dominated by polarizability with a small contribution from electrostatics. Therefore, the balance between molecular polarizability and electrostatics controls the differential binding affinity and structural recognition with 1(4+). For the first time, we report that individual molecular properties of substituted guests correlate with the binding energies of corresponding 1(4+) inclusion complexes. Direct correlations between the 1(4+) binding energies and the computed molecular polarizability, maximum hardness, softness, and electronegativity of the guest have been identified. It is now plausible to consider the design and construction of new supramolecular assemblies based upon a few select molecular properties of the constituent molecules.