The thermodynamic basis for enantiodiscrimination: Gas-phase measurement of the enthalpy and entropy of chiral amine recognition by dimethyldiketopyridino-18-crown-6

Discrimination between the enantiomers of 1-phenylethylamine (PhEt) and alpha(1-naphthyl)ethylamine (NapEt) by the chiral ligand protonated dimethyldiketopyridino-18-crown-6 was studied using Fourier transform ion cyclotron resonance mass spectrometry to perform variable-temperature equilibrium (van't Hoff) experiments in the gas phase. The heterochiral complexes [(S,S)-ligand with (R)-amine, for example] have more-favorable enthalpy in both studied cases than the homochiral complexes; the differences are -6.7 +/- 0.7 kJ mol(-1) for the PhEt enantiomers and -10.0 +/- 1.2 kJ mol(-1) for the NapEt enantiomers. Entropy disfavors the heterochiral complexes by -14.8 +/- 2.2 J mol(-1) K-1 for PhEt and by -20.0 +/- 3.9 J mol(-1) K-1 for NapEt; entropyenthalpy compensation is evident. These results suggest that enantiodiscrimination in these complexes is enthalpic and that locking of methyl rotors in the thermodynamically disfavored complexes is probably not important. Computational methods were also used to determine complex geometries at the HF/6-31+G* level (diffuse functions on O and N atoms only), and energies at these geometries were determined using the same basis set with MP2 and B3LYP methods. The computed geometries have shorter hydrogen-bonding distances in the heterochiral complexes than those in the homochiral ones. The computational results also correctly predict that the heterochiral complexes are energetically favored. The calculations at most levels fail to reproduce the experimental finding that enantiodiscrimination of NapEt is greater than that of PhEt.