Intrinsic contributions to chiral recognition: Discrimination between enantiomeric amines by dimethyldiketopyridino-18-crown-6 in the gas phase

We have employed Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to investigate and quantify the recognition of chiral amines in the gas phase by the chiral crown ethers (RR)- and (S,S)-dimethyldiketopyridino-18-crown-6, using a new procedure wherein the relatively involatile chiral ligand is easily ionized via electrospray to produce a protonated host molecule. A neutral chiral amine and an achiral reference amine, which are generally fairly volatile, were introduced into the ion trapping cell, where they reacted with the protonated host to form crown-ammonium complexes. Equilibrium constants were determined for exchange of the chiral and achiral amine guests. Electrospray of the other enantiomeric host, followed by guest exchange equilibrium constant determination, enabled characterization of the effects of chirality on complexation equilibria. Comparison of the equilibrium constants for the two enantiomeric hosts measures the relative degree of recognition for a given guest. In all cases, binding of the guest with absolute configuration opposite those of the host stereocenters is preferred. The free energy of binding the preferred enantiomer of alpha(1-naphthyl)ethylamine is 3.5 +/- 0.6 kJ mol(-1) greater than for the nonpreferred enantiomer, in agreement with results obtained using an older ligand transfer method. Enantiomeric preferences (all in kJ mol(-1)) for sec-butylamine (0.3 +/- 0.4), cyclohexylethylamine (0.9 +/- 0.2), and methylbenzylamine (2.4 +/- 0.5) illustrate intrinsic factors contributing to chiral recognition, including steric bulk and the importance of pi-pi stacking interactions to anchor the guest. The interactions of sec-butylamine and cyclohexylethylamine can be described using a three point binding model, while the aromatic amines are more consistent with the four-point binding model described by Cram. The data suggest that recognition in this system arises largely from differing degrees of methyl rotor locking for the two enantiomers, with accompanying differences in the entropy of complexation.