| 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 (R,R)- and ( S,S)-dimethyldiketopyridino-18-crown-6, using a new procedure wherein the relatively nonvolatile chiral ligand is easily ionized via electrospray to produce a protonated host molecule, which is then trapped and allowed to react with neutral amines. Equilibrium constants were determined for exchange of chiral and achiral amine guests. The degree of chiral recognition is determined by making this measurement for the two enantiomers of the chiral amines. It was found that binding of the guest with absolute configuration opposite those of the host stereocenters is preferred. The free energy of binding the preferred enantiomer of naphthylethylamine is 3.5 ± 0.6 kJ mol-1 more favorable than for the nonpreferred enantiomer. Enantiomeric preferences (all in kJ mol-1) for sec-butylamine (0.3 ± 0.4), cyclohexylethylamine (0.9 ± 0.2), and phenylethylamine (2.4 ± 0.5) illustrate the intrinsic factors contributing to chiral recognition, including steric bulk and the importance of π-π stacking interactions to anchor the guest. Measurement of the temperature dependence of the equilibrium constant of the amine-exchange reaction reveals that chiral recognition in the system is enthalpically driven, while entropy opposes recognition. ΔH° = –10.0 ± 1.2 kJ mol-1 for the recognition of naphthylethylamine, and –7.7 ± 0.7 kJ mol-1 for phenylethylamine. Larger enthalpy changes for the former guest probably reflect stronger π-π stacking interactions. The entropy changes (ΔS°) for the recognition of naphthylethylamine and phenylethylamine are –20.0 ± 3.9 and –17.8 ± 2.2 J mol-1 K -1, respectively. The amine-exchange method is also employed for studying chiral recognition using FABMS. Although the degree of chiral recognition by FABMS is lower than that by FTICR/MS, FABMS is simple and fast, and is suitable for fast screening analysis. The analytical utility of the chiral recognition method by FTMS is also discussed. |
