NMR characterization of 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate binding to chiral molecular micelles

Abstract

NMR spectroscopy was used to characterize the binding of the chiral compound 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP) to five molecular micelles with chiral dipeptide headgroups. Molecular micelles have covalent linkages between the surfactant monomers and are used as chiral mobile phase modifiers in electrokinetic chromatography. Nuclear overhauser enhancement spectroscopy (NOESY) analyses of (S)-BNP:molecular micelle mixtures showed that in each solution the (S)-BNP interacted predominately with the N-terminal amino acid of the molecular micelle's dipeptide headgroup. NOESY spectra were also used to generate group binding maps for (S)-BNP:molecular micelle mixtures. In these maps, percentages are assigned to the (S)-BNP protons to represent the relative strengths of their interactions with a specified molecular micelle proton. All maps showed that (S)-BNP inserted into a previously reported chiral groove formed between the molecular micelle's dipeptide headgroup and hydrocarbon chain. In the resulting intermolecular complexes, the (S)-BNP protons nearest to the analyte phosphate group were found to point toward the N-terminal Halpha proton of the molecular micelle headgroup. Finally, pulsed field gradient NMR diffusion experiments were used to measure association constants for (R) and (S)-BNP binding to each molecular micelle. These K values were then used to calculate the differences in the enantiomers' free energies of binding, Delta(DeltaG). The NMR-derived Delta(DeltaG) values were found to scale linearly with electrokinetic chromatography (EKC) chiral selectivities from the literature.