Use of NMR Binding Interaction Mapping Techniques to Examine Interactions of Chiral Molecules with Molecular Micelles

Abstract

NMR spectroscopy was used to investigate the association of four chiral molecules with the molecular micelle poly(sodium N-undecanoyl-l-leucylvalinate) (poly(SULV)). Adding poly(SULV) to the background electrolyte in electrokinetic chromatography (EKC) allows enantiomeric resolution to be achieved because enantiomers interact differentially with the chiral centers on the micelle headgroups as they both move in the electric field. Pulsed field gradient diffusion experiments were used to measure molecular micelle association constants for enantiomers of each analyte. These association constants were consistent with EKC elution order for the compounds 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP), 1,1'-bi-2-naphthol (BOH), and Troger's base. In addition, nuclear Overhauser enhancement spectroscopy, nuclear Overhauser effect difference, and intermolecular cross relaxation diffusion experiments were used to generate binding interaction maps for each chiral analyte. These maps showed that BNP and BOH inserted into the surfactant headgroup's major chiral groove and interacted predominately with the leucine chiral center. (+)-Troger's base was also found to insert into the major chiral groove. However, this compound instead interacted with the valine chiral atom. In diffusion experiments with long diffusion times, the linearized diffusion plots for each analyte-molecular micelle mixture showed curvature characteristic of intermolecular cross relaxation. The magnitude of this effect scaled linearly with the analytes' free energies of binding.

Water‐soluble calix[4]resorcinarenes as chiral NMR solvating agents for bicyclic aromatic compounds

“…53 The relative effectiveness of 1-4 is compared herein for a series of bicyclic substrates that include 1-(1-naphthyl)ethylamine (5), N,N-dimethyl-1-(1-naphthyl)ethylamine (6), propranolol (7), 1-amino-2-indanol (8), 2-methylindoline (9), 1-methyltryptophan (10), the methyl ester of tryptophan (11), and the sodium salt of tryptophan (12). Compounds 5-11 are analyzed as their hydrochloride salts.…”

“…Chiral, water-soluble micelles have been reported, but these systems have not been widely studied in NMR applications. [11][12][13] The most useful water-soluble, chiral NMR reagents are cavity compounds. The interior of the cavity is often hydrophobic, such that the hydrophobic portion of organic salts is stabilized by insertion into the cavity in water.…”

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…Their goal was to provide guidelines for selection of a chiral agent to reduce the screening process. NMR is a popular approach for defining specific interactions leading to chiral recognition, typically for CD-analyte complexes [35,36] but also for micellar studies [37].…”

Electrokinetic chromatography with polymeric pseudostationary phases

“…Two reports have appeared using spectroscopic studies along with EKC studies to generate a consistent model for the mechanism of interaction between enantiomers and the chiral polymer poly(sodium undecenyl leucylvalinate) (poly(SULV)) [63,64]. Pulsed field gradient NMR experiments give relative binding constants for enantiomers that are consistent with EKC migration results [63,64].…”