Development of novel brush-type chiral stationary phases based on terpenoid selectors: HPLC evaluation and theoretical investigation of enantioselective binding interactions

The terpenoid chiral selectors dehydroabietic acid, 12,14-dinitrodehydroabietic acid and friedelin have been covalently linked to silica gel yielding three chiral stationary phases CSP 1, CSP 2 and CSP 3, respectively. The enantiodiscriminating capability of each one of these phases was evaluated by HPLC with four families of chiral aromatic compounds composed of alcohols, amines, phenylalanine and tryptophan amino acid derivatives and β-lactams. The CSP 3 phase, containing a selector with a large friedelane backbone is particularly suitable for resolving free alcohols and their derivatives bearing fluorine substituents, while CSP 2 with a dehydroabietic architecture is the only phase that efficiently discriminates 1,1′-binaphthol atropisomers. CSP 3 also gives efficient resolution of the free amines. All three phases resolve well the racemates of N-trifluoracetyl and N-3,5-dinitrobenzoyl phenylalanine amino acid ester derivatives. Good enantioseparation of β-lactams and N-benzoyl tryptophan amino acid derivatives was achieved on CSP 1.In order to understand the structural factors that govern the chiral molecular recognition ability of these phases, molecular dynamics simulations were carried out in the gas phase with binary diastereomeric complexes formed by the selectors of CSP 1 and CSP 2 and several amino acid derivatives. Decomposition of molecular mechanics energies shows that van der Waals interactions dominate the formation of the diastereomeric transient complexes while the electrostatic binding interactions are primarily responsible for the enantioselective binding of the (R)- and (S)-analytes. Analysis of the hydrogen bonds shows that electrostatic interactions are mainly associated with the formation of N–H⋯OC enantioselective hydrogen bonds between the amide binding sites from the selectors and the carbonyl groups of the analytes. The role of mobile phase polarity, a mixture of n-hexane and propan-2-ol in different ratios, was also evaluated through molecular dynamics simulations in explicit solvent.

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Dehydroabietoyl chlorideC20H27ClO[α]D23=+59.0 (c 1, ethanol)

N-(10′-Undecenyl)dehydroabietamideC31H49NO[α]D23=+57.7 (c 1, ethanol)

12,14-Dinitrodehydroabietoyl chlorideC20H25ClN2O5[α]D23=+47.5 (c 1, acetone)

N-(10′-Undecenyl)-12,14-dinitrodehydroabietamideC31H47N3O5[α]D23=+36.9 (c 1, acetone)

4′-(N-10″-Undecenylamide)-1′-friedelan-3α-yl-benzoateC49H77NO3[α]D23=-6.4 (c 0.94, CH2Cl2)