Protocol for determining enantioselective binding of chiral analytes on chiral chromatographic surfaces

Lipkowitz, Kenny B.; Demeter, David A.; Zegarra, Richard; Larter, Raima; Darden, Thomas A.

doi:10.1021/ja00219a017

Cited by 96 publications

(54 citation statements)

References 2 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the docking simulations, the sorbate molecules and the zeolite structure were treated as flexible bodies (i.e., the inclusion of the flexible change). An expression developed by Lipkowitz et al 3 was utilized to calculate the enantioselectivity.…”

Section: Hymentioning

confidence: 99%

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

Jirapongphan¹,

Warzywoda²,

Budil³

et al. 2007

Chirality

View full text Add to dashboard Cite

Insight into enantioselective separation utilizing chiral-modified zeolite HY could be useful in designing a chiral stationary phase for resolving pharmaceutical compounds. A model was employed to better understand the enantioseparation of valinol in zeolite HY that contains (+)-(1R;2R)-hydrobenzoin as a chiral modifier. This model incorporates the zeolite support and accounts for the flexible change. Results from grand canonical Monte Carlo and molecular dynamics simulations indicate that the associated diastereomeric complex consists of a single (+)-(1R;2R)-hydrobenzoin and a single valinol molecules located in the zeolite HY supercage. Supercage-based docking simulation predicted an enantioselectivity of 2.6 compared with that of 1.4 measured experimentally. Also, the supercage-based docking simulation demonstrated a single binding motif in the S complex, and two binding motifs in the R complex. The multiple binding modes in the R complex resulted in its lower stability. This is hypothesized to be the origin of the weaker binding between (-)-(R)-valinol and the chiral modifier, and explains why (+)-(R)-valinol is retained more in the chiral-modified zeolite system studied.

show abstract

Section: Hymentioning

confidence: 99%

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

Jirapongphan¹,

Warzywoda²,

Budil³

et al. 2007

Chirality

View full text Add to dashboard Cite

show abstract

“…The latter, indeed, may have conformational potential energy surfaces that have either multiple minima or a flat profile. 10,11 Solvent effects, on the other hand, can be neglected to a first approximation, as suggested by several reports. 11,12 With the aim to propose an accurate computational method for experimentally well characterized molecular systems, a validated computational protocol 13 was applied to the prediction of DDG of complexation in a system with relevance to the HPLC separation of enantiomeric species.…”

Section: Introductionmentioning

confidence: 95%

“Quasi flexible” automatic docking processing for studying stereoselective recognition mechanisms, part 2: Prediction of ΔΔG of complexation and ¹H‐NMR NOE correlation

Alcaro¹,

Gasparrini²,

Incani³

et al. 2007

J Comput Chem

View full text Add to dashboard Cite

The purpose of this work is to apply the global molecular interaction evaluation ("Glob-MolInE") computational protocol to the study of two molecular complexes characterized by a chiral selector and a couple of enantiomeric selectands experimentally known to give large difference in the free energy of complexation much higher than the experimental error normally associated to the molecular mechanic calculations. We have considered the well known diastereomeric complexes between the selector (S)-N-(3,5-dinitrobenzoyl)-leucine-n-propylamide (S)-1 and the selectands (R) or (S)-N-(2-naphthyl)-alanine methyl ester 2, widely studied by enantioselective HPLC, NMR and X-ray. The experimental difference of free energy of complexation between [(S)-1*(R)-2] and [(S)-1*(S)-2] (-1.34 kcal/mol) was reproduced by the new computational protocol with an excellent confidence error. Detailed results about the conformational search, the "quasi-flexible" docking and the thermodynamic estimation are presented in this work. A remarkable correlation between the theoretical results and experimental data (NOE measurements, X-ray crystallographic structure of the [(S)-1*(S)-2] complex and the free energy of complexation) supports the validity of the computational approach and underline the importance of the conformational multiplicity in the definition of the macroscopic properties of the complex in solution.

show abstract

“…The chiral recognition mechanisms that separate chiral solutes having p-donor groups have been investigated by HPLC (Pirkle and Welch, 1984;Wainer and Alembik, 1986;, NMR spectrometry (Pirkle and Pochapsky, 1987), X-ray crystallography , Raman spectrometry (Horvóth et al, 1998) and computational studies (Lipkowitz et al, 1988;Topiol et al, 1988). The aim of these studies has been to clarify the interactions required for forming diastereomeric complexes that achieve complete enantiomeric separations.…”

Section: Introductionmentioning

confidence: 99%

A study of chiral recognition for NBD‐derivatives on a Pirkle‐type chiral stationary phase

Kato¹,

Fukushima²,

Shimba³

et al. 2001

Biomedical Chromatography

View full text Add to dashboard Cite

A chiral stationary phase (CSP 1) derived from an (S)-N-3,5-dinitrobenzoyl-1-naphthylglycine showed excellent enantiomeric separation for amino acid derivatives with a fluorogenic reagent, 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), in high-performance liquid chromatography (HPLC). We compared elution profiles (separation factor and elution order) of NBD-amino acids and their analogs on HPLC, to determine the diastereomeric complex between the chiral moiety of CSP 1 and NBD-amino acid, which is responsible for the chiral recognition. (1)H-NMR studies of a mixture of model compound of CSP 1 and NBD-Ala suggest that the diastereomeric complex is composed of two hydrogen bonding sites at the amino proton and oxygen atom, and a pi-pi interaction by the benzofurazan structure (2,1,3-benzoxadiazole) of NBD-amino acid. Furthermore CSP 1 was able to separate esters, amides and alpha-methyl amino acids derivatized with NBD-F.

show abstract

Protocol for determining enantioselective binding of chiral analytes on chiral chromatographic surfaces

Cited by 96 publications

References 2 publications

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

“Quasi flexible” automatic docking processing for studying stereoselective recognition mechanisms, part 2: Prediction of ΔΔG of complexation and ¹H‐NMR NOE correlation

A study of chiral recognition for NBD‐derivatives on a Pirkle‐type chiral stationary phase

Contact Info

Product

Resources

About

Protocol for determining enantioselective binding of chiral analytes on chiral chromatographic surfaces

Cited by 96 publications

References 2 publications

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

“Quasi flexible” automatic docking processing for studying stereoselective recognition mechanisms, part 2: Prediction of ΔΔG of complexation and 1H‐NMR NOE correlation

A study of chiral recognition for NBD‐derivatives on a Pirkle‐type chiral stationary phase

Contact Info

Product

Resources

About

“Quasi flexible” automatic docking processing for studying stereoselective recognition mechanisms, part 2: Prediction of ΔΔG of complexation and ¹H‐NMR NOE correlation