Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Morris, Kevin; Billiot, Eugene; Billiot, Fereshteh; Ingle, Jordan A.; Krause, Kevin B.; Lewis, Corbin R.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin

doi:10.1080/01932691.2018.1479267

Cited by 11 publications

(17 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When constructing the AABMM systems for MD simulation analysis, surfactant monomer chains were connected with covalent bonds at the end of each monomer's hydrocarbon tail. The method used was consistent with our previous work and is illustrated in Figure 1(a) [21]- [27]. Figure 1…”

Section: Methodssupporting

confidence: 66%

“…These insights will then be used to build in silico predictive models that will identify the best AABMM selector for a given separation problem. Previous computational studies, however, have focused only on the AABMMs SULV, SUVL and SULL [21]- [27]. This study, therefore, seeks to expand that work by comparing the structures and properties of the nine different AABMM shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous MD simulation work focused on the AABMM SULL, SULV, and SUVL. Initial studies characterized the structural and dynamic properties of these micellar systems while subsequent work investigated chiral ligand association with each AABMM [21]- [27]. Throughout these studies, MD simulation predictions were compared to available experimental data.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

Billiot

Fang

Morris

2019

OJPC

Self Cite

View full text Add to dashboard Cite

The enantiomers of chiral drugs often have different potencies, toxicities, and biochemical properties. Therefore, the FDA and other worldwide regulatory agencies require manufactures to test and prove the enantiomeric purity of chiral drugs. Amino acid based molecular micelles (AABMM) have been used in chiral CE separations since the 1990's because of their low environmental impact and because their properties can easily be tuned by changing the amino acids in the chiral surfactant head groups. Using molecular dynamics simulations to investigate the structures and properties of AABMM is part of an ongoing study focusing on investigating and elucidating the factors responsible for chiral recognition with AABMM. The results will be useful for the proper design and selection of more efficient chiral selectors. The micelles investigated contained approximately twenty covalently linked surfactant monomers. Each monomer was in turn composed of an undecyl hydrocarbon chain bound to a dipeptide headgroup containing of all combinations of L-Alanine, L-Valine, and L-Leucine. These materials are of interest because they are effective chiral selectors in capillary electrophoresis separations. Molecular dynamics simulation analyses were used to investigate how the sizes and positions of the headgroup amino acid R-groups affected the solvent accessible surface areas of each AABMM chiral center. In addition, headgroup dihedral angle analyses were used to investigate how amino acid R-group size and position affected the overall headgroup conformations. Finally, distance measurements were used to study the structural and conformational flexibilities of each AABMM headgroup. All analyses were performed in the context of a broader study focused on developing structure-based predictive tools to identify the factors responsible for a) self-assembly, b) function, c) higher ordered structure and d) molecular recognition of these amino acid based mo-How to cite this paper: Billiot, A., Fang,

show abstract

Section: Methodssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

Billiot

Fang

Morris

2019

OJPC

Self Cite

View full text Add to dashboard Cite

show abstract

“…Molecular micelles can be used at lower concentrations than conventional micelles, because the critical micelle concentration is zero. There were two amino acid-based molecular micelles, poly-(sodium undecyl-( l )-leucine-leucine) [72] and poly-(sodium undecyl-( l )-leucine-valine) [73], which were studied for the resolution of various racemates.…”

Section: Macromoleculesmentioning

confidence: 99%

“…Molecular modelling can help the researcher understand the different steps involved in the molecular recognition process, the non-bonding interactions involved between the analyte and the CS and the binding energies for their association. During this review period, ten studies utilised molecular modelling, with the intention of understanding chiral recognition mechanism and elution migration order [22,32,35,44,60,62,72,73,94,95]. Molecular modelling has also been utilised to design new CSs [40].…”

Section: Molecular Modelling and Nmr Studiesmentioning

confidence: 99%

Chiral Selectors in Capillary Electrophoresis: Trends during 2017–2018

Quirino

2019

Molecules

View full text Add to dashboard Cite

Chiral separation is an important process in the chemical and pharmaceutical industries. From the analytical chemistry perspective, chiral separation is required for assessing the fit-for-purpose and the safety of chemical products. Capillary electrophoresis, in the electrokinetic chromatography mode is an established analytical technique for chiral separations. A water-soluble chiral selector is typically used. This review therefore examines the use of various chiral selectors in electrokinetic chromatography during 2017–2018. The chiral selectors were both low and high (macromolecules) molecular mass molecules as well as molecular aggregates (supramolecules). There were 58 papers found by search in Scopus, indicating continuous and active activity in this research area. The macromolecules were sugar-, amino acid-, and nucleic acid-based polymers. The supramolecules were bile salt micelles. The low molecular mass selectors were mainly ionic liquids and complexes with a central ion. A majority of the papers were on the use or preparation of sugar-based macromolecules, e.g., native or derivatised cyclodextrins. Studies to explain chiral recognition of macromolecular and supramolecular chiral selectors were mainly done by molecular modelling and nuclear magnetic resonance spectroscopy. Demonstrations were predominantly on drug analysis for the separation of racemates.

show abstract

Past, present, and future developments in enantioselective analysis using capillary electromigration techniques

2020

View full text Add to dashboard Cite

Past, present, and future developments in enantioselective analysis using capillary electromigration techniques Enantioseparation of chiral products has become increasingly important in a large diversity of academic and industrial applications. The separation of chiral compounds is inherently challenging and thus requires a suitable analytical technique that can achieve high resolution and sensitivity. In this context, CE has shown remarkable results so far. Chiral CE offers an orthogonal enantioselectivity and is typically considered less costly than chromatographic techniques, since only minute amounts of chiral selectors are needed. Several CE approaches have been developed for chiral analysis, including chiral EKC and chiral CEC. Enantioseparations by EKC benefit from the wide variety of possible pseudostationary phases that can be employed. Chiral CEC, on the other hand, combines chromatographic separation principles with the bulk fluid movement of CE, benefitting from reduced band broadening as compared to pressure-driven systems. Although UV detection is conventionally used for these approaches, MS can also be considered. CE-MS represents a promising alternative due to the increased sensitivity and selectivity, enabling the chiral analysis of complex samples. The potential contamination of the MS ion source in EKC-MS can be overcome using partial-filling and counter-migration techniques. However, chiral analysis using monolithic and open-tubular CEC-MS awaits additional method validation and a dedicated commercial interface. Further efforts in chiral CE are expected toward the improvement of existing techniques, the development of novel pseudostationary phases, and establishing the use of chiral ionic liquids, molecular imprinted polymers, and metalorganic frameworks. These developments will certainly foster the adoption of CE(-MS) as a well-established technique in routine chiral analysis.

show abstract

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Cited by 11 publications

References 41 publications

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

Chiral Selectors in Capillary Electrophoresis: Trends during 2017–2018

Past, present, and future developments in enantioselective analysis using capillary electromigration techniques

Contact Info

Product

Resources

About