Surface-modified three-dimensional graphene nanosheets as a stationary phase for chromatographic separation of chiral drugs

Abstract

Carbon-based stationary phases for chromatographic separation have been commercially available since the 1980s. Porous graphitic carbon liquid chromatography columns are known to be highly resistant to aggressive mobile phases and extreme pH values of solvents and eluents, an important advantage compared to conventional silica-based alternatives. In our work, we demonstrate a new variant of carbon-based stationary phases for liquid chromatography, specifically developed for chiral separation. Mesoporous three-dimensional graphene nanosheets (3D GNS), functionalized with tetracyanoethylene oxide (TCNEO) and (S)-(+)-2-pyrrolidinemethanol, demonstrate pharmaceutical-grade chiral separation of model ibuprofen and thalidomide racemic mixtures when used as Chiral Stationary Phases (CSPs), with performance parameters comparable to currently commercially available CSPs. Simple covalent attachment of functionalization groups to the surface of mesoporous three-dimensional graphene nanosheets makes these carbon-based CSPs chemically stable and up to an order of magnitude less expensive than standard silica-based analogues.

Covalent Epitope Decoration of Carbon Electrodes using Solid Phase Peptide Synthesis

“…The relatively strong D-line, as well as the presence of spectral background, indicate the rather non-uniform structure of the utilized material. TCNEO-treated graphite demonstrated significant spectral changes, with the appearance of a strong broad-range fluorescent signal, consistent with prior findings 22,23 . Upon reduction, the fluorescence intensity decreased, consistent with the Auger results above.…”

“…Upon reduction, the fluorescence intensity decreased, consistent with the Auger results above. The C-N line at around 2230 cm −1 , usually appearing in Raman spectra of TCNEO-modified few-layer graphene or highly uniform graphite, was masked by strong fluorescence signal in our samples 23 . Biotinylation and SPPS induced further changes in the spectra, particularly in the fluorescence component.…”

“…More recently, covalent functionalization of pristine graphene and graphite at both edge and internal molecular sites has been achieved with benzyne 21 and tetracyanoethylene oxide (TCNEO) 22 , the latter of which decorated the carbon surface with reactive nitrile groups. Subsequent attachment of more complex functional groups resulted in a material that could be used as a stationary phase for chiral chromatographic separation 23 .…”

Enantiomeric Recognition and Separation by Chiral Nanoparticles

“…Interestingly, computational simulations using density functional theory also showed the applicability of nanoporous graphene, when functionalized by a chiral bouncer molecule [171]. In another exciting work, Candelaria et al [105] demonstrated the fabrication of new type of chemically stable, versatile and cost-effective graphene-based CSPs for enantiomeric separation using LC. The group employed functionalized mesoporous 3D graphene nanosheets for the enantiomeric separation of pharmaceutical grade racemic mixtures of model ibuprofen and thalidomide.…”

Chiral counter‐current chromatography: A survey of its instrument, mechanism, procedure, and applications

“…1 Particularly in pharmaceutical industry, the demand for single enantiomer has keep rising because the pharmacological effect of lots of chiral medicines is restricted to one of the enantiomers. 2,3 People expend so much effort to find more efficient ways of procuring single pure enantiomers to meet the grow demand in pharmaceutical industry. Although enormous steps have been made in asymmetric synthesis, 4 chiral separation is still the most common method of getting single pure enantiomer and plays an important role in the industrial production of enantiomers because of its reliability and applicability in industry.…”