Marianna Messina

Application of charged single isomer derivatives of cyclodextrins in capillary electrophoresis for chiral analysis

The review focuses on the role of ionic or ionisable single isomer derivatives (SIDs) of cyclodextrins on the separation of chiral analytes in capillary electrophoresis (CE), covering the period since the year 2000. The advantages of using pure compounds are discussed, as well as the ways to optimise the separations in the context of a rational approach to these techniques. Specific attention is paid to the modulation of the selector-analyte interaction. The advantage due to a detailed knowledge of equilibria occurring in solution during the CE run is underlined, particularly in the case of the presence of metal complexes, as occurs in chiral ligand exchange capillary electrophoresis (CLECE).

Chiral separation of amino acids derivatised with fluorescein isothiocyanate by single isomer derivatives 3-monodeoxy-3-monoamino-β- and γ-cyclodextrins: the effect of the cavity size

Thirteen enantiomeric pairs of α-amino acids derivatised with fluorescein isothiocyanate (FITC-AAs) were separated in capillary electrophoresis (CE) using as chiral selectors the single isomer derivatives (SIDs) 3-monodeoxy-3-monoamino-β- and γ-cyclodextrins. The chiral separation data obtained by these strictly homologous compounds, show different behaviours, allowing to hypothesise a possible structure of the obtained selector-analyte complexes, as well as highlighting the crucial role of the cavity size and the significant effects on the resolution obtained by small differences in the structural characteristics of these analytes.

Mass spectrometry detection as an innovative and advantageous tool in ligand exchange capillary electrophoresis.

The copper(II) complex of a modified cyclodextrin, namely 6‐mono‐deoxy‐6‐[4‐(2‐aminoethyl)imidazolyl]‐β‐CD (CDmh), previously synthesized and characterized in our laboratory and already used as chiral selector for ligand exchange capillary electrophoresis (LECE) with optical detection, is investigated here in LECE using electrospray‐mass spectrometry (ESI‐MS) as the detection device. The potential of this hyphenated method is compared with the results previously obtained with optical detection by studying the chiral resolution of tryptophan racemate. Chiral separation conditions compatible with LECE‐ESI‐MS could be achieved based on the figures of merit obtained by LECE‐UV. Interestingly, the values of LOD obtained by LECE‐ESI‐MS were significantly better than those obtained by LECE‐UV and thus, ESI‐MS detection seems to open new perspectives in chiral separations by LECE.

Diaminotrehalose‐capped β‐cyclodextrin, a new member of hemispherodextrins: Synthesis, thermodynamic and spectroscopic characterization and its exploitation in chiral electrokinetic chromatography

The diaminotrehalose-capped derivative of β-CD, a new member of hemispherodextrins, was synthesized and characterized by NMR spectroscopy. Its protonation constants were determined by potentiometry, and the inclusion of both the enantiomers of dansyl-phenylalanine was investigated by NMR spectroscopy. Its stereoselective properties were exploited in electrokinetic chromatography by separating four enantiomeric pairs of dansyl derivatives of amino acids.

The 3-amino-derivative of γ-cyclodextrin as chiral selector of Dns-amino acids in electrokinetic chromatography

The enantioseparation of the enantiomeric pairs of 10 Dns derivatives of alpha-amino acids was successfully carried out by using for the first time the 3-amino derivative of the gamma-cyclodextrin. The effects of pH and selector concentration on the migration times and the resolutions of analytes were studied in detail. 3-Deoxy-3-amino-2(S),3(R)-gamma-cyclodextrin (GCD3AM) shows very good chiral recognition ability even at very low concentrations at all the three investigated values of pH, as shown by the very large values of selectivity and resolution towards several pairs of amino acids. The role played by the cavity, the substitution site and the protonation equilibria on the observed properties of chiral selectivity, on varying the specific amino acid involved, is discussed.

Simultaneous separation of different enantiomeric pairs in capillary electrophoresis by mixing different hemispherodextrins, a very versatile class of receptors

Six different racemates of the profen family were used as analytes in order to test the chiral selector properties of three members of a new class of cyclodextrin derivatives, hemispherodextrins (HMs), in capillary electrophoresis. In addition to experiments carried out to separate each enantiomeric pair one by one, other experiments were carried out on samples containing all six enantiomeric pairs. Electropherograms were obtained either by adding a single HM to the background electrolyte (BGE), or a binary mixture of HMs. The results obtained confirm the excellent chiral selector properties of the HMs, and furthermore show that these compounds can also be used for achiral selection. When mixing different HMs, a complementary effect in chiral selectivity is observed, which, in our opinion, deserves further study.

Optimisation methodology in the chiral and achiral separation in electrokinetic chromatography in the case of a multicomponent sample of dansyl amino acids.

Two different chiral selectors synthesised in our laboratory were used to test the possibility of separation for a sample consisting of ten different enantiomeric pairs of dansyl-derivatives of α-amino acids in electrokinetic chromatography. It was possible to observe all the peaks, though only partly resolved, due to the twenty analytes through an accurate strategy of choice of the experimental conditions. As a part of this strategy, a procedure of identification of the single peaks in the electropherograms called LACI (lastly added component identification) has been developed.

Chiral separation of terbutaline and non-steroidal anti-inflammatory drugs by using a new lysine–bridged hemispherodextrin in capillary electrophoresis

HighlightsA new capped derivative of &bgr;‐cyclodextrin was synthesised and characterised.The formation of its complex with copper(II) ion was observed in solution.Its ability as selector both for chiral and non chiral separation was verified in capillary electrophoresis. Abstract A method for the separation of a mixture of terbutaline and non‐steroidal anti‐inflammatory drugs was developed using capillary electrophoresis with a new hemispherodextrin, ad hoc designed, the lysine − bridged hemispherodextrin (THLYSH). The use of lysine residues to bridge the trehalose capping unit moiety to the cyclodextrin cavity gives rise to a receptor with two long chains with amine nitrogen atoms, whose charge can be easily tuned as a function of the solution pH. The new hemispherodextrin was accurately characterised by ESI–MS and NMR spectroscopy, also highlighting its protonation behaviour. Circular dichroism and ESR spectroscopy measurements were also carried out to test its inclusion ability towards anthraquinone‐3‐sulfonate and its metal coordination ability towards copper(II) ion, respectively. Analogously to the other hemispherodextrins, the main skill of this new derivative lies in its chiral selector properties, as shown by the separation of the enantiomeric pairs of terbutaline and ibuprofen, flurbiprofen, suprofen and tiaprofenic acid by capillary electrophoresis. The focused use of the solution equilibria involved in the separations made it possible to understand the phenomena occurring in solution, and to finely tune the charge status of the receptor. In this way the chiral separation of the racemic mixture was successfully obtained, even if the receptor was individually used, differently by the other hemispherodextrins previously studied whose chiral separation capabilities are present only if used as binary mixtures.