Ketoprofen enantioseparation with a <i>Cinchona</i>
 alkaloid based stationary phase: Enantiorecognition mechanism and release studies

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The enantiomers of trans-paroxetine (the selectand) were separated on four chiral stationary phases incorporating either quinine [ZWIX(+), ZWIX(+A)] or quinidine [ZWIX(-), ZWIX(-A)] and (R,R)-aminocyclohexanesulfonic acid [in ZWIX(-), and ZWIX(+A)] or (S,S)-aminocyclohexanesulfonic acid [in ZWIX(+), and ZWIX(-A)] chiral selectors. The zwitterion nature of the phases is due to the presence of either (R,R)- or (S,S)-aminocyclohexanesulfonic acid in the selector structure bearing the quinuclidine moiety. ZWIX(+) and ZWIX(-) phases are available on the market with the commercial names CHIRALPAK ZWIX(+) and CHIRALPAK ZWIX(-), respectively. With the aim of rationalizing the enantiomer elution order with the above chiral stationary phases, a molecular dynamic protocol was applied and two energetic parameters were initially measured: selectand conformational energy and selectand interaction energy. In the search for other descriptors allowing a better fitting with the experimental evidences, in the present work we consider an energetic parameter, defined as the selector conformational energy, which resulted to be relevant in the explanation of the experimental elution order in most of the cases. Very importantly, the computational data produced by the present study strongly support the outstanding role of the conformational energy of the chiral selector as it interacts with the analytes.

Section: Discussionsupporting

confidence: 80%

Exploring the enantiorecognition mechanism of Cinchona alkaloid‐based zwitterionic chiral stationary phases and the basic trans‐paroxetine enantiomers

Sardella

Macchiarulo

Urbinati

et al. 2017

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“…In the following sections, we intend to demonstrate that the combination of a molecular dynamics protocol and an advanced statistical analysis workflow, allows to computationally derive the most abundant putative binding modes occurring between the SO and the SA enantiomers depicted in Figure 1. The accordance between in silico simulations and the chromatographic results is first evaluated with a computational method previously developed in our group to study the enantiorecognition process with low‐molecular weight zwitterionic Cinchona alkaloid‐based SOs [28]. Afterward, the intra‐ and intermolecular interactions dynamically interplaying in the context of the SO–SA binding are identified, ending up with the binding modes assignment through interaction fingerprint analysis.…”

Section: Resultsmentioning

confidence: 99%

“…In order to evaluate the ability of the simulation system to reproduce the thermodynamic of retention, which means, inter alia, the EEO, a well‐established analysis [16,28,30] was applied, calculating three descriptors: the interaction energy between SO and SA (INTER), the SA conformational energy (SELF_SA), and the SO conformational energy (SELF_SO). More details on these three variables are reported in the Experimental Section.…”

Section: Resultsmentioning

confidence: 99%

Binding modes identification through molecular dynamic simulations: A case study with carnosine enantiomers and the Teicoplanin A2‐2‐based chiral stationary phase

Sardella

Ianni

Cossignani

et al. 2020

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In the present study, an in silico methodology able to define the binding modes adopted by carnosine enantiomers in the setting of the chiral recognition process is described. The inter-and intramolecular forces involved in the enantioseparation process with the Teicoplanin A2-2 chiral selector and carnosine as model compound are successfully identified. This approach fully rationalizes, at a molecular level, the (S) < (R) enantiomeric elution order obtained under reversed-phase conditions. Consistent explanations were achieved by managing molecular dynamics results with advanced techniques of data analysis. As a result, the time-dependent identification of all the interactions simultaneously occurring in the chiral selector-enantiomeric analyte binding process was obtained. Accordingly, it was found that only (R)-carnosine is able to engage a stabilizing charge-charge interaction through its ionized imidazole ring with the carboxylate counter-part on the chiral selector. Instead, (S)-carnosine establishes intramolecular contacts between its ionized functional groups, that limit its conformational freedom and impair the association with the chiral selector unit. K E Y W O R D Smolecular dynamics, binding modes, enantioseparation, chiral chromatography, teicoplanin 1728

“…For example, it was shown that surface proximity as well as sophisticated linker chemistry may significantly improve enantioselectivity [4][5][6][7]. Since the development of Cinchona carbamate type anion exchangers [8], several studies focused on the systematic optimization of the selector structure have been performed [9][10][11][12][13][14][15], including research focused on different anchoring strategies [4,16,17]. Importantly, longer retention times and slightly enhanced enantioselectivity were achieved by attaching the selector by the carbamoyl unit double bond, in comparison to the selector of a similar structure bonded by the cinchonan double bond.…”

Section: Introductionmentioning

confidence: 99%

Effect of different immobilization strategies on chiral recognition properties of Cinchona‐based anion exchangers

Kohout

Wernisch

Tůma

et al. 2018

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In the enantiomeric separation of highly polar compounds, a traditionally challenging task for high-performance liquid chromatography, ion-exchange chiral stationary phases have found the main field of application. In this contribution, we present a series of novel anion-exchange-type chiral stationary phases for enantiomer separation of protected amino phosphonates and N-protected amino acids. Two of the prepared selectors possessed a double and triple bond within a single molecule. Thus, they were immobilized onto silica support employing either a thiol-ene (radical) or an azide-yne (copper(I)-catalyzed) click reaction. We evaluated the selectivity and the effect of immobilization proceeding either by the double bond of the Cinchona alkaloid or a triple bond of the carbamoyl moiety on the chromatographic performance of the chiral stationary phases using analytes with protecting groups of different size, flexibility, and π-acidity. The previously observed preference toward protecting groups possessing π-acidic units, which is a typical feature of Cinchona-based chiral stationary phases, was preserved. In addition, increasing the bulkiness of the selectors' carbamoyl units leads to significantly reduced retention times, while very high selectivity toward the tested analytes is retained.