Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

Abstract

Liquid‐phase enantioseparations have been fruitfully applied in several fields of science. Various applications along with technical and theoretical advancements contributed to increase significantly the knowledge in this area. Nowadays, chromatographic techniques, in particular HPLC on chiral stationary phase, are considered as mature technologies. In the last thirty years, CE has been also recognized as one of the most versatile technique for analytical scale separation of enantiomers. Despite the huge number of papers published in these fields, understanding mechanistic details of the stereoselective interaction between selector and selectand is still an open issue, in particular for high‐molecular weight chiral selectors like polysaccharide derivatives. With the ever growing improvement of computer facilities, hardware and software, computational techniques have become a basic tool in enantioseparation science. In this field, molecular docking and dynamics simulations proved to be extremely adaptable to model and visualize at molecular level the spatial proximity of interacting molecules in order to predict retention, selectivity, enantiomer elution order, and profile noncovalent interaction patterns underlying the recognition process. On this basis, topics and trends in using docking and molecular dynamics as theoretical complement of experimental LC and CE chiral separations are described herein. The basic concepts of these computational strategies and seminal studies performed over time are presented, with a specific focus on literature published between 2015 and November 2018. A systematic compilation of all published literature has not been attempted.

Enantioselective HPLC Analysis to Assist the Chemical Exploration of Chiral Imidazolines

“…Indeed, this family of CSPs has demonstrated to produce successful enantioseparations for most of the reported chiral chromatography applications [1,3,[7][8][9]. Although the chiral recognition mechanism with these cellulose-and amylose-based chiral selectors are still a matter of profound debate, it is widely accepted that a sequence of "chiral grooves" hosting the polar carbamate or ester residues exists along the main chain of the helix, with the phenyl rings being projected outwards the polymer chain [1, 3,6,[10][11][12]. When mobile phases typical of the normal-phase (NP) elution mode are used, the analyte enantiomers can activate stereoselective interactions with the polar carbamate or ester groups via hydrogen bonding with the O atom and/or the NH and C=O groups, as well as dipole-dipole interaction with the C=O residue located within the above cavities [1, 3,6,[10][11][12].…”

“…Although the chiral recognition mechanism with these cellulose-and amylose-based chiral selectors are still a matter of profound debate, it is widely accepted that a sequence of "chiral grooves" hosting the polar carbamate or ester residues exists along the main chain of the helix, with the phenyl rings being projected outwards the polymer chain [1, 3,6,[10][11][12]. When mobile phases typical of the normal-phase (NP) elution mode are used, the analyte enantiomers can activate stereoselective interactions with the polar carbamate or ester groups via hydrogen bonding with the O atom and/or the NH and C=O groups, as well as dipole-dipole interaction with the C=O residue located within the above cavities [1, 3,6,[10][11][12]. Besides these polar contacts, π-π stacking interactions between the phenyl groups on the CSP and an aromatic region or an unsaturated portion of the solute may play some role in chiral recognition, especially when analyses are run in the reversed-phase (RP) mode [13][14][15][16][17].…”

“…One of the main advantages of polysaccharide-type CSPs is the "multimodal" nature of their chiral recognition capacity, which makes them compatible with all of the most relevant chromatographic mobile phase regimes. Even though polysaccharide-type CSPs are most commonly operated under NP conditions [1, 3,6,[10][11][12], employing mixtures of n-hexane with polar organic alcohol modifiers, these phases have also been shown to produce excellent enantioselective levels both with RP and polar organic (PO) or polar ionic (PI) eluent systems [13][14][15][16][17]. Moreover, with the new generation of "immobilized CSPs" where the chiral selector is covalently grafted onto a pre-functionalised solid support, eluent components previously prohibited with the first generation of polymeric phases can be also used, thus allowing the possibility to explore additional stereoselectivity profiles [11,18].…”

Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

“…Beer's group described a chiral selenium-containing receptor for enantiomeric discrimination of dicarboxylates [24]. Following previous studies on XB-based high performance liquid chromatography (HPLC) enantioseparations [31][32][33][34][35][36], our groups demonstrated that ChB can participate in the recognition process underlying the enantioseparation of sulfur-containing atropisomeric 4,4 -bipyridine 1 on a cellulose-based chiral stationary phase [37].…”

Elucidation of the chromatographic enantiomer elution order for praziquantel: An experimental and theoretical assessment

“…In recent years, the computational approach applied in the study of DCs has been reported in the literature as a complementary tool to HPLC analyses. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] The main goal of these theoretical works is to aid in the elucidation mechanism of chiral discrimination, as well as in the EEO, by obtaining structural and energetic parameters at the molecular level involved in the complexation process.…”