Interactions between pyrazole derived enantiomers and Chiralcel OJ: Prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations

Abstract

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Molecular dynamics simulations of enantiomeric separations as an interfacial process in HPLC

“…For covalently-bonded selectors, the length of the tether is a variable. [36][37][38][39] Third, there is the option of the representation of the solvent system: (a) explicitly atomistic solvent molecules of the appropriate solvent composition can be used, 33,34 (b) or a continuum model for the solvent with variable dielectric constant adjusted for the composition, [40][41][42][43][44][45] or (c) vacuum. [46][47][48] Fourth, there is the option of keeping some parts of the system rigid to increase the efficiency of the MD runs.…”

“…36,39,57 The one-body distribution maps for the S and R analytes in β-cyclodextrin provide similarly useful insights. 44 Indeed, many such examples are provided by Cann et al, 36,37,40 and such radial distribution functions aid in understanding the separation process in the case of Whelk-O1 and proline-based CSPs. By making specific derivatives in silico, and looking at various distribution functions, it is easy to test for syntheses that may be profitably carried out to improve separation factors in various solvent conditions.…”

“…To customize the selectivity properties of the molecule, the hydroxyl groups have been substituted using other functional groups. MD studies of chiral analytes interacting with cyclodextrin and its functionalized family of molecules have so far been largely limited to simulations in vacuum only,62 or in a continuum solvent with a variable dielectric constant parameter [43][44][45][46]49. MD of enantiomers in cyclodextrin in explicit water molecules have also been carried out, but unless done for sufficiently long simulation times, water molecules may not even have the opportunity to make their way inside the cup, as when simulation times are 10 ns or less.…”

Noncovalent interactions in high-performance liquid chromatography enantioseparations on polysaccharide-based chiral selectors

“…The set of data emerging from the MD experiment is the trajectory which describes coordinates and energies of the chiral partners in the system and their variation with time. In most studies focused on cellulose-and amylose-based derivatives as selectors [70,[78][79][80], the interaction energy (E int ) between enantiomer and selector is calculated on the basis of the energies of the selector-enantiomer complex, the selector and the enantiomer (eq. 2) (2) where the E int term derived from the contributions of the vdW and the electrostatic (es) interaction terms eq.…”

“…In 2016, Huang and co-workers modelled the enantioselection of chiral pyrazole derivative 24 on cellulose tris(4-methylbenzoate) by means of MD (100 ps of simulation time) accounting for solvent implicitly [80]. In this study, a 12-mer fragment was built to model cellulose tris (4-methylbenzoate), with the terminal monomers replaced by methyl groups, and seven mixtures were used as custom solvents.…”