Molecular Dynamics Simulations of Amylose- and Cellulose-Based Selectors and Related Enantioseparations in Liquid Phase Chromatography

Abstract

In the last few decades, theoretical and technical advancements in computer facilities and computational techniques have made molecular modeling a useful tool in liquid-phase enantioseparation science for exploring enantioselective recognition mechanisms underlying enantioseparations and for identifying selector–analyte noncovalent interactions that contribute to binding and recognition. Because of the dynamic nature of the chromatographic process, molecular dynamics (MD) simulations are particularly versatile in the visualization of the three-dimensional structure of analytes and selectors and in the unravelling of mechanisms at molecular levels. In this context, MD was also used to explore enantioseparation processes promoted by amylose and cellulose-based selectors, the most popular chiral selectors for liquid-phase enantioselective chromatography. This review presents a systematic analysis of the literature published in this field, with the aim of providing the reader with a comprehensive picture about the state of the art and what is still missing for modeling cellulose benzoates and the phenylcarbamates of amylose and cellulose and related enantioseparations with MD. Furthermore, advancements and outlooks, as well as drawbacks and pitfalls still affecting the applicability of MD in this field, are also discussed. The importance of integrating theoretical and experimental approaches is highlighted as an essential strategy for profiling mechanisms and noncovalent interaction patterns.

HPLC and SFC Enantioseparation of (±)-Trans-β-Lactam Ureas on Immobilized Polysaccharide-Based Chiral Stationary Phases—The Introduction of Dimethyl Carbonate as an Organic Modifier in SFC

“…Polysaccharide CSPs are classified into two types, coated and immobilized, based on the chemistry of the application of the chiral selector on the chromatographic support matrix (usually silica). In the coated type, the polymeric chiral selector (amylose or cellulose derivatives) is physically coated by an adsorption process, whereas, in the immobilized type, the chiral selector is bound by a chemical process [25]. The coated polysaccharide CSPs have limited resistance to many solvents, whereas the immobilized CSPs are more robust, and can be used with non-standard solvents, such as acetone, chloroform, dichloromethane, ethyl acetate, tetrahydrofuran, etc.…”

“…In the HPLC mode, either a standard mobile phase consisting of n-hexane/2-PrOH (90/10, v/v) or a polar organic mobile phase consisting of 100% alcohol (MeOH or EtOH) was used. The immobilized-type chiral columns contain a chiral selector covalently bound to the silica gel support, which enables the use of an extended range of the organic solvents [25,26], so, in this study, 100% DMC was used as a non-standard solvent in HPLC mode and in combination with an alcoholic modifier (DMC/alcohol; 80/20, v/v) in SFC mode. The effects of mobile phases: CO 2 /alcohol (80/20, v/v), CO 2 /DMC/alcohol (70/24/6, v/v/v), and CO 2 /DMC/alcohol (60/32/8, v/v/v) on the separation were investigated in SFC mode.…”

Update on chiral recognition mechanisms in separation science

“…For summaries of general features of polysaccharide-based chiral selectors see, for example [14][15][16][17][18][19][20][21]23]. Molecular modeling approaches have been summarized recently [58][59][60][61] as have applications of polysaccharide CSPs to the enantioseparations [62,63] or the preparation of polysaccharide selectors [63,64]. Depending on the derivatization, the cellulose or amylose CSPs differ in size and shape of the chiral grooves [19,65].…”