Polysaccharide‐based chiral stationary phases as halogen bond acceptors: A novel strategy for detection of stereoselective σ‐hole bonds in solution

Abstract

In the last few years, halogen bonds have been exploited in a variety of research areas both in the solid state and in solution. Nevertheless, several factors make formation and detection of halogen bonds in solution challenging. Moreover, to date, few chiral molecules containing electrophilic halogens as recognition sites have been reported. Recently, we described the first series of halogen-bond-driven enantioseparations performed on cellulose tris(3,5-dimethylphenylcarbamate) by high-performance liquid chromatography. Herein the performances of amylose tris(3,5-dimethylphenylcarbamate) as halogen bond acceptor were also investigated and compared with respect to cellulose tris(3,5-dimethylphenylcarbamate). With the aim to explore the effect of polysaccharide backbone on the enantioseparations, the thermodynamic parameters governing the halogen-dependent enantioseparations on both cellulose and amylose polymers were determined by a study at variable temperature and compared. Molecular dynamics were performed to model the halogen bond in polysaccharide-analyte complexes. Chiral halogenated 4,4'-bipyridines were used as test compounds (halogen bond donors). On this basis, a practical method for detection of stereoselective halogen bonds in solution was developed, which is based on the unprecedented use of high-performance liquid chromatography as technical tool with polysaccharide polymers as molecular probes (halogen bond acceptors). The analytical strategy showed higher sensitivity for the detection of weak halogen bonds.

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

“…The extraordinary ability (separation factor value, α, equal to 2.69) exihibited by the glycopeptide‐type chiral selector (SO) in discriminating the two carnosine enantiomers (the selectand, SA) [4], stimulated us to gain more insight into the molecular basis governing the underlying stereorecognition mechanism. A multitude of computational approaches, including docking and molecular dynamic simulations together with descriptive methods, have been so far applied to facilitate the comprehension of the intricate multifactorial process materializing in enantioselective analysis settings [6–10].…”

Enantioselective separation of twelve pairs of enantiomers on polysaccharide‐based chiral stationary phases and thermodynamic analysis of separation mechanism

“…For the chloro‐substituted CSPs (Chiralpak IC and Chiralpak ID), the presence of chlorine atoms on the phenyl ring may be the reason for their higher enantioselectivity abilities. The chlorine atom was reported to have a double role : (a) the stereoelectronic properties of the chlorine (electron‐withdrawing inductive effect) can influence close sites. In detail, the chloro‐substituted phenyl ring was π‐acidic, and could promote π‐π interaction with π‐basic phenyl ring of the enantiomer, further leading to a better chiral recognition.…”

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

“…In the last years, our groups investigated the factors governing HPLC enantioseparation of atropisomeric halogenated 4,4’‐bipyridines on polysaccharide‐based CSPs . Following these studies, we have demonstrated the contribution of XB and chalcogen bonds (ChBs) for the enantiorecognition of analytes on CDMPC under NP elution conditions.…”

“…On this basis, we used the ESH concept to model XB in CDMPC‐ and ADMPC‐halobipyridine complexes by MD simulations (10 ns of simulation time) (Fig. ).…”

“…It is worth noting that the rate increases to 75% considering the CDMPC exclusively, whereas it decreases to 37.5% for ADMPC. This evidence could be related to the fact that on ADMPC other entropy‐driven forces had been found to control enantiorecognition along XB . Consequently, it was likely that an exclusive XB model does not adequately describe XB‐driven enantioseparations on the amylose‐based CSP.…”