Enantioseparations by Modern UHPLC

Dear Colleagues, 

In the past two decades, the combination of columns packed with small porous particles (sub-2-μm) and the use of ultrahigh pressure liquid chromatography (UHPLC), commercially available since 2004, has become preponderant in both biomolecular and pharmaceutical analysis. The advantages of UHPLC are well known and extensively described in numerous articles; essentially, either ultrafast separations without a loss in efficiency or higher efficiency without considerable speed gain (high-resolution UHPLC) can be achieved. UHPLC has opened completely new horizons, both in terms of column efficiency (with plates per meter values as high as 250,000−300,000) and analysis time (subminute separations). Furthermore, UHPLC has proven to be both cost saving (with regard to solvent consumption) and more environmentally friendly. Although important goals have been achieved in the ultrafast separation of achiral compounds, enantioselective LC remains solidly attached to 3- and 5-μm totally porous particles and back-pressure values in the HPLC range. Why should the analysis of chiral molecules, a major field in both pharmaceutical analysis and enantioselective synthesis, not benefit from this important instrumental and materials evolution in liquid chromatography? While some subminute chiral separations have been reported in the literature, little has been done to consistently exploit sub-2-μm particles to enhance both speed analysis and column efficiency in the separation of chiral analytes, probably because small porous particles of high superficial area (necessary to obtain enantioselectivity similar to that of one of the HPLC materials) have only recently been introduced to the market. In 2010, our research group illustrated the transition of a brush-type chiral stationary phase (CSP), namely the DACH-DNB phase, from HPLC to UHPLC, demonstrating that small porous particles can be functionalized and successfully used for ultrafast separations. Since then, sub-1-μm mesoporous silica particles functionalized with a cyclodextrin derivative have been prepared by Ai et al., while, very recently, Chankvetadze and co-workers presented some preliminary results on a polysaccharide-based CSP obtained by coating core−shell particles with a nominal diameter of 2.6 μm. Brush-type CSPs are prepared through totally synthetic procedures, which are easily reproducible. However, while the most commonly used reversed-phase (RP) and hydrophilic interaction chromatography (HILIC) chemistries are now available and widely employed in the sub-2-μm format, chiral chromatography has only partly benefited from these technological advancements. Indeed, enantioselective LC is essentially performed on 3-μm and 5-μm totally porous particles; however, the potential of enantioselective UHPLC (eUHPLC) in terms of high speed, resolution and throughput has not been exploited yet for reasons that are both practical and fundamental. From a practical viewpoint, the adaptation of the surface modification chemistry of classical chiral stationary phases to smaller particles is not always easy. An additional complication comes from smaller particles tending to aggregate during synthesis, leading to CSPs characterized by non-optimal performance in terms of permeability and efficiency. Moreover, the mechanical resistance and long-term stability of particles functionalized with chiral selectors are also major concerns when high-flow and/or high-pressure conditions are applied. Finally, among the practical reasons that have slowed the transition to ultrafast chiral separations, we should mention that the most commercially available UHPLC equipment is not fully compatible with many apolar solvents used in normal phase (NP) chromatography, the most common mode of operation in chiral chromatography. However, the scarcity of fundamental studies of mass-transfer mechanisms in CSPs has also represented a major obstacle to the systematic development of sub-2-μm packing materials for eUHPLC applications. In 2010, some of the authors of this Special Issue published a paper illustrating the transition of a brush-type CSP from HPLC to UHPLC, which demonstrated the feasibility of ultrafast chiral separation.

As such, this Special Issue is focused on the identification of emerging UHPLC methods as well as on the description of the application of existing methods for the analysis of chiral compounds.

Prof. Dr. Claudio Villani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• high-performance liquid chromatography
• enantioseparation
• chirality