Computational screening of homochiral metal–organic frameworks for enantioselective adsorption Xiaoying Bao, Linda J. Broadbelt ⇑ , Randall Q. Snurr ⇑ Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, United States article info Article history: Received 16 May 2011 Received in revised form 2 August 2011 Accepted 3 August 2011 Available online 16 August 2011 Keywords: Metal–organic frameworks Adsorption Chiral separations Enantioselective separation Molecular simulation abstract Molecular simulations were used to screen a diverse collection of eight homochiral metal–organic frame- works (MOFs) for their ability to separate 19 chiral compounds by enantioselective adsorption. The sim- ulation model was validated by comparison with available experimental data. It was found that high enantioselectivity is strongly correlated with a close match between the size of the pore and the size of the chiral sorbate molecule. However, there is also a possibility of no enantioselectivity even when the size of the pore matches with the size of the chiral sorbate molecule. A four-point model was used to explain this observation, and a solution to promote high enantioselectivity has been proposed. Ó 2011 Elsevier Inc. All rights reserved. 1. Introduction Producing single enantiomer compounds is a vital task for the pharmaceutical, agricultural, fragrance and food industries [1]. In recent years, chromatographic separation is gaining much atten- tion for the large-scale preparation of commercial enantiopure compounds [2–6]. The most important part of chiral chromatogra- phy is the chiral stationary phase (CSP) [7,8], which selectively interacts with the two enantiomers to be separated. Conventional CSPs include polysaccharide and its derivatives, cyclodextrin and its derivatives, ‘‘Pirkle type’’ CSPs, chiral polymers, ligand exchang- ers, imprint polymers and protein columns [7]. The capacities of these conventional CSPs are generally low to moderate due to their nonporous nature [6]. For preparative chromatographic separation, a high column capacity helps to improve the productivity [9] and reduce the total operational cost [10]. Homochiral metal–organic frameworks (HMOFs) are a new fam- ily of organic–inorganic hybrid, microporous materials that can potentially serve as CSPs [11–21]. HMOFs are usually synthesized by using metals as nodes and chiral linkers as connectors [16,20]. One of the most prominent advantages of using HMOFs as CSPs is their high capacity, which is made possible by their highly porous frameworks. To date, more than 30 HMOFs with different metal nodes, linkers and topologies are available [16], and some of them possess desirable pore sizes and chemical and thermal stability for enantioselective separation. With the invention of new linkers, metal nodes and the broad range of possible topologies, it is ex- pected that even more HMOFs will be made available in the near fu- ture. Thus, design criteria based on a fundamental understanding of structure/function relationships are desirable for the development of new HMOFs for enantioselective adsorption. So far, only limited enantioselective separation experiments using HMOFs as adsorbents have been reported in a few scattered studies, making it difficult to infer any general design criteria [22– 26]. Recently, molecular modeling has been successfully applied for the screening of chiral metal surfaces for enantioselective sep- aration [27,28]. Molecular modeling has also proven useful in pre- dicting and understanding adsorption of H 2 , CO 2 , and other non- chiral molecules in MOFs [29–31]. Modeling is an effective way to reveal molecular level insights and suggest general design crite- ria, and there are a growing number of cases where molecular modeling has predicted adsorption properties in MOFs that are in good agreement with experimental results. In this work, molecular modeling is applied for the screening of the enantioselective separation capabilities of a diverse collection of eight HMOFs for 19 chiral compounds. The eight HMOFs cover a variety of different linkers and metal nodes, and a range of pore radii from 1.85 to 4.63 Å. These HMOFs are stable upon solvent re- moval and they also offer good chemical and thermal stability that is needed for preparative chromatography. Due to their relatively small pore sizes and the lack of any dangling functionalities in their pores, the HMOFs were assumed to be rigid during the simulation. 1387-1811/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.micromeso.2011.08.008 ⇑ Corresponding authors. E-mail addresses: broadbelt@northwestern.edu (L.J. Broadbelt), snurr@ northwestern.edu (R.Q. Snurr). Microporous and Mesoporous Materials 157 (2012) 118–123 Contents lists available at SciVerse ScienceDirect Microporous and Mesoporous Materials journal homepage: www.elsevier.com/locate/micromeso