Please cite this article in press as: Zhang et al., A Chiral Metal-Organic Material that Enables Enantiomeric Identification and Purification, Chem
2017), http://dx.doi.org/10.1016/j.chempr.2017.07.004
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Article
A Chiral Metal-Organic Material
that Enables Enantiomeric
Identification and Purification
Shi-Yuan Zhang,1,8 Cheng-Xiong Yang,2,8 Wei Shi,2,3,4,5,* Xiu-Ping Yan,2,4,6,* Peng Cheng,2,3,4,5
Lukasz Wojtas, and Michael J. Zaworotko1,9,
7
*
SUMMARY
The Bigger Picture
We show that CMOM-3S, a previously unreported porous crystalline metal-
organic material that exhibits intrinsic homochirality, serves as a general-
purpose chiral crystalline sponge (CCS) and a chiral stationary phase (CSP) for
gas chromatography (GC). The properties of CMOM-3S are enabled by nano-
sized channels connected to adaptable molecular recognition sites that mimic
enzyme-binding sites. Further, CMOM-3S is composed of inexpensive compo-
nents, facile to prepare, and requires only trace amounts of analyte. When
coupled with the thermal and hydrolytic stability of CMOM-3S, these features
mean that a coated fused silica capillary column in which CMOM-3S serves as
a CSP is both more versatile and more robust than three benchmark commercial
columns. That the enantiomer with the longer GC retention time is consistently
captured in CCS experiments enables CMOM-3S to serve as a powerful tool to
enable both chiral purification and enantiomer identification.
Enantiomeric identification of new
chemical entities (NCEs) and
natural products represents an
analytical challenge that has an
impact on technologies as diverse
as pharmaceuticals,
agrochemicals, flavorings, and
fragrances. Currently, assays to
identify enantiomers involve
comparison with reference
standards, which are unavailable
for NCEs. Here, we detail a
protocol for chiral discrimination
that eliminates the need for
enantiomerically pure reference
standards and requires only trace
amounts of analyte. A thermally
and hydrolytically robust
INTRODUCTION
Whereas natural processes can exhibit exquisite discrimination over chirality, the
same cannot be said in general about synthetic, process, and analytical chemistry.
1
In 1848, Pasteur kick-started the field of stereochemistry when he reported that
homochiral metal-organic
crystallization of racemic compounds can afford spontaneous resolution (racemic
conglomerates), but this remains the exception rather than the norm. Today,
enantiomeric separation and identification matters to technologies as diverse as
pharmaceuticals, agrochemicals, flavorings, fragrances, and asymmetric synthesis.
However, chiral identification remains a scientific and technological challenge,
particularly for new chemical entities (NCEs). The state of the art for separation of
enantiomers, chiral chromatography, is based upon the use of chiral stationary
phases (CSPs), which require enantiomerically pure reference standards for enan-
material, CMOM-3S, enables
chromatographic separations and
single-crystal X-ray diffraction to
work synergistically because it is
stable enough to serve as a chiral
stationary phase and its
recognition sites are specific
enough to act as a homochiral
crystalline sponge.
2
tiomer identification. Other techniques such as mass spectrometry and infrared/
UV-visible spectroscopy are likewise limited. Here, we reveal that CMOM-3S, a
3
–5
porous crystalline metal-organic material (MOM),
is the first homochiral MOM
6
that serves as both a general-purpose chiral crystalline sponge (CCS) and a CSP
for gas chromatography (GC). CMOM-3S thereby enables CSP and CCS to work syn-
ergistically to enable enantiomer purification and identification. This CSP-CCS
method requires no reference standard and only trace amounts of analyte (Figure 1).
Chiral separations represent one of the most difficult of preparative and analytical
separations because enantiomers have identical physical and chemical properties
and most separation methods tend to rely on differences in boiling points or
Chem 3, 1–9, August 10, 2017 ª 2017 Elsevier Inc.
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