Journal of Chromatography A, 1530 (2017) 1–18

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Journal of Chromatography A
j o ur na l ho me page: www.elsevier.com/locate/chroma

Review article

Metal-organic frameworks as stationary phase for application in

chromatographic separation
a,∗ b,∗
Juan Zhang , Zilin Chen
a
School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430073, China
b
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and Wuhan University School of Pharmaceutical Sciences,
Wuhan University, Wuhan, 430071, China

artic l e in f o a b s t r a c t

Article history:
Metal-organic frameworks (MOFs) as a subclass of coordination polymers, have attracted wide
Received 29 June 2017
interest in various field. Herein, we focus on its application in chromatographic separation due to its
Received in revised form 24 October 2017
Accepted 26 October 2017
excellent phys- ical and chemical properties such as large surface area, high porosity, uniform pore
Available online 27 October 2017 sizes and structural diversity. In 2014, a review was published to summarize the most significant
advances in MOFs, and their applications in separation science. The present review was an extensive
Keywords:
update on applications of MOFs in chromatographic separation from 2014 to the present such as
Metal-organic frameworks high-performance liquid chromatog- raphy (HPLC), capillary electrochromatography (CEC), nano-
High-performance liquid liquid chromatography (nano-LC), and gas chromatography (GC). Besides, the typical applications of
chromatography Capillary MOFs in solid-phase microextraction (SPME) were also discussed. Except the presentation of
electrochromatography experimental data, the limitations and prospects were also summarized in this review, which can
Gas chromatography offer an outlook and reference on further study of applications of MOFs.
Chiral separation
© 2017 Elsevier B.V. All rights reserved.
 J. Zhang, Z. Chen / J. Chromatogr. A 1530 (2017) 1–18
2
1. Introduction
Metal-organic frameworks (MOFs), a class of microporous
crys- talline hybrid materials [1], was first introduced in 1995 by
Yaghi et al. [2]. As shown in Fig. 1, MOFs are formed by
coordination of metal cations (or cationic clusters) with
multifunctional organic linkers. It is also known as porous
coordination polymers, which are one of the most promising
advanced porous materials with extremely high porosity (50–
90% free volume) [3]. Over the past two decades, thousands of
MOFs have been reported and studied because of the flexibility
and variability of metal secondary building units and organic
linkers [4,5].
Compared with the traditional porous materials such as
organic polymer and inorganic zeolites, MOFs have a high
degree of des- ignability and adjustability in their structures and
functions [6,7]. It is attributed to the organic ligands which can
be easily designed and modified by robust synthetic reaction.
Furthermore, the metal nodes or the organic linker of MOFs
provide great opportunities for post-synthesis modification. New
functional groups can be introduced into MOFs for the
improvement of the properties of MOFs without changing the
connectivity or topology [8–10]. This approach expands the
variety of MOFs, improving its properties, most importantly it
limits the loss of activity of certain groups in MOFs synthesis.
The structural flexibility of MOFs is appeared in extensive
porosity and larger surface area ranging from 1000 to
10000 m2/g [4]. These aspects have made MOFs become an ideal
candidate for storage of fuels, gas adsorption, catalysis
applications. Additionally, MOFs also possess excellent solvent
and thermal sta- bility [11,12]. When MOFs are exposed into the
boiled methanol, benzene, water or high temperature up to 400
◦
C, their structures are nearly unchanged.
All the above significant properties of MOFs, including large
surface area and porosity, uniform pore sizes, tunable surface
chemistry, structural diversity, excellent thermal and solvent
stability, make MOFs highly promising in diverse applications
including gas separation and storage [13,14], supercapacitors
[15,16], catalysis [17,18], chemical sensing [19,20], biomedical
imaging and drug delivery [21,22]. In recent years, various MOFs
are synthesized and explored as separation media in analytical
chem- istry [1,23,24]. To some extent, MOFs are usually
synthesized via one-pot self-assembly reactions between ligands
and metal salts in solutions at a certain temperature [25,26]. The
synthetic con- ditions are mild and easily controlled to obtain
flexible and ideal structure. The MOFs prepared by this method
are usually packed
as stationary phases for high-performance liquid chromatography
(HPLC). Apart from the one-pot hydrothermal synthesis, the
MOFs prepared by a stepwise approach such as layer-by-layer
assemble [27,28], liquid phase epitaxy [29,30] and template-induced
[31,32], are generally coated on the inner surface of capillary
column for capillary electrochromatography (CEC) and gas
chromatography (GC) separation.
In this review, we present a summary and recommendation of
experimental results concerning the applications of MOFs in
chro- matographic separation including non-chiral and chiral
separation from 2014 to present, including HPLC, CEC, nano-
liquid chromatog- raphy (nano-LC), and GC. Besides, the typical
applications of MOFs in solid-phase microextraction (SPME)
were also discussed.
2. Application of MOFs in chromatographic separation
2.1. Non-chiral separation
Due to the significant properties of MOFs, such as flexibility
and specific structural features, MOFs have been regarded as
ideal mate- rials to be used as stationary phases in
chromatography. In term of separation techniques such as HPLC,
CEC, nano-LC or GC, the sepa- ration mechanism always
depends on the molecular sieving effect, van der Waals
interactions and the special group interactions in MOFs [23,33].
Moreover, the subtle matching of size, shape of the analytes and
the MOFs micropores also contributes to the sepa- ration to some
extent [34]. Metal site in MOFs has a tremendous influence on
their adsorption property directly associated with the separation
performance [35]. The partial positive charges on the metal sites
in MOFs have been demonstrated to improve adsorption
selectivity for separation of different polarity compounds [36].
2.1.1. High-performance liquid chromatography
HPLC is a widely used chromatographic technique in
separation science. The core of HPLC is the separation materials
filled in the column. Nowadays, there are several MOFs explored
as stationary phase for HPLC in recent years, which have been
summarized in Table 1.
UiO-66 is a zirconium based MOF built up from hexamers of
eight coordinated ZrO6(OH)2 polyhedra and terephthalate ligands
[37]. It consists of octahedral and tetrahedral cavities of 11 and
8 Å in diameter, respectively, which shares triangular
microporous windows measuring approximately 5–7 Å. In
addition to its unique porous structure, UiO-66 also exhibits a
suitable mechanical stabil- ity as well as an excellent chemical
resistance toward solvents such as water, benzene,
dimethylformamide (DMF) and acetone, which is very suitable to
use as a packing material in separation by HPLC. Zhao et al.
prepared slurry-packed UiO-66 columns and studied their
chromatographic performance to separate substituted ben- zenes
and polycyclic aromatic hydrocarbons (PAHs) using both
normal-phase (NP) and reverse-phase (RP) HPLC modes [38].
Fig. 2 shows the NP-HPLC separations of the benzene,
substituted ben- zenes and several PAHs on the UiO-66 column.
They illustrated that the analytes separation on a UiO-66 column
was an exothermic pro-
cess, controlled by both enthalpy change (OH) and entropy change
(OS). However, the UiO-66 column efficiency was low,
probably resulting from the broad particle size distribution and
irregular shape of the prepared UiO-66.
There are some other MOFs packed as stationary phases for
HPLC. Shu et al. prepared a MIL-53(Al)-packed column, which
was firstly applied to separate phthalate acid esters (PAEs) by
HPLC
[26]. To study the thermodynamic properties of the separation of
PAEs, the enthalpy change (OH), entropy change (OS), and
Gibbs- free energy change (OG) was calculated by van’t Hoff
 J. Zhang, Z. Chen / J. Chromatogr. A 1530 (2017) 1–18
equation. The results showed that the separation of PAEs 3
was controlled by
Table 1
The applications of metal-organic frameworks in HPLC.

Separation matrix Surface area Pore diameter Pore volumn Analytes Ref Yea
(nm) . r
2 −1 3 −1
(m g ) (cm g )

UiO-66 1200 0.8, 1.1 / Substituted benzenes and its [38 201
] 4
isomers, PAHs
MIL-53(Al) / / / Phthalate acid esters [26 201
] 6
MIL-53(Fe) 19 0.013 Aromatic isomers; [39 201
] 5
alkylbenzene, naphthalene,
aniline and PAHs
pyridine-grafted MIL-101(Cr) 1245 / 0.73 Tocopherols [41 201
] 5
MIL-125(Ti) particles / / / Aromatic positional isomers, [25 201
] 6
PAHs, aryl halides, cis/trans
alkyl functionalized
cyclohexane
Macroporous HKUST-1 1616 9.6 0.71 Styrene and ethylbenzene [43 201
] 4
particles
Macroporous HKUST-1 1240 / 0.261 0.274 Styrene and ethylbenzene [44 201
] 4
monoliths
Silica-UiO-66 composite / / / Substituted aromatics, [45 201
] 4
chlorobenzene and PAHs
HKUST-1@SiO2 composite 1655 / 0.18 Hydrocarbons [46 201
] 6
UiO-66@SiO2 shell- 276.0−371.1 / / Substituted benzene and [47 201
core microparticles structural isomers ] 5
UiO-66@SiO2 shell- / 0.6−1.1 / Alkyl benzenes and PAHs [48 201
core microparticles ] 6
UiO-66@SiO2 shell-core 478, 669, 136, 0.6, 0.8 and 1.1 / Xylene isomers, substituted [49 201
479 ] 7
microparticles benzenes and PAHs
UiO-67 coated magnetic silica / / / Phenol derivatives [51 201
] 5
MIL-100(Fe) coated magnetic / / / Aromatic hydrocarbons [52 201
] 6
silica
HKUST-1 coated magnetic / / / Pyridine and bipyridine, [53 201
three ] 5
silica chloroaniline isomers
Core-shell SOS@ZIF-8 495 1.2, 1.8 0.19 Aromatic compounds [54 201
spheres ] 5
ILI-01@SiO2 core-shell 148.9 9.0 / Amides, vitamins, nucleic [55 201
acid bases, and nucleosides ] 6

both OH and OS. High resolution separation of PAEs was As for separation of polar compounds, the separation mechanism
obtained with reliable reproducibility. However, the MIL-53(Al) is based on both hydrogen- bonding and coordination interactions.
packed col- umn exhibited low efficiency and high backpressure, MOFs are typically crystalline microporous materials formed
which might also due to wide particle size distribution and by metal ions or clusters linked with organic ligands. Introduc-
irregularity of MIL- 53(Al). MIL-53(Fe) was also synthesized tion of mesopores or macropores into MOFs may be particularly
and packed as stationary phase for RP-HPLC separation of
positional isomers [39]. Four types of positional isomers (xylene,
nitroaniline, chlorotoluene and dichlorobenzene isomers) were
separated using acetonitrile/H2O as the mobile phase, presented
in Fig. 3. In addition, the influence of the metal center of the
MIL-53 framework on their chromato- graphic behaviors was
also investigated, because it has been found that the metal center
of MOFs greatly affects their performance in chromatographic
separation [40]. The results showed that the MIL- 53(Fe) packed
column exhibited better separation performance than the MIL-
53(Al, Cr) packed columns. Yan’s group reported post-synthetic
modification of MIL-101(Cr) with pyridine and its application as
a novel stationary phase for HPLC separation of tocopherols [41].
As was shown in Fig. 4, the pyridine-grafted MIL- 101(Cr)
column offered rapid separation of tocopherols with high column
efficiency (85,000 plates/m for 6-tocopherol). The prepared
column presented good reproducibility without loss of resolution
and efficiency after 3–6 months uses (Fig. 4). Hawes et al.
prepared polymorphic MOFs materials, which were employed as
stationary phases for small-scale separation of complex mixtures
of PAHs and polar compounds [42]. They revealed that the
interaction mech- anism of the PAHs with the MOF stationary
phases was expected to consist of a combination of surface-based
effects and (partial) entry of the analytes into the MOFs pores.
useful in improving mass transport and efficiency for its appli-
cations in separation science. However, there are rather limited
reports on the fabrication of macroporous MOFs for chromato-
graphic separation. Adhamed et al. reported a simple
solvothermal modification of HKUST-1 (as a model MOFs)
with hydroquinone for the formation of macroporous MOFs
particles by etching mech- anism [43]. The macroporous
HKUST-1 particles were packed into a column for HPLC. It
exhibited improved mass transport and separation efficiency for
styrene and ethylbenzene with the pres- ence of macropores
within the MOFs particles. In the same year, the same group
prepared hierarchically porous HKUST-1 monolith with
interconnected macropores by a powder-packing synthesis
approach [44]. The structure and porosity of the monoliths can
be better controlled through directly adjusting precursors in the
synthesis process. The synthesized HKUST-1 monoliths
possessed highly stability with intrinsic micropores, additional
mesopores and particularly macropores, and were demonstrated
for the fast HPLC separation of ethylbenzene and styrene
within 2 min.
Due to the polydispersity of most MOFs particles and their
non- spherical, irregular shape, directly packed MOFs column
usually caused high backpressure, low column performance and
obvious peak broadening. In order to improve the
chromatographic per- formance of MOFs packing column,
synthesis of monodisperse MOFs particles with spherical shape
is a good choice to circum- vent the disadvantages of columns
packed with irregular MOFs particles. Perre et al. developed a
method to synthesize monodis- perse, nearly spherical MIL-
125(Ti) particles, which was used as stationary phase in liquid
chromatography [25]. The structure of MIL-125(Ti) contains
both small tetrahedral cages and large octa- hedral cages,
playing a fundamental role in the shape selective separation of
molecules with similar size. The MIL-125(Ti) frame- work
displayed a trans selectivity for cis/trans difunctionalized
Fig. 2. NP-HPLC separations of benzene, SBs, and several PAHs on a UiO-66 column. Conditions: mobile phase, n-hexane/DCM with different ratios in each separation; flow
rate, 1.0 mL min−1 ; UV detection at 210 nm; and column temperature 30 ◦C.
Reprinted from Ref. [38]. Copyright 2014 Elsevier.
Fig. 3. Chromatograms for HPLC on the MIL-53(Fe) packed column. Mobile phase:
ACN/H2O with different ratios. (A) (100/0); (B) (80/20); (C) (100/0); (D) (70/30);
flow rate of 0.6 mL min−1 . All the separations were performed at room temperature
and
monitored with a UV detector at 254 nm.
Reprinted from Ref. [39]. Copyright 2015 Royal Society of Chemistry.
cyclohexane molecules with high selectivity and resolution for
1,3- dimethylcyclohexane and 4-ethylcyclohexanol.
Besides, much attention has been paid to fabrication of MOFs-
based composites with uniform spherical structure, which could
overcome the shortcomings of the directly packed MOFs-based
stationary phases and were employed as stationary phases for
HPLC separation. Recently, MOFs modified silica-based stationary
phases that could combine both excellent separation selectivity of
MOFs and packed characteristics of silica were reported. Silica-
UiO- 66 composite was fabricated using a facile solvothermal
reaction just by mixing the silica and precursor solution of UiO-66
[45]. It was used as liquid chromatographic stationary phase for
fast and efficient separation of substituted aromatics, chlorobenzene
compounds and PAHs. However, few UiO-66 were attached on
silica surface by this mix preparation method revealed by SEM
in the study. It might result from the irregular shapes and large
size distributions of stationary phase, and the leakage of UiO-66
nanoparticles through the chromatographic column filter, which
were harmful for the chromatography performance of the col-
umn. Nuzhdin et al. prepared HKUST-1 silica aerogel composite
(HKUST-1@SiO2) and studied as a stationary phase for the efficient
separation of unsaturated hydrocarbons from saturated aliphatics
by conventional liquid chromatography (LC) [46]. HKUST-1@SiO2
was prepared via an advanced sol-gel method and subsequent
drying in supercritical CO 2 to minimize the deterioration of the
individual properties of the MOF and silica aerogel structures.
The HKUST-1@SiO2 composite column showed good separation of
cyclohexene or benzene from cyclohexane by LC.
An alternate strategy towards the development of MOFs-
based composite stationary phases is to prepare shell-core type
MOFs/silica composite particles. Zhang et al. developed a facile
one-pot solvothermal synthesis method for fabrication of UiO-
Fig. 4. HPLC chromatograms of tocopherols: (a) different ratios of hexane/isopropanol as the mobile phase; (b) different injected masses. (c) Effect of the injected mass of
tocopherols on column efficiency. (d) Comparison of HPLC chromatograms of tocopherols obtained after 3–6 months on the same column. All separations were carried out
on the pyridine-grafted MIL-101(Cr) packed column 2 at room temperature using hexane/isopropanol (96/4, v/v) as mobile phase at a flow rate of 0.5 mL min −1 with a UV
detector at 290 nm.
Reprinted from Ref. [41]. Copyright 2015 Elsevier.

66@SiO2 shell-core microspheres for HPLC separation [47]. The

RP separation of xylene isomers, substituted benzenes and PAHs,
density and particle size of the MOFs shell could be easily
with efficiencies up to 32400 plates/m (styrene, k 1.59) and
controlled by adjusting the concentration of reactants, reaction
37200 plates/m (anisole, k 2.90), respectively.
temperature and time. The UiO-66@SiO 2 column is suitable for
Recently, homogenous MOFs were fabricated on the surface
separation of structural isomers due to its molecular sieving
of supporting template by a liquid phase epitaxy (LPE) process
effect and reverse shape selectivity. Ethybenzene and xylene
with a step-by-step fashion [50]. It is a promising method to
were separated with high efficiency and low backpressure on the
produce homogenous MOFs with high quality, as well as well-
prepared shell-core stationary phase. However, the solvothermal
controlled orientation and thickness on a suitably functionalized
deposition of UiO- 66 crystals on the silica core using a total
surface as a nucleation template. Franzreb’s group first reported
reaction time of 24 h is rather time-consuming. Arrua et al.
the fabri- cation of well-defined core-shell UiO-67 magnetic
deposited UiO-66 nanocrystals on carboxylic acid-modified silica
microparticles by this LPE process and packed into HPLC
particles by microwave-assisted solvothermal synthesis to obtain
columns to inves- tigate the interactions between core-shell UiO-
UiO-66@SiO2 shell-core particles and packed as stationary
67 and a set of dissolved phenol derivatives at a more
phases for HPLC [48]. This approach offers an efficient synthesis
fundamental level by means of experimental and simulated
of MOFs using shorter synthesis times than conventional
HPLC [51]. Afterwards, they also homogenously coated
solvothermal methods. Though it needed to adjust the number of
HKUST-1 and MIL-100(Fe) onto the outer surface of magnetic
growth cycles to control the density of MOFs, each deposition
silica microparticles by the same LPE method to yield a core-
step of the UiO-66 crystals required less than 2 h. The prepared
shell architecture and packed into the HPLC column for
composite exhibited an unusual flow-dependent separa- tion
separation [52,53]. HKUST-1 magnetic particles offered sharp
selectivity (FDSS) effect for the isocratic separation of small
sepa- ration performance for the aromatic nitrogen heterocycles
molecules. UiO-66 has two types of microporous cavities (1.1
pyridine
and
and 4,4r-bipyridine, due to size exclusion effects of the crystalline
0.8 nm) which are accessible by 0.6 nm windows. The effect was
MOFs material. The interactions and mass transfer mechanisms
observed for solutes in which the molecular sizes were compa-
between analytes and MOFs solid phases were revealed by the
rable to the micropore size of the UiO-66 shell. After that, they
experiments and the simulation using modern chromatographic
also used UiO-66@SiO 2 shell-core particles as stationary phases
modeling software. Compared with the former related
for the separation of small organic molecules [49]. They focused
MOFs@SiO2 shell-core particles, the magnetic properties as
on investigating the impact of both the UiO-66 shell thickness
carrier materials in Franzreb’s works greatly facilitates the
and silica core porosity on the FDSS effect. The results indicated
frequent solid-liquid sepa- ration steps required during the
the composite phases obtained with the 5 µm mesoporous
synthesis of the MOF shell by the LPE method, and ensures the
particles and two depositions of UiO-66 particles exhibited the
complete removal of unattached MOF from the composite
best sepa- ration performance. The particles were also tested for
particles.
the NP and
Fig. 5. Electrochromatograms on NKU-1-poly (BMA-co-EDMA) monolith 5 and poly (BMA-co-EDMA) monolith 5. Conditions: capillary, 100 µm inner diameter, 41.5
cm total length and 32.5 cm effective length; separation voltage, 25 kV; temperature, 25 ◦ C; UV-vis detector, 254 nm. Mobile phase: acetonitrile/0.01 mol/L acetate (pH
6.0) (75:25, v/v) (a, c, and d); acetonitrile/0.01 mol/L acetate (pH 6.0) (70:30, v/v) (b). (a) Analytes-alkylbenzenes: (1) acetone (2) 2,5-dihydroxyacetophenone (3)
acetophenone(4) butyrophe- none (5) toluene (6) ethylbenzene (7) propylbenzene (8) butylbenzene; (b) Analytes-PAHs: (1) naphthalene (2) acenaphthylene (3) fluorene
(4) anthracene(5) fluoranthene
(6) pyrene (7) benzo (a) anthracene (8) benzo (b) fluoranthene; (c) Analytes-aniline series: (1) acetanilide (2) 4-fluoroaniline (3) 2-nitroanline (4) 1-naphthylamine; (d)
Analytes-naphthyl substitutes: (1) 1-naphthol (2) 1-methylnaphthalene (3) 1-chloronaphthalene (4) 1-bromonaphthalene.
Reprinted from Ref. [56]. Copyright 2016 Elsevier.

Ahmed et al. used the recently developed spheres-on-spheres

2.1.2. Capillary electrochromatography
(SOS) silica microspheres as support for the nucleation and
CEC is a hybrid technique combining HPLC and CE,
growth of zeolite imidazolate framework-8 (ZIF-8) nanocrystals
theoretically resulting in high selectivity and separation
to result in core-shell SOS@ZIF-8 spheres [54]. The prepared
efficiency. At present, three approaches are used for column
composite spheres were evaluated as stationary phase for
preparation in CEC: (i) open tubular capillary, (ii) particle-
chromatographic separation of aromatic molecules by HPLC,
packed capillary and (iii) monolithic capillary. The recent
with column efficiency reaching up to 19 000 plates/m.
applications of MOFs in CEC were summarized in Table 2. There
Furthermore, SOS@ZIF-8 spheres were thermally treated to
are few references reported about MOFs as pack- ing materials
generate SOS@ZnO spheres that were utilized as catalyst for the
for CEC, which might be due to widely distributed sizes and
photodegradation of methyl orange.
irregular shapes, resulting in low column efficiency, high column
By further in-depth investigation of analytes targets of the
backpressure, and undesirable peak shapes. Due to its high
reported MOFs-based stationary phases, most of them focus
permeability, monolithic capillary column has drawn great
on the separation of weakly polar compounds as well as isomers
attrac- tions in CEC. Many reports presented the incorporation of
via hydrophobicity, G-G, size-exclusion, shape selectivity or
various nano- and micro-particles into the monolithic matrix to
hydrogen bonding interactions. The separation of polar
enhance the separation of small molecules using polymeric
compounds is sel- dom reported. Recently, ionic liquids organic
monoliths [24]. Therefore, there is no exception of MOFs, which
ligands-based MOFs nanocrystals were facilely fabricated and
can incorporate into polymer monolith to form MOF-based
further exploited to grow on the surface of carboxyl-silica [55].
composites as station- ary phases for CEC.
The new ILI-01@SiO2 shell- core stationary phase was prepared
Zhang et al. incorporated a new lanthanide metal-organic
by adjustment the growth cycles and further packed for HPLC
frameworks NKU-1 into poly(butyl methacrylate-co-ethylene
separation. The new prepared column exhibited hydrophilic
dimethacrylate) (poly(BMA-co-EDMA)) monolith and its perfor-
interaction. Polar analytes, includ- ing amides, vitamins,
mance was evaluated by CEC [56]. Compared with transition
nucleic acid bases, and nucleosides, were separated with rapid
ions used mostly in MOFs, lanthanide (Ln) ions have higher
separation time and excellent selectivity.
affinity for donor atoms and ligands, which are favorable to
Since MOFs have been widely applied in HPLC separation,
stabilize the frameworks [57]. The resulting hybrid monolithic
there are also many other types of MOFs and related composite
column exhibited much better chromatograph performance in
particles that have not yet been used as stationary phases for
separat- ing four groups of small molecules, including
HPLC. There- fore, it is still meaningful to develop the novel
alkylbenzenes, PAHs, aniline series and naphthyl substitutes than
MOFs or MOFs-based material as stationary phases for HPLC
poly (BMA-co-
separation.
Table 2
The applications of metal-organic frameworks in CEC, nano-LC and GC.

Separation matrix Surface area (m2 Analytes Form Separation R ye

g−1 ) mode e ar
f.
NKU-1-poly (BMA-co-EDMA) 11.708 alkylbenzenes, PAHs, aniline series Incorporation CEC [ 2
and 5 0
6 1
] 6
monolith naphthyl substitutes
cZIF-8-poly(BMA-co-EDMA) 255 or 339 PAHs and NSAIDs Incorporation CEC [ 2
5 0
8 1
] 7
monoliths
ZIF-8 nanocrystals / Phenolic isomers Coating CEC [ 2
6 0
0 1
] 6
ZIF-8 / Cationic and neutral analytes Coating CEC [ 2
6 0
1 1
] 7
MIL-100(Fe) / Neutral, acidic and basic analytes Coating CEC [ 2
6 0
2 1
] 3
CAU-1@PMMA 423 Aromatic carboxylic acids, basic sulfa Coating CEC [ 2
6 0
3 1
] 3
drugs and peptides
ZIF-90 / Isomers of substituted benzene, Covalently CEC [ 2
bonding 6 0
4 1
] 4
amines and NSAIDs
HKUST-1 / Benzene series, phenolic acids, and Covalently CEC [ 2
bonding 3 0
0 1
] 5
benzoic acids derivatives
MOF-5 / Substituted benzenes, acidic and Covalently CEC [ 2
basic bonding 2 0
9 1
] 6
analytes
MOF-180 / Benzene series, benzoic acids and Covalently CEC [ 2
bonding 6 0
5 1
] 6
amines
ZIF-8 / Diphenol isomers, benzene series Covalently CEC [ 2
bonding 6 0
6 1
] 7
HKUST-1-poly(GMA-co- / PAHs, EB and St, phenols and Incorporation cLC [ 2
EDMA) aromatic 7 0
1 1
] 4
monolith acid
HKUST-1-poly(MAA-co- / Benzenediols, xylenes, thylbenzenes, In situ grafting cLC [ 2
EDMA) 7 0
2 1
] 5
monolith and styrenes
MIL-53(Al)-poly 26.92−85.12 Alkylbenzenes Incorporation cLC [ 2
(HMA-co-EDMA) monolith 7 0
3 1
] 6
UiO-66 614.3 n-hexane and cyclohexane Packing GC [ 2
7 0
5 1
] 4
Cu(Fe)-BTC 1300–2100, Alkanes, propane, propylene, and Packing IGC [ 2
7 0
4 1
] 5
aromatic hydrocarbons
[Cu2(bdc)2(dabco)] / C1-C7 Coating GC [ 2
2 0
8 1
] 4
[Cu2(cam)2(dabco)] and / Alkane and aromatic hydrocarbons Coating GC [ 2
2 0
7 1
] 5
[Cu2(cam)2(bi
py)] HKUST-1 / Cyclohexane and ether compounds Coating IGC [ 2
8 0
7 1
] 5
ZIF-90 / Alkanes, benzene homologues; Coating GC [ 2
8 0
2 1
] 5
ketones, alcohols, aldehydes
ZIF-8-poly(BuMA-co-EDMA) 56.8 Linear alkanes, polar solvents, Incorporation GC [ 2
9 0
0 1
 ] 5
monoliths structural isomers, gas mixtures
Core–shell PDMS- MOF 5 / Gases and liquids Packing GC [ 2
7 0
8 1
] 4
microspheres
ZIF-8@PDMS core- / Xylene isomers Packing GC [ 2
3 0
4 1
] 6
shell microspheres and natural gas mixtures
184 silicone@MAF-5 / PAHs and Coating GC [ 2
8 0
1 1
] 6
organochlorine pesticides (OCPs)
Graphene-ZIF8 composite / Branched alkane isomers and Coating GC [ 2
aromatic 8 0
4 1
] 6
material positional isomers
MIL-101(Cr) 3990 Hydrocarbons Packing GC [ 2
7 0
7 1
] 7
ZSM-20 zeolite or IRMOF-8 / Ethane/ethylene Packing GC [ 2
7 0
6 1
] 7

EDMA) monolith column (Fig. 5). The maximal column

wall. Therefore, they used bare fused silica capillary for further
efficiency of NKU-1-poly (BMA-co-EDMA) monolith was
coat- ing. To make sure the phase ratio was high enough, the
210,000 plates/m. Carrasco-Correa et al. prepared carbonized ZIF-
number of the growth cycles was set as 10. Separation of nine
8 with different par- ticle size and subsequently incorporated in
phenolic iso- mers was done with column performance for o-
methacrylate-based monolithic columns for CEC [58]. By
nitrophenol 208 860 plates/m. The next year, Pan et al. adapted
adding small amounts of cZIF–8 micro/nano-particles into the
the same method to prepare the ZIF-8 coated capillary column as
monolithic matrix, the chro- matographic performance of
separation channel for simultaneous separation of target analytes
composite columns was improved due to the strengthening
belonging to differ- ent classes (cationic and neutral analytes) by
interaction with aromatic compounds via hydrophobic and G-
a single 1-D capillary electrochromatography [61]. The
G interactions. These columns showed good separation ability
developed method exhibited the advantages of cationic and
towards PAHs and non-steroidal anti- inflammatory drugs
neutral analytes simultaneous separa- tion achieved within a
(NSAIDs).
single 1-D CEC running process, and no need of switching buffer
Besides incorporation of MOFs into polymer monolith for
solution in the process of separation. The elec- tropherograms for
CEC, there is a comparatively straightforward separation mode
separation of six model cationic analytes and four neutral
named as open tubular capillary electrochromatography (OT-
analytes on bare capillary and ZIF-8 coated capillary columns
CEC) just by coating or bonding MOFs on the inner surface of
were shown in Fig. 6. Additionally, the developed method was
capillary as station- ary phase for chromatographic separation.
employed in the analysis of urine samples with satisfactory
OT-CEC has attracted increasing attention due to its advantages
recoveries.
of ease of column prepa- ration and no need for end frits and
There are also some other MOFs materials applied in OT-
particles packing [59]. Qu et al. prepared ZIF-8 nanocrystals
CEC. A new type of MIL-100(Fe) coated capillary column was
coated capillary column by a layer-by- layer method for OT-
prepared by a novel in situ layer-by-layer self-assembly method
CEC [60]. The coating was formed by coating ZIF-8 nanocrystals
for OT- CEC [62]. In a controllable manner, a series of OT-
on either bare fused silica capillary wall or the capillary column
capillary column with different cycles coating of MIL-100 (Fe)
pre-modified with amino groups. Interestingly, they found that
was prepared. The results showed 10 cycle coating of MIL-100
the existence of the amino groups did not bene- fit or even
(Fe) was best, too less caused less separation mediums and
hindered the growth of ZIF-8 crystal onto the capillary
interaction sites on the

Fig. 6. The electropherograms for separation of six model cationic analytes and-
four neutral analytes on bare capillary (A) and ZIF-8 coated capillary columns
(B). Separation conditions: 15% (v/v) methanol, 20 mM NaAc-HAc buffer, pH 5.5;
Injection: 0.5 psi, 3 s; applied voltage: +25 kV; detection wavelength: 214 nm;
capillary: 75 m i.d., 40.2 cm total length (30 cm effective length); capillary temper-
ature: 25 ◦C. Peak identification: 1, dopamine, 2, synephrine, 3, norepinephrine, 4,
epinephrine, 5, isoprenaline, 6, terbutaline, 7, praziquantel, 8, flavanone, 9,
4,5,6,7,8- pentamethoxyflavanone, 10, 6-methoxyflavanone.
Reprinted from Ref. [61]. Copyright 2017 Elsevier.
inner wall and too more caused strong interactions between the
column and analytes. The prepared column exhibited excellent
separation ability and stability. Yan’s group reported the
incorpo- ration of MOFs CAU-1 (CAU = Christian-Albrechts-
University) into polymethyl methacrylate (PMMA) to produce a
new composite CAU-1@PMMA coated capillary for OT-CEC
[63]. The incorpora- tion of CAU-1 into PMMA increases not
only surface area, but also electroosmotic flow (EOF), further
improving the chromatographic performance. Most of above
MOFs open tubular capillary columns were prepared by coating
method, Yan’s group also reported a directly covalent bonding
approach to prepare ZIF-90 capillary column for OT-CEC [64].
ZIF-90 was prepared at room temper- ature, and modified with 3-
aminopropyltriethoxysilane (APTES). The APTES modified ZIF-
90 was then directly immobilized onto the capillary wall via
covalently bonding at room temperature. The ZIF-90 bonded
column provided excellent performance for the sep- aration of
the studied isomers, neutral and basic compounds and NSAIDs.
In our group, we have done many works about MOFs cova-
lently bonded on the inner wall of capillary as stationary phase
for OT-CEC. The growth of HKUST-1 on the inner wall of
capil- lary by using LPE process was carried out at room
temperature for OT-CEC [30]. The fabricated HKUST-1@capillary
could be suc- cessfully used for the separation of benzene series,
phenolic acids, and benzoic acids derivatives. High column
efficiency of
1.5 × 105 plates/m for methylbenzene was achieved. Besides, we
used the same method to immobilize MOF-5 and MOF-180 with
exceptional porosity, a cage size of 15×23 Å, on the inner wall of
COOH-terminated capillary to produce a novel stationary phase
for OT-CEC [29,65]. It has been demonstrated that the MOFs
modi- fied capillary column exhibited good performance for
separation of acidic, basic, and neutral analytes. Recently, we
developed a bio-inspired PDA functionalization to immobilize
ZIF-8 onto the inner surface of silica capillary for OT-CEC [66].
Firstly, a poly- dopamine layer was spontaneously assembled
inside the capillary. Secondly, due to noncovalent adsorption and
covalent reaction ability, polydopamine could attract and anchor
zeolitic imidazo- late framework-8 onto the inner surface of
capillary for separation. Three groups of compounds including
acidic, basic, and neutral
compounds were well separated on the ZIF-8 bonded column.
Based on the bio-inspired PDA functionalization, covalent-
organic frameworks (COFs), another advanced porous organic
material, which has similar properties to MOFs except the
structure with- out metal ion, were immobilized on the inner
surface of capillary for OT-CEC [67]. The fabricated column
showed excellent separa- tion ability towards substituted benzene
with column efficiency of 154060 plates/m for methylbenzene.
After that, we also in-situ syn- thesized COF-LZU1 on the inner
wall accomplished by Schiff base reaction for OT-CEC [68]. The
prepared capillary column exhibited good separation efficiency
and selectivity of neutral compounds, amino acids and NSAIDs.
2.1.3. Nano-liquid chromatography
MOFs were also incorporated in organic polymer monolith
for capillary liquid chromatography (cLC). Its applications were
sum- marized in Table 2. As we known, organic polymer
monoliths are usually used to separate macromolecules such as
proteins and nucleotides, but they exhibit poor behavior in
separating small molecules. To increase the efficiency of the
organic poly- mer monoliths for separating small molecules,
incorporation of porous or nonporous particles into the monolith
might be a good choice to improve the performance [69,70].
Yang et al. incor- porated HKUST-1 nanoparticles into
poly(glycidylmethacrylate- co-ethylene dimethacrylate)
(poly(GMA-co-EDMA)) monoliths to afford stationary phases
with enhanced chromatographic perfor- mance of small
molecules in the reversed phase capillary liquid
chromatography(RP-cLC) [71]. The effect of HKUST-1
nanopar- ticles in the polymerization mixture on the
performance of the monolithic column was explored in detail.
The HKUST-1- poly(GMA-co-EDMA) monolith exhibited
enhanced resolution and high column efficiency ranging from 16
300 to 44 300 plates/m in the separation of various compounds
including PAHs, ethylbenzene and styrene, phenols and aromatic
acid in RP-cLC. Recently, the same research group examined the
in situ grafting of HKUST-1 on the surface of poly(methacrylic
acid-co-ethylene dimethacrylate) (poly(MAA-co-EDMA))
monolith instead of incorporation [72]. The technique of in situ
layer-by-layer self-assembly synthesizing HKUST-1 in
poly(MAA-co-EDMA) monolith in a capillary column resulted
in good chromatographic performance with increasing HKUST-1
density. The column was explored for separation of small
molecules in RP mode with high resolution and good selectivity.
Yusuf et al. employed a monolithic capillary column containing
a composite of metal–organic framework MIL-53(Al) incorpo-
rated into poly(hexyl methacrylate-co-ethylene dimethacrylate)
(poly(HMA-co-EDMA)) to enhance the separation of mixtures
of small aromatic compounds by using cLC [73]. The addition of
10 mg/mL MIL-53(Al) microparticles led to a high permeability
col- umn with higher micropores content in the monolithic
matrix and increased the Brunauer-Emmett-Teller surface area
from 26.92 to
85.12 m2/g. The prepared column exhibited high-resolution sepa-
ration for a series of alkylbenzenes in less than 8 min with 14710
plates/m efficiency for propylbenzene. The results indicated an
exothermic separation in that with the temperature increase the
mass transfer was improved, leading to an increased linear
velocity and a reduced retention time.
2.1.4. Gas chromatography
Various MOFs-based materials have been demonstrated in
several publications for high resolution GC, with applications
sum- marized and shown in Table 2. In term of MOFs in GC, the
columns were most commonly prepared by directly packing
MOFs crystals into stainless steel column or coating on the inner
surface of capil- lary for adsorption and separation.
Autie-Castro et al. packed the metal-organic frameworks Cu-
BTC and Fe-BTC into stainless steel columns (12 cm of long and
2 mm of internal diameter) for the separation of alkanes (nC 5 to of the MOFs-crystallites prepared by the solvothermal synthesis
nC9), propane, propylene, and aromatic hydrocarbons by inverse
gas chromatography [74]. The nature of such behavior was dis-
cussed according to the possible guest-host interactions during the
molecules adsorption and retention in the column and considering
the molecules size and shape and the porous framework topology.
Compared with the Fe-BTC with gel-like features, Cu-BTC column
was found to have higher adsorption and separation, which was
ascribed to its long-range ordered crystal structure and molecules
accessibility to its porous framework. Bozbiyik et al. studied the
adsorption and separation of n-hexane and cyclohexane on the UiO-
66 by pulse GC and vapor phase breakthrough experiments [75].
They found that cyclohexane was adsorbed preferentially over
linear n-hexane in this structure, because cyclohexane fit better
in the cages of UiO-66, leading to a more negative adsorption
enthalpy, together with a lower loss of entropy during adsorp-
tion as compared to n-hexane. Pires et al. packed two types of
families ZSM-20 zeolite and the IRMOF-8 into 100 mm×3.2 mm
stainless steel tube, respectively, and used as stationary phases
for ethane/ethylene separation by GC [76]. The micropore vol-
umes, obtained from the t-plots, are 0.67 cm 3 g−1 and 0.33 cm3 g−1
for the IRMOF-8 and the zeolites, respectively, illustrating the
highest adsorption capacity of the MOFs. These two materi-
als showed the reversed selectivity towards the ethane/ethylene
separation. Belarbi et al. presented separation of hydrocarbons
on MIL-101(Cr) packed column by GC and in-depth revealed
the hydrocarbons/MIL-101(Cr) interactions by Henry’s constants
which were calculated by the slope of adsorption isotherms [77].
They revealed the differences between those Henry’s constants on
series of hydrocarbons sorbates were attributed either to differ-
ent van der Waals interaction (size effect) or to the presence of
unsaturation leading to a stronger interaction, especially in the
case of aromatics. They therefore demonstrated that the adsorp-
tion isotherms are a powerful way to predict the chromatographic
separation of compounds.
Efficient chromatographic separation in packed columns
require the homogeneous and suitable particle size of stationary
phase to circumvent issues associated with pressure drops and
bad peak shape. Immobilizing the MOFs on an inert template
(named core) to form core-shell composite can increase the
particle size suit- ably and might be more favorable for
chromatographic separation. Manju et al. report a simple
procedure for directed crystallisation of MOF-5 on the thermally
stable poly(dimethylsiloxane) (PDMS) microspheres to afford
core-shell PDMS-MOF-5 microspheres [78]. The core-shell
microspheres were sieved (60–80 mesh) and packed as a
stationary phase for gas chromatographic separation of per-
manent gases and liquids. The loading of MOF-5 on the core
PDMS
resulted in a tremendous increase in the surface area (2850 m2
g−1),
compared with the non-porous nature of PDMS microspheres
(8 m2 g−1). The prepared column was employed to separate a
nat- ural gas mixture. It is confident to see that the method
reported here could be applied to prepare any PDMS (core)-
MOF (shell) combination and used to generate novel stationary
phase for chro- matographic separations. Recently, they used the
same method to successfully fabricate ZIF-8@PDMS shell-core
microspheres for efficient separation of liquid and gas mixtures
including xylene iso- mers and natural gas mixtures [34]. The
formation of ZIF-8 was confirmed by PXRD, SEM micrographs,
energy dispersive analysis, thermogravimetry and FT-IR
spectroscopy. However, the separa- tion performance was not
very satisfactory, with bad peak shape and wide peak width,
which might due to the inhomogeneous and impure packing
microspheres.
Various MOFs materials were coated onto the inner surface
of capillary by “dynamic method” to form open-tubular capil-
lary column for GC. It was fabricated by slowly flushing slurries
through fused silica capillaries. The fabricated columns showed same cyclic layer deposition procedure and employed as a
a high separation power proving the potential of MOFs for gas stationary phase for the gas chromatographic sepa- ration of
chromatographic applications. Metal-azolate frameworks various analytes possessing different modes of interaction
(MAFs) are a class of azolate ligands MOFs which have
excellent ther- mal and chemical stability [79,80]. Tian et al.
first exploited the porous MAF-5 ([Zn[(eim)2], Heim = 2-
ethylimidazole) as station- ary phase for gas chromatography
by a novel dynamic coating method [81]. In this study, 184
silicone elastomers were used as the protective thin film over
MAF-5 to propose a novel dynamic coating strategy to
fabricate firm and mechanically stable coating on fused silica
capillary column. The prepared 184 silicone@MAF-5 capillary
column was successfully applied for the rapid separa- tion of
PAHs and organo-chlorine pesticides (OCPs), with column
efficiency up to 9045 plates/m for benzene. Besides, the
thermo- dynamic parameters and chromatographic retention of
all probe molecules were investigated on the 184
silicone@MAF-5 column and the results showed the separation
of analytes was a complex balance of thermodynamic and
kinetic factors. Yan’s group reported a facile approach to
fabricate a ZIF-90 bonded capillary column for GC separation
[82]. ZIF-90 was directly grown onto the inner wall of the
carboxyl modified capillary via the coordination between Zn(II)
and carboxyl group. The capillary column successfully
separated the apolar compounds (alkanes, benzene
homologues) and polar compounds (ketones, alcohols,
aldehydes), shown in Fig. 7. Taking into account the
complementary features of graphene assembled structures and
MOFs, the counter-diffusion method was employed to directly
deposit ZIF-8 on 3D graphene to obtain graphene-ZIF-8
composite material by Qu’s group [83]. Next, they presented
the separation performance of graphene-ZIF-8 composite
material as stationary phase for capillary GC [84]. The
stationary phase exhib- ited high selectivity and resolving
capability for branched alkane isomers and aromatic positional
isomers, with column efficiency of 5000 plates/m for n-
dodecane (k = 1.22). In addition, it also attained high resolution
for geometric cis-/trans-isomers.
Recently, layer-by-layer deposition methods developed by
Wöll
et al. have enabled the preparation of non-interpenetrating large
pore MOFs on various surfaces [85,86]. The cyclic layer
deposi- tion technique was formed directly during the coating
procedure inside the capillary via a precipitations reaction
anchoring the MOFs layer via a bifunctional self-assembled
monolayer (SAM) onto the fused silica. Mertens’s group
applied the cyclic deposition method based on the technique of
the so called “controlled SBU approach” and anchored via
SAMs to prepare [Cu2(bdc)2(dabco)] coated GC capillary
column [28]. The fabricated column exhibited a high sep-
aration power for the light hydrocarbons C1-C7. The
interaction between the stationary phase and the analytes was
character- ized by chromatographic parameters, including
resolution factors and selectivity as well as thermodynamic data
which were deter- mined from the temperature-dependent
measurements of the retentions times of these analytes.
Afterwards, they used the same method to coat two isoreticular
pillared-layer frameworks (PLFs) [Cu2(cam)2(dabco)] and
[Cu2(cam)2(bipy)] on CO2H-terminated SAM modified
capillary as stationary phases for GC application [27]. This type
of MOFs has shown to be suitable for the dip depo- sition on
various surface. Chromatographic parameters, including
resolution factors and selectivity, as well as thermodynamic
data characterizing the interaction between the stationary phase
and the analytes were determined from the temperature-
dependent retentions times. The prepared PLFs capillary
columns exhibited an analytes size depending retention
behavior from the differ- ent chromatographic parameters.
Both columns offered excellent properties for the high
resolution of light hydrocarbons including isomers. In the same
year, they prepared HKUST-1 coated capil- lary column by the
Fig. 7. Gas chromatograms on ZIF-90 bonded capillary column (30 m long × 0.53 mm i.d.) at a N2 flow rate of 2 mL min−1 for the separation: (A) linear alkanes using a
temperature program of 80 ◦ C for 1 min, then 15 ◦ C min−1 –260 ◦C; (B) benzene homologues using a temperature program of 100 ◦ C for 1 min, then 5 ◦ C min−1 –240 ◦ C;
(C) aldehydes using a temperature program of 50 ◦ C for 1 min, then 10 ◦ C min−1 –250 ◦C; (D) n-alcohols using a temperature program of 90 ◦ C for 1 min, then 10 ◦ C
min−1 –250 ◦ C;
(E) 2-alcohols using a temperature program of 90 ◦ C for 1 min, then 10 ◦ C min−1 –250 ◦ C; (F) ketones using a temperature program of 50 ◦ C for 1 min, then 10 ◦ C min−1 –250
◦
C. Reprinted from Ref. [82] Copyright 2015 Royal Society of Chemistry.

due to their differences in polarity and the presence of free elec-

application in GC is limited. Yusuf et al. presented a novel
tron pairs [87]. The influence of donor and acceptor areas of the
composite stationary phase by incorporating a poly(butyl
MOF-lattice on the adsorption of different analytes were studied
methacrylate- co-ethylene dimethacrylate) (poly(BuMA-co-
using inverse GC. The determination of a London force
EDMA)) monolithic capillary monolithic column with ZIF-8
governed reference system and the determination of the
microparticles for GC applications using a conventional low-
interaction Gibbs free energies of a set of analytes allowed the
pressure GC instrument [90]. The addition of ZIF-8 micro-
separation of their interactions into nonspecific and specific
particles (10 mg/mL) signifi- cantly increased the BET surface area
contributions.
of poly(BuMA-co-EDMA) monolith by 3.4-fold. Highly efficient
Besides, incorporation of MOFs into monolithic column is
separation of various small molecules, such as linear alkanes, polar
also an alternative to form stationary phase for GC. The
solvents, structural isomers, gas mixtures was achieved, due to the
incorpora- tion to create exactly tailored pores may offer new
high surface area, flexi- ble pores, excellent permeability of the
separation possibilities. Although MOFs-polymer composites
monolithic matrix along with its capillary size and the interactions
fabricated by incorporation of MOFs into monolithic column has
of ZIF-8. Fig. 8 shows the comparison of separation of organic
been widely used as stationary phase for HPLC [88], cLC [71] and
solvents mixture by using
CEC [89], its
Fig. 8. Separation of polar organic solvents mixture using control column (a), and
ZIF-8-(BuMA-co-EDMA)-2 column (b). Conditions: isothermal 100 ◦C; inlet pres-
sure1 MPa; split injection. Peaks: diethyl ether (1), acetone (2), dichloromethane
(3), tetrahydrofuran (4), and chloroform (5).
Reprinted from Ref. [90]. Copyright 2015 Elsevier.
poly(BuMA-co-EDMA) monolithic column and ZIF-8-
poly(BuMA- co-EDMA) column, which indicated an
enhancement of separation performance on the latter column.
2.2. Chiral separation
As a new functional material, the studies of MOFs have
expanded into chiral recognition [91–93]. Chirality is endowed to
MOFs when the organic linkers of the structure are chiral
themselves or the arrangement of components into the solid
is chiral. Homochiral MOFs with defined pore structures can
be generated by three approaches [93,94]. The most common
and reliable approach is to utilize metal-containing nodes and
stereochemically pure chiral organic bridging ligands to obtain
network structural homochiral MOFs. The second approach for
synthesis of homochiral MOFs is to utilize achiral metal nodes and
bridging ligands under chiral influ- ence. In the third approach,
homochiral MOFs are synthesized from achiral components based
on the phenomenon of spontaneous res- olution during crystal
growth. The chiral recognition abilities of MOFs mostly
depended on the single-handed helical channels on the surface of
the crystal MOFs, in which the steric fit between the chiral
cavities and conformation of the enantiomers may play an
important role in chiral recognition [95]. Besides, the
hydrogen- bond, G-G and dipole–dipole interaction between the
functional groups in MOFs and chiral analytes might also
contribute to the chiral recognition. Molecular modeling used to
explore the chiral recognition mechanisms of MOFs concluded
that the enantioselec- tivity is strongly correlated with a close
match between the size of the pore and the size of the chiral
sorbate molecule [96–98]. In brief, the chiral recognition is the
result of a combination of various interactions. Up to now,
various novel homochiral metal- organic frameworks were
synthesized and applied in asymmetric catalysts, enantioselective
separations due to its intriguing helical topologies, molecular
chirality, and porous functionalities. Here, we focus on the
application of homochiral MOF in HPLC, GC and CEC
enantioseparation.
2.2.1. High-performance liquid chromatography
Hailili et al. synthesized the Mn 4O cluster-based 3D
homochiral MOF (Me 2NH2)2[Mn4O(D-cam)4] (H · 2O)5 (D-cam = D-
camphorates) with a planar tetracoordinated oxygen and
enantiopure D-camphoric acid, and was used as new station-
ary phase for HPLC [99]. The as-synthesized homochiral MOF
Fig. 9. HPLC enantioseparation of racemates on the packed 1 column (10 cm
long × 4.6 mm i.d.): (a) (±)-ibuprofen, (b) (±)-phenyl-1-propanol, (c) (±)-
phenylethylamine and (d) (±)-benzoin at 25 ◦C. Inserted molecular models with
the lowest energy and the sizes correspond to the MKDs considered van der Waals
radii, obtained from Gaussian 03.
Reprinted from Ref. [102]. Copyright 2014 American Chemical Society.
exhibited a uniform cubic shape with 5–10 µm particle size,
which is very suitable for packing without any further crushing
process. The packed column showed high resolution and good
selectivity
± for ( )-ibuprofen and ( )-1-phenyl-1,2-ethanediol,
however, the peak shape and column efficiency was not good
which might be due to the strong interaction of analytes with the
chiral MOFs. The chiral recognition mechanism was estimated to
the dominated hydrogen-bonding and electrostatic interactions.
Tanaka et al. synthesized the (R)-CuMOF-1-silica composite
from a mixture of (R)-2,20-dihydroxy-1,10-binaphthalene-6,60-
dicarboxylic acid, Cu(NO3)2 and monodisperse spherical silica
gel in DMF under solvothermal conditions [100]. The synthe-
sized composite was packed in to stainless steel column (15 cm
length, 4.6 mm i.d.) for enantioseparation of various sulfox-
ide enantiomers with mobile phase of hexane/EtOH (50/50)
and hexane/i-PrOH (90/10). Later, other (R)-MOF-silica
compos-
ites were prepared by the previous method using enantiopure (R)-
2,2r-dihydroxy-1,1r-binaphthalene-6,6r-dicarboxylic acid or (R)-
2,2r-dimethoxy-1,1r-binaphthalene-6,6r-dicarboxylic acid as a
starting material for enantiomeric HPLC separation towards many
kinds of enantiomers, such as sulfoxides, sec-alcohols, b-lactams,
benzoins, flavanones and epoxides [101]. Although the chiral
columns showed good chiral recognition ability, the peak shape
and column efficiency were not satisfactory, which might be due
to the inhomogeneous of packing material.
Kuang et al. synthesized a novel molecular sieve-like
homochi- ral MOF assembled by a enantiopure pyridyl-
functionalized salen ligand, [N-(4-Pyridylmethyl)-l-leucine
· HBr]
(l-HL) [102]. The as- synthesized homochiral MOF showed non-
interpenetrated 3D porous frameworks, which was packed for
enantioseparation by HPLC based on the relative sizes of the
chiral channels and the resolved molecules.
± Four racemates of
( )-ibuprofen,± ( )-phenyl- 1-propanol, ( )-phenylethylamine and
( )-benzoin were baseline separated by using hexane/isopropanol
as the mobile phase (Fig. 9), with a good selectivity factor (a =
2.4) and resolution ± (Rs = 4.1) within 6 min for ( )-ibuprofen.
Only the analyte with a critical size around 9.2–9.4 Å can
incorporate into homochiral MOF demon- strating its molecular
sieve-like behavior.
Yuan’s group made a great contribution on chiral separa-
tion by using homochiral MOFs as chiral stationary phases. A
Fig. 10. HPLC chromatograms on the packed Cd-MOF column (25 cm long × 2.1 mm i.d.) for the separation of racemates. (A) 1-(1-naphthyl)ethanol, (B) 1,1 r-bi-2-naphthol,
(C) 1-(4-chlorophenyl)ethanol, (D) benzoin, (E) 1-(9-anthryl)-2,2,2-trifluoroethanol, and (F) trans-stilbene oxide at 25 ◦C using different ratio of hexane/DCM as the mobile
phase at a flow rate of 0.1 mL min −1 . The signals were monitored with a UV detector at 254 nm.
Reprinted from Ref. [106] Copyright 2016 Wiley-VCH.
homochiral helical MOF [Zn2(D-cam)2(4,4r-bpy)]n (4,4r-bpy =
4,4r- bipyridine) consisting of homochiral layers pillared by
bipyridine ligands was reported as stationary phase for HPLC
[103]. The homochiral layer was formed by the left- and right-
handed heli- cal chains in an orderly arrangement. The SEM
image for the as-synthesized crystal exhibited a uniform cubic
shape with 5–10 µm particle size, which can be conveniently
used as a chi- ral stationary phase in HPLC. The chiral column
showed good selectivity and lower column pressure for HPLC
enantiomeric sep- aration of nine racemates that contain alcohol,
phenol, aldehyde, ketone, base, amide, and a chiral drug. After
that, homochi- ral MOFs [Cu 2(D-cam)2(4,4r-bpy)]n and [Co2(D-
cam)2(TMDPy)] (TMDPy = 4,4 r-trimethylenedipyridine) was
reported to be pre- pared from enantiopure D-cam and the
auxiliary ligands, and was packed as chiral stationary phase for
HPLC [104,105]. Both columns showed high resolution of
positional isomers and chiral compounds. Recently, his group
report a
· homochiral MOF [Cd2(D- cam)3] 2Hdma 4dma, packed
as a new chiral stationary phase for enantioseparation by HPLC
[106]. The separation properties of the chiral MOF packed
column were evaluated by nine race- mates of alcohol, naphthol,
ketone, and base compounds (Fig. 10). Among them, 1-(1-
naphthyl)ethanol and 1,1r-bi-2-naphthol were baseline separated
with resolution of 1-(1-naphthyl)ethanol up to 4.55. The
possible chiral recognition mechanism investigated mostly
depended on the pore size, shape of the channel, and host- guest
interaction effects of the stationary phase [1]. In addition, many
other interactions such as hydrogen, dipole-dipole, disper- sion
force, and so on that come from MOF and the mobile phase may
also affect the enantioselectivity.
2.2.2. Capillary electrochromatography and nano-
liquid chromatography
In 2014, Yuan’s group reported the first work of an chiral
MOF [In3O(obb)3(HCO2)(H2O)]· solvent as chiral stationary phase
in particulate packed CEC [107]. The fabricated capillary column
gave fast enantioseparation of (±)-hydrobenzoin, (±)-1-phenyl-
1,2-ethanediol, and clenbuterol within 3 min. The relative
standard deviations (RSDs) for the retention time of run-to-run,
day-to-day, and column-to-column were 1.51-3.63, 1.83-3.98,
and 3.42-5.66%, respectively, illustrating the good stability and
reproducibility of the prepared chiral column. Unfortunately, the
MOF-packed col- umn showed only between 1100 and 3900
plates/m for tested racemates and low resolution of 0.42 for
chiral drug clen- buterol. In other work [108], the same chiral
MOF material, ·
[In3O(obb) 3(HCO 2)(H2O)] solvent was
synthesized and evaluated as CSP in different separation mode of
HPLC,GC and CEC. The same chiral material showed different
chiral recognition abilities in three separation mode, which might
be attributed to the different separa- tion condition causing the
different helical structure and properties of the MOF.
Several chiral MOFs have also been developed as CSP for OT-
CEC. For instance, Yuan’s group reported the first example of using
[Zn2(D-Cam)2(4,4r-bpy)]n as CSP for OT-CEC separation of chiral
drugs and positional isomers [109]. The MOF was dynamically
coated onto the surface of capillary which had been pretreated by
sodium silicate solution to granulate the inner wall and obtain a
stable stationary phase particles layer. Baseline separations of
fla- vanone and praziquantel were achieved on the MOF coated
column with high resolution of more than 2.10. The column-to-
column RSDs for the retention times (3%) confirmed the good
reproducibil- ity of the column preparation.
Homochiral 3D helical MOF AlaZnCl shows a zeolitic (unh)
topol- ogy with permanent porosity containing pore aperture
(12.5 Å) [110]. It possesses not only homochiral hydrophilic
porous struc- ture, moisture stable property and good solvent
stability, but also ease of preparation at room temperature, which
makes it an attrac- tive candidate for enantioseparation in OT-
CEC. Pan et al. coated homochiral MOF AlaZnCl on the inner
wall of fused silica capil- lary by an in situ, layer-by-layer self-
assembly approach at room temperature for OT-CEC [111]. The
coating thickness of AlaZnCl on the capillary inner wall greatly
impacted the enantiosepara- tion ability could be controlled by
varying the number of solution
(Zn(CH3CO2)2 2H 2O and l-HL) cycles. Six model analytes (two
· 2.2.3. Gas chromatography
amine drugs and four monoamine neurotransmitters) were used
to evaluate the enantioseparation performance of the prepared
column. The results illustrated the modal analytes could be well
separated with the 10 cycles capillary column. The author also
stud- ied the possible chiral recognition mechanism of the
homochiral AlaZnCl capillary column and revealed that their
chiral recognition was not only affected by the chiral interaction
between groups, but also by the spatial structure of the MOF.
Recently, in situ seed- ing MOFs on the surface of supports with
the use of nucleating agents has attracted increasing attention due
to its simple and rapid synthesis relative to traditional
solvothermal methods [31,112]. The same group in situ
synthesized the homochiral MOF [Zn(s- nip) 2]n in the capillary
inner wall by using ZnO nanoparticles as efficient nucleating
agents for OT-CEC [32]. The total synthesis procedures of this
new developed preparation protocol were less than three hours
compared with our previous proposed layer-by- layer self-
assembly method. The characterization of IR, SEM and EDS
illustrated the successful formation of [Zn(s-nip) 2]n in the
capillary. Besides, the results of thermogravimetric analysis indi-
cated the good thermal stability up to 370 ◦C. The capillary
column was used for separation of monoamine neurotransmitters
enan- tiomers, nitrophenol isomers and bisphenols analogues.
Although the enantioseparation ability towards analytes such as
epinephrine and isoprenaline were not very well, in situ
fabricating MOFs using nucleating agents in the capillary open
an avenue for application of other chiral MOFs in CEC.
Ye et al. prepared the homochiral MOF material [Cu(mal)
(bpy)] H2O, which· was modified onto capillary for OT-CEC
enantioseparation [113]. They utilized the carboxyl groups
prevalent in the ligands of MOFs particles to react with 3-
aminopropyltriethoxysilane (APTES) to form amido bonds, and
further covalently bonded onto the inner wall of capillary
through silanization. The column was characterized by X-ray
diffraction, thermogravimetric analysis, particle size distribution
analysis, nitrogen absorption characterization, FTIR
spectroscopy, SEM, and energy-dispersive X-ray spectroscopy
(EDX). It exhibited success- ful separation of ephedrine-
pseudoephedrine hydrochloride and DL-penicillamine
enantiomers. However, the DL-phenylalanine enantiomers were
only partly separated. The modified capillary column was also
used to analysis of traditional Chinese medicine ephedra in real
samples. After that, they used the same method
to attach another homochiral MOF material, [Zn2(D-cam)2(4,4r-
bpy)]n to the inner wall of capillary as the chiral stationary
phase for OT-CEC [114]. Compared with their previous work, the
[Zn2(D-cam)2(4,4r-bpy)]n-modified capillary column possessed
higher thermal stability, a wider linear range and better separation
ability toward DL-phenylalanine. Their studies also illustrated the
modification method was effective for many other MOFs materials,
which broadened the application of MOFs in chiral analysis.
It has been proved that incorporation of nanomaterials in
polymer monoliths is an effective way to regulate and control
of their surface chemistry and separation performance [24,115].
Taking into account of these, chiral nanomaterials also can
be incorporated to form novel composite monolith for enan-
tioseparation. A novel chiral monolith capillary column was
prepared by incorporation chiral MOF [Zn2(bdc)(L-lac)(dmf)]
(DMF) prepared from, zinc nitrate, benzene dicarboxylic acid,
and L- lactic acid, into poly(4-vinylpyridine-co-ethylene
dimethacrylate) (poly(VP-EDMA)) monolith to obtain the
desirable enantioselective stationary phase for chiral separation
by
± nano-LC [116]. They used ( )-methyl phenyl sulfoxide as
target analyte to evaluate the enan- tioseparation± ability. The
baseline separation of ( )-methyl phenyl sulfoxide showed the
positive effect of chiral MOF.
The chiral MOF (H2sala = N-(2-hydroxybenzyl)-l-alanine)-
coated capillary column used in GC for separation of
enantiomers was first reported by Yuan’s group [117]. After that,
several other chiral MOFs have also been utilized as chiral
stationary phases in GC. A chiral MOF Ni(D-cam)(H 2O)2 with
unusual integration of molecular chirality, absolute helicity, and
3-D intrinsic chiral net was chosen as stationary phase for GC
separation [118]. The open tubular column prepared by a
dynamic coating method showed good separations of isomer and
linear alkanes mixture, especially for racemates. Yuan’s group
also reported the fab- rication of a three-dimensional (3D) chiral
nanoporous MOF, [(CH3)· 2NH2][Cd(bpdc)1.5] 2DMA, which was
coated as capillary× column (2 m long 75 µm i.d.) by a dynamic
coating method for GC separation of racemates, Grob’s test
mixture, normal alka- nes, normal alcohols, and isomers [119].
The chiral recognition mechanism was estimated, though the
influence of the chiral microenvironment on the chiral properties
of chromatographic systems was complicated. The prepared
MOFs possessed large chiral pore with 19.4 Å which was
suitable for the chiral guests accessible to chiral channel for
chiral recognition. Besides, other interactions between racemates
and 3D chiral nanoporous MOFs, such as hydrogen bonding, van
der Waals forces, dipole–dipole and dispersion, had also played
some role in chiral recognition. The MOFs-coated capillary
column exhibited good reproducibility with RSDs of 0.23 and
2.1% for retention time and peak area, respectively, and great
separation efficiency with theoretical plates of 2180 plates/m.
As we all known, cyclodextrins (CDs) and its derivatives are
one of the most commonly used and promising chiral selectors
in chiral recognition. Yuan’s group made an initial effort to com-
bine chiral MOF Co(D-Cam)1/2(bdc)1/2(tmdpy) with
permethylated þ-CD to investigate whether the use of chiral
MOF can enhance GC separation of enantiomers on a
cyclodextrin stationary phase [120]. The composite capillary
column was prepared by dynamic coating method combining
with a static coating. For comparison, their corresponding single
coated column MOF column and per- methylated þ-CD column
were also prepared. The results revealed enhanced resolution and
high column efficiency on the novel chiral column, which might
be ascribed to the inherent characteristics of chiral MOF, such as
its helical channels and infinite extension three- dimensional
supramolecular reticular structure. Afterwards, they also
incorporated [Cd(LTP)2]n and InH(d-C10H14O4)2 into a perme-
thylated þ-CD to afford chiral capillary columns for GC
separation of racemates [121,122]. Compared with column of
permethylated þ-CD, the columns of composite chiral MOFs-
permethylated þ- CD showed better selectivity on recognition of
the racemates and higher resolution ability.
2.3. Application in solid-phase microextraction
Solid-phase microextraction (SPME) is a powerful technique
commonly used in sample preparation for extraction of analytes.
The core of SPME is to develop novel materials as sorbent coat-
ings, providing high extraction efficiency, high selectivity as well
as robust chemical stability. MOFs have also received spotlight
in the field of sample preparation [123] because of its inherent
high spe- cific surface area which provides a large adsorption
capacity and its specific pore structure and size which enables
selective adsorption of small molecules [124]. Here, we pay
attention on its application on SPME. The main results with
important parameters have been summarized and listed in Table
3.
Recently, a novel on-fiber derivatization SPME assay was
devel- oped for putrescine (Put) and cadaverine (Cad) in situ
extraction by GC–MS [125]. Firstly, ZIF-8 was coated on
stainless wire by a layer-by-layer method and further
employed to encapsu-
 late derivatization reagent of isobutyl chloroformate (IBCF, 40 ◦C,

[130]

[137]
Ref

[127]

[134]

[136]
15 min) for extraction. The ZIF-8 coating not only had the merits of
[125] preventing IBCF from hydrolysis through its hydrophobic property
but also could load more IBCF because of its high specific sur-
face area, thereby increasing sensitivity. Ouyang et al. fabricated a
series of isoreticular bio-MOFs-coated fibers using a neutral
silicone sealant as bridging agent for PAHs and OCPs
microextraction by GC–MS [126]. The prepared SPME fibers
Instrument

showed excellent extrac- tion efficiency with LOD in the range of

GC–MS HPLC-FLU GC–MS

GC–MS GC-µECD
<8.9% <6.1%HPLC-UV GC–MS GC–MS GC–MS

HPLC-UV
CEC-UV GC
0.23-2.3 ng/L for analytes. They also prepared NH2-MIL-53(Al)-
coated fiber for SPME which showed good precision, low LODs of
0.025-0.83 ng/ L for synthetic musks (SMs) and 0.051-0.97 ng/L
for OCPs [127]. In our group, we developed a novel bio-inspired
polydopamine (PDA) method to immobilize ZIF-8 inside the
chemical resistance poly(ether ketone) (PEEK) tube for online in-
tube SPME by HPLC-FLU [128]. The pre- pared tube exhibited
excellent extraction efficiency towards six polycyclic aromatic
<11.4% <8.7% hydrocarbons (PAHs), with enrichment fac- tor from 550 to 734.
<13.3%
RSD%

Afterwards, Lv et al. used the same method to adhere MIL-53(Fe)

<6.4% <12%

<7.3%

on stainless steel wire to form coating for polychlorinated biphenyls

(PCBs) extraction by GC–MS [129]. In addition, other MOFs as
SPME coating were reported including thin film E-MOF-5 prepared
by cathodic electrodeposition [130], UiO-66 by in situ covalent
0.1–200/500 µg/kg
Linear range (ng/L)

bonding [131], and UiO-67 by sol-gel technique [132].

0.05–30 µmol/L

In order to enhance the extraction efficiency of MOFs, vari-

10–500 1–1000

0.17–100 ng/g 0.1–500

ous MOFs-based composite fiber have been prepared for SPME.

Recently, a non-coated stainless steel SPME arrow was dipped
in the ZIF-8/PVC suspension for several times to obtain a uni-
form and thick coating for amines extraction from wastewater and
food samples [133]. Jin et al. reported a novel SPME fiber fab-
ricated by a porous aromatic framework 48 (PAF-48)/gel hybrid
material through a sol-gel process [134]. The PAF-48/gel-coated
0.003–0.06 µg/kg

fiber showed excellent extraction efficiency towards styrene and

4.2–17.3 nmol/L
LOD (ng/L)

Water, PM2.5, food Fruit and vegetable0.05–1.58 ng/g 0.02–0.30

six volatile aromatic compounds (benzene, toluene, ethylbenzene,

0.025–0.97

p, m, o-xylenes) with LODs of 0.003-0.06 µg/kg. Huang et al.

fabricated a novel hybrid MIL-101(Cr)-polymeric monolith as sta-
tionary phase for penicillin SPME [135]. The hybrid monolith
0.0271, 0.0332

possessed unique micro- and mesopore sizes which increased the

accessibility of the mobile phase and analytes, further improved
the efficiency of the adsorption and desorption processes of the
Matrix

Water and soil Water Milk

analytes. Besides listed above, several other developments of

MOFs-composite as extraction materials have been reported for
Human urine

SPME including novel polystyrene/MOF-199 nanofiber prepared by

Pond water and river water Fish

electrospinning [136], MOF@MON-based fiber by sonogashira cou-

pling reaction [137], covalent bonding of MOF-5/graphene oxide
hybrid composite to stainless steel support [138].
Analytes

3. Conclusion
Estrogens PAHs

Triazole fungicides PAHs

Typical applications of MOFs and MOF-based SPME fibers. Table 3

In review of these research works, we believe that MOFs

SMs and OCPs PAHs
materials cadaverine PAHs and OCPs

provide great potential for the future application in

Aldehydes

chromatographic sepa- rations and sample preparation due to

their controllable synthesis, good thermal stability, large specific
ylamine and triethylamine Styrene and six VACs Penicillin

surface area and controllability of the pore size. When MOFs

were employed as packed station- ary phase for HPLC, CEC, and
GC, they showed excellent stability. However, the
F-5 film UiO-66 coated fiber UiO-67 coated fiber
NH2-MIL-53(Al)-coated fiber PDA-ZIF-8

chromatographic performance of some MOFs was not

satisfactory because of its irregular shapes and wide particle size
@MON-based fiber MOF-5/GO Composite

distributions. In order to address the problem, the monodis- perse

ExtractionPutrescine,

MOFs spherical particles and MOFs-based composites with

uniform spherical structure were synthesized to increase the par-
ticle size suitability and packed into column for separation. The
MOF-polymer monolith column was prepared by incorporation
method and further served as stationary phase for HPLC, CEC,
and GC application. By incorporation of MOF particles, the
surface area, permeability and separation efficiency of polymer
monolith
were significantly improved. Such incorporation excluded the
dis- advantages of directly using MOFs as stationary phase.
Besides, the open-tubular MOFs capillary columns mostly
prepared by dynamic coating method also showed good
results for CEC and GC separation. However, the instability
of coating was the main shortcoming of this type of column.
Recently, some other well- controlled method such as
covalent-bonding, liquid-phase epitaxy process, layer-by-layer
deposition have been developed to prepare the capillary
column for OT-CEC.
Homochiral metal-organic frameworks as a member of
MOFs family has attracted much attention on its application in
chiral separation. Various homochiral MOFs have been
synthesized, and packed into the column or coated on the
inner surface of capillary for HPLC, CEC and GC
enantioseparation. In addition, it was also incorporated into
polymer solution to afford chiral MOFs-based hybrid
monolith column for chiral separation.
Currently, most of the reported studies have been
focused on MOFs synthesis and the chromatographic
performance. The detailed separation mechanism is still not
very clear, since some has been stated the perfect match
between the guest analyte and the framework size and shape.
The interactions such as hydrogen bonding, hydrophobic, G-G,
dipole-dipole, steric hindrance might also contribute to the
separation. Except that, some fundamen- tal and important
information about specific porous properties of the materials
(such as surface area, pore size and pore volume), related
to separation mechanism are not offered. Considering sep-
aration performance, almost all synthesized MOFs and
homochiral MOFs eclipsed compared to commercial C18 and
chiral column. We believe the major mandatory factor is the
irregular shape and wide particle size distribution of
synthesized MOFs.
Also, an increasing use of MOFs and related composite
materials in SPME have been reported in recently. The MOF
and MOF-based SPME fibers exhibited high extraction
efficiency and reproducibil- ity. In most cases, the MOF-based
fibers showed better extraction performance compared to
commercial coatings. Despite good per- formance of MOF-
based SMPE fiber reported, efforts still need to be done in
designing novel MOFs with higher stability. Moreover, the
application in more complex samples should also be
considered.
To date, the application of MOFs materials in
chromatographic separation is only in scientific explorations.
What urgently to be considered is to develop its practical
application value. In the near future, taking into account of
separation and extraction mecha- nism, to design and
synthesize novel MOFs and homochiral MOFs with well-
controlled structures for practical application is a priority of
our studies.