Polyoxometalate-Based Frameworks as Adsorbents for Drug of Abuse Extraction from Hair Samples

Article abstract of DOI:10.1021/acs.inorgchem.0c02769

The linkage of molecular components into functional heterogeneous framework materials has revolutionized modern materials chemistry. Here, we use this principle to design polyoxometalate-based frameworks as high affinity adsorbents for drugs of abuse, leading to their application in solid-phase extraction analysis. The frameworks are assembled by the reaction of a Keggin-type polyanion, [SiW12O40]4-, with lanthanoids Dy(III), La(III), Nd(III), and Sm(III) and the multidentate linking ligand 1,10-phenanthroline-2,9-dicarboxylic acid (H2PDA). Their reaction leads to the formation of crystalline 1D coordination polymers. Because of the charge mismatch between the lanthanoids (+3) and the dodecasilicotungstate (-4), we observe incorporation of the PDA2- ligands into crystalline materials, leading to four polyoxometalate-based frameworks where Keggin-type heteropolyanions are linked by cationic {Lnn(PDA)n} groups (Ln = Dy (1), La (2), Nd (3), and Sm (4)). Structural analysis of the polyoxometalate-based frameworks suggested that they might be suitable for surface binding of common drugs of abuse via supramolecular interactions. To this end, they were used for the extraction and quantitative determination of four model drugs of abuse (amphetamine, methamphetamine, codeine, and morphine) by using micro-solid-phase extraction (D-μSPE) and high-performance liquid chromatography (HPLC). The method showed wide linear ranges, low limits of detection (0.1-0.3 ng mL-1), high precision, and satisfactory spiked recoveries. Our results demonstrate that polyoxometalate-based frameworks are suitable sorbents in D-μSPE for molecules containing amine functionalities. The modular design of these networks could in the future be used to expand and tune their substrate binding behavior.

Full text of DOI:10.1021/acs.inorgchem.0c02769

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Article
Polyoxometalate-Based Frameworks as Adsorbents for Drug of
Abuse Extraction from Hair Samples
Shadi Derakhshanrad, Masoud Mirzaei,* Carsten Streb,* Amirhassan Amiri, and Chris Ritchie*
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ABSTRACT: The linkage of molecular components into functional heterogeneous
framework materials has revolutionized modern materials chemistry. Here, we use this
principle to design polyoxometalate-based frameworks as high affinity adsorbents for
drugs of abuse, leading to their application in solid-phase extraction analysis. The
frameworks are assembled by the reaction of a Keggin-type polyanion, [SiW12O40]4−,
with lanthanoids Dy(III), La(III), Nd(III), and Sm(III) and the multidentate linking
ligand 1,10-phenanthroline-2,9-dicarboxylic acid (H2PDA). Their reaction leads to the
formation of crystalline 1D coordination polymers. Because of the charge mismatch
between the lanthanoids (+3) and the dodecasilicotungstate (−4), we observe
incorporation of the PDA2− ligands into crystalline materials, leading to four
polyoxometalate-based frameworks where Keggin-type heteropolyanions are linked
by cationic {Lnn(PDA)n} groups (Ln = Dy (1), La (2), Nd (3), and Sm (4)).
Structural analysis of the polyoxometalate-based frameworks suggested that they might
be suitable for surface binding of common drugs of abuse via supramolecular interactions. To this end, they were used for the
extraction and quantitative determination of four model drugs of abuse (amphetamine, methamphetamine, codeine, and morphine)
by using micro-solid-phase extraction (D-μSPE) and high-performance liquid chromatography (HPLC). The method showed wide
linear ranges, low limits of detection (0.1−0.3 ng mL−1), high precision, and satisfactory spiked recoveries. Our results demonstrate
that polyoxometalate-based frameworks are suitable sorbents in D-μSPE for molecules containing amine functionalities. The
modular design of these networks could in the future be used to expand and tune their substrate binding behavior.
Herein, we report the synthesis and characterization of four
1D framework materials together with their application as solid
sorbents for the extraction of four model drugs of abuse
(amphetamine, methamphetamine, codeine, and morphine)
from hair samples using dispersive micro-solid-phase extraction
(D-μSPE). This concept based on the well-documented
observation that organic molecules can interact and bind to
POMs by electrostatics, hydrogen bonding, or multiple weak
(e.g., van der Waals or dispersion) interactions is well
documented.14
We propose that this concept can be harnessed for the binding
of analytes, e.g., pharmaceuticals or drugs, which feature a
positive charge (e.g., when protonated) or hydrogen-bonding
site, so that the cationic analyte binds by electrostatic, dipolar,
and/or hydrogen-bonding interactions to the anionic POM
surface sites.5,6,15,16 Prime examples for suitable substrates are
opiates and amphetamines which are widely abused drugs and
1. INTRODUCTION
The past decade has seen tremendous progress in the
development and use of crystalline framework materials that
contain polyoxometalates either as anionic guests within the
framework pores or as structural building block within the
framework itself.1−3 Structural analysis of these polyoxometa-
late-based frameworks suggested their use in applications such as
sequestration and extraction.4 The synthesis or “self-assembly”
of materials of this type can be achieved by using a variety of
protocols and componentry, including, the use of preformed
POM precursors or the generation of the polyanion in situ.
Linkage of the POM by using one or more of the following (e.g.,
transition metals, lanthanoids, main group elements, and organic
linkers) enables the merging of the component properties and
can offer a facile route to crystalline POM-based materials for
technologically relevant applications.5,6 In recent years, POMs
have been incorporated into organic−inorganic frameworks as
guests or templates to construct novel hybrid materials that have
attracted considerable scientific attention in the fields of
environmental remediation, pollutant removal, and extraction
methods.4,7−9 This merging of organic and inorganic
componentry has led to new properties such as large pores
with high specific surface area, opening new opportunities in
separation and adsorption technologies.4,10−13
Received: September 16, 2020
Published: January 12, 2021
https://dx.doi.org/10.1021/acs.inorgchem.0c02769
© 2021 American Chemical Society
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Table 1. Molecular Structures and Chemical Properties of the Target Drugs
Table 2. Crystal Data for 1−4
1
2
3
4
empirical formula
Mr (g mol−1
temperature (K)
crystal system
space group
a (Å)
b (Å)
c (Å)
β (deg)
C42H60N6NaO82SiDy3W12
4527.40
130
trigonal
R3
20.3329(3)
C56H40N8O154Si2La6W24
8591.00
130
monoclinic
Pc
13.2137(2)
25.9371(4)
24.4190(3)
103.369(1)
0.22 × 0.08 × 0.05
8142.2(2), 2
44.63
0.021, 0.324
43389, 20705, 18345
0.052
C28H38N4O75SiNd3W12
4297.63
130
monoclinic
P21/c
13.1840(2)
26.5991(3)
24.3955(3)
102.768(1)
0.16 × 0.10 × 0.08
8343.53(19), 4
44.825
0.038, 0.223
34264, 17229, 15297
0.067
C56H82N12Na2O158Si2Sm6W24
8867.99
130
monoclinic
P21/c
13.0615(2)
26.1386(4)
24.1245(3)
101.6169(14)
0.14 × 0.04 × 0.02
8067.6(2), 2
48.07
0.116, 0.756
43644, 13219, 11185
0.077
)
18.7830(3)
crystal size (mm)
V (Å3), Z
0.07 × 0.05 × 0.03
6725.0(2), 1
42.00
μ (mm−1
min, Tmax
)
T
0.414, 0.646
measured, independent and observed reflns 16473, 5164, 5109
Rint
0.026
0.632
(sin θ/λ)max (Å−1
)
0.633
0.632
0.587
R[F2 > 2σ(F2)], wR(F2), S
reflns, parameters, restraints
0.025, 0.066, 1.06
5164, 426, 1
1.09, −2.31
0.016(4)
0.074, 0.217, 1.03
20705, 1691, 2
6.91, −3.70
0.053(10)
0.069, 0.198, 1.06
17229, 1121
7.82, −3.73
0.083, 0.214, 1.10
13219, 1116, 357
4.98, −2.83
Δρmax, Δρmin (e Å−3
)
absolute structure parameter
CCDC no.
1842657
1897934
1897935
1897937
contain amines with high pKa values and are therefore easily
protonated (Table 1). Quantitative analysis of these kinds of
drugs relies on hair analysis as a convenient method of drug
monitoring. Compared with the determination of drugs in the
blood and urine, hair analysis has advantages such as simple
sample preservation, noninvasive sample collection, and long-
term stability of the analyte in hair.17,18 Disadvantages include
external contamination (particularly important for smoked
drugs), low concentration of analytes, complex matrices, and the
limited sample size, resulting in the need for substantial sample
treatment prior to analysis.19−21 To this end, dispersive micro-
solid-phase extraction (D-μSPE) has emerged as a powerful
miniaturization concept based on solid-phase extraction (SPE)
techniques. D-μSPE exhibits significant advantages over tradi-
tional SPE with respect to short extraction time, simple
procedure, and low sample and solvent consumption.22−28
Given the importance of the analyte−adsorbent interactions, the
design of advanced adsorbents for the detection of pharma-
ceuticals and in particular frequently abused substances is a
current research focus.
Here, we propose the use of POMs embedded in hybrid
organic−inorganic frameworks as suitable binding sites to
extract and preconcentrate highly basic drugs of abuse, enabling
their facile subsequent analysis by D-μSPE and high-perform-
ance liquid chromatography (HPLC). POMs are polyanionic
molecular metal oxide clusters, formed by the acid-driven
condensation of small metal oxo precursors in aqueous
solution.29,30 The prime POM prototype is the plenary Keggin
anion, [Xn+M12O40](8−n)− (X: e.g., B, Si, P; M: e.g., Mo, W),
whose versatile chemistry has been explored in a variety of
fields.31 POMs are currently used in a wide range of applications
and are therefore of general scientific interest across numerous
fields of research including biochemistry, magnetism, nano-
structured materials, energy conversion/storage, and cataly-
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sis.32−41 This work is based on the recent report by some of us
that Keggin anions can be linked into framework materials by
using lanthanide cations and organic phenanthroline dicarbox-
ylate ligands.44
hair samples, the appropriate amounts of standard solutions of target
drugs were added to the pretreated hair samples.
Extraction Procedure. 5.0 mL of the pretreated hair sample
containing a certain amount of target drugs was adjusted to pH 5
(phosphate buffer) and then placed in a glass vial. 30 mg of the
adsorbent (1−4) was added to the sample and sonicated for 5 min.
Then, the mixture was centrifuged and the supernatant discarded.
Thereafter, the adsorbed analytes were eluted with 200 μL of 20%
ammonia in acetonitrile under sonication, for 2 min. After centrifuging
the solution, the desorption solvent was transferred to another vial and
dried by a gentle flow of nitrogen gas. Then, the residue was redissolved
in 20 μL of acetonitrile solvent and analyzed by HPLC.
2. EXPERIMENTAL SECTION
Materials and Instruments. All chemicals were purchased
commercially (reagent grade) and were used without further
purification, except for 1,10-phenanthroline-2,9-dicarbaldehyde diox-
ime (H2phendox or PDOX) which was synthesized according to a
reported procedure.42,43 The drugs including amphetamine, meth-
amphetamine, codeine, and morphine were obtained from Sigma-
Aldrich (St. Louis, MO) (see Table 1). Standardized stock solutions
were prepared at 10 ng mL−1 levels in HPLC-grade methanol and
stored at 4 °C. The analysis solutions were obtained by appropriate
dilution of the stock standard solutions with deionized water. Hair
samples were cut as close as possible to the scalp in the posterior apex
with a scissors. Drug-free hair was obtained from healthy volunteers
with no known exposure to drugs of abuse. The drug-containing hair
samples were received from Ebnesina Hospital (Mashhad, Iran).
Elemental analyses (CHN) were performed by using a Thermo
Finnigan Flash-1112EA microanalyzer. The IR spectra were recorded in
the range 4000−400 cm−1 on a Buck 500 IR spectrometer with the
sample prepared as a pressed KBr pellet. A summary of the
crystallographic data and the structure refinements are provided in
Table 2. Chromatographic separations were performed with a Knauer
HPLC instrument equipped with a UV detector. The target analytes
were separated by using an ODS3 column (4.6 mm ID × 250 mm
length, 5 μm particle diameter). The mobile phase (flow rate of 1.0 mL
min−1) was a mixture of 0.05 M aqueous phosphate buffer (pH 4) and
acetonitrile (30:70 v/v) with isocratic elution. The wavelength of the
UV detector was set to 210 nm.
Synthesis and Characterization. Synthesis of Hybrid 1. The
synthetic procedure and structure of 1 were reported previously by
some of us.44 Anal. Calcd for C42H60N6NaO82SiDy3W12: C, 11.13; H,
1.32; N, 1.85; Na, 0.50; Si, 0.61; Dy, 10.76; W, 48.50%. Found: C,
11.10; H, 1.24; N, 1.78; Na, 0.47; Si, 0.58; Dy, 10.45; W, 48.44%. IR
(KBr pellet, cm−1): 3423, 1613, 1568, 1468, 1388, 1307, 967, 914, 789,
712 (Figure S11b).
Synthesis of Hybrid 2. This hybrid framework was prepared similarly
to 1, except that La(NO3)3·6H2O (54 mg, 0.125 mmol) was used
instead of Dy(NO3)3·6H2O. Yellow plate crystals were obtained in 57%
yield (based on W). Anal. Calcd for C56H40N8O154Si2La6W24: C, 7.82;
H, 0.46; N, 1.30; Si, 0.65; La, 9.70; W, 51.40%. Found: C, 7.95; H, 0.53;
N, 1.32; Si, 0.62; La, 9.87; W, 51.77%. IR (KBr pellet, cm−1): 3432,
1733, 1630, 1606, 1452, 1378, 1209, 916, 789, 711 (Figure S11c).
Synthesis of Hybrid 3. This hybrid framework was prepared similarly
to 1, except that Nd(NO3)3·6H2O (55 mg, 0.125 mmol) was used
instead of Dy(NO3)3·6H2O. Yellow needle crystals were obtained in
48% yield (based on W). Anal. Calcd for C28H38N4O75SiNd3W12: C,
7.82; H, 0.88; N, 1.30; Si, 0.65; Nd, 10.05; W, 51.10%. Found: C, 7.96;
H, 0.95; N, 1.43; Si, 0.67; Nd, 9.96; W, 51.28%. IR (KBr pellet, cm−1):
3374, 1596, 1562, 1463, 1388, 1392, 1306, 963, 914, 796, 715 (Figure
S11d).
3. RESULTS AND DISCUSSION
Synthesis. The synthesis of the polyoxometalate-based
frameworks was achieved by the hydrothermal reaction of
lanthanide salts, organic ligands, and H4[SiW12O40]·xH2O. See
the Experimental Section for details. Control of solution pH
(between pH 3.0−3.5) and temperature (130 °C) is key to
obtaining the hybrid materials reported herein. The reactions
gave crystalline products suitable for structure determination
using single-crystal X-ray diffraction (SCXRD) analysis. Powder
X-ray diffraction further demonstrated the bulk purity of 1−4.
Structure Description of 1−4. SCXRD data, data
collection, and structure refinement details are summarized in
Table 2. Diffraction data of the polyoxometalate-based frame-
works were collected on an Agilent SuperNova single-crystal X-
ray diffractometer with graphite-monochromated Cu Kα
radiation (λ ∼ 1.54 Å) at 130 K (Table 2). The structures for
1−4 were solved by direct methods using the program SHELXS
and refined by full-matrix least-squares methods on F2 using
SHELXL. Note that compound 1 had been reported previously
by some of us.44 Multiscan absorption correction was applied.
Crystallographic details can be found in the CIF files. The CIF
files are available free of charge from the Cambridge Crystallo-
graphic Data Centre CCDC.
Structural analysis of the SCXRD data indicates 1−4 all
contain the silicotungstate Keggin polyanion [SiW12O40]4−
(hereafter: W12). The crystal structure of 1 is described in a
previous publication.44 It is worth mentioning that the range of
the Ln−O distances are consistent with effects of the lanthanide
contraction (ionic radius: La3+ > Nd3+ > Sm3+ > Dy3+).
Moreover, in all four polyoxometalate-based frameworks, we
observe distinct Ln−O distances: Ln−O(H2O) > Ln−Oterminal
>
Ln−OPDA, highlighting different bonding strengths in the order
O
PDA > Ot > O(H2O).
The hybrid frameworks are formed by linkages between the
PDA2− ligands Ln(III) ions and Keggin polyanions in
tetradentate chelating-bridging coordination mode, resulting
in 1D zigzag Ln−PDA complex chains, namely, −Ln1(PDA)−
Ln2−Ln1(PDA)−. The zigzag Ln−PDA complex chains are
joined together by the coordination of [La2(PDA)2] units in 2
and 3 and [Na2La2(PDA)2] units in 4.
Synthesis of Hybrid 4. This hybrid framework was prepared similarly
to 1, except that Sm(NO3)3·6H2O (56 mg, 0.125 mmol) was used
instead of Dy(NO3)3·6H2O. Yellow needle crystals were obtained in
5 2 % y i e l d ( b a s e d o n W ) . A n a l . C a l c d f o r
C56H82N12Na2O158Si2Sm6W24: C, 7.58; H, 0.92; N, 1.90; Na, 0.52; Si,
0.63; Sm, 10.15; W, 49.53%. Found: C, 7.65; H, 0.95; N, 1.94; Na, 0.58;
Si, 0.66; Sm, 10.25; W, 50.20%. IR (KBr pellet, cm−1): 3412, 1613,
1564, 1466, 1389, 1308, 965, 914, 794, 712 (Figure S11e).
Hair Samples. The hair specimen was washed with methanol,
acetone, and deionized water to remove contamination on the hair
surface. After drying, the hair was cut into very fine pieces, weighed
(∼50 mg), and digested in methanol at 55 °C for 5 h. The extracted
compounds were filtered, then dried under a stream of nitrogen gas, and
finally redissolved in 5.0 mL of deionized water. Also, for spiking the
Hybrid 2. A view of the asymmetric unit of 2 is presented in
Figure S4. Hybrid 2 crystallized in the monoclinic space group
Pc. As shown in Figures S5 and S6, the compound can be
described as a 1D coordination polymer based on two Keggin
polyanions, [SiW12O40]4−, four [La(PDA)]+ fragments, and two
La(III) which represent 1D chainlike architecture. The
polyanions [SiW12O40]4− act as monodentate ligands and
coordinate to a [La(PDA)]+ fragment via a terminal oxo ligand.
The host metal−organic cations are constructed from PDA2−
ligands and La(III) centers with slightly different local
coordination environments. Each La atom is coordinated with
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Figure 1. Mixed polyhedral, ball and stick representation of 2 along the crystallographic c-axis (top and bottom right) and a-axis (bottom left) without
polyanions for clarity. C, black; H, white; N, blue; La, teal; O, red; Si, gray; W, orange.
Figure 2. Mixed polyhedral, ball and stick representation of 4. C, black; H, white; N, blue; Na, pink; O, red; Si, gray; Sm, maroon; W, orange.
different coordination modes that are shown in Figure 1. Two
nine-coordinated La(III) atoms (La3 and La4) are linked by two
PDA2− ligands through O1,O2-bridging mode to generate a
[La2(PDA)2] unit. In addition, adjacent [La2(PDA)2] units are
linked by two other La(III) atoms through carboxylate oxygen
atoms from PDA2− to form the host cation. La2 is coordinated to
two nitrogen and two carboxylate oxygen atoms from PDA2−
and five oxygen atoms from coordinated water molecules. Also,
La1 is connected to two carboxylate oxygen atoms from PDA2−
and six oxygen atoms from coordinated water molecules. Finally,
La3 and La4 are linked by the same coordination mode. They
are coordinated to two nitrogen and three carboxylate oxygen
atoms from two different PDA2− ligands and oxygen atoms from
coordinated water molecules.
A remarkable feature of 3 is that each Keggin cluster connects to
one Nd(III) ion (Figure S9). In 3, crystallographically
independent Nd3, Nd1, and Nd2 are 8-, 9-, and 10-coordinated,
displaying distorted square antiprism, distorted monocapped
square antiprism, and distorted dicapped square antiprism
coordination geometry, respectively. It should be noted that in
both polyoxometalate-based frameworks the 1D chain is
stacked. The metal−organic fragment in 3 is a supramolecular
isomer of that in 2, and the basic Nd(III)-PDA2− unit is
[Nd2(PDA)2]. The [Nd2(PDA)2] units are further connected
by other PDA2− ligands and La(III) atoms. It is interesting to
note that a chain presents a wave-shaped single strand viewed
along the crystallographic b-axis (Figure S8). In addition, Nd−
(O)2−Nd is a direct ligand bridge which links the chains.
Hybrid 4. 4 is structurally closely related to 3 and crystallizes
in a monoclinic crystal system with the space group P21/c. The
asymmetric unit 4 is composed of one W12 cluster, two
crystallographically independent PDA2− ligands, three crystallo-
graphically unique Sm3+ ions, two Na+ ions, and numbers of
Hybrid 3. The host−guest assemblies in 2 and 3 are similar.
As shown in Figure S7, the asymmetric unit of 3 is composed of
one Keggin anion, two crystallographically independent PDA2−
ligands, three crystallographically unique Nd3+ ions, and
numbers of coordinated and uncoordinated water molecules.
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coordinated and uncoordinated water molecules (Figure S9).
such as the amount of adsorbent (10−50 mg), desorption
conditions (eluent, eluent volume, and elution time), extraction
time (1−7 min), pH (3−6), and salt effect (0−10% w/v) were
studied. The general trends are that higher amount of adsorbent
and longer elution/extraction times result in higher recoveries.
With respect to pH value, we suggest that two trends could lead
to the data observed in Figure 4e: at high pH values, the analytes
are less protonated, thereby lowering the binding affinity to the
frameworks. At low pH, surface protonation of the frameworks
could become possible, thereby lowering electrostatic inter-
actions with the analyte. A similar argument can be made for the
effects of NaCl addition: we suggest that the presence of NaCl
introduces competing Na+ cations which can also bind to the
framework surface. In addition, solution interactions between
the analytes and the NaCl ions are possible. In addition,
modification of the ionic strength of the solvent can lead to an
increased solubility of the analytes and therefore reduce their
binding to the framework materials. The following experimental
conditions yielded the best results: (a) 30 mg of the adsorbents
(Figure 4a); (b) eluent, acetonitrile/ammonia (80/20 v/v)
(Figure 4b); (c) volume of the eluent, 200 μL; (d) elution time,
2 min (Figure 4c); (e) extraction time, 5 min (Figure 4d); (f)
sample pH, 5 (Figure 4e), and without addition of NaCl (Figure
4f).
Method Validation. Under optimized conditions, we then
examined the linearity, the lower limit of detection (LOD),
precision, and extraction recovery (%) of the D-μSPE-HPLC-
UV method (Table 3). The calibration curve for HPLC-UV
analysis was acquired by using different drug concentrations
solution. The good linearity was achieved for all of the analytes,
with correlation coefficients (r) higher than 0.9959, in the range
0.3−300 ng mL−1 (0.7−300 ng mL−1 for amphetamine, 0.3−
300 ng mL−1 methamphetamine, and 1.0−200 ng mL−1 for
codeine and morphine). The LOD was defined as the lowest
concentration at which a signal-to-noise ratio of 3 (S/N = 3) was
observed which ranged from 0.1 to 0.3 ng mL−1. The
repeatability of the method was investigated in hair samples at
two concentration levels (5.0 and 50 ng mL−1). As shown in
Table 3, the relative standard deviation (RSD) was in the range
4.1−5.5%, which is satisfactory. The extraction recoveries
obtained were in the range 78.6−84.1%.
Crystal structure analysis reveals that compound 4 consists of
4 −
three main parts: [SiW1 2 O4 0
]
polyoxoanion,
{Na2Sm2(PDA)2} groups, and Sm3−Sm2(PDA)−Sm3 linear
chains. In compound 4, crystallographically independent Sm1,
Sm2, and Sm3 are all 11-coordinated, displaying a distorted
monocapped pentagonal antiprism coordination geometry. As
shown in Figure 2, there are three types of Sm ions (Sm1, Sm2,
and Sm3) in 4: Sm1 is linked with other Sm1 atoms through two
bridging oxygen and three nitrogen atoms from PDA2−, Na+ ion
from NaOH, a terminal oxygen atom from POM, and other
oxygen atoms from coordination H2O molecules. The Sm2
atom displays 11-coordination geometry established by three
nitrogen atoms (N4, N5, and N6), two carboxylate oxygen
atoms (O51 and O53) from PDA2−, and the other oxygen atoms
from coordinated water molecules. The last type of Sm(III)
(Sm3) ions is connected to two carboxylate oxygen atoms (O54
and O52) from PDA2− to construct PDA−Sm3−PDA linear
chains, Na+ ion from NaOH, and the other oxygen atoms from
coordinated water molecules (Figure 2 and Figure S10).
Drug Adsorption Experiments for Ln-Functionalized
Polyoxotungstates−Organic Frameworks. As outlined in
the Introduction, the organic−inorganic nature of 1−4 led us to
propose them as suitable adsorbents for organic drug molecules.
To this end, we explored the extraction performance of the four
polyoxometalate-based frameworks toward four model drugs of
abuse (i.e., amphetamine, methamphetamine, codeine, and
morphine) in hair samples. As all analytes tested feature basic
amine groups, their protonation degree can be controlled by the
solution pH. We propose that this introduction of a cationic
charge allows increased interactions of the model drugs with the
adsorbent surface. To this end, we quantitatively explored the
extraction performance of 1−4 (Figure 3). As can be seen in
Analysis of Real Samples. To assess the applicability of the
proposed method, the D-μSPE-HPLC-UV method was applied
to extract and determine of amphetamine, methamphetamine,
codeine, and morphine in the hair of drug abusers. Real hair
samples of drug abusers were obtained from a Hospital in
Mashhad, Iran. Five hair samples were collected and analyzed by
the D-μSPE-HPLC-UV method. These samples were further
confirmed by LC-MS. The results from each sample are listed in
Table S1. To investigate the effect of the matrix, the relative
recovery of the method was studied by spiking of the target
analytes at two concentration levels (5.0 and 50 ng mL−1) to
each real sample. As shown in Table S1, the relative recoveries
were in the range 93.4−98.2% with an RSD of 5.9−7.3%. Note
that at this stage we do not observe a clear correlation between
adsorptive properties and crystal structure polymorph of
polyoxometalate-based frameworks 1−4, and further (kinetic)
binding studies are required to gain more insights into the role of
the exact structure on the substrate binding properties.
Figure 3. Extraction efficiency of 1−4 for the D-μSPE of the target
drugs.
Figure 3, the order of the extraction efficiency for the D-μSPE of
the target drugs is as follows: 4 > 2 > 3 > 1 (Figure 3). Notably,
despite their different structures, the extraction recoveries (i.e.,
binding affinity of the drugs to the framework materials) are all
in a similar range. We suggest that this could be related to the
fact that all drugs have similar pKa values (Table 1) and that
electrostatic interactions rather than specific structural features
control the binding of the substrate to the framework.
4. CONCLUSION
In this work, we report the first example of the use of
polyoxometalate-based modular organic−inorganic frameworks
Based on this initial finding, the Sm-containing 4 was used for
more detailed extraction analyses. To investigate the best
condition for the extraction of target drugs, several parameters
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Article
Figure 4. Effects of (a) adsorbent amount, (b) eluent, (c) elution time, (d) extraction time, (e) pH of sample, and (f) effect of NaCl concentration on
the extraction performance.
Table 3. Analytical Figures of Merit of the D-μSPE Method of the Drugs of Abuse
precision
analyte
linear range (ng mL−1
)
LOD (ng mL−1
)
correlation coeff (r)
ER (%)
5.0 ng mL−1
50 ng mL−1
amphetamine
methamphetamine
codeine
0.7−300
0.3−300
1.0−200
1.0−200
0.2
0.1
0.3
0.3
0.9975
0.9966
0.9988
0.9959
85.6
89.5
82.3
81.6
5.1
4.9
4.5
5.5
4.7
4.4
4.1
4.9
morphine
for the extraction and quantitative analysis of drugs of abuse.
Four 1D coordination polymers based on Keggin-type
heteropolytungstates linked by lanthanoids (Dy, Sm, La, and
Nd) and organic PDA2− ligands were synthesized and used as
adsorbents for the D-μSPE extraction and adsorption of four
drugs of abuse (amphetamine, methamphetamine, codeine, and
morphine). We report high extraction efficiency, wide linear
range, and low limits of detection, making this an intriguing new
application field for polyoxometalate-based heterogeneous
materials, even when by using complex sample matrices. Future
work will explore in more detail the interaction between the
POM and the drug molecules and will assess and optimize the
materials for usage under “real-life” conditions.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c02769.
Figures S1−S11, IR spectra, and SCXRD analyses of 1−4
(PDF)
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CCDC 1842657, 1897934, 1897935, and 1897937 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
AUTHOR INFORMATION
■
Corresponding Authors
Masoud Mirzaei − Department of Chemistry, Faculty of Science,
Ferdowsi University of Mashhad, Mashhad 9177948974,
Iran; orcid.org/0000-0002-7256-4601;
Franco Castillo, I.; Mitchell, S. G.; Guttel, R.; Streb, C. Water
̈
Email: mirzaeesh@um.ac.ir
Purification and Microplastics Removal Using Magnetic Polyoxome-
talate-Supported Ionic Liquid Phases (magPOM-SILPs). Angew.
Chem., Int. Ed. 2020, 59 (4), 1601−1605.
Carsten Streb − Institute of Inorganic Chemistry I, Ulm
University, 89081 Ulm, Germany; orcid.org/0000-0002-
5846-1905; Email: carsten.streb@uni-ulm.de
Chris Ritchie − School of Chemistry, Monash University,
Clayton 3800, Victoria, Australia; orcid.org/0000-0002-
1640-6406; Email: Chris.Ritchie@monash.edu
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Z.-M. Functionalized polyoxometalate-based metal−organic cubocta-
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Authors
Shadi Derakhshanrad − Department of Chemistry, Faculty of
Science, Ferdowsi University of Mashhad, Mashhad
9177948974, Iran
Amirhassan Amiri − Department of Chemistry, Faculty of
Sciences, Hakim Sabzevari University, Sabzevar 96179-
76487, Iran
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Polyoxometalates-based heterometallic organic−inorganic hybrid
materials for rapid adsorption and selective separation of methylene
blue from aqueous solutions. Chem. Commun. 2015, 51 (16), 3336−
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(19) Duvivier, W. F.; van Putten, M. R.; van Beek, T. A.; Nielen, M. W.
(Un) targeted Scanning of Locks of Hair for Drugs of Abuse by Direct
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.0c02769
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
M.M. gratefully acknowledges the financial support from the
Ferdowsi University of Mashhad (Grant 3/42201), the Iran
Science Elites Federation (ISEF), Zeolite and Porous Materials
Committee of Iranian Chemical Society, and the Iran National
Science Foundation (INSF). M.M. also acknowledges the
Cambridge Crystallographic Data Centre (CCDC) for access to
the Cambridge Structural Database. C.S. gratefully acknowl-
edges financial support by Ulm University and Helmholtz
Gemeinschaft HGF. C.R. thanks Monash University and the
Australian Research Council for financial support.
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