Selective recognition and extraction of the uranyl ion from aqueous solutions with a recyclable chelating resin

Article abstract of DOI:10.1039/c3sc51507a

An ion exchange polymer 1, incorporating a chelating ligand engineered for the uranyl ion was prepared and its ability to remove uranium from aqueous solutions was studied. The chelating module was shown to form a 1:1 complex with the uranyl ion in solution. Comparisons of 1 with the standard imidodiacetate chelating resin, Chelex 100 were performed in uranyl extraction experiments. 1 effectively extracts uranyl ion from aqueous solutions, including spiked seawater, and is fully recyclable for at least 15 extraction cycles.

Full text of DOI:10.1039/c3sc51507a

Chemical Science
View Article Online
View Journal | View Issue
EDGE ARTICLE
Selective recognition and extraction of the uranyl ion
from aqueous solutions with a recyclable chelating
resin†
Cite this: Chem. Sci., 2013, 4, 3601
a
b
a
*
Aaron C. Sather, Orion B. Berryman and Julius Rebek, Jr
An ion exchange polymer 1, incorporating a chelating ligand engineered for the uranyl ion was prepared
and its ability to remove uranium from aqueous solutions was studied. The chelating module was shown to
form a 1 : 1 complex with the uranyl ion in solution. Comparisons of 1 with the standard imidodiacetate
chelating resin, Chelex 100 were performed in uranyl extraction experiments. 1 effectively extracts
uranyl ion from aqueous solutions, including spiked seawater, and is fully recyclable for at least 15
extraction cycles.
Received 28th May 2013
Accepted 1st July 2013
DOI: 10.1039/c3sc51507a
www.rsc.org/chemicalscience
prospect of tapping the Earth's oceans for their vast quantities
of uranium has inspired many research programs and recent
Introduction
Since their initial discovery over 100 years ago, ion exchange
polymers have found many uses in industrial processes, catal-
ysis, analytical chemistry, and metal binding.1 To improve
selectivity for metal ions, polymeric materials impregnated with
chelating groups have been developed.2,3 Among the rst
commercially available chelating resins, and perhaps the most
widely studied, are the polystyrene-supported imidodiacetates,
Dowex A-1 and Chelex 100.4 Generally, the imidodiacetate
ligand binds a range of divalent metal ions forming two ve-
membered ring chelates upon complexation.5 For instance,
Chelex 100 has been employed in columns to separate metal
mixtures, in batch mode to remove various metal ions from
aqueous solutions, and analytically to determine the concen-
tration of aqueous metal ions. While Chelex 100 has found an
assortment of applications, pH and ionic strength of the matrix
can greatly diminish the extraction efficiency and selectivity for
a desired metal ion.
success has been realized with metal–organic frameworks
(MOFs)7 and amidoxime-laden bers.8,9 Chelex 100 has also
been used to recover uranium from aqueous systems,10
although the desired selectivity is precluded by the preferences
of the imidodiacetate ligand for the alkali earth metals and
various other divalent metal cations. In general, extraction is
oen thwarted by the abundance of other metal cations and the
relatively low concentration of the targeted uranyl ion at 3 ppb.
The geometry of the linear uranyl ion limits coordination
about its equator to 4–6 donor atoms11 and its shape provides a
means for effecting selectivity.12 Careful ligand design has
revealed unique reactivity at the otherwise inert uranyl oxygen
atoms13 and has also allowed for the controlled self-assembly of
large polyhedra.14 Here we report a chelating resin—tailored to
the uranyl ion—for extraction from aqueous systems of varying
concentration, pH and ionic strength. The chelate is a rigid
preorganized ligand that surrounds the uranyl ion with three
carboxylates derived from Kemp's triacid15 (6 donor atoms),
forming a stable 1 : 1 complex in solution.16 The application of
Kemp's triacid derivatives has proved useful in selective recog-
nition of heterocycles,17 especially nucleic acid components,18
and the key structural notion—convergent functional groups—
should provide the same advantage for ions. The new polymer
(1) is completely recyclable with no detectable aging and shows
unusual activity for a carboxylate ligand in solutions of high
ionic strength. The activity of 1 for uranyl extraction compares
favorably with Chelex 100.
The selective recovery of the uranyl ion—whether it be for
environmental remediation, nuclear waste processing,6 or har-
vesting for energy production—is an ongoing challenge. The
aThe Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps
Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. E-mail:
jrebek@scripps.edu; Fax: +1 858-784-2876; Tel: +1 858-784-2255
bThe Chemistry and Biochemistry Department, University of Montana, 32 Campus
Drive, Missoula, MT, 59812, USA
† Electronic supplementary information (ESI) available: Additional experimental
details, synthesis and characterization of ligands 7a and 8, synthesis and
characterization of recyclable chelating resin 1, solution behavior of 7a and 8
with the uranyl ion, detailed extraction studies of Chelex 100 and 1 buffered at
pH 5 with acetate–acetic acid, detailed extraction studies of Chelex 100 and 1
with seawater spiked with the uranyl ion, uranyl uptake of 1 uranyl solutions
buffered at pH 5 with acetate–acetic acid, and recovery of the uranyl ion from 1.
See DOI: 10.1039/c3sc51507a
Results and discussion
Synthesis of UO2 chelating monomers 7a and 8
The synthesis of the chelating monomer is shown in Fig. 1 and
begins with a Pd(0)-catalyzed Sonogashira reaction between
This journal is ª The Royal Society of Chemistry 2013
Chem. Sci., 2013, 4, 3601–3605 | 3601

View Article Online
Chemical Science
Edge Article
Fig. 2 (a) 1H NMR spectrum of uranyl ligand 8. (b) 1H NMR spectrum of uranyl
ligand 8 with 3.1 equiv. of NaOAc added. (c) 1H NMR spectrum of uranyl ligand 8
with 3.1 equiv. of NaOAc and 1 equiv. of uranyl nitrate added. The inset highlights
the diagnostic benzylic protons (marked by an asterisk).
into an A,B quartet and a singlet. Due to symmetry, in the
locked, rigid conformation of the complex, the protons on two
of the benzylic arms are diastereotopic, giving rise to the
observed splitting. In fact, when less than 1 equivalent of uranyl
ion is added to a basic solution of 8, separate signals appear for
uncomplexed deprotonated ligand (Fig. 2b) and complex
(Fig. 2c). This behavior suggests that 8 is in slow exchange with
the complex on the NMR timescale, and augurs well for high
affinity to the uranyl ion. The 1H NMR solution studies also
show that Boc-protected ligand 7a behaves identically to 8 and
their respective complexes persist upon treatment with addi-
tional uranyl ion (Fig. S1–S4†).
Next, we immobilized the highly hydrophobic ligand 8 on a
solid support. Because resin swelling impacts the reactivity of
the bound functional groups, we chose a polyethylene glycol
(PEG) containing resin to assure our material would swell in
aqueous conditions, giving maximum exposure of the ligands to
solution.20 A TentaGel resin offers this on a minimally cross-
linked polystyrene core.21 The combination of the PEG groups
and low crosslinking ensures the desired swelling properties
over an array of solvents and conditions. Initial attempts to
immobilize our chelating ligand involved a reductive amination
with amine 7b and an aldehyde-functionalized TentaGel.22 But
the desired aminated product was obtained in widely variable
and irreproducible yields. Perhaps the low solubility of 7b,
which is essentially a large, hydrophobic amino acid was to
blame. When the primary amine of 7b was converted to the
azide 8, its solubility in organic media greatly improved.
Fig. 1 Synthesis of chelating monomers 7a and 8. Reagents and conditions: (a)
Pd(PPh3)4, CuI, TEA, 90 ꢁC, 24 h, 92%; (b) Pd/C, H2, MeOH, rt, 24 h, 96%; (c)
(CH2O)n, AcOH/HBr, ZnBr2, 90 ꢁC, 3 days, 77%; (d) DMSO, KCN, rt, 24 h, 96%; (e)
HCl/AcOH, reflux, 48 h; (f) MeOH, SOCl2, reflux, 2 h, 80% from (e); (g) Boc2O,
DCM, TEA, rt, 19 h, 81%; (h) N2H4, EtOH, reflux, 2 days, 93%; (i) 6, pyr, DMAP,
80 ꢁC, 18 h, 89%; (j) TFA (5%) in DCM, rt, 3 h, 99%; (k) imidazole-1-sulfonyl azide
hydrochloride, K2CO3, MeOH, rt, 19 h, 91%.
N-(4-pentynyl)phthalimide and 5-iodo-meta-xylene. The result-
ing alkyne was fully reduced, and the aromatic ring of 2 was
subsequently functionalized by bromomethylation. Nucleo-
philic displacement of the bromides with KCN gave 3 in excel-
lent yield. The cyano and phthalimide groups were hydrolyzed
under acidic conditions, then Fischer esterication provided 4
in 80% yield over two steps. The primary amine of 4 was pro-
tected with di-tert-butyl dicarbonate (Boc) and subsequent
treatment with hydrazine afforded 5. The anhydride acid chlo-
ride of Kemp's triacid,15 6 smoothly acylated 5 and installed the
carboxylic acid chelating groups of 7a. Removal of the Boc group
with TFA afforded 7b and copper catalyzed conversion of the
resulting primary amine to the alkyl azide with imidazole-1-
sulfonyl azide hydrochloride19 completed the synthesis of
monomer 8 in 11 linear steps, on multi-gram scale.
The binding pocket of 8 (ref. 16) features three organized
carboxylates that converge on the uranyl ion through bidentate
interactions, and N–H bonds directed toward one of the uranyl
oxygens. The aromatic ring is modied for attachment (via a
click reaction) to an appropriately functionalized solid support.
However, with either 7a or 8, we had the opportunity to study
Synthesis of recyclable chelating resin 1 and UO2 extraction
the binding of uranyl in solution prior to immobilization. The A TentaGel resin functionalized with a primary amine 9
1H NMR spectrum of ligand 8 in methanol-d4 is shown in Fig. 2. (ꢀ0.48 mmol gÀ1) was acylated with propiolic acid using
Treatment of 8 with sodium acetate (NaOAc) results in a N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in
broadening of the signals, but upon addition of 1 equivalent of CH2Cl2 (Fig. 3).23 The use of EEDQ as the coupling reagent was
uranyl nitrate, the signals shi and sharpen. Upon complex critical for clean amide bond formation as traditional carbo-
formation with uranyl, the benzylic protons (highlighted by an diimides led to a dark red-purple impurity that was formed
asterisk in the gure) are shied upeld by ꢀ0.5 ppm and split rapidly and trapped within the resin. Presumably, the colored
3602 | Chem. Sci., 2013, 4, 3601–3605
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Edge Article
Chemical Science
Table 1 Extraction of UO2 solutions with 1 and Chelex 100
Resin 1
Chelex 100
U solutions
(% recovery)a
(% recovery)a
400 ppm U (pH 5 acetate)b
400 ppb U (pH 5 acetate)c
400 ppb U (pH 8.4 seawater)c
85 Æ 4
77 Æ 4
83 Æ 2
88 Æ 4
96 Æ 4
10 Æ 6
a
Uncertainties are 2 standard deviations for three replicate samples.
b
c
Both resins exposed to 1 mL U solution. Both resins exposed to 7
mL U solution.
recovered (Tables S1–S12†). Both Chelex 100 and resin 1 extract
a similar quantity of uranyl ion under these conditions.
2+
The concentration of UO2 was then dropped 1000-fold to
400 ppb. To aid analysis at this dilution, each sample of resin
was exposed to 7 mL uranyl solution and treated as before.
Again both resins were capable of extracting the uranyl ion,
although Chelex 100 outperforms 1 under these conditions:
acetate buffer at pH 5. Using seawater spiked with 400 ppb
uranyl ion (pH 8.4) revealed a marked difference between the
two resins. Resin 1 maintains its capacity to extract uranyl ion
while the efficiency of Chelex 100 drops signicantly. The high
concentrations of the other cations in seawater (Na+, Ca2+, K+,
Mg2+)27 effects the selectivity of Chelex 100 and the salt matrix
slows down the chelating reaction.28 The imidodiacetate ligands
of Chelex 100 are exposed and well suited to interact with the
other cations at superior concentrations found in seawater.
However, these competitors show no effect on the ability of 1 to
extract uranyl ion. The well-dened, preorganized binding
pocket of 1 disfavors interactions with these cations, and pref-
erence for uranyl ion is retained. The IR spectra of the respective
uranyl complexes of 7a, 8, and 1 display similar stretches for the
uranyl ion, suggesting that once immobilized, the ligand
behaves as it did in solution (see ESI†). Additionally, both resins
were tested on unspiked seawater, at its natural uranyl
concentration of 3.3 ppb (see ESI†) and neither 1 nor Chelex 100
was capable of extracting uranyl in detectable amounts.
Fig.
3
Synthesis of recyclable chelating resin 1 and schematic of 1:UO2.
Reagents and conditions: (a) DCM, propiolic acid (3 equiv.), EEDQ (3 equiv.),
À10 ꢁC 4 h, then warm to rt; (b) 8 (2 equiv.), Hunig's base (50 equiv.), [Cu(MeCN)4]
¨
PF6 (0.1 equiv.), rt, 20 h, 70%.
impurity arises from polymerization of the propiolic acid, but
with EEDQ the resin maintained its pale yellow appearance. The
reaction's progress was conveniently monitored using IR by
following the developing amide stretching frequency. The azide
ligand 8 was reliably attached to the alkyne-functionalized
TentaGel 10 via a copper-catalyzed azide–alkyne cycloaddition
reaction (CuAAC).24 The use of copper(I) iodide as a catalyst led
to discoloration of the resin, but tetrakis(acetonitrile)copper(I)
hexauorophosphate provided 1 as a pale yellow resin. Again, IR
showed the appearance of new carbonyl stretches (carboxylic
acids, amides, and imides) that mostly overlap in one broad
peak (see ESI†). Resin 1 was analyzed by elemental analysis; the
nal loading of the ligand was ꢀ0.22 mmol gÀ1 (70% conver-
sion) as determined by mass gain and amount of 8 recovered.25
We tested extraction of the uranyl ion from aqueous solu-
tions with resin 1 at varying concentrations, pH and ionic
strength, as well as in the presence of other metal cations. For
comparison, all extraction experiments were run in parallel with
an equimolar amount of Chelex 100.26 The rst extraction
studies were carried out in a 0.1 M acetate buffer at pH 5 with a
uranyl concentration of 400 ppm (Table 1). Each sample was
agitated on a nutating mixer for 18 hours, the solution was
collected, and the resin was washed several times with deion-
ized water. The samples were then dried under vacuum, and the
complexed uranyl ion was removed from 1 by treatment with
0.5 M HNO3. The uranyl concentration of the acidic solution
was determined by Inductively Coupled Plasma-Atomic Emis-
The stability of
1 to the uranyl recovery conditions
(0.5 M HNO3) was determined by subjecting a single sample to
multiple extractions at a uranyl concentration of 400 ppm in
Fig. 4 Repetitive extraction–release cycles of the uranyl ion from resin 1 at
400 ppm in acetate buffer (pH 5). No statistically significant degradation of the
sion Spectroscopy (ICP-AES) and reported as percent uranyl resin was detected after 15 cycles.
This journal is ª The Royal Society of Chemistry 2013
Chem. Sci., 2013, 4, 3601–3605 | 3603

View Article Online
Chemical Science
Edge Article
5 (a) S. Chaberek Jr and A. E. Martel, J. Am. Chem. Soc., 1954,
74, 5052–5056; (b) J. Jiang, J. C. Renshaw, M. J. Sarseld,
F. R. Livens, D. Collison, J. M. Charnock and H. Eccles,
Inorg. Chem., 2003, 42, 1233–1240; (c) J. Jiang,
M. J. Sarseld, J. C. Renshaw, F. R. Livens, D. Collison,
J. M. Charnock, M. Helliwell and H. Eccles, Inorg. Chem.,
2002, 41, 2799–2806.
6 B. Benedict, T. H. Pigford and H. W. Levi, in Nuclear Chemical
Engineering, McGraw-Hill, New York, 1981.
7 M. Carboni, C. W. Abney, S. Liu and W. Lin, Chem. Sci., 2013,
4, 2396–2402.
8 (a) T. Kawai, K. Saito, K. Sugita, T. Kawakami, J. Kanno,
A. Katakai, N. Seko and T. Sugo, Radiat. Phys. Chem., 2000,
59, 405–411; (b) N. Seko, A. Katakai, S. Hasegawa,
M. Tamada, N. Kasai, H. Takeda, T. Sugo and K. Saito,
Nucl. Technol., 2003, 144, 274–278.
9 (a) G. Tian, S. J. Teat, Z. Zhang and L. Rao, Dalton Trans.,
2012, 41, 11579–11586; (b) G. Tian, S. J. Teat and L. Rao,
Dalton Trans., 2013, 42, 5690–5696; (c) S. Vukovic,
L. A. Watson, S. O. Kang, R. Custelcean and B. P. Hay,
Inorg. Chem., 2012, 51, 6619–6624.
10 D. H. Phillips, B. Gu, D. B. Watson and C. S. Parmele, Water
Res., 2008, 42, 260–268.
11 (a) I. Feldman and L. Koval, Inorg. Chem., 1963, 2, 145–150;
(b) A. C. Sather, O. B. Berryman and J. Rebek Jr, Chem.
Commun., 2013, 49, 6379–6381.
Fig. 5 Rate of uranyl uptake of resin 1 at 400 ppm U buffered at pH 5 in acetate–
acetic acid buffer.
acetate buffer at pH 5 (Fig. 4, S5, and Table S13†). The extrac-
tion/acid release was repeated a total of 15 times with no loss of
extraction efficiency, showing that 1 is completely recyclable
and insensitive to treatment with acid.
The rate of uranyl uptake by 1 was also examined at 400 ppm
in acetate buffer at pH 5 (Fig. 5). For this purpose, the
concentration of uranyl ion remaining in solution was moni-
tored with ICP-AES over time. Aer 2.5 minutes, 48% of the
uranyl ion is removed from solution (Table S14†) and extraction
is complete aer 40 minutes (85% uranyl extracted) with no
additional uptake observed aer a period of 24 hours.
12 (a) T. S. Franczyk, K. R. Czerwinski and K. N. Raymond, J. Am.
Chem. Soc., 1992, 114, 8138–8146; (b) S. C. Bart and K. Meyer,
Conclusions
´
Struct. Bonding, 2008, 127, 119–176; (c) J.-C. Berthet, P. Thuery,
J.-P. Dognon, D. Guillaneux and M. Ephritikhine, Inorg.
Chem., 2008, 47, 6850–6862; (d) P. A. Giesting and
P. C. Burns, Crystallogr. Rev., 2006, 12, 205–255.
We have developed a new ion exchange resin 1, engineered for
extraction of uranyl ion from aqueous solutions. The behavior
of resin precursors 7a and 8 were determined in solution prior
to incorporation into a solid support. A 1 : 1 binding stoichi-
ometry between the rigid monomers and the uranyl ion is
indicated. Both resin 1 and Chelex 100 performed well in
acetate buffer at pH 5 while only resin 1 maintained its uranyl
extraction efficiency in seawater and allows it to function in the
presence of other cations. Resin 1 was also fully recyclable,
showing no degradation aer 15 extraction–release cycles. A full
selectivity series of 1 for a variety of transition metals will be
reported in due course.
13 (a) P. L. Arnold, D. Patel, C. Wilson and J. B. Love, Nature,
2008, 451, 315–317; (b) P. L. Arnold, E. Hollis, G. S. Nichol,
J. B. Love, J.-C. Griveau, R. Caciuffo, N. Magnani, L. Maron,
L. Castro, A. Yahia, S. O. Odoh and G. Schreckenbach,
J. Am. Chem. Soc., 2013, 135, 3841–3845.
14 (a) G. E. Sigmon, J. Ling, D. K. Unruh, L. Moore-Shay,
M. Ward, B. Weaver and P. C. Burns, J. Am. Chem. Soc.,
2009, 131, 16648–16649; (b) S. Pasquale, S. Sattin,
´
´
E. C. Escudero-Adan, M. Martınez-Belmonte and J. de
Mendoza, Nat. Commun., 2012, 3, 785; (c) P. Thuery and
B. Masci, Supramol. Chem., 2003, 15, 95–99.
Notes and references
15 (a) D. S. Kemp and K. S. Petrakis, J. Org. Chem., 1981, 46,
5140–5143; (b) J. Rebek Jr, B. Askew, M. Killoran,
D. Nemeth and F.-T. Lin, J. Am. Chem. Soc., 1987, 109,
2426–2431.
1 S. D. Alexandratos, Ind. Eng. Chem. Res., 2009, 48, 388–398.
2 S. K. Sahni and J. Reedijk, Coord. Chem. Rev., 1984, 59, 1–139.
3 G. Schmuckler, Talanta, 1965, 12, 281–290.
4 (a) D. E. Leyden and A. L. Underwood, J. Phys. Chem., 1964, 16 A. C. Sather, O. B. Berryman and J. Rebek Jr, J. Am. Chem.
68, 2093–2097; (b) J. L. Sides and C. T. Kenner, Anal. Soc., 2010, 132, 13572–13574.
Chem., 1996, 38, 707–711; (c) M. Pesavento, R. Biesuz, 17 (a) K. S. Jeong, A. V. Muehldorf and J. Rebek Jr, J. Am. Chem.
M. Gallorini and A. Profumo, Anal. Chem., 1993, 65, 2522–
2527; (d) R. R. Greenberg and H. M. Kingston, Anal. Chem.,
Soc., 1990, 112, 6144–6145; (b) T. K. Park, J. Schroeder and
J. Rebek Jr, J. Am. Chem. Soc., 1991, 113, 5125–5127.
´
1983, 55, 1160–1165; (e) A. P. Mykytiuk, D. S. Russell and 18 (a) A. Galan, J. de Mendoza, C. Toiron, M. Bruix,
R. E. Sturgeon, Anal. Chem., 1980, 52, 1281–1283; (f)
W. W. V. Berkel, A. W. Overbosch, G. Freenstra and
J. M. J. Maessen, J. Anal. At. Spectrom., 1988, 3, 249–257; (g)
G. Schmuckler, Talanta, 1965, 10, 745–751.
G. Deslongchamps and J. Rebek Jr, J. Am. Chem. Soc., 1991,
´
113, 9424–9425; (b) G. Deslongchamps, A. Galan, J. de
Mendoza and J. Rebek Jr, Angew. Chem., Int. Ed. Engl.,
1992, 31, 61–63.
3604 | Chem. Sci., 2013, 4, 3601–3605
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Edge Article
Chemical Science
19 E. D. Goddard-Borger and R. V. Stick, Org. Lett., 2007, 9, 24 V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless,
3797–3800.
Angew. Chem., Int. Ed., 2002, 41, 2596–2599.
25 I. Sucholeiki, in High-Throughput Synthesis Principles and
Practices, Marcel Dekker Inc., New York, 2001.
26 Bio-Rad, Chelex 100 and Chelex 20 Chelating Ion Exchange
Resin Instruction Manual, Bio-Rad Laboratories, Hercules,
CA, LIT200 Rev B.
20 W. Li and B. Yan, J. Org. Chem., 1998, 63, 4092–4097.
21 R. Quarrell, T. D. W. Claridge, G. W. Weaver and G. Lowe,
Mol. Divers., 1995, 1, 223–232.
22 K. A. Mirica, S. T. Phillips, S. S. Shevkoplyas and
G. M. Whitesides, J. Am. Chem. Soc., 2008, 130, 17678–17680.
23 C. W. Tornøe, C. Christensen and M. J. Meldal, J. Org. Chem., 27 K. Schwochau, Top. Curr. Chem., 1984, 124, 91–133.
2002, 67, 3057–3064.
28 S.-C. Pai, Anal. Chim. Acta, 1988, 211, 257–270.
This journal is ª The Royal Society of Chemistry 2013
Chem. Sci., 2013, 4, 3601–3605 | 3605