Immobilization of a hexaphyrin(1.0.1.0.0.0) derivative onto a tentagel-amino resin and its use in uranyl cation detection

Article abstract of DOI:10.1039/b718627d

The synthesis of an isoamethyrin derivative containing two CH ₂CH₂CO₂CH₃ moieties in the β-pyrrolic positions and its use in the colorimetric detection of the uranyl cation after immobilization onto a solid supp

Full text of DOI:10.1039/b718627d

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Immobilization of a hexaphyrin(1.0.1.0.0.0) derivative onto a tentagel-amino
resin and its use in uranyl cation detection†‡
Patricia J. Melfi, Salvatore Camiolo, Jeong Tae Lee, Mehnaaz F. Ali, John T. McDevitt,* Vincent M. Lynch and
Jonathan L. Sessler*
Received 3rd December 2007, Accepted 7th January 2008
First published as an Advance Article on the web 7th February 2008
DOI: 10.1039/b718627d
The synthesis of an isoamethyrin derivative containing two
CH2CH2CO2CH3 moieties in the b-pyrrolic positions and its
use in the colorimetric detection of the uranyl cation after
immobilization onto a solid support is reported.
generate a microchip with highly selective detection limits, as well
as strippable coatings.4a,c Such advances notwithstanding, we felt
it would be advantageous to produce immobilized systems based
on isoamethyrin since previous work with this macrocycle has
demonstrated greater specificity in terms of “sensing” the uranyl
cation without interference from, e.g., lanthanide cations. For
initial work, we decided to focus on a tentagel amino-terminated
polystyrene-poly(ethylene glycol) graft co-polymer resin (90 lm,
0.30 mmol g−1 NH) as the solid support.
Nuclear waste, byproducts from weapon production and com-
mercial power plants, is a source of potential environmental
contamination and a source of strategic concern. This concern
is providing an incentive to develop new methods to recognize
and sense the critical components in such wastes, including inter
+
+
alia the uranyl (UO22+), neptunyl (NpO2 ) and plutonyl (PuO2 )
cations. While considerable work along these lines has been
performed, particularly in the area of uranyl cation recognition, to
date cation detection has typically relied on spectroscopic methods
(UV-visible, fluoresence, phosphorescence or atomic absorption)
or potentiometric techniques.1–3 Surprisingly, only a handful of
simple colorimetric sensors for the high-valent actinides (i.e.,
chemical entities that change color upon exposure to these cations)
have been reported.4–6
Isoamethyrin (hexaphyrin(1.0.1.0.0.0), 1) is an expanded por-
phyrin that undergoes spontaneous, air-mediated oxidation and
a dramatic change in both color and spectroscopic properties
when exposed to the uranyl or neptunyl cations.6 Additionally,
it was demonstrated that, with the exception of copper salts,
isoamethyrin preferentially forms a coordination complex with
the uranyl cation (e.g., 2) over other common metal salts.7 As
a first step towards developing this expanded porphyrin as a
potentially useful actinide sensor, we report here the synthesis of
a derivative modified at two b-pyrrolic positions and its successful
immobilization onto a solid support. Qualitative and quantitative
evidence that the resulting system changes color upon exposure to
the uranyl cation is also presented.
Immobilized sensors are attractive both for their inherent
convenience and because they lend themselves to a format
involving multiple sensor arrays, a modality that permits the
simultaneous detection and quantitation of multiple analytes.8
Indeed, a range of organic ligands have been immobilized onto
solid supports, such as resins, silica gel, or cotton, and studied for
uranyl extraction and sensing.1,4,9 In the area of actinide cation
detection, a notable sensor is arsenazo III, which has been used to
This choice of an amino-terminated resin dictated the need
for a carboxy-functionalized isoamethyrin derivative; symmetry
considerations, coupled with a desire to mimic as closely as
possible the electronic features of 1, led us the dicarboxylic acid
7 as our functionalized isoamethyrin target. While b-substitution
of porphyrins is well known,10 reports of expanded porphyrins
functionalized at the b-pyrrolic positions with groups other than
alkyl are still surprisingly few in number.11 Given this limited
precedent, we considered that the use of a diformyl bis-methylester
bipyrrole precursor, such as 3 (Scheme 1), would provide the
simplest entry into the chemistry of b-pyrrole functionalized
isoamethyrin chemistry.
Precursor 3 was prepared in eight steps from monopyrrolic
precursors using standard methods as detailed in the ESI.‡ With
it in hand, isoamethyrin 6 was obtained in two steps using a
modification of previously published procedures.12 Specifically, 3
was condensed with two equivalents of ethyl-methyl bipyrrole,
4, to afford an open chain hexapyrrin precursor, 5, which was
immediately carried onto the next step. This involved exposing a
CH2Cl2 solution of 5 to a solution of 1.0 M FeCl3 in 2 M aqueous
HCl for 4 h. Following chromatographic purification and an acid
wash, the bis-HCl salt of isoamethyrin 6 was isolated in 40% yield.
Single crystals suitable for X-ray crystallography were grown
by slow evaporation of the bis-chloride salt of 6 in a CH2Cl2–
cyclohexane solution.§ The core of the macrocycle was observed to
be essentially planar, in spite of the fact that the methyl ester groups
are separated from one another. Further details can be found in the
ESI.‡ The 1H NMR and UV-vis spectra of H262+·2Cl−, like those
Department of Chemistry and Biochemistry, 1 University Station-A5300,
The University of Texas at Austin, Austin, Texas, 78712-0165, USA.
E-mail: mcdevitt@mail.utexas.edu, sessler@mail.utexas.edu
† CCDC reference numbers 661301 and 661302. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/b718627d
‡ Electronic supplementary information (ESI) available: Synthetic details
for 4–8 and X-ray data for 6 and 8. See DOI: 10.1039/b718627d
1538 | Dalton Trans., 2008, 1538–1540
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Fig. 1 Top and side views of 8 showing a partial atom labelling scheme.
Ellipsoids are scaled to the 30% probability level. All hydrogens, and the
alkyl substituents in the side view have been removed for clarity. U–N
˚
bond lengths lie in the range 2.5169(6)–2.7260(7) A. The O–U–O angle is
178.2(5)◦ and the O–U–N bond angles range from 99.8(4) to 80.1(4)◦.
Scheme 1 Synthesis of isoamethyrins 6 and 7.
it was considered likely that it would prove impossible to view
any putative uranyl cation-induced color changes. Accordingly,
isoamethyrin coverage levels ranging from 5–20% of the open
amino groups/bead were used. This level of immobilization
corresponds to 0.0015–0.006 mmol g−1.
of H212+·2Cl−, are consistent with the presence of an antiaromatic
ring current. The UV-visible spectrum for H252+·2Cl− was also
similar to that of H212+·2Cl− at 378 (e/dm3 mol−1 cm−1 24 600), 494
(81 100) and 596 (32 500) nm. A minor hyperchromic effect and
bathochromic shifts in the peak maxima were, however, observed.
Macrocycle 6, like 1, was found to interact with the uranyl
cation. Specifically, adding an excess of UO2(OAc)2 in CH3OH
to a solution of 6 in a 50 : 50 v/v mixture of CH2Cl2–CH3OH
led to formation of the uranyl complex, 8, in 24% isolated
yield after a period of 48 h. Direct structural and spectroscopic
comparisons between 8 and the previously reported isoamethyrin–
uranyl complex, 2, provided support for the proposed structure.
Crystals suitable for X-ray diffraction analysis were grown from
slow evaporation of a solution of 8 in CH2Cl2–CH3OH.§ Although
three molecules of 8 were observed in the unit cell, the differences
(involving the b-substituents) are minor. Thus, only one of the
three molecules is shown in Fig. 1. The macrocycle must twist
slightly to accommodate the relatively small size of the uranyl
When functionalized with isoamethyrin in this way, each bead
has an approximate diameter of 220 lm and was expected to act
as a miniaturized cuvette ensemble for the detection of uranyl
cations. The reactivity of these beads with uranyl salts was thus
investigated. As has been previously established, the ‘free base’
form of the macrocycle is necessary for uranyl cation coordination.
In the case of the acid salt of immobilized 7, this ‘free base’ was
formed by washing the beads with a 10% NaOH solution. Upon
exposure to a 0.024 M uranyl acetate solution in methanol for
9 days,15 the bead changes from a golden yellow color to a pink–
red (cf . inset to Fig. 2). It has been previously demonstrated that,
in the case of 1 and 2, this color change is reflected as a shift of the
Soret band kmax by about 40 nm.7
1
cation. Analysis of the H NMR spectra revealed that like its
analogues 1 and 2, the ring current of 6 changes from paratropic,
or antiaromatic, to diatropic, or aromatic, upon coordination of
the metal cation, as is evidenced inter alia by an upfield shift of the
meso-H signal (see ESI‡). Again, some differences between 8 and 2
were observed in their respective UV-visible spectra. As compared
to 2, the Q-like band of 8 was found to be somewhat broader and
shifted to longer wavelengths. Likewise, both the Soret and Q-like
bands of 8 were significantly less intense than those of 2.
To effect immobilization of the functionalized isomethyrin 6 to
the amino-terminated tentagel resin, the methyl ester groups were
hydrolyzed to give the corresponding diacid 7 in accord with a
previously established procedure.13 Attachment was then effected
using a slight modification of the solid-phase synthetic procedures
typically used to functionalize this resin.14
Given the high pigmentation of the macrocycle, successful
immobilization was easily discernable by the naked eye. In fact,
it was quickly determined that 100% coverage of the amino sites
with isoamethyrin resulted in an opaque bead; it was so dark that
Fig. 2 Intensity values in the red (red line), green (green line) and blue
(blue line) channels for a bead containing the free base of isoamethyrin
(left side, 6.4% amine coverage) and a bead exposed to 0.0024 M uranyl
acetate for nine days (right side).16
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0.71073 A, l = 0.193 mm−1, crystal size 0.40 × 0.07 × 0.04 mm, 8068
reflections collected, 8068 unique (Rint = 0.0779). The final wR(F2) was
0.1512 (all data). CCDC 661301. For 8: C123H142N15O15U2.50, M = 2665.59,
monoclinic, space group P2/c, a = 40.592(2), b = 16.1043(6), c =
˚
With the beads in hand, analysis was performed in a custom-
designed flow cell, as has been described by Goodey et al.8a
The substrate-induced color changes in receptor functionalized
tentagel beads were then quantified into red, green and blue
channels, as is shown in Fig. 2. In this approach, the red, green
and blue color intensities are extracted using a CCD video chip
before and after exposure to an analyte (the uranyl cation in the
present instance). Images of blank beads were used to establish
the reference light intensity, while those of the derivatized beads
are used to extract the absorbance values of the three effective
color windows. Applying this procedure to the isoamethyrin
functionalized beads, reveals a significant increase in the intensity
of the red channel subsequent to treatment with the uranyl cation
(cf . Fig. 2). By comparison, the changes in the green and blue
channels are slight.
◦
3
˚
˚
17.9271(6) A, b = 94.662(2) , U = 11680.3(8) A , T = 153(2) K, Z =
4, k(Mo-Ka) = 0.71073 A, l = 3.528 mm−1, crystal size 0.27 × 0.06 ×
˚
0.04 mm, 41835 reflections collected, 17429 unique (Rint = 0.1001). The
final wR(F2) was 0.1669 (all data). CCDC 661302. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/b718627d
1 (a) J. L. Sessler, P. J. Melfi and G. D. Pantos, Coord. Chem. Rev., 2006,
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Strictly speaking, the change in the red channel reflects two
events in the system, namely oxidation of the macrocycle (from
antiaromatic to aromatic) and coordination of the uranyl cation
to the oxidized form of the macrocycle. In our experience to date,6,7
these events have always been closely coupled. However, this need
not be the case. Indeed, it is fully conceivable that oxidation
can take place separate from and prior to metal complexation.
Moreover, we believe that, unlike UV-visible spectroscopy, RGB
analysis may allow us separate these two events and monitor solely
metal complexation. To the extent this proves possible, it may
allow us to decrease the time required for cation complexation by
carrying out a preliminary ligand oxidation step. This, in turn,
would lead to improved response times, as would be required for
a practical sensor system. Efforts along these lines are in progress.
In conclusion, the use of a b-methyl ester bipyrrole precursor
allows for the synthesis of a functionalized isoamethyrin that
can be readily hydrolyzed and attached to a tentagel amino-
derivatized solid support. Preliminary studies provide support
for the conclusion that the resulting systems allow for the color-
based detection of the uranyl cation, albeit with response kinetics
that are still far short of being practical for a working sensor
array. Further studies, including competition with common metal
salts and kinetic studies of both the ligand oxidation and metal
coordination process, are necessary and in progress.
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T. Curey, A. Tsao, G. Simmons, J. Wright, S.-J. Yoo, Y. Sohn, E. V.
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Acknowledgements
P. J. M would like to thank M. Griffen and G. D. Pantos for helpful
discussions. Pyrrole S1 was obtained as a gift from Pharmacyclics,
Inc. This work was supported by the Department of Energy Ofiice
of Basic Energy Sciences (grant DE-FG02–01ER15186 to J. L. S.)
and the Robert A. Welch Foundation (grants F-1018 and F-1193
to J. L. S. and J. T. M., respectively).
13 J. Davis, PhD Thesis, The University of Texas at Austin, CA, 2001.
14 Solid-Phase Synthesis: A Practical Guide, ed. S. A. Kates and F. Alberi-
cio, Marcel Dekker, Inc., New York, 2000.
15 While a color change was observed after one day, this extended reaction
time was employed to ensure complete coordination of the uranyl cation
by the appended isoamethyrin obtained from 7.
16 Beads were arranged into a flow cell, as has been described by Goodey
et al.,8a and washed with water for 10 min before being analyzed. The
camera exposure was 7.36 ms.
Notes and references
§ Crystallographic details: for 6: C48H61Cl2N6O4.50, M = 864.93, or-
thorhombic, space group Pbca, a = 25.8233(3), b = 10.4391(10), c =
3
˚
˚
33.9936(16) A, U = 9163.7(10) A , T = 153(2) K, Z = 8, k(Mo-Ka) =
1540 | Dalton Trans., 2008, 1538–1540
This journal is
The Royal Society of Chemistry 2008
©