Enhancement of anion recognition exhibited by a halogen-bonding rotaxane host system

Article abstract of DOI:10.1021/ja105263q

We report the first use of solution-phase halogen bonding to control and facilitate the assembly of an interlocked structure through the bromide anion-templated formation of a rotaxane based upon an iodotriazolium axle. The incorporation of a halogen atom into the rotaxane host cavity dramatically improves the anion-recognition capabilities of the interlocked receptor, giving unusual iodide selectivity in a competitive aqueous medium.

Full text of DOI:10.1021/ja105263q

Published on Web 08/05/2010
Enhancement of Anion Recognition Exhibited by a Halogen-Bonding
Rotaxane Host System
Nathan L. Kilah,† Matthew D. Wise,† Christopher J. Serpell,† Amber L. Thompson,†
Nicholas G. White,† Kirsten E. Christensen,‡ and Paul D. Beer*,†
Chemistry Research Laboratory, Department of Chemistry, UniVersity of Oxford, Mansfield Road, Oxford OX1 3TA,
United Kingdom, and Diamond Light Source, Harwell Science and InnoVation Campus,
Didcot OX11 0DE, United Kingdom
Received June 16, 2010; E-mail: paul.beer@chem.ox.ac.uk
halogen atom into the rotaxane host cavity dramatically improves
the anion-recognition capabilities of the interlocked receptor.
We recently described the first example of the use of solution
halogen bonding to facilitate the chloride anion-templated assembly
Abstract: We report the first use of solution-phase halogen
bonding to control and facilitate the assembly of an interlocked
structure through the bromide anion-templated formation of a
rotaxane based upon an iodotriazolium axle. The incorporation
of a halogen atom into the rotaxane host cavity dramatically
improves the anion-recognition capabilities of the interlocked
receptor, giving unusual iodide selectivity in a competitive aque-
ous medium.
of a 2-bromo-functionalized imidazolium-threading pseudorotax-
ane.9 This discovery, together with recent advances in the prepara-
tion of 5-iodo-1,2,3-triazoles by a novel copper(I)-catalyzed
azide-alkyne cycloaddition reaction,10 prompted us to investigate
the possibility of utilizing 5-iodo-1,2,3-triazolium groups for the
anion-templated assembly of interpenetrated and interlocked systems.
The 5-iodo-1,2,3-triazole 1 was prepared from 1-tert-butyl-4-
(iodoethynyl)benzene and 1-n-octylazide using a modified literature
procedure with a copper(I)-tris[(1-benzyl-1H-1,2,3-triazol-4-yl)-
methyl]amine (TBTA) catalyst.10 Subsequent methylation of 1 with
trimethyloxonium tetrafluoroborate gave 2·BF4 in high yield
(Scheme 1).
Halogen bonds are formally noncovalent interactions formed
between polarized halogen atoms functioning as electrophilic centers
(Lewis acids) toward neutral or anionic Lewis bases. These
attractive interactions arise from the terminal positive polarization
of a covalently bonded halogen atom along the direction of the
R-X bond, which concomitantly produces a perpendicular “belt”
of negative electron density around the halogen.1 The polarization
effect is most prominent in the less electronegative halogens (Br
and I) and is further enhanced by their covalent bonding to electron-
withdrawing groups. Halogen bonds are largely underexploited in
solution-phase supramolecular chemistry,2 which is surprising given
their analogy to ubiquitous hydrogen bonding3 and their increasing
manipulation in the crystal engineering of magnetic and conducting
materials4 and liquid-crystal phases.5
Scheme 1. Synthesis of 5-Iodo-1,2,3-triazolium Tetrafluoroboratea
Inspired by the pervasive roles negatively charged species play
in a range of chemical, biological, medical, and environmental
processes, the design of host systems for anion-recognition ap-
plications is an ever-increasing field of research.6 The plethora of
positively charged and neutral acyclic and macrocyclic synthetic
anion receptors reported to date utilize almost exclusively electro-
static, hydrogen-bonding, Lewis acid-base, and anion-π interac-
tions for their efficacy of operation in polar organic and aqueous
solvent media. In view of their stringent linear directionality and
strength comparable to hydrogen bonds, it is surprising that the
incorporation of halogen bonding into anion receptor design has
remained largely dormant.7
a Reagents, conditions and yields: (i) 5% CuI, 5% TBTA, THF, RT, N2,
87%; (ii) (Me3O)BF4, CH2Cl2, RT, N2, 94%.
Anion exchange of dichloromethane solutions of 2 · BF4 with
excess ammonium chloride, bromide, and iodide solutions provided
the corresponding halide salts in quantitative yield. Crystals of 2·Cl,
2·Br, and 2·I suitable for X-ray structural analysis11 were obtained,
and significant halogen bonding was observed in all three salts, as
the distance between the iodine of the 5-iodo-1,2,3-triazolium motif
and the halide anion is 79-84% of the sum of the van der Waals
radii while the C-I· · ·X- angle is very close to the expected linear
arrangement arising from the terminal polarization of the iodine
atom. Full crystallographic details for the three structural determina-
tions are given in the Supporting Information (SI).
We have exploited anion templation in the construction of three-
dimensional interlocked anion host molecular frameworks that
display a high degree of selectivity for the templating anion.8 In a
significant step forward for highlighting the potential importance
of halogen bonding in anion supramolecular chemistry, herein we
demonstrate the first use of solution-phase halogen bonding to
control and facilitate the anion-templated assembly of an interlocked
structure. Importantly, we then show that the incorporation of a
Halogen-bond anion-templated pseudorotaxane assembly studies
with 2·X (X ) Cl, Br, I, BF4) and macrocycle 3 were undertaken
1
by H NMR titration experiments via the addition of increasing
amounts of the 5-iodo-1,2,3-triazolium salt to a solution of the
1
macrocycle in CDCl3. Significant perturbations in the H NMR
spectra of 3 were observed upon the addition of each of the halide
salts of 2. Downfield shifts for the interior and exterior isophthala-
† University of Oxford.
‡ Diamond Light Source.
9
10.1021/ja105263q  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 11893–11895 11893

C O M M U N I C A T I O N S
Scheme 2. Halogen-Bond Halide Anion-Templated
Pseudorotaxane Formation
formation, the corresponding hydrogen-bonding threads 4·X (X
) Cl, Br, I) were prepared and investigated analogously to the
threads 2·X. Table 1 shows that the association constant values of
the halogen-bonding ion pairs are significantly larger than their
hydrogen-bonding counterparts. Interestingly, as observed with the
iodo-functionalized triazolium systems, the most stable pseudoro-
taxane assembly is formed with the bromide salt 4·Br.
Halogen-bonding templated threading was confirmed by 1H NMR
ROESY spectroscopy for a 1:1 mixture of 2·Br and 3 in CDCl3
(see the SI).
After it was established that iodotriazolium halide salts are
capable of forming anion-templated interpenetrative assemblies, the
synthesis of a halogen-bonding rotaxane was undertaken (Scheme
3).
Scheme 3. Synthesis of Rotaxane 7·Bra
mide protons and the amide protons were observed, with simulta-
neous upfield shifting and splitting of the hydroquinone protons.
The splitting and upfield shift of the hydroquinone protons is
diagnostic of pseudorotaxane formation, as it corresponds to the
interaction of the electron-deficient triazolium heterocycle with the
electron-rich hydroquinone counterparts (Scheme 2). Pseudorotax-
ane assembly association constants (Ka) were calculated from
monitoring of the exterior (b) and interior (c) isophthalamide
resonances and the hydroquinone resonances (g and h) using
WinEQNMR212 with 1:1 binding stoichiometry (Table 1 and the
SI). The association constant values determined from the titration
data for the interior isophthalamide (c) and upfield hydroquinone
(h) resonances were in good agreement, importantly indicating that
both the halide anion and the iodotriazolium thread are simulta-
neously bound by the macrocycle.
Table 1. Association Constants Ka for Pseudorotaxane Formation
between Triazolium Salts and Macrocycle 3 in CDCl3 at 293 K
a Reagents and conditions: (i) 10 wt % Grubbs’ II catalyst, CH2Cl2, RT,
N2.
a
ion pair
Ka (M-1
)
2·Cl
2·Br
2·I
2·BF4
4·Cl
4·Br
4·I
538(17)
1188(93)
392(24)
29(19)
490(38)
610(31)
232(8)
Reaction of an equimolar mixture of bisvinyl-functionalized
derivative 5 and iodotriazolium axle 6·Br with Grubbs’ II catalyst
in CH2Cl2 solution followed by purification using preparative-plate
thin-layer chromatography gave rotaxane 7·Br in 15% yield. The
isolated rotaxane was characterized by 1H, 13C{1H}, and 1H ROESY
NMR spectroscopy and high-resolution electrospray ionization mass
spectrometry (ESI-MS). Analysis of the 1H NMR spectrum of 7·Br
revealed significant upfield shifts and splitting of the hydroquinone
protons, diagnostic of the interaction of the electron-deficient
iodotriazolium heterocycle of the axle with the electron-rich
hydroquinone macrocycle counterparts. A significant downfield shift
and broadening was observed for the interior isophthalamide ArH
proton and the amide protons. 1H ROESY NMR spectroscopy
revealed a number of through-space cross-peaks between the axle
and the macrocycle (see the SI). The pivotal importance of the
a Obtained from hydroquinone proton g. Errors in parentheses.
The iodotriazolium bromide thread 2·Br forms the strongest
pseudorotaxane assembly association, followed by the chloride and
iodide salts. It is noteworthy that 2·BF4 exhibits a very weak
association with macrocycle 3, which serves to highlight the crucial
importance of the iodine-halide halogen-bond templation mech-
anism for interpenetrative assembly. To contrast the efficacy of
halogen bonding relative to hydrogen bonding for pseudorotaxane
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C O M M U N I C A T I O N S
Figure 1. X-ray crystal structure of 7·Br. Nonacidic hydrogens and minor components of disordered residues have been omitted for clarity.
bromide anion template to the rotaxane synthesis was further
emphasized by the lack of ESI-MS or H NMR evidence for the
halogen-bond donation by the iodotriazolium axle significantly
enhances the rotaxane’s anion-recognition properties in comparison
with the hydrogen-bonding analogue, providing unusual selectivity
for iodide. The fabrication of halogen-bond donor motifs into
molecular and interlocked anion host structural design is continuing
in our laboratories.
1
interlocked structure when the synthesis was repeated with 6·BF4.
Crystals of 7·Br suitable for structural analysis were grown from
toluene by a thermal-gradient method,13 permitting the collection
of diffraction data using synchrotron radiation (Figure 1). The
structure unambiguously confirms the interlocked nature of the
system and the vital role played by halogen-bonded anion templa-
tion in its assembly. The bromide anion is coordinated by both the
triazolium iodine atom and the amide protons. The halogen bond
is lengthened slightly [3.127(4) vs 3.0927(4) Å] and bent [165.07(15)
vs 177.74(9)°] relative to the iodotriazolium bromide salt 2·Br, an
effect due to competitive hydrogen bonding with the bromide anion.
The assembly is further stabilized by charge-assisted π-π stacking
and secondary hydrogen bonding between the triazolium methyl
group and the polyether chain of the macrocycle.
Repeated washings with aqueous NH4PF6 removed the bromide
anion template to give rotaxane 7·PF6. Preliminary 1H NMR
bromide anion titration experiments with 7·PF6 in 1:1 CDCl3/
CD3OD gave a WinEQNMR2-determined association constant of
>104 M-1, which is remarkably at least an order of magnitude larger
than that for the hydrogen-bonded triazolium rotaxane analogue
(Ka ) 970 M-1).14 Analogous halide anion titration experiments
of 7·PF6 in 45:45:10 CDCl3/CD3OD/D2O using tetrabutylammo-
nium salts provided further evidence of the superior anion-
recognition capabilities of this halogen-bonding rotaxane host
system. Bromide and iodide are both bound strongly by 7·PF6 in
this competitive aqueous solvent mixture, with a selectivity
preference for the larger halide anion (Table 2), in contrast to the
protic triazolium analogue, which was bromide-selective.14 This
preference for iodide may be attributed to the accessibility of the
binding site to larger anions (Figure 1) and weaker competition
for the more lipophilic halide by the aqueous solvent medium.
Acknowledgment. N.L.K. thanks the Royal Commission for
the Exhibition of 1851 for a Research Fellowship. C.J.S. thanks
the EPSRC and Johnson Matthey for a CASE Studentship. N.G.W.
thanks the Clarendon Fund and Trinity College for a studentship.
We also gratefully thank Diamond Light Source for an award of
beam time on I19 (MT1858).
Supporting Information Available: Full details of syntheses and
characterization, 1H NMR binding studies, and crystallography (includ-
ing CIFs). This material is available free of charge via the Internet at
http://pubs.acs.org.
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Table 2. Association Constants Ka for Anion Binding by Rotaxane
7 in 45:45:10 CDCl3/CD3OD/D2O at 293 K
a
anion
Ka (M-1
)
Cl-
Br-
I-
457(4)
1251(10)
2228(171)
a Obtained from exterior isophthalamide proton
tetrabutylammonium salts. Errors in parentheses.
b
using
In summary, we have demonstrated the utility of the halogen-
bonding 5-iodo-1,2,3-triazolium group for the halide anion-tem-
plated formation of interpenetrated assemblies and the bromide
anion-templated synthesis of the first halogen-bonding interlocked
host system. Anion-binding investigations revealed that the iodine
JA105263Q
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J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 11895