Nitrate anion templated synthesis of a [2]catenane for nitrate recognition in organic-aqueous solvent media

Article abstract of DOI:10.1039/c4cc03200d

The first example of a catenane synthesised using a nitrate anion template is demonstrated. Removal of the templating anion reveals a mechanically interlocked molecular host system which is capable of recognising nitrate selectively over a range of more basic mono-anionic oxoanions in a competitive organic-aqueous solvent mixture. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03200d

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Nitrate anion templated synthesis of a [2]catenane
for nitrate recognition in organic–aqueous
solvent media†‡
Cite this: Chem. Commun., 2014,
50, 8124
Received 29th April 2014,
Accepted 4th June 2014
Matthew J. Langton and Paul D. Beer*
DOI: 10.1039/c4cc03200d
www.rsc.org/chemcomm
The first example of a catenane synthesised using a nitrate anion
Herein we report the first example of a nitrate-templated
template is demonstrated. Removal of the templating anion reveals a synthesis of a [2]catenane, which recognises nitrate with
mechanically interlocked molecular host system which is capable of impressive selectivity over acetate, dihydrogen phosphate and
recognising nitrate selectively over a range of more basic mono-anionic hydrogen carbonate, in a competitive organic–aqueous solvent
oxoanions in a competitive organic–aqueous solvent mixture.
mixture (Fig. 1).
Previous design strategies to enhance nitrate recognition
Stimulated by the important roles anions play in a range of within synthetic anion receptors have centred around constructing a
biological, medical and environmental processes, the design of host in which multiple hydrogen bond donors are arranged in a
anion receptors capable of strong and selective recognition is an complementary trigonal arrangement, to favour binding of the
area of supramolecular chemistry of ever increasing interest.1 The trigonal planar nitrate anion over anions of different geometries.5–11
nitrate anion in particular is an important target for binding, sensing Recently we reported such a strategy for assembling a nitrate anion
and sequestering, due to its role in the eutrophication of natural selective [2]rotaxane.20 We reasoned that integrating a bidentate
water courses as a consequence of its over-use in agricultural hydrogen bond donor group into one macrocycle and a monodentate
fertilisers.2 Furthermore, exposure to increased nitrate levels hydrogen bond donor group into the other cyclic component would
have been implicated in a number of adverse health conditions
such as methemoglobinemia (blue-baby syndrome) in infants.3
The development of nitrate receptors has been hampered by the
low affinity of the anion for hydrogen bonds, in addition to being
strongly solvated.4 As such, receptors reported to date have
typically been restricted to operating only in organic solvents.5–11
Mechanically interlocked molecules, such as rotaxanes and catenanes,
have attracted much interest due to their potential in nano-
technological and molecular machine applications.12–15 Such struc-
tures, however, also have applications in host–guest chemistry for
molecular recognition and sensing, utilising their unique three
dimensional topologies to augment guest recognition.16,17 In particu-
lar the use of discrete anion templation has been demonstrated
as a means to prepare rotaxane hosts capable of high levels of
anion recognition for the templating anion.18 However, examples of
catenane host structures for guest recognition remain relatively rare,
especially those capable of binding anionic guests.19
Chemistry Research Laboratory, Department of Chemistry, University of Oxford,
Mansfield Road, Oxford, OX1 3TA, UK. E-mail: paul.beer@chem.ox.ac.uk;
Fax: +44 (0)1865-272-690
† This communication is dedicated to Prof. Seiji Shinkai on the occasion of his
70th birthday.
‡ Electronic supplementary information (ESI) available. See DOI: 10.1039/
Fig. 1 Catenane nitrate receptor.
c4cc03200d
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Scheme 1 Synthesis of asymmetric macrocycle precursor 12ÁNO3.
produce a [2]catenane host structural framework containing an
The synthesis of the [2]catenane was achieved using
interlocked tridentate binding cavity of complementary shape nitrate templation, via a RCM strategy (Scheme 2). An initial
for nitrate recognition.
pseudorotaxane assembly was prepared by mixing 12ÁNO3 with
The asymmetric macrocycle precursor 12ÁNO3 incorporates two macrocycle 1322 in dry CH2Cl2. Addition of Grubbs’ second
hydrogen bond donor motifs: the positively charged 3,5-bis-amide generation RCM catalyst afforded the [2]catenane. Analysis of
pyridinium and neutral isophthalamide, to coordinate to two of the the H NMR spectrum of the crude reaction mixture revealed
1
nitrate anion’s oxygen atoms. The precursor is functionalised with that the catenane was formed in approximately 25% yield; the
vinyl groups to facilitate ‘‘clipping’’ ring closing metathesis (RCM) other products being the cyclised form of 12+ and non-interlocked
catenane formation when threaded via nitrate anion templation macrocycle 13. Catenane 14ÁNO3 was isolated in an overall yield of
through an isophthalamide containing macrocycle. The multistep 20% following purification by silica gel chromatography, and fully
synthesis of 12ÁNO3 is shown in Scheme 1. The convergent characterised by 1H, 13C and 1H ROESY NMR, and high resolution
1
synthesis commenced with the EDC-mediated coupling of amine 121 mass spectrometry (see Fig. 2 and ESI‡). The H NMR spectra of
with the asymmetrically de-esterified acids 2 and 3, to yield macrocycle 13, catenane 14ÁNO3, and macrocycle precursor 12ÁNO3
compounds 4 and 5. These were subsequently deprotected to the are compared in Fig. 2A. Of particular note is the upfield shift and
acid forms (6 and 7 respectively) using KOH. Coupling of splitting of the hydroquinone protons d and e, which is diagnostic of
compound 6 with mono BOC-protected 1,3-diaminopropane 8 aromatic donor–acceptor interactions between the hydroquinones in
afforded compound 9, from which the BOC protecting group was macrocycle 13 and the electron-deficient pyridinium motif in the
cleaved using trifluoroacetic acid to afford amine 10, as the other macrocycle, and confirms the interlocked nature of the
ammonium salt. This was then coupled to 7 to give the neutral catenane. Further confirmation of the interlocked structure is
pyridine compound 11, which was methylated using CH3I to obtained in the 1H ROESY NMR spectrum of 14ÁNO3, which reveals
produce the asymmetric pyridinium–isophthalamide macrocycle multiple through space interactions between the two interlocked
precursor 12ÁI. Anion exchange using a nitrate-loaded Amberlites macrocycles (see ESI‡). Synthesis of the catenane was also attempted
anion exchange resin afforded the nitrate salt, 12ÁNO3.
using both the chloride and hexafluorophosphate (PF6À) salts of 12+.
Scheme 2 Nitrate-templated synthesis of [2]catenane 14ÁNO3.
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Fig. 2 (A) Partial 1H NMR spectra of (a) macrocycle 13, (b) catenane 14ÁNO3 and (c) macrocycle precursor 12ÁNO3 in 1 : 1 CDCl3–CD3OD (500 MHz,
298 K). For atom labels see Scheme 2, *denotes residual solvent peak. (B) High resolution electrospray ionisation mass spectrum of catenane 14ÁNO3
(top) with theoretical isotope model for [M–NO3 + Na+]2+ (bottom).
À
1H NMR analysis of the crude reaction mixtures revealed a catenane nitrate, albeit by a modest amount. It has previously been
yield of o10% with chloride23 and no interlocked product in the demonstrated that analogous acyclic receptors, bearing the
case of PF6À, highlighting the crucial templating role of the nitrate same bidentate hydrogen bond donating functionality as 12+,
anion in the synthesis of the catenane. In order to investigate the bind chloride exclusively in the same solvent mixture, with no
anion recognition properties of the new catenÀane, it was necessary to nitrate association being observed.20 This serves to highlight
anion exchange to the non-coordinating PF6 salt by washing with the crucial role that the three-dimensional tridentate binding
aqueous NH4PF6. 1H NMR anion binding titration experiments were cavity of catenane 14ÁPF6 plays in enhancing the recognition
conducted in the competitive aqueous solvent mixture of 45 : 45 : 10 and selectivity of the host towards the nitrate anion.
CDCl3–CD3OD–D2O. Binding of nitrate, added as the tetrabutyl-
In conclusion, we have demonstrated the first example of
ammonium salt, results in strong upfield perturbation of the nitrate-templated catenane formation. Removal of the templating
internal pyridinium proton 3 (Dd = 0.21 ppm after 10 equiv.), nitrate anion results in an interlocked catenane host which displays
which is diagnostic of the anion binding within the catenane’s impressive selectivity for nitrate over a range of more basic
interlocked binding cavity. Addition of other mono-charged oxoanions, even in a highly competitive organic–aqueous solvent
oxoanions led to significantly smaller perturbations of this mixture. The utilisation of templating anions for the synthesis of
proton (see Table 1). WinEQNMR224 analysis of the titration interlocked molecular architectures for recognition and sensing
data determined the 1 : 1 stoichiometric association constants applications is continuing in our laboratories.
shown in Table 1.
M.J.L would like to thank the EPSRC for a DTA studentship.
The trigonal, tridentate binding cavity of the catenane host
is highly selective for nitrate, over the other mono-charged
oxoanions. The selectivity over acetate is particularly note-
worthy, which despite being five orders of magnitude more
basic, is not bound by the catenane. Dihydrogenphosphate is
also not bound, and only weak binding was observed for
hydrogen carbonate. This observed selectivity for nitrate over
more basic oxoanions can be attributed to the excellent size and
geometry match of the catenane’s complementary binding
cavity with the trigonal planar nitrate anion. For comparison,
the association constant with the spherical chloride anion,
which lacks the trigonal geometric preference, was determined
in the same solvent mixture and found to be lower than that of
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