Copper(II)-directed synthesis of neutral heteroditopic [2]rotaxane ion-pair host systems incorporating hydrogen and halogen bonding anion binding cavities

Article abstract of DOI:10.1039/c7dt02832f

Neutral heteroditopic [2]rotaxane ion-pair host systems were synthesised via a Cu(ii) directed passive metal template strategy. Each rotaxane contains discrete, axle-separated interlocked binding sites for a guest anion and a transition metal countercatio

Full text of DOI:10.1039/c7dt02832f

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Copper(II)-directed synthesis of neutral
heteroditopic [2]rotaxane ion-pair host systems
incorporating hydrogen and halogen bonding
anion binding cavities†
Cite this: DOI: 10.1039/c7dt02832f
a
a
a
b
Asha Brown,
Paul D. Beer
Katrina M. Mennie, Owen Mason, Nicholas G. White
and
a
*
Neutral heteroditopic [2]rotaxane ion-pair host systems were synthesised via a Cu(II) directed passive
metal template strategy. Each rotaxane contains discrete, axle-separated interlocked binding sites for a
guest anion and a transition metal countercation. The anion binding sites are composed of convergent
X–H (X = C, N) hydrogen bond donor groups, or mixed X–H and C–I hydrogen and halogen bond donor
Received 2nd August 2017,
Accepted 12th September 2017
groups, whereas an equivalent three-dimensional array of amine, pyridine and carbonyl oxygen donor
1
groups comprise the transition metal binding site. H NMR titrations experiments in CDCl
3
/CD
3
OD or
DOI: 10.1039/c7dt02832f
3 3 2
CDCl /CD OD/D O solvent mixtures reveal that the heteroditopic [2]rotaxane host systems are capable
rsc.li/dalton
of cooperative anion recognition in the presence of a co-bound Zn(II) cation.
binding sites for both an anion and a countercation, can offer
significantly enhanced anion binding affinities compared to
The development of selective receptors and sensors for anions simpler monotopic receptors. However, despite the plentiful
is an important research goal owing to the fundamental roles examples of non-interlocked ion-pair receptors, reports of
played by negatively charged species in a range of chemical, interlocked rotaxane-based anion host systems which are
Introduction
5
,6
1
–3
medical and environmental processes.
One promising capable of simultaneously binding a metal cation are compara-
approach to the design of selective anion complexants entails tively scarce. Rare examples include heteroditopic rotaxane
the use of mechanically interlocked rotaxane architectures: systems which bind an anion and an alkali metal, lanthanide
7
–10
these molecules can be designed to incorporate shielded, or transition metal cation as a contact ion-pair.
In addition
hydrophobic binding cavities whose size and topology com- we have reported a heteroditopic [2]rotaxane host system
plement the geometry and hydrogen-bonding requirements of which recognises halide anions and alkali metal cations in an
1
1
a target guest anion. We have developed this approach by ‘axle-separated’ binding fashion, along with a number of
using the interior cavities of rotaxane molecules as three- anion-binding rotaxane and catenanes which incorporate a
dimensional scaffolds on which to append both hydrogen and host-separated transition metal cation as a luminescent or
1
2–18
halogen bond donor groups, enabling the selective recognition electrochemical reporter group.
of a range of complementary guest anions in competitive Herein we describe the design and synthesis of new neutral
4
solvent media. By taking advantage of allosteric effects, heteroditopic [2]rotaxane ion-pair host systems which contain
heteroditopic ion-pair receptors, which contain specific discrete interlocked binding cavities for both an anion and a
transition metal cation. The anion and cation recognition sites
are separated by the rotaxane’s axle component. Convergent
hydrogen and halogen bond donor groups are used for anion
a
Chemistry Research Laboratory, Department of Chemistry, University of Oxford,
Mansfield Road, Oxford, OX1 3TA, UK. E-mail: paul.beer@chem.ox.ac.uk
b
recognition while the transition metal binding sites are lined
with amine, pyridine and carbonyl oxygen groups. The rotax-
anes were assembled via a recently developed copper(II)
Research School of Chemistry, The Australian National University, Canberra, ACT,
Australia
†
Electronic supplementary information (ESI) available: Synthetic procedures
1
and characterisation data for all new compounds; H NMR and UV-visible spec-
troscopic titration protocols and binding data; crystallographic CIF files and
refinement details, and selected bond lengths and angles from the X-ray crystal
structures. CCDC 1560763–1560766. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c7dt02832f
19 1
passive template strategy. H NMR titration experiments were
used to investigate the anion-recognition properties of the
new [2]rotaxane host systems in the presence of a co-bound
Zn(II) cation.
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Results and discussion
Design and synthesis
The general design of the target heteroditopic [2]rotaxane host
systems incorporating individual, axle-separated interlocked
binding cavities for an anion and a transition metal counter-
cation is illustrated schematically in Fig. 1.
The macrocycle component integrates an isophthalamide
anion recognition site, which is located opposite to a tris-
amine binding site for transition metal cations. The axle com-
ponents are also able to simultaneously interact with both an
anion and a countercation, via divergent anion- and cation-
binding functional groups. In the first [2]rotaxane design
(Fig. 1a) this is achieved using a 2,2-bipyridyl-4,4-bis-amide-
functionalised axle component: the bipyridyl nitrogen donor
atoms constitute a transition metal chelate ligand, while the
amide groups serve as a bidentate hydrogen-bond (HB) donat-
ing anion recognition motif. The second [2]rotaxane design Scheme 1 Synthesis of the Cu(II)-complexed tris-amine/isophthala-
(
Fig. 1b) incorporates an alternative 4-iodopyridyl-2,6-dicarbo- mide-functionalised macrocycle 3·Cu(ClO
4
)
2
. Reagents and conditions:
, r.t., 48 h, 44%; (ii) diethyl-
, MeOH, r.t., overnight; (iv) NaBH , CH Cl , MeOH,
r.t., 6 h, 70%; (v) Cu(ClO ·6H O, CH Cl , MeOH, r.t, 18 h, 98%.
(
i) 4-Dimethylaminopyridine, Et
3 2 2
N, CH Cl
nyl pyridine-based axle component. It was anticipated that the
enetriamine, CH Cl
2
2
4
2
2
2
,6-dicarbonylpyridyl functionality would be capable of triden-
4
)
2
2
2
2
tate complexation to a transition metal cation, while the
polarised iodine atom provides a potential halogen-bond (XB)
donating anion binding locus. Halopyridin(ium) motifs have
not yet been widely explored as a class of XB donor in the
Crystals of macrocycle 3·Cu(ClO ) suitable for X-ray struc-
4
2
tural determination were grown by layered diffusion of di-
isopropyl ether into a CH CN solution of the complex.‡ In the
2
0–22
anion coordination field,
where the majority of studies
3
have so far focused on haloimidazolium, halotriazole/triazo-
solid state the Cu(II) centre is coordinated to the macrocycle’s
three secondary amine nitrogen donor atoms N20, N23 and
N26 (Cu40–N distances: 2.086[4], 2.071[3] and 1.994[4] Å) in
addition to two acetonitrile solvate molecules (Cu40–N41 and
Cu40–N44 distances: 2.009[4] and 2.190[5] Å) in an almost
2
3
lium and haloperfluoroarene XB donor groups.
Synthesis of macrocycle component. The macrocycle com-
ponent of the rotaxanes was prepared by adaptation of the
one-pot, two step reductive amination reaction employed by
Ghosh and co-workers for the synthesis of related tris-amine-
2
6
perfect (τ = 0.035) square pyramidal coordination geometry.
A weakly coordinating perchlorate anion is also located in
proximity to the Cu(II) cation (Cu40–O48 distance: 2.829[4] Å).
The isophthalamide group is held in a syn–syn conformation
by NH⋯·O hydrogen bonding interactions with a carbonyl
group of an adjacent macrocycle; these intermolecular hydro-
gen bonding interactions link the macrocycle molecules in an
infinite zig-zag chain, which is aligned with the crystallo-
graphic a axis (Fig. 2).
1
9,24,25
functionalised cyclic structures.
Condensation of iso-
phthaloyl dichloride with two equivalents of the primary
amine-derivative 1·HCl provided the requisite bis-aldehyde pre-
cursor 2 in 44% yield. Sequential treatment of the bis-aldehyde
with bis(2-aminoethyl)amine followed by NaBH
MeOH afforded macrocycle 3 in 70% yield. After stirring
macrocycle 3 with Cu(ClO ·6H O in CH Cl : MeOH 1 : 1, the
corresponding copper(II) complex 3·Cu(ClO was isolated in
8% yield (Scheme 1).
4 2 2
in CH Cl /
4
)
2
2
2
2
4 2
)
9
Pseudorotaxane assembly investigations. Recently Ghosh
and co-workers have demonstrated copper(II)-templated
pseudorotaxane assembly between a tris-amine-functionalised
macrocycle and a range of bipyridine, phenanthroline and
19,24,25,27–29
2
-pyridyl-benzimidazole threading compounds.
Similarly, evidence for the formation of copper(II)-templated
pseudorotaxane assemblies between the new isophthalamide-
containing copper-complexed macrocycle 3·Cu(ClO ) and 2,2-
4
2
bipyridyl and 4-iodopyridyl-2,6-dicarbonyl threading ligands
was obtained using UV-visible spectroscopy and X-ray crystallo-
graphy techniques. For the purposes of the pseudorotaxane
‡
Crystallographic data (including structure factors) have been deposited with
Fig. 1 Schematic illustration of the heteroditopic [2]rotaxane ion-pair
host systems.
the Cambridge Crystallographic Data Centre (CCDC 1560763–1560766†). Full
refinement details are provided in the ESI.†
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Fig. 3 Changes in the visible absorption spectra of a 3 mM solution of
4 2 3
macrocycle 3·Cu(ClO ) in CH CN on addition of an increasing concen-
tration of compound 4. Inset: Change in absorbance at 600 nm as a
function of [4]. The square data points represent experimental data; the
continuous line represents the calculated binding isotherm for K =
352 M−
1
.
2
1
(
19) M− for the pyridyl-threaded pseudorotaxane assembly
in CH CN. The equilibrium constant for the
4 2
assembly of the more stable 3·2,2-bipyridine·Cu·(ClO )
Fig. 2 Solid state structure of the macrocyclic Cu(II) complex 3·4·Cu(ClO
)
2
4
3
3
·Cu(ClO : (i) content of the asymmetric unit; (ii) infinite zig-zag chain
4 2
)
formed through intramolecular NH⋯O hydrogen bonding interactions.
Non-polar hydrogen atoms, non-coordinating solvent molecules and
the non-coordinating perchlorate counteranion have been omitted for
clarity.
complex was observed to be too high to allow accurate data
fitting at the millimolar concentrations of the titration experi-
ment and a lower limit of K > 10 M was therefore estimated,
4
−1
in both CH CN and the more competitive solvent DMSO.
3
The pseudorotaxane assemblies were also characterised in
the solid state (Fig. 4). Crystals suitable for X-ray structural
determination were grown by layered diffusion of diisopropyl
Scheme 2 Copper(II)-template
formation
of
pseudorotaxane
assemblies comprising macrocycle 3 and 2,2-bipyridine or 4-iodopyridyl
threading ligands.
assembly investigations unsubstituted 2,2-bipyridine was used
as a model threading ligand in place of a 4,4-bis-amide func-
tionalised analogue owing to the prohibitively low solubilities
of simple 4,4-bis-amide functionalised 2,2-bipyridine deriva-
tives (Scheme 2).
Titration of 2,2-bipyridine and 4-iodopyridyl-2,6-dicarbonyl Fig. 4 Solid state structures of the pseudorotaxane assemblies 3·2,2-
bipyridine·Cu·(ClO (top) and 3·4·Cu·(ClO (bottom). For clarity, non-
)
2
4 2
)
4 2 3
into a 3 mM solution of the macrocycle 3·Cu(ClO ) in CH CN
4
polar hydrogen atoms, non-coordinating solvent molecules and non-
coordinating perchlorate couteranions have been omitted, and only one
of the two crystallographically independent pseudorotaxane complexes
contained within the asymmetric unit is shown for the 3·2,2-
induced gradual bathochromic shifts in the maximum absor-
bance of the Cu(II) d–d transitions (Fig. 3 and Fig. S18, ESI†).
3
0
Global fitting of the titration data using Specfit software indi-
cated a 1 : 1 stoichiometric association constant of K = 2352 bipyridine·Cu(ClO
4 2
) structure.
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ether into a CH
3
CN solution of macrocycle 3·Cu(ClO
4
)
2
con- Cu(II) cation and the macrocycle secondary amine nitrogen
taining an excess of 2,2′-bipyridine or the iodopyridyl com- atoms N20, N23 and N26 (Cu55–N distances: 1.909[17]–
pound 4. For the 3·2,2-bipyridine·Cu·(ClO structure the 2.090[5] Å) complete the cation’s distorted octahedral coordi-
4 2
)
asymmetric unit contains two crystallographically independent nation sphere. A perchlorate counteranion is again held in
pseudorotaxane complexes. In each of the independent com- close proximity to the macrocycle’s isophthalamide binding
plexes the copper(II) centre is coordinated to the two nitrogen cleft by a series of C–H⋯O and N–H⋯O hydrogen-bonding
atoms of the 2,2′-bipyridyl moiety (Cu–N distances: 2.002[4]– interactions.‡
2
.078[4] Å) and three nitrogen atoms of the macrocycle diethyl-
Synthesis and characterisation of [2]rotaxanes
enetriamine group (Cu–N distances: 2.019[4]–2.198[4] Å) in a
distorted trigonal bipyramidal arrangement (τ = 0.80, 0.68),
2
6
Synthesis of a [2]rotaxane incorporating a hydrogen bonding
and a parallel stacking arrangement between the macrocycle 2,2-bipyridyl bis-amide axle component. The target 2,2-bipyri-
aromatic 4-alkoxybenzyl and interpenetrated 2,2′-bipyridyl dyl 4,4-bis-amide containing [2]rotaxane 8 was prepared via a
groups is observed. In addition, a perchlorate counteranion is mono-stoppering strategy, as illustrated in Scheme 3. An
held in close proximity to each of the macrocycle’s isophthala- amide coupling reaction was employed during the key rotax-
mide binding cleft by short NH–O and CH–O contacts.
In the solid state structure of the 3·4·Cu·(ClO
ane-forming step. Reaction of the carboxylic acid derivative 5
assembly (prepared by a multi-step procedure described in the ESI†)
4
)
2
the 2,6-pyridyl-bis-ester threading component similarly inter- with N-hydroxysuccinimide in the presence of dicyclohexy-
penetrates the macrocycle’s cavity, with the iodine XB donor sub- carbodiimide (DCC) yielded the activated ester 6, which was
stituent projecting towards the macrocycle’s isophthalamide immediately reacted with the primary amine-functionalised
3
1
binding cleft. Coordinative bonds between the Cu(II) cation stoppering compound 7 in the presence of the macrocycle
and the pyridyl nitrogen and carbonyl oxygen atoms of the 3·Cu(ClO ) in CH CN/CH Cl 1/1. In order to facilitate purifi-
4
2
3
2
2
4
-iodopyridyl-2,6-bis-ester moiety are observed (Cu55–N40 dis- cation and characterisation of the [2]rotaxane product, the
tance: 2.030[5] Å; Cu55–O48 and Cu55–O52 distances: 2.370[5] paramagnetic Cu(II) cation template was removed by extraction
and 2.406[55] Å). Three additional Cu–N bonds between the with an aqueous EDTA/NH OH solution during work-up.
4
Scheme 3 Synthesis of the [2]rotaxane 8·Zn(ClO
4
)
2
. Reagents and conditions: (i) N-Hydroxysuccinimide, N,N’-dicyclohexylcarbodiimide, CH
2 2
Cl ,
r.t., 18 h; (ii) Et
3
N, CH
2
Cl
2
, CH
3
CN, r.t., 72 h; (iii) EDTA/NH OH(aq), 24%; (iv) Zn(ClO ·6H O, CH Cl , MeOH, r.t., 1 h. 82%.
4
4
)
2
2
2
2
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Subsequent purification by preparative thin layer chromato- porating a 4-iodopyridyl axle component, and amide func-
graphy (CH Cl /MeOH/sat. NH OH ) afforded the metal-free tional groups were installed in place of ester groups at the 2
2
2
4
(aq)
1
rotaxane 8 in 24% yield. In preparation for H NMR titration and 6 positions on the pyridine ring in order to provide
experiments, rotaxane 8 was then stirred with Zn(ClO
4
)
2
in greater chemical stability (Scheme 4).
CH Cl /MeOH to provide the diamagnetic zinc-complexed
A solid state structure of the complex 3·9·Cu(ClO ) provides
2
2
4 2
rotaxane 8·Zn(ClO
4
)
2
in 82% yield after recrystallisation.
confirmation of the successful Cu(II) directed formation of an
Synthesis of a [2]rotaxane incorporating a halogen bonding orthogonal pseudorotaxane assembly between the tris-amine
-iodopyridyl-2,6-dicarbonyl axle component. Initial attempts macrocycle and the modified bis-amide based threading
4
to employ an analogous activated ester stoppering strategy to ligand (Fig. 5).‡ The bis-azide-terminated threading compound
the synthesis of a halogen bonding rotaxane incorporating a 11 was therefore stirred with two equivalents of the alkyne-
3
2
4
-iodopyridyl-2,6-bisester axle centrepiece proved to be very functionalised stoppering compound 13 in the presence one
low yielding and inefficient. In addition, during the course of equivalent of the macrocycle 3·Cu(ClO , Cu(CH CN) PF
these preliminary experiments we observed the 4-iodopyridyl- TBTA and DiPEA in a CH Cl /CH CN solvent mixture. After
,6-bis-ester motif to be unstable towards ester hydrolysis and treatment of the crude product with EDTA/NH OH(aq), the
4
)
2
3
4
6
,
2
2
3
2
4
subsequent decarboxylation during chromatographic purifi- metal-free rotaxane 14 was purified by preparative thin layer
cation on silica. An alternative Cu(I)-catalysed azide–alkyne chromatography and isolated in 27% yield. The Zn(II) complex
cycloaddition (CuAAC) based stoppering methodology was 14·Zn(ClO ) was obtained in 86% yield by treatment of com-
4
2
4 2 2
therefore used to synthesise a halogen bonding rotaxane incor- pound 14 with Zn(ClO ) ·6H O. For comparison purposes the
Scheme 4 Synthesis of the [2]rotaxanes 14·Zn(ClO
4
)
2
and 15·Zn(ClO
, TBTA, DiPEA, CH Cl
4
)
2
. Reagents and conditions: (i) Methanesulfonyl chloride, Et
3
N, CH Cl
2
2
, 0 °C
to r.t.; (ii) NaN
r.t., 1 h.
3
, DMF, 50 °C; (iii) Cu(CH
3
CN)
4
PF
6
2
2
, CH CN, r.t., 48 h; (iv) EDTA/NH OH(aq); (v) Zn(ClO ·6H O, CH
3
4
4
)
2
2
2
Cl , MeOH,
2
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Fig. 5 Solid state structure of the pseudorotaxane assembly
3
4 2
·9·Cu·(ClO ) . For clarity, non-polar hydrogen atoms, non-coordinating
solvent molecules and non-coordinating perchlorate couteranions have
been omitted.
analogous [2]rotaxane 15·Zn(ClO ) , which lacks the iodine
4
2
halogen bond donor substituent, was also synthesised via the
same method and obtained in comparable yield.
Characterisation of metal-free [2]rotaxanes. The metal-free
rotaxanes 8, 14 and 15 were fully characterised by electrospray
1
13
mass spectrometry and H and C NMR spectroscopies. A
comparison of the H NMR spectrum of the metal-free [2] Fig. 7 (i) Comparative partial H NMR spectra of the macrocycle tris-
rotaxane 8 with those of its non-interlocked macrocycle and
1
1
amine macrocycle 3 (top), [2]rotaxane 14 (middle) and non-interlocked
axle component (bottom)§ in 1 : 1 CDCl : CD OD at 293 K.
3 3
axle components § in CDCl /CD OD (Fig. 6(i)) reveals signifi-
3
3
cant upfield shifts in the signals for the aromatic macrocycle
aromatic 4-alkoxybenzene protons f and g and bipyridine
protons 2 and 3 upon formation of the [2]rotaxane. This is sug-
gestive of mutual shielding of the aromatic π systems by stabi-
lising donor–acceptor interactions. Further evidence for this is
provided by the observation of through-space ROE interactions
between protons 2 and 3 and f and g in the 2-D ROESY spec-
trum of the rotaxane (Fig. 6(ii)). Similar upfield perturbations
in the shifts of the macrocycle protons f and g were observed
upon formation of the 4-iodopyridyl containing rotaxane 14
(
Fig. 7), suggesting the existence of similar intercomponent
aromatic donor–acceptor interactions in this [2]rotaxane.
However for this system no through-space interactions
between the interlocked components were observed by ROESY
spectroscopy, possibly as a result of the fluxional dynamic
nature of the system.
Characterisation of Zn(II)-complexed [2]rotaxanes. Successful
formation of the three Zn(II) rotaxane complexes was evidenced
by MALDI mass spectrometry, which revealed peaks centred at
1
927.2, 2197.8 and 2071.1, corresponding to the [M − 2ClO −
4
+
H] ions for compounds 8·Zn(ClO ) , 14·Zn(ClO ) and 15·Zn
4
2
4 2
1
(
ClO
4
)
2
respectively. The H NMR spectrum of the Zn(II)
is compared with that of the metal-free
complex 8·Zn(ClO )
4 2
rotaxane 8 in Fig. 8. In the presence of the Zn(II) cation the two
sides of the axle become inequivalent on the timescale of the
NMR experiment as a result of slower dynamic conformational
1
Fig. 6 (i) Comparative partial H NMR spectra of the macrocycle tris-
amine macrocycle 3 (top), [2]rotaxane 8 (middle) and non-interlocked
axle component (bottom)§ in 1 : 1 CDCl
3
: CD
the H– H ROESY NMR spectrum of the metal-free rotaxane 8 in
: 1 CDCl : CD OD at 293 K.
3
OD at 293 K; (ii) section of
1
1
§The non-interlocked axle components of the [2]rotaxanes 8 and 14 were iso-
1
3
3
lated as side-products of the rotaxane synthesis reactions.
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Zn(II) complex 14·Zn(ClO
4
)
2
are shown in Fig. 9. The observed
splitting of the axle proton signals and diastereotopic splitting
of the macrocycle CH proton signals again suggests a
2
reduction from the original C2v symmetry of the metal-free
rotaxane 14 upon metal binding. Both the axle iodopyridyl
proton signal 1′ and macrocycle alkoxybenzene signals f and g
are observed to shift upfield in the presence of the Zn(II)
cation. In addition through-space interactions between
protons f and g and 1 and 1′ are observed in the ROESY spec-
trum (Fig. S16, ESI†), consistent with an interlocked co-confor-
mation which involves parallel face-to-face stacking between
the 4-alkoxybenzene and 4-iodpyridine functional groups.
1
Fig. 8 Partial H NMR spectra of the metal free rotaxane 8 (top) and
zinc-complexed rotaxane 8·Zn(ClO
4 2 3 3
) (bottom) in CDCl : CD OD 1 : 1 at
298 K. Proton assignments for compound 8 are shown in Fig. 6.
Anion recognition properties of the heteroditopic [2]rotaxanes
[
2]Rotaxane 8·Zn(ClO
the Zn(II)-complexed rotaxane 8·Zn(ClO
NMR titration experiments in CDCl : CD OD 1 : 1. The tetra-
4 2
) . The anion recognition properties of
1
4 2
) were probed by H
interconversion, and a splitting of the majority of the axle
proton signals and macrocycle CH proton signals is conse-
quently observed, consistent with a reduction from C2v point
group symmetry to lower C symmetry. The aromatic bipyri-
dine protons 1 and 2 and macrocycle ethylene CH protons
3
3
2
butylammonium salts of a range of halide and oxoanions were
titrated into a solution of the rotaxane in CDCl : CD OD 1 : 1,
3
3
s
which resulted in perturbations of the chemical shifts signals
of protons 1–3, 1′–3′ and c which surround the rotaxane’s
interlocked binding cavity. In all cases the kinetics of exchange
2
i and j are deshielded by the presence of the cation within the
metal binding cavity. Conversely, the signals for the macro-
cycle aromatic protons f and g undergo significant upfield
shifts, presumably because the Zn(II) cation locks the macro-
cycle and axle components in a co-conformation in which the
π electron clouds of the axle bipyridyl and macrocycle 4-alkoxy-
benzene groups overlap. ROESY spectroscopy indicated several
through-space coupling interactions between the bipyridyl
protons 1, 1′, 2′, 3 and 3′ and the macrocycle aromatic protons
f and g, as well as one between the internal macrocycle proton
c and internal bipyridyl aromatic proton 3′, which is consistent
with the proposed conformation in which the axle bipyridine
group is intercalated between the macrocycle 4-alkoxybenzene
groups, with the isophthalamide and bipyridyl-bis-amide
groups converging towards a central anion binding cavity
1
were observed to be fast on the H NMR timescale at 500 MHz,
allowing association constants to be calculated by fitting the
chemical shift changes of the internal macrocycle proton c to
3
3
a 1 : 1 stoichiometric binding model using WinEQNMR soft-
ware (Table 1 and Fig. S19, ESI†). Addition of chloride,
bromide, iodide and nitrate anions induced downfield shifts
in the signals for the internal axle bipyridine proton 3 and
macrocycle isophthalamide proton c, consistent with multi-
dentate hydrogen bond donation from the axle bipyridine and
macrocycle isophthlamide groups to the encapsulated guest
anion (Fig. 10). The calculated association constants (Table 1)
−
−
−
−
reveal a selectivity for Cl and Br over I and NO
3
which can
be attributed to a combination of size-complementary, anion
(Fig. S8, ESI†).
Similar effects were observed upon complexation of Zn(II) to
1
the pyridyl-containing [2]rotaxanes 14 and 15. Illustrative Table 1 Stability constants,
spectra for the 4-iodopyridyl-functionlised rotaxane 14 and its [2]rotaxane host systems 8·Zn(ClO
with various anions in CDCl : CD
5 : 45 : 10 at 298 K
K
(M− ), for 1 : 1 complexes of the
4 2 4 2 4 2
) , 14·Zn(ClO ) and 15·Zn(ClO )
3
3
OD 1 : 1 or CDCl
3
: CD
3
OD : D
2
O
4
Ka (M−1)
X−
8·Zn·(ClO
)
b
14·Zn·(ClO
)
c
c
4
2
4
2
4 2
15·Zn·(ClO )
Cl−
1160
920
535
1080
500
925
540
—
−
Br
−
I
165
830
−
4
d
AcO
>10
3
NO −
270
570
315
a
Determined by fitting changes in the chemical shift of the internal
macrocycle proton c to a 1 : 1 stoichiometric binding isotherm using
3
3
WinEQNMR software. Errors associated with the curve fitting process
estimated expanded uncertainties at the 95% confidence interval
(
b
level) are <10%. All anion added as TBA salts. In CDCl
3
: CD
3
OD 1 : 1.
c
d
In CDCl : CD OD : D O 45 : 45 : 10. Addition of TBAAcO resulted in
3 3 2
1
1
Fig. 9 Partial H NMR spectra of the metal free rotaxane 14 (top) and
the appearance of a new set of H NMR signals in slow exchange with
OD 1 : 1 the spectrum of the original zinc(II) complexed rotaxane, which was
zinc-complexed rotaxane 14·Zn(ClO
4
)
2
(bottom) in CDCl
3
: CD
3
at 298 K. Proton assignments for compound 14 are shown in Fig. 7.
attributed to direct acetate anion ligation to the metal cation.
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Fig. 10 Partial H NMR spectra of the [2]rotaxane 8·Zn(ClO
presence of (i) 0, (ii) 1 and (iii) 5 equivalents of TBACl in CDCl
: 1 at 298 K.
4
)
2
in the
1
Fig. 11 Partial H NMR spectra of the [2]rotaxane 14·Zn(ClO
presence of (i) 0, (ii) and (iii) equivalents of TBACl in
CDCl : CD OD : D O 45 : 45 : 10 at 298 K.
4 2
) in the
3
: CD OD
3
1
5
1
3
3
2
basicity and anion solvation effects. The rotaxane’s overall
selectivity for acetate anions is incongruent with the selectivity
behaviour exhibited by structurally related interlocked host
molecules, which have previously been shown to bind chloride
and bromide anions in preference to more basic acetate
anions owing to the superior size-complementarity between
these spherical halide anions and the interlocked binding cav-
induced progressive downfield shifts in the aromatic cavity
proton signals 1′ and c (Fig. 11). In contrast, on addition of
TBAOAc a new set of peaks appeared in slow exchange with the
original signals, which may again indicate a different binding
mode involving direct ligation of the acetate anion to the
metal cation. Stoichiometric 1 : 1 association constants for the
1
3,34
3
3
ities of the host molecule.
A possible explanation is that
halide and nitrate anions were determined by WinEQNMR
the [2]rotaxane 8·Zn(ClO ) interacts with acetate anions via a
4
2
analysis of the titration data, monitoring proton c (Table 1 and
Fig. S21, ESI†). The association constants displayed in Table 1
for both the iodopyridine-functionalised XB rotaxane 14·Zn
different binding mode involving direct ligation of the acetate
anion to the Zn(II) cation. This is supported by analysis of the
chemical shift changes of the bipyridine protons 1 and 1′,
which move upfield in the presence of acetate, but downfield
in the presence of halide anions (Fig. S20, ESI†).
(
(
ClO
ClO
4
4
)
)
2
2
and C–H hydrogen bonding analogue compound 15·Zn
show in general that both rotaxanes exhibit less
effective discrimination between the halide and nitrate anions
compared to the bipyridyl rotaxane system 8·Zn(ClO . For
rotaxanes 14·Zn(ClO and 15·Zn(ClO the binding affinities
Notably, negligible spectral perturbations were observed
when halide anions were added to CDCl /CD OD solutions of
3 3
4 2
)
4
)
2
4 2
)
the neutral [2]rotaxane 8 in the absence of a co-bound Zn(II)
cation, which highlights the important role of the metal ion in
cooperatively enhancing the rotaxane’s anion binding affinities
via a combination of preorganisation and electrostatic effects.
for bromide, iodide and nitrate with respect to chloride are
increased, and an overall preference for bromide is observed.
This trend may be partially influenced by solvation factors: it
is likely that the addition of a 10% volume of D O to the
2
[
2]Rotaxane 14·Zn(ClO ) . For the [2]rotaxane 14·Zn(ClO ) ,
4 2 4 2
solvent mixture would result in a larger increase in the com-
petitive desolvation penalty for the relatively hydrophilic chlor-
ide anion than for the more hydrophobic bromide, iodide and
nitrate anions. The iodo-functionalised [2]rotaxane 14·Zn
1
H NMR titration experiments were performed in a more com-
petitive aqueous–organic solvent mixture CDCl : CD OD : D
5 : 45 : 10.¶ Addition of the TBA salts of halide and nitrate
anions to a 1.5 mM solution of the host in this solvent mixture
3
3
2
O
4
(
ClO
binding affinities than the C–H hydrogen bonding control
system 15·Zn(ClO . In particular nitrate and iodide are
4 2
) displays broadly comparable but slightly higher anion
4 2
)
¶
3 3
When the titration experiments were attempted in CDCl : CD OD 1 : 1 the equi-
bound with noticeably higher affinities by the rotaxane
bearing an iodine substituent. The differing anion recognition
libria appeared to be more complex and we were unable to obtain quantitative
1
binding data. As well as observing gradual shifts in the H NMR signals, an extra
behaviours displayed by rotaxane hosts 14·Zn(ClO
4 2
) and 15·Zn
set of peaks was observed to appear in slow exchange with the original signals,
possibly indicating a competing binding mode involving direct binding of the
anion to the metal cation in a contact ion-pair fashion.
(
ClO are best explained by an interplay between size com-
4 2
)
plementary considerations and subtle differences in host sol-
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vation and pyridyl C–H bond polarisation ensuing from the Allan, Mark Warren, Harriott Nowell, and Sarah Barnett) for
presence of the lipophilic and electronegative iodine substitu- technical support.
ent, along with a possible contribution from C–I⋯X− halogen
bonding interactions for the iodo-functionalised [2]rotaxane
1
4·Zn(ClO ) . In general the presence of the iodine substituent
4 2
Notes and references
results in only modest improvements in the receptor’s anion
recognition capabilities, suggesting that the C–I⋯X XB contri-
bution to anion binding by the [2]rotaxane 14·Zn(ClO ) is rela-
tively minor, with Coulombic and C–H⋯X and N–H⋯X HB
interactions playing a more dominant role, or that the steric
requirements of the iodine atom do not allow for favourable
XB and HB interactions between the rotaxane’s macrocycle
component isophthalamide and axle component iodopyridyl
groups to occur in a fully synergistic manner.
−
1 J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor
Chemistry, Royal Society of Chemistry, 2006.
2 N. H. Evans and P. D. Beer, Angew. Chem., Int. Ed., 2014, 53,
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3 N. Busschaert, C. Caltagirone, W. Van Rossom and
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4 A. Caballero, F. Zapata and P. D. Beer, Coord. Chem. Rev.,
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4
2
−
−
5
S. K. Kim and J. L. Sessler, Chem. Soc. Rev., 2010, 39, 3784–
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3
Conclusions
2
Three new heteroditopic [2]rotaxane ion-pair host systems
which contain axle separated interlocked binding cavities for
an anion and a transition metal cation were synthesised using
7
8
9
5
1
a copper(II) directed passive metal template strategy. H NMR
titration experiments revealed the [2]rotaxanes are capable of
cooperatively binding halide and nitrate anions in the pres-
ence of a co-bound zinc(II) cation. The hydrogen-bonding [2]
4 2
rotaxane 8·Zn(ClO ) was found to bind chloride and bromide
1
0 M. J. Langton, O. A. Blackburn, T. Lang, S. Faulkner and
P. D. Beer, Angew. Chem., Int. Ed., 2014, 53, 11463–
1
selectively over nitrate and iodide anions in a competitive
protic CDCl : CD OD 1 : 1 solvent mixture. The related [2]rotax-
3
3
1466.
1 R. C. Knighton and P. D. Beer, Chem. Commun., 2014, 50,
540–1542.
2 N. H. Evans, C. J. Serpell and P. D. Beer, Chem. Commun.,
011, 47, 8775–8777.
3 L. M. Hancock, E. Marchi, P. Ceroni and P. D. Beer, Chem.
Eur. J., 2012, 18, 11277–11283.
ane host system 14·Zn(ClO
pyridine XB donor group, and a C–H HB control system 15·Zn
ClO were both found to display enhanced affinities for
4 2
) which contains a potential iodo-
1
1
1
1
1
(
4 2
)
bromide and iodide with respect to chloride in a more com-
2
petitive CDCl : CD OD : D O 45 : 45 : 10 aqueous–organic
3
3
2
solvent mixture. Subtle differences between the anion reco-
gnition properties of the XB functionalised rotaxane 14·Zn
–
4 J. Lehr, T. Lang, O. A. Blackburn, T. A. Barendt,
(
ClO4)2 and HB analogue 15·Zn(ClO4)2 were observed,
suggesting that the XB contribution to anion binding by the
2]rotaxane 14·Zn(ClO is relatively minor, with Coulombic
S. Faulkner, J. J. Davis and P. D. Beer, Chem. – Eur. J., 2013,
19, 15898–15906.
[
4 2
)
1
1
1
1
5 J. Y. C. Lim, M. J. Cunningham, J. J. Davis and P. D. Beer,
Dalton Trans., 2014, 43, 17274–17282.
6 A. Brown, M. J. Langton, N. L. Kilah, A. L. Thompson and
P. D. Beer, Chem. – Eur. J., 2015, 21, 17664–17675.
7 M. J. Langton, I. Marques, S. W. Robinson, V. Félix and
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8 In a related example, an ion-pair rotaxane host system
which binds anions in the presence of a co-bound tetra-
butylammonium cation has recently been reported:
J. R. Romero, G. Aragay and P. Ballester, Chem. Sci., 2016, 8,
−
−
and C–H⋯X and N–H⋯X HB interactions playing a more
dominant role.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
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We thank the European Research Council (under the 19 S. Saha, I. Ravikumar and P. Ghosh, Chem. Commun., 2011,
th
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7
Framework programme (FP7/
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2
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