Anion induced and inhibited circumrotation of a [2]catenane

Article abstract of DOI:10.1039/b719304a

The first example of a catenane capable of performing circumrotation via an anion switching methodology is described; of particular interest is a conformational locking mechanism which results from chloride coordination in the catenane binding cavity. The Royal Society of Chemistry.

Full text of DOI:10.1039/b719304a

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Anion induced and inhibited circumrotation of a [2]catenanew
a
b
b
a
a
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Ka-Yuen Ng, Vitor Felix, Sergio M. Santos, Nicholas H. Rees and Paul D. Beer*
Received (in Austin, TX, USA) 16th December 2007, Accepted 9th January 2008
First published as an Advance Article on the web 30th January 2008
DOI: 10.1039/b719304a
The first example of a catenane capable of performing circum-
rotation via an anion switching methodology is described; of
particular interest is a conformational locking mechanism which
results from chloride coordination in the catenane binding cavity.
solution. Of particular interest were the observed through
space proton–proton correlation signals between the ortho-
pyridinium proton b of the pyridinium macrocycle with the
hydroquinone and polyether protons of the phenolic contain-
ing macrocycle (see dotted lines in Fig. S7w). This is indicative
of the expected intercalation of the electron deficient positively
charged pyridinium ring motif between the electron rich
hydroquinone groups stabilised by favourable p–p stacking
interactions (Fig. 1).
Inspired by the potential applications mechanically bonded
molecules may have as molecular switches and machines, the
interest being shown in their construction and surface assem-
bly is ever increasing.1 However, the use of rotaxane and
catenane cavities as binding domains for the recognition and
sensing of guest species remains largely underdeveloped2
which is surprising given their unique three-dimensional topo-
logical interlocked cavity design. In addition, such mechani-
cally bonded ‘host’ molecules have the possibility of exhibiting
host–guest binding induced molecular-machine like beha-
viour.3 Whereas cations have been frequently used to effect
switching between states,4 by contrast examples of anion
mediated interlocked switches are rare and have been, to our
knowledge, restricted to rotaxane based systems.5 We report
herein a new [2]catenane (1+) which undergoes phenolate
anion induced intra-ring circumrotation of one macrocycle
around the other on addition of base. Furthermore, chloride
anion recognition at the catenane’s binding site inhibits the
rotation process.
The addition of one molar equiv. of base DBUÀor phos-
phazene base P1-tBu-tris(tetramethylene)7 to 1+PF6 resulted
in significant downfield shifts of the pyridinium para proton c
and amide proton d in a variety of solvents including 9 : 1 d-
chloroform : d6-DMSO (Hc Dd = 0.49 ppm, Hd Dd = 0.40
ppm), d3-acetonitrile (Hc Dd = 0.93 ppm, Hd Dd = 1.70 ppm),
d3-nitromethane (Hc Dd = 0.15 ppm, Hd Dd = 0.27 ppm)8 and
d6-DMSO (Hc Dd = 0.09 ppm, Hd Dd = 0.10 ppm) (Fig. 2).
Similar observations were also noted when N1,N3-bishexyl-5-
hydroxyisophthalamide was added to the pyridinium macro-
À
cycle 2+PF6 in the presence of base. These results suggest
that following deprotonation of the catenane’s phenol group
by base, the presence of the phenolate anion in the isophtha-
lamide containing macrocycle induces the pyridinium macro-
cycle to undergo a circumrotation which results in the
negatively charged phenolate anion being stabilised via hydro-
gen bonding with the bis-amide pyridinium motif’s cleft
(Scheme 2). Further evidence for the phenolate anion induced
circumrotation of the catenane comes from the absence of any
pyridinium proton b–hydroquinone and polyether proton
correlation signals in the rotated conformer’s ROESY
spectrum (see ESIw).
Adapting our recently reported general method of using
anions to template the formation of a range of interpenetrated
and interlocked structures,6 the new [2]catenane 1+ClÀ was
synthesised in 37% yield by mixing equimolar amounts of
pyridinium containing macrocycle 2+IÀ and acyclic bis-vinyl
derivative 3 in the presence of TBA chloride template, fol-
lowed by addition of Grubbs’ first generation RCM catalyst
(Scheme 1). Purification by column chromatography and
subsequent anion exchange afforded the target catenane
It is noteworthy that the addition of trifluoroacetic acid
(TFA) reverses the rotation process back to the catenane’s
intercalated pyridinium group co-conformation.
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1
1+PF6 which was characterised by H, 13C, 19F NMR and
It was of further interest to investigate whether chloride
anion complexation in the unique catenane’s interlocked
binding pocket would inhibit the phenolate anion induced
electrospray MS (see ESIw).
1
ROESY H–1H NMR spectroscopy was used to determine
the relative co-conformational orientations of the two macro-
À
cyclic rings of 1+PF6 in 9 : 1 d-chloroform : d6-DMSO
a Inorganic Chemistry Laboratory, Department of Chemistry,
University of Oxford, South Parks Road, Oxford, UK OX1 3QR.
E-mail: paul.beer@chem.ox.ac.uk; Fax: +44 (0)1865-272690;
Tel: +44 (0)1865-285142
b
´
Departamento de Quımica, CICECO e Escola Superior de Saude,
Universidade de Aveiro, 3810-193 Aveiro, Portugal.
´
E-mail: vitor.felix@ua.pt; Fax: +351 234-370084;
Tel: +351 234-370729
w Electronic supplementary information (ESI) available: Synthesis
and characterisation data for compounds 1–3, general procedures
for 1H NMR titrations and ROESY spectra and supporting molecular
mechanics structures. See DOI: 10.1039/b719304a
Scheme 1 Synthesis of [2]catenane 1+PF6
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Fig. 1 Structure of catenane 1+
.
rotatioÀn process. Proton NMR titration experiments of
1+PF6 with TBA chloride in 9 : 1 d-chloroform : d6-DMSO
revealed typical downfield shifts of both types of amide
protons, d and g, along with pyridinum/aromatic c and f
protons indicative of halide encapsulation. Subsequent addi-
tion of phosphazene base P1, however, did not result in any
significant change in the spectrum (Fig. 3).
The ROESY spectrum of 1+ClÀ was recorded before and
after the addition of base. Both ROESY spectra show that all
the important correlation peaks are preserved after deproto-
nation (see ESIw). This suggests chloride ion complexation in
the catenane binding pocket inhibits the pyridinium contain-
ing macrocycle from rotating to the phenolate site on base
addition.
Scheme 2 Strategy for anion induced circumrotation.
Further insights into the catenane co-conformations of 1+,
4 and 4ÁClÀ were obtained by molecular dynamics (MD)
simulations, using the AMBER99 software. The lowest energy
conformers for these three interlocked structures were ob-
tained in the gas phase by simulated annealing methods.
Subsequently, their dynamic behaviour in solution was eval-
uated in acetonitrile at 300 K during 10 ns, using uncon-
strained molecular dynamics simulations.w The molecular
mechanics (MM) lowest energy structure found for 1+
(Fig. 4) exhibits the pyridinium and phenol moieties interca-
lated between the two hydroquinone aromatic rings of the
ether linkages of the opposite chains, at average interplanar
distances consistent with the existence of p–p stacking inter-
actions. The OH group of the phenolic ring is hydrogen
bonded to the central ether oxygen of the pyridinium macro-
cycle at an O–HÁ Á ÁO distance of 1.81 A. It is noteworthy that
the amide groups of the pyridinium unit adopt a syn disposi-
tion while those from the phenol bisamide cleft are anti. This
co-conformation is stabilised by two N–HÁ Á ÁO hydrogen
bonds between an amide carbonyl of the phenolic chain and
the two N–H binding sites of the pyridinium macrocycle, at
N–HÁ Á ÁO distances of 2.35 and 2.23 A.
Fig. 3 1H NMR titration (500 MHz, 298 K, 9 : 1 d-chloroform :
d6-DMSO) of (a) 1+PF6À, (b) addition of 1 molar equiv. of TBACl to
(a) and (c) addition of 1 molar equiv. of phosphazene base P1 to (b).
MD simulations in acetonitrile show that the two
N–HÁ Á ÁOamide hydrogen bonds occur simultaneously for large
periods, at average distances of 2.57(33)10 and 2.40(32) A; the
binding interactions between the phenol group and the poly-
ether oxygen atoms of the pyridinium macrocycle oscillate
between one and two bifurcated O–HÁ Á ÁOether hydrogen
bonds.
The conformational analysis carried out for the phenolate
[2]catenane 4 yielded a folded interlocked structure with both
Fig. 2 1H NMR (500 MHz, 298 K) of (a) 1+PF6 in 9 : 1 d-chloroform : d6-DMSO and (b) after addition of 1 molar equiv. of P1 base.
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The design of anion switchable interlocked systems is con-
tinuing in our laboratories.
Ka-Yuen Ng would like to thank the Clarendon Fund and
the Overseas Research Student (ORS) Awards Scheme for a
scholarship. Sergio M. Santos acknowledges Fundac¸ ao para a
´
Ciencia e Tecnologia (FCT) for financial support in the form
of PhD scholarship SFRH/BD/29596/2006.
Fig. 4 MM structure of 1+ showing the p–p stacking arrangement
and hydrogen bonds (cyan dashes). Only the hydrogen atoms of the
bisamide clefts are shown for clarity.
Notes and references
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Fig. 5 MM structure of 4 showing the hydrogen bonds between the
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pyridinium cleft and phenolate oxygen donor. Details as in Fig. 4.
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8 Value at 0.6 equiv. of phosphazene base P1; the peaks broadened
into baseline upon further addition of base in d3-nitromethane.
9 D. A. Case, T. A. Darden, T. E. Cheatham, III, C. L. Simmerling, J.
Wang, R. E. Duke, R. Luo, K. M. Merz, D. A. Pearlman, M.
Crowley, R. C. Walker, W. Zhang, B. Wang, S. Hayik, A. Roit-
berg, G. Seabra, K. F. Wong, F. Paesani, X. Wu, S. Brozell, V.
Tsui, H. Gohlke, L. Yang, C. Tan, J. Mongan, V. Hornak, G. Cui,
P. Beroza, D. H. Mathews, C. Schafmeister, W. S. Ross and P. A.
Kollman, AMBER9, University of California, San Francisco, 2006.
10 Values in parentheses correspond to the standard deviation of the
mean (N = 50 000), so that 2.57(33) is equivalent to 2.57 Æ 0.33.
The remaining cases will follow this presentation.
Fig. 6 MM structure of the chloride locked complex 4ÁClÀ. Details as
in Fig. 4.
bisamide groups adopting a syn disposition (Fig. S11 in ESIw).
However, when this conformation was immersed in acetoni-
trile and submitted to an MD run, the structure unfolded itself
in the first 100 ps, after breaking two N–HÁ Á ÁOether hydrogen
bonds, and remained so until the end of the simulation (10 ns).
The corresponding molecular mechanics minimised average
structure is depicted in Fig. 5. During the course of the
simulation, the phenolate ring is maintained intercalated
between the two hydroquinone motifs, at interplanar distances
consistent with either face-to-face or face-to-edge p–p stacking
interactions, whereas the two N–HÁ Á ÁOphenolate hydrogen
bonds were kept at average distances of 2.23(27) and
2.27(28) A.
The lowest energy conformation search of 4ÁClÀ yielded a
structure (Fig. 6) having the chloride encapsulated into the
[2]catenane cavity in a tetrahedral fashion, establishing four
N–HÁ Á ÁClÀ hydrogen bonds ranging from 2.26 to 2.50 A. The
corresponding MD simulation shows that the four hydrogen
bonds occur simultaneously during most of the simulation
period leading to N-HÁ Á ÁCl average distances of 2.46(18),
2.46(18), 2.60(22) and 2.59(22) A.
The MD structures thus described for 1+, 4 and 4ÁClÀ are
1
entirely consistent with H NMR solution studies.
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Chem. Commun., 2008, 1281–1283 | 1283