Sulfate anion-templated assembly of a [2]catenane

Article abstract of DOI:10.1039/b808094a

The sulfate anion's templating role in catenane formation is demonstrated for the first time; a novel bis-pyridinium nicotinamide [2]catenane is prepared in a remarkable high yield and is shown to exhibit selectivity for sulfate, the templating anion. The Royal Society of Chemistry.

Full text of DOI:10.1039/b808094a

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Sulfate anion-templated assembly of a [2]catenanew
Buqing Huang,a Sergio M. Santos,b Vitor Felixb and Paul D. Beer*a
Received (in Austin, TX, USA) 12th May 2008, Accepted 8th June 2008
First published as an Advance Article on the web 13th August 2008
DOI: 10.1039/b808094a
The sulfate anion’s templating role in catenane formation is
demonstrated for the first time; a novel bis-pyridinium nicotina-
mide [2]catenane is prepared in a remarkable high yield and is
shown to exhibit selectivity for sulfate, the templating anion.
The strategic use of anions as potential templating reagents for
the designed assembly of molecular architectures remains in its
infancy,1 which is somewhat surprising given the rapid growth
in the field of anion supramolecular chemistry in recent years.2
Rare examples, where specific inorganic anions have been
demonstrated to play a templating role in the synthesis of
organic-based systems, have been largely restricted to expanded
porphyrins,3 polypyrrolic,4 hexaurea5 and peptidic6 macro-
cycles. During the past few years, we have developed a general
method of using the chloride anion to template the formation of
a range of interpenetrated and interlocked assemblies.7 With a
view to discovering other potential anion templating species for
mechanical bond formation, we have recently demonstrated
that the sulfate anion is capable of templating the formation of
a pseudorotaxane assembly between two neutral components.8
Encouraged by this observation, we now report the unprece-
dented templating role of sulfate in the synthesis of a [2]cate-
nane structure. In fact, to the best of our knowledge, no
examples of the sulfate anion-templated synthesis of interlocked
molecular architectures exist in the literature. The novel bis-
pyridinium nicotinamide [2]catenane, 12+, is obtained in a
remarkably high yield exclusively with this oxodianion, and
its unique interlocked binding domain is shown to exhibit
Scheme 1
Condensation of nicotinic acid chloride 2 with vinyl-
functionalised amine derivative 311 gave amide 4 in 80% yield.
The reaction of 3 with bromo acetyl bromide afforded bro-
momethylene-functionalised amide compound 5 in 92% yield.
The alkylation of 4 with 5 in refluxing acetonitrile solution
produced the acyclic bis-vinyl pyridinium nicotinamide deri-
vative 6+ as its bromide salt. Anion exchange using silver
sulfate, ammonium chloride and silver hexafluorophosphate
gave the respective acyclic pyridinium nicotinamide salts,
selectivity for sulfate, the templating anion.
Influenced by Sauvage et al.’s imaginative exploitation of
the tetrahedral directing nature of the copper(I) cation for
catenane formation,9 in an analogous fashion, the sulfate
dianion is an attractive potential template for the orthogonal
assembly of two monocationic positively-charged compo-
nents.10 With this in mind, the acyclic bis-vinyl pyridinium
nicotinamide cation 6+ was initially prepared as a precursor
for subsequent sulfate anion-templated double ring-cyclized
formation of the target catenane.
(6+)2SO42À, 6+ClÀ and 6+PF6 (Scheme 1).
À
The simple addition of Grubbs’ second generation RCM
2À
catalyst to a dichloromethane solution of (6+)2SO4 at room
a Department of Chemistry, Inorganic Chemistry Laboratory,
University of Oxford, South Parks Road, Oxford, UK OX1 3QR.
E-mail: paul.beer@chem.ox.ac.uk; Fax: +44 (0)1865 272690;
temperature, followed by purification using preparative silica
TLC, gave the target [2]catenane, 12+SO42À, in a remarkable
yield of 80% (Scheme 2). It is noteworthy that analogous RCM-
catalysed reactions with the chloride, bromide or hexafluoro-
phosphate salts of 6+ failed to produce any catenane. This
highlights the crucial templating role of sulfate where, in addition
to favourable electrostatic interactions, the orthogonal arrange-
ment of four amide hydrogen bond-donating groups from two
molecules of 6+ complements the anion’s tetrahedral shape.
Tel: +44 (0)1865 285142
b
´
´
Departamento de Quımica, CICECO and Secc¸a˜o Autonoma de
Cieˆncias da Sau´de, 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 and 6, general procedures
for 1H NMR titration and supporting molecular dynamic simulations.
See DOI: 10.1039/b808094a
ꢀc
This journal is The Royal Society of Chemistry 2008
4610 | Chem. Commun., 2008, 4610–4612

View Article Online
À
À
)
and 6+PF6
2
Table 1 Association constants (/MÀ1) for 12+(PF6
with SO42À, ClÀ, BrÀ and OAcÀ at 298 K in 1 : 1 d-chloroform/
d4-methanola
ClÀ
BrÀ
OAcÀ
2À
SO4
À
1
6
a
2+(PF6
)
2200
1120
780
100
55
0
0
1850
2
À
+PF6
Errors less than 10%, determined by monitoring the ortho-pyridinium
proton k.
cavity. The hydroquinone protons split into four doublets and
move upfield, indicative of p–p stacking interactions.
ESI-MS revealed an intense doubly-charged molecular ion
at m/z = 592.23, corresponding to 12+, for all the catenane
salts and a singly-charged ion at m/z = 1219.65 for the
chloride complex 12+ClÀ.
Proton NMR anion titration studies of the catenane
2+(PF6À)2 were undertaken in a 1 : 1 CDCl3/CD3OD solu-
Scheme 2 Sulfate-templated catenation.
1
Removal of the sulfate-templating anion from the catenane
was achieved via exchange with chloride upon the addition of
tion, alÀong with the acyclic pyridinium nicotinamide derivative
6+PF6 for comparison purposes. Both the amide and ortho-
pyridinium protons of the catenane shifted significantly down-
field upon addition of sulfate and chloride anions.
BaCl2, followed by silver hexafluorophosphate conversion to
1
1
2+(PF6À)2. All the catenane salts were characterised by H
NMR, ESI-MS and elemental analysis (see ESIw). Fig. 1
Interestingly, by way of contrast, with acetate and bromide,
modest perturbations were seen, suggesting weak binding. Job
plot and WinEQN MR12 analysis of the titration data enabled
association constants for 1 : 1 complexes to be determined.
Table 1 shows that the catenane strongly and selectively binds
sulfate in preference to chloride, bromide and acetate, where the
latter two anions are verÀy weakly bound. In stark contrast, the
acyclic receptor 6+PF6 forms the strongest complex with
acetate, followed by sulfate, chloride and bromide. No doubt,
the topologically-constrained, unique catenane binding pocket
complements the tetrahedral geometry of sulfate, which
accounts for the observed selectivity trend. The non-comple-
mentary trigonal planar acetate anion presumably is unable to
1
À
compares the H NMR spectra of 6+PF6À, 12+ClÀPF6 and
1
2+SO42À. Upon sulfate-templated catenation, amide protons
j, p and ortho-pyridinium nicotinamide proton k are signifi-
cantly shifted downfield by Dd = 2.15, 2.12 and 2.02, respec-
tively, which indicates strong anion binding in the catenane
penetrate the catenane’s anion binding domain. With 6+PF6
,
À
as commonly found for acyclic receptor systems, the oxobasicity
of the coordinating anion dictates the strength of binding.2
Further insights into catenane structure and selectivity
trends were gained by molecular dynamic simulations using
AMBER913 software and the general amber force field
(GAFF)14 by following the experimental procedure described
in the ESI.w Determination of the lowest energy co-conforma-
tions of several species studied was performed via gas phase
simulated annealing procedures.
Fig. 2 Lowest energy structure of 12+SO42À, obtained by gas phase
simulated annealing molecular dynamics. Hydrogen bonds are shown
as yellow dashes. Non-interacting hydrogens have been omitted for
clarity.
Fig. 1 1H NMR spectra (CDCl3, 298 K) of (a) 6+PF6À, (b)
(1+)2SO4 and (c) 12+ClÀPF6
.
2À
À
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 4610–4612 | 4611

View Article Online
encapsulated within the catenane cavity, with average dis-
tances between the four oxygen atoms and N–H binding sites
ranging from 1.87 to 2.13 A (calculated using a cut off of
2.5 A). Also, an average of 4.69 hydroxyl hydrogens from
methanol, were found to be oriented towards and within 3.4 A
of the sulfate oxygens, thus completing the anion’s first
coordination shell and stabilizing its negative charge.
In contrast, for 12+ClÀ, only 1.14 hydroxyl hydrogens were
found within the same distance of the chloride, clearly indicating
that this anion was now highly enclosed by the catenane,
hindering its contact with the outer solvent medium. In this case,
average N–HÁ Á ÁClÀ distances ranging from 2.35 to 2.68 A were
obtained, using a 3.0 A cut off. Interestingly, despite the more
compact association of the catenane with chloride, the calculated
Fig. 3 Lowest energy structure of 12+CH3CO2À, obtained by gas
phase simulated annealing molecular dynamics. Details as in Fig. 2.
2À
relative binding free energies of SO4
and ClÀ to 12+ at
300 K unambiguously indicate the former to be favoured by
12.93 kcal molÀ1, corroborating the experimental anion titration
results. The association process was found to be enthalpy driven,
with an entropic contribution of TDS = À26.01 kcal molÀ1. In
summary, the sulfate anion has been demonstrated as a highly
efficient templating motif for catenane formation.
S. M. S. acknowledges FCT—Fundac¸ ao para a Ciencia e
Fig. 4 Lowest energy structure of 12+ClÀ, obtained by gas phase
Tecnologia—for their financial support under a PhD scholar-
ship SFRH/BD/29596/2006. The authors acknowledge the
FCT, with co-participation of the European Community
funds FEDER, for their financial support under project
PTDC/QUI/68582/2006 (V. F.).
simulated annealing molecular dynamics. Details as in Fig. 2.
2À
The lowest energy structure obtained for 12+SO4 pre-
sents, as expected from the experimental data, the anion within
the catenane binding pocket, establishing multiple hydrogen
bonds to the amide hydrogens of the catenane chains (Fig. 2).
It is interesting to note that the pyridinium rings are almost
coplanar, rather than being arranged in a perpendicular
fashion relative to each other, as depicted in Scheme 2. None-
theless, the former disposition allows for the simultaneous
establishment of six hydrogen bonds, with distances ranging
from 1.69 to 2.43 A, whereas the latter disposition would only
allow four. The two sets of staggered stacking rings (each
formed by a pyridinium and hydroquinone unit) are consistent
with p–p interactions, despite the offset of one set of rings,
which are dislocated from the stacked position due to the size of
the anion and the spatial disposition adopted by the amides. A
Notes and references
1 R. Vilar, Angew. Chem., Int. Ed., 2003, 42, 1460.
2 J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor Chemistry,
Royal Society of Chemistry, Cambridge, 2006; Supramolecular
Chemistry of Anions, ed. A. Bianchi, K. Bowman-James and E.
Garcıa-Espana, Wiley-VCH, New York, 1997; Anion Coordination
´
Chemistry II, ed. P. A. Gale, Coord. Chem. Rev., 2007, 250(23).
3 J. L. Sessler, T. D. Mody and V. Lynch, J. Am. Chem. Soc., 1993,
115, 3346.
4 E. A. Katayev, G. D. Pantos, M. D. Reshetova, V. N. Khrustalev,
V. M. Lynch, Y. A. Ustynyuk and J. L. Sessler, Angew. Chem., Int.
Ed., 2005, 44, 7386.
5 D. Meshcheryakov, V. Bohmer, M. Bolte, V. Hubscher-Bruder,
F. Arnaud-Neu, H. Herschbach, A. Van Dorsselaer, I. Thondorf
and W. Mogelin, Angew. Chem., Int. Ed., 2006, 45, 1648.
6 (a) S. Otto and S. Kubik, J. Am. Chem. Soc., 2003, 125, 7804;
(b) M. Bru, I. Alfonso, M. I. Burguete and S. V. Luis, Angew.
Chem., Int. Ed., 2006, 45, 6155.
7 P. D. Beer, M. R. Sambrook and D. Curiel, Chem. Commun., 2006,
2105; M. D. Lankshear and P. D. Beer, Acc. Chem. Res., 2007, 40, 657.
8 M. J. Chmielewski, L. Zhao, A. Brown, D. Curiel, M. R.
Sambrook, A. L. Thompson, S. M. Santos, V. Felix, J. J. Davis
and P. D. Beer, Chem. Commun., 2008, 3154.
similar co-conformation was encountered for 12+CH3CO2
À
(Fig. 3), in which three hydrogen bonds are present (N–HÁ Á ÁO
distances of 1.79, 1.83 and 2.09 A), and the relative disposition
of the aromatic rings resembles that of 12+SO42À. However, as
suggested by the solution titration studies, the acetate anion is
not included in the catenane cavity. The effect of the nature of
the anion on the spatial organization of the catenane is quite
remarkable when the anion is ClÀ. The relatively small size of
chloride (compared to the stereoelectronic requirements of
acetate and sulfate) allows for complete staggered stacking of
the aromatic rings, along with p–p interactions, and thus the
adoption of an overall elongated co-conformation, having
N–HÁ Á ÁClÀ distances ranging from 2.14 to 3.35 A. Further-
more, an almost perpendicular disposition of the pyridinium
rings relatively to each other is adopted (Fig. 4).
9 C. O. Dietrich-Buchecker, J.-P. Sauvage and J. P. Kintzinger,
Tetrahedron Lett., 1983, 24, 5095; C. O. Dietrich-Buchecker,
J.-P. Sauvage and J. M. Kern, J. Am. Chem. Soc., 1984, 106, 3043.
10 For examples of sulfate anion templation see: refs. 4 and 6a; B.
Hasenknopf, J.-M. Lehn, N. Boumediene, A. Dupont-Gervais, A.
Van Dorsselaer, B. O. Kneisel and D. Fenske, J. Am. Chem. Soc.,
1997, 119, 10956; J. Sa
´
Mendoza, J. Am. Chem. Soc., 1996, 118, 277; V. Kra
nchez-Quesada, C. Seel, P. Prados and J. de
l, F. P.
´
Schmidtchen, K. Lang and M. Berger, Org. Lett., 2002, 4, 51.
11 M. R. Sambrook, P. D. Beer, J. A. Wisner, R. L. Paul and A. R.
Cowley, J. Am. Chem. Soc., 2004, 126, 15364.
12 M. J. Hynes, J. Chem. Soc., Dalton Trans., 1993, 311.
13 AMBER9, University of California, San Francisco, 2006.
14 J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman and D. A.
Case, J. Comput. Chem., 2004, 25, 1157.
The dynamic behaviour of the previously described co-
conformations was evaluated in a solution of 1 : 1 CH3OH/
CHCl3 using conventional molecular dynamics. The
2À
results obtained show that 12+SO4 was stable during the
entire course of the simulation (10 ns), having the anion
ꢀc
This journal is The Royal Society of Chemistry 2008
4612 | Chem. Commun., 2008, 4610–4612