Self-assembly of a [2 x 2] hydrogen bonded grid

Article abstract of DOI:10.1039/a903446c

Formation of 24 cooperative hydrogen bonds drives the spontaneous assembly of a rigid bifunctional trimelamine and bis(barbituric acid) to give selectively the [2 x 2] hydrogen-bonded grid, in preference to the corresponding [1 x 1] or polymeric assemblie

Full text of DOI:10.1039/a903446c

Self-assembly of a [2 3 2] hydrogen bonded grid
Piotr Lipkowski,a Anna Bielejewska,a Huub Kooijman,b Anthony L. Spek,b† Peter Timmerman*a and David
N. Reinhoudt*a
a Laboratory of Supramolecular Chemistry and Technology, MESA+ Research Institute, University of Twente, PO
Box 217, NL-7500 AE Enschede, The Netherlands. E-mail: d.n.reinhoudt@ct.utwente.nl.
b Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry, Utrecht University, Padualaan 8,
NL-3584 CH Utrecht, The Netherlands
Received (in Liverpool, UK) 28th April 1999, Accepted 3rd June 1999
Formation of 24 cooperative hydrogen bonds drives the
spontaneous assembly of a rigid bifunctional trimelamine
and bis(barbituric acid) to give selectively the [2 3 2]
hydrogen-bonded grid, in preference to the corresponding
[1 3 1] or polymeric assemblies.
measurements which give an average MW of 2500, very close
to the calculated MW of 2800.§ Furthermore, MALDI-TOF
mass spectrometry after Ag+ labeling12 shows a small but
distinct signal for the Ag+ complex of 2b2•32 (m/z 2924; calc.
for C152H180N44O12•109Ag+ = 2924) together with that for the
(open) 2b•3 (not shown) (m/z 1517; calc. for
C76H90N22O6•109Ag+ = 1517). The presence of the latter is due
to destruction of assembly 2b2•32 upon addition of AgO2CCF3,
most likely due to strong coordination of Ag+ to the hydrogen-
bonded triazine nitrogen.¶
In 1992 Youinou and co-workers reported the formation of a
[Cu4(dppn)4](CF3SO3)4 complex in which the dppn [3,6-bis(2A-
pyridyl)pyridazine] ligands are perpendicularly oriented pair-
wise around four Cu+ centers thus forming a sandwich-type
complex.1 Very similar structures generally referred to as
[n 3 n] ‘metallosupramolecular grids’ have been reported by
Lehn and co-workers.2–4 Information storage both on the
covalent and on the supramolecular level determines the overall
size [n 3 n] and shape (grid vs. helix) of the assembly.5 We are
currently investigating the self-assembly of [n 3 m] hydrogen-
bonded grids using the melamine–barbituric acid (M•BA)
binding motif.6 The formation of six cooperative hydrogen
bonds between dimelamine 1 and 5,5-diethylbarbituric acid
(DEB) (Kass = 7.6 3 104 M21 in CDCl3) restricts the rotations
around the Ctriazine–NH, the NH–CH2, and the CH2–Cphenyl
bonds in 1, giving the semi-rigid flat assembly 1•DEB.7 Here
we describe the formation of [2 3 2] grid 2b2•32, the simplest
example of this type of hydrogen-bonded assemblies.8 The grid
has been fully characterized by 2D NMR spectroscopy,
MALDI-TOF mass spectrometry, and vapor pressure osmo-
metry (VPO).
1
The H NMR spectrum of the 1+1 mixture of 2b and 3 in
CDCl3 confirms the exclusive formation of the [2 3 2] grid
2b2•32. The spectrum of 2b2•32 at 60 °C [see Fig. 2(a)] shows
a broad signal at d14.0 (NHbarb), a singlet at d 7.65 ppm (ArH)
and two signals at d 7.1 (NHxylyl + ArH) and 6.76 (NHxylyl).
Both the NHbutyl and the NH2 protons coincide with the
aromatic proton signals for the four benzyl groups (d 7.4–7.2).
Furthermore, three singlets at d 4.84, 4.62 and 4.51 (CH2Ar) and
a doublet at d 3.33 [NHCH2(CH2)2CH3] are observed. At lower
temperatures ( < 30 °C), two signals are observed at d 14.6 and
14.0, one broad and one sharp,∑ and a complex pattern of signals
The synthesis of trimelamine 2b starts from cyanuric chloride
via successive reactions with Bn2NH (1.0 equiv.) and BuNH2
(1.0 equiv.), followed by refluxing in neat m-xylylenediamine
to give 4 in 92% yield (Scheme 1). Reaction of 4 with cyanuric
chloride (0.5 equiv.) and subsequent aminolysis of the corre-
sponding chloride 2a with excess of NH3 gives 2b in 85%
yield.9 Bis(barbituric acid) derivative 3 was synthesized starting
with the alkylation of diethyl 2-ethylmalonate with 1,3-diiodo-
propane in 35% yield,10 followed by reaction with urea (NaOEt/
EtOH) in 25% yield.11
Assembly of 2b and 3 can in principle lead to three different
hydrogen-bonded structures (see Scheme 1), i.e. the [1 3 1]
assembly 2b•3, the [2 3 2] (grid) assembly 2b2•32, and the
polymeric assembly [2b•3]n. Bis(barbituric acid) 3 was de-
signed such that the formation of the [1 3 1] assembly, which
would be preferred on entropic grounds,† is impossible. The
short n-propyl spacer does not allow two barbituric acid
moieties of one molecule of 3 to bind simultaneously to both
binding sites of one molecule of 2b. The X-ray crystal structure
of free 3‡ [see Fig. 1(a)] clearly confirms this picture and shows
that the conformation adopted in the solid state is fully
consistent with formation of the [2 3 2] grid 2b2•32 [see Fig.
1(b)]. Furthermore, the high extent of preorganization in the
monomeric units 2b and 3 reduces the likelihood of hydrogen-
bonded polymerization ([2b•3]n).
Addition of 1.0 equiv. of 2b to a suspension of 3 in CDCl3
results in rapid dissolution of both components. Conclusive
evidence for the formation of assembly 2b2•32 comes from VPO
Scheme 1 Representation of the different types of hydrogen-bonded
assemblies (i.e. [1 3 1], [2 3 2] and [n 3 n]) that can be formed via
hydrogen bond formation between trimelamine 2b and bis(barbituric acid)
3. Only the [2 3 2] assembly is experimentally observed.
† Address correspondence concerning crystallography to this author.
Chem. Commun., 1999, 1311–1312
1311

characteristic resonances at d 7.0 and 4.7. This experiment
confirms the assumption that the thermodynamic stability of
grid 2b2•32 is significantly higher than that of 2b•DEB2 and
12•3. Further studies on how structural parameters influence the
stability of [2 3 2] grids are currently in progress.
This work was supported in part (A. L. S.) by the Netherlands
Foundation of Chemical Research (SON) with financial aid
from the Netherlands Organisation for Scientific Research
(NWO).
Notes and references
† Based on the melting point index for hydrogen-bonded assemblies IT
=
m
HB/(N 2 1) (where HB = number of H-bonds in the assembly and N =
number of monomeric units in the assembly) (ref. 14), the stability of
[1 3 1] assembly 2b•3 is higher (IT = 12) than [2 3 2] assembly 2b2•32
m
(IT = 8) and the polymeric assembly [2b•3]n (IT = 6).
m
m
Fig. 1 (a) X-Ray crystal structure of 3; white (small and large) atoms
represent hydrogen and carbon atoms, grey (light and dark) atoms represent
oxygen and nitrogen atoms. The barbiturate moiety [containing atom O(5)]
is slightly distorted from planarity towards an envelope conformation
(maximum deviation from the least-squares plane is 0.131(1) Å [for C(7)]).
This distortion is most likely caused by the acceptance of intermolecular
hydrogen bond formation [involving O(5) and O(6)]. (b) Three isomeric
conformations of the [2 3 2] assembly 2b2•32.
‡ Crystal data for 3: C15H20N4O6, Mr = 352.35, colourless, block-shaped
¯
crystal (0.2 3 0.2 3 0.3 mm), triclinic, space group P1 (no. 2) with a =
6.5364(6), b = 10.8100(12), c = 11.7511(12) Å, a = 79.960(5), b =
85.799(6), g = 88.868(6)°, V = 815.38(14) Å3, Z = 2, Dc = 1.435 g cm23
,
F(000) 372, m(Mo-Ka) = 0.1 mm21, 23889 reflections measured, 3717
independent, Rint = 0.0582, (1.6 < q < 27.4°, T = 150 K, Mo-Ka
radiation, graphite monochromator, l = 0.71073 Å) on an Enraf-Nonius
Kappa-CCD area detector on rotating anode. Data were collected for Lp
effects but not for absorption. The structure was solved by automated direct
methods (SHELXS96). Refinement on F2 was carried out by full-matrix
least-squares techniques (SHELXL-96) for 286 parameters. Hydrogen
atoms were located on a difference Fourier map and their coordinates were
included as parameters in the refinement. Refinement converged at a final
wR2 value of 0.0898, R1 = 0.0317 [for 3522 reflections with Fo > 4s(Fo)],
S = 1.023. A final difference Fourier showed no residual density outside
–0.24 and 0.32 e Å23. CCDC 182/1276. See http://www.rsc.org/suppdata/
cc/1999/1311/ for crystallographic data in .cif format.
§ The experimentally determined average MW is slightly lower than the
calculated MW, because assembly 2b2•32 is in equilibrium with the free
components 2b and 3 (concentration dependant on association constant of
the complex). Moreover, the presence of a small excess of one of the
components [ ~ 5% deviation from exact 1:1 stoichiometry (w/w)] will
further decrease the average MW.
¶ Destruction of assembly 2b2•32 by Ag+ ions was confirmed independantly
by 1H NMR spectroscopic measurements, which show the gradual
disappearance (over several hours) of the proton signals after the addition of
AgO2CCF3.
∑ The broadness of these signals is related to the proton exchange rate with
residual water present. The NHbarb proton bound to the outer melamine unit
(d 14.6) is much broader than the NHbarb proton bound to the inner
melamine unit (d 14.0), because this proton is more exposed to the solvent
(breakage of 3 vs. 6 hydrogen bonds).
Fig. 2 1H NMR spectra (400 MHz) of (a) [2 3 2] assembly 2b2•32 at 60 °C;
(b) [2 3 2] assembly 2b2•32 at 240 °C; (c) [1 3 2] assembly 2b•DEB2 at
240 °C; (d) 1+1 mixture of [2 3 2] assembly 2b2•32 and [1 3 1] assembly
1•DEB at 20 °C.
for the CH2Ar protons and for the NHCH2(CH2)2CH3 protons is
observed [see Fig. 2(b)]. The absence of any other signals in the
d 15–13 region clearly rules out the presence of alternative
assemblies (i.e. [1 3 1] or polymeric) or the existence of more
than one isomeric form [trans-trans, cis-trans and cis-cis, see
Fig. 1(b)]. The less symmetrical cis-trans isomer can be ruled
out based on symmetry arguments, but which of the two other
isomers is the most stable one is at present unknown.
1 M.-T. Youinou, N. Rahmouni, J. Fischer and J. A. Osborn, Angew.
Chem., Int. Ed. Engl., 1992, 31, 733.
The decoalescence of the proton signals for the two
heterotopic NHbarb protons around 30 °C clearly illustrates the
much higher kinetic stability of grid 2b2•32 compared to
assembly 2b•DEB2, which shows an averaged (broad) signal
around d 14.0 for these two protons even at 250 °C [see Fig.
2(c)]. The reason is that exchange of these protons in 2b2•32
involves the simultaneous cleavage of 12 hydrogen bonds,
while exchange in 2b•DEB2 only requires six hydrogen bonds
to be broken. Interestingly, the exchange between the two
NHbarb protons in 2b2•32 is significantly faster in the presence
of an equivalent amount of the two-component assembly
1•DEB [averaged signal around d 14.0 is observed, see Fig.
2(d)]. This is due to the fact that components 1 and DEB
temporarily occupy the non-hydrogen bonded sites in 2b•DEB2
during the exchange process, thus decreasing the activition
barrier for this process.13
2 P. N. W. Baxter, J.-M. Lehn, J. Fischer and M.-T. Youinou, Angew.
Chem., Int. Ed. Engl., 1994, 33, 2284.
3 P. N. W. Baxter, J.-M. Lehn, B. Kneisel and D. Fenske, Chem.
Commun., 1997, 2231.
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Fenske, Angew. Chem., Int. Ed. Engl., 1997, 36, 1842.
5 J.-M. Lehn, Supramolecular Chemistry, Concepts and Perspectives,
VCH, Weinheim, 1995.
6 S.-K. Chang and A. D. Hamilton, J. Am. Chem. Soc., 1988, 110, 1318;
J.-M. Lehn, M. Mascal, A. DeCian and J. Fischer, J. Chem. Soc., Chem.
Commun., 1990, 479; J. P. Mathias, E. E. Simanek, J. A. Zerkowski, C.
T. Seto and G. M. Whitesides, J. Am. Chem. Soc., 1994, 116, 4316.
7 C. M. Marjo, unpublished results.
8 J. Yang, E. Fan, S. J. Geib and A. D. Hamilton, J. Am. Chem. Soc., 1993,
115, 5314.
9 J. P. Mathias, E. E. Simanek and G. M. Whitesides, J. Am. Chem. Soc.,
1994, 116, 4326.
10 A. C. Cope, H. L. Holmes and H. O. House, Org. React., 1957, 9,
107.
11 E. Fischer and A. Dilthey, Ann. 1904, 335, 334.
12 K. A. Jolliffe, M. Crego Calama, R. Fokkens, N. M. M. Nibbering, P.
Timmerman and D. N. Reinhoudt, Angew. Chem., Int. Ed., 1998, 37,
1294.
Finally we studied the thermodynamic stability of 2b2•32 as
compared to that of 2b•DEB2 and 12•3. The melting point index
for hydrogen-bonded assemblies IT = HB/(N 2 1) predicts
that an equimolar mixture of [1 3 2]massembly 2b•DEB2 (IT
=
m
6) and [2 3 1] assembly 12•3 (IT = 6) is thermodynamically
m
13 J. Rao, J. Lahiri, L. Isaacs, R. M. Weis and G. M. Whitesides, Science,
1998, 280, 708.
14 M. Mammen, E. E. Simanek and G. M. Whitesides, J. Am. Chem. Soc.,
1996, 118, 12614.
unstable, and would rearrange to give preferentially the [2 3 2]
assembly 2b2•32 (IT = 8) and [1 3 1] assembly 1•DEB (IT
=
m
m
6).14 Analysis of the H NMR spectrum of a 1:1 mixture of
2b•DEB2 and 12•3 clearly shows that neither one of the two
assemblies is present. Diagnostic is the absence of the
1
Communication 9/03446C
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Chem. Commun., 1999, 1311–1312