Crystal engineering: A unique cyclic assembly of a 40 membered module composed from two alternating units each of benzenehexacarboxylic acid (mellitic acid, MA) and 2,5-bis-(4-pyridyl)-1,3,4-oxadiazole (4-BPO): Assembly of modules to macromolecules by intermolecular hydrogen bonding

Article abstract of DOI:10.1007/s10870-008-9458-z

Individually prepared, equivalent amounts of 2,5-bis-(4-pyridyl)-1,3,4- oxadiazole (4-BPO) and benzenehexacarboxylic acid (mellitic acid, MA) when mixed, deposited long rods, whose X-ray structure showed a unique assembly of 40 membered planar modules composed from two alternating units each of MA and 4-BPO, rather than the anticipated helical profile. Several novel features of complexes of MA with organic molecules are seen here. In almost all cases the intermolecular hydrogen bonding between MA anions is so stable that the MA anions and the complementary cations lie in separate planes. This barrier is overcome in the present case. The basic module associates to form quartets by very simple hydrogen bonding of the carboxylic groups of MA. The quartet assembly is characterized by the rotation of the left hand pair compared to the right hand pair. The mode of the macromolecular assembly is clear, that is, they are layered in alternating planes. Space group: P2₁/c with a = 9.181(1) A, b = 9.624(1) A, c = 29.390(2) A, and β = 94.626(4)°. The modules are embedded in an extensively hydrogen bonded MA network. The assembly profile of MA and 4-BPO is unique and should be a harbinger for the design of novel functional assemblies. The 40-membered module mimics the self-assemblies of peptides and can be important in the design of "Haptens" from simple molecules.

Full text of DOI:10.1007/s10870-008-9458-z

J Chem Crystallogr (2009) 39:201–208
DOI 10.1007/s10870-008-9458-z
ORIGINAL PAPER
Crystal Engineering: A Unique Cyclic Assembly of a 40
Membered Module Composed from Two Alternating Units Each
of Benzenehexacarboxylic Acid (Mellitic Acid, MA) and 2,5-Bis-
(4-pyridyl)-1,3,4-oxadiazole (4-BPO): Assembly of Modules
to Macromolecules by Intermolecular Hydrogen Bonding
Isabella L. Karle Æ Y. B. R. D. Rajesh Æ
Subramania Ranganathan
Received: 28 March 2008 / Accepted: 1 August 2008 / Published online: 21 August 2008
Ó U.S. Government 2008
Abstract Individually prepared, equivalent amounts of
,5-bis-(4-pyridyl)-1,3,4-oxadiazole (4-BPO) and benzene-
Keywords Macrocyclic module (40) ꢀ
2
Non-covalent self-assembly ꢀ Modules to supramolecules
hexacarboxylic acid (mellitic acid, MA) when mixed,
deposited long rods, whose X-ray structure showed a unique
assembly of 40 membered planar modules composed from
two alternating units each of MA and 4-BPO, rather than the
anticipated helical profile. Several novel features of com-
plexes of MA with organic molecules are seen here. In
almost all cases the intermolecular hydrogen bonding
between MA anions is so stable that the MA anions and the
complementary cations lie in separate planes. This barrier is
overcome in the present case. The basic module associates to
form quartets by very simple hydrogen bonding of the car-
boxylic groups of MA. The quartet assembly is characterized
by the rotation of the left hand pair compared to the right
hand pair. The mode of the macromolecular assembly is
clear, that is, they are layered in alternating planes. Space
Introduction
Benzenehexacarboxylic acid (mellitic acid, MA) where the
six carboxylic groups are arranged around a benzene core,
suggests itself as a unit for examining diverse types of
molecular topology by the choice of the organic bases in salt
formation. In spite of the fact that several complexes of MA
with organic counterparts have been studied by X-ray crys-
tallography, factors that control the topology still remain
elusive. Extensive investigations by us have shown that the
options available are limited, arising out of preference by
MA anions for the formation of hydrogen bonding networks,
either as sheets or ribbons, resulting in the placement of the
anions and cations in separatedomains. Thus, it has become a
challenge to design complexes of MA with organic bases
where they intermingle, overcoming the advantages of iso-
lation. This is accomplished in the present work.
˚
˚
group: P2 /c with a = 9.181(1) A, b = 9.624(1) A,
1
˚
c = 29.390(2) A, and b = 94.626(4)°. The modules are
embedded in an extensively hydrogen bonded MA network.
The assembly profile of MA and 4-BPO is unique and should
be a harbinger for the design of novel functional assemblies.
The 40-membered module mimics the self-assemblies of
peptides and can be important in the design of ‘‘Haptens’’
from simple molecules.
A general profile of complexes of MA with organic bases
would be helpful for predicting the nature of new complexes.
-2
In the case of MA anions, they form extended sheets, in an
approximate hexagonal arrangement, that may or may not
incorporate water molecules. The cations generally are orga-
-4
nized orthogonal to the anion sheets. MA anions assemble
as uninterrupted ribbons, mediated by pairs of direct MA–MA
hydrogen bonds that form 14 membered ring structures. The
continuing interest in MA–organic salts arises from the
promise they have shown in the formation of structures with
varied properties, the unknown potential they hold, and the
hope that designs of MA salts with a measure of predictability
become possible by choice of the organic bases.
I. L. Karle (&)
Laboratory for the Structure of Matter, Naval Research
Laboratory, Code 6030, 4555 Overlook Avenue, SW,
Washington, DC 20375-5341, USA
e-mail: isabella.karle@navy.nrl.mil
Y. B. R. D. Rajesh ꢀ S. Ranganathan
Discovery Laboratory, Organic III, Indian Institute of Chemical
Technology, Hyderabad 500 607, India
123

2
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J Chem Crystallogr (2009) 39:201–208
The versatility of MA, in forming crystalline salts with
organic bases, is illustrated with a few examples:
0
The crystal arising from MA and 2,2 -bipyridyl (BP) has
the unusual composition MA BP (H O) Sheets of
28
8
16
2
-
2
MA are interspersed by infinite stacks of orthogonally
disposed mono protonated BP. The deprivation of water
molecules, at *140 °C, that play a major role in the
structure (Fig. 1a), clearly shows channels (Fig. 1b) that
can be filled by water or ammonia, thus demonstrating the
potential of such salts in the design of macroporous
materials [1].
-5
2+
In the dense and hard ionic crystal MA 2.5 EDA
-
5
(
where EDA is ethylene diamine) the MA ions form a
continuous ribbon by strong OHꢀꢀꢀO=C hydrogen bonds,
-
5
rather than sheets, as in Fig. 1. Each MA in the ribbon is
-5 2+
Fig. 2 Tightly packed ionic crystal MA . 2.5 EDA . Hydrogen
bonds are represented by dashed lines [2]. The view is looking down
-5
the ribbon in the center with only one MA ion shown
2+
surrounded by EDA ions and water molecules as shown in
-n
Fig. 2. TheenormousflexibilityofM ionsincraftingtightly
packed salts with counter ions is exhibited where a compli-
cated energy balancing system is naturally in place [2].
Anunusualanion–cationinterlockingsystemresultedfrom
MA–phenanthroline complexation (MA–PL) (Fig. 3a). The
Another unique feature of the MA–PL complex are the con-
-2
tinuous sheets that form the hydrogen bonded MA counter
ion. Interestingly these sheets have a profile shown in Fig. 3b
+
structural representation highlights perfect stacking of PL at
˚
.5 A intervals. The complex is marginally semiconducting.
-
2
-2
3
where a central MA ion connects to four surrounding MA
-2
Fig. 1 (a) The mellitic acid ion (MA ) layer with water molecules in the MA–BP crystal. (b) Open channels arising from the loss of water at
40 °C in the MA–BP crystal [1]
1
1
23

J Chem Crystallogr (2009) 39:201–208
203
-2
Fig. 3 (a) An infinite interlocked assembly of MA–PL complex [1]. (b) Sheet structure of MA in the MA–PL complex at right angles to (a).
-
There are no water molecules in the crystal. Each MA ion participates with 8 hydrogen bonds to form the sheet
2
ions by four pairs of hydrogen bonds without any intervening
results in an effective p–p interaction to produce a con-
H O molecules.
2
ducting crystal. A side view is presented in Fig. 4.
The above brief account gives an idea of the potential of
MA–organic salt complexes. The work reported in the
present paper highlights yet another novel and unique
property of these systems. This work resulted from a search
for compounds that may provide helical structures with
MA and led to the identification of 2,5-bis-(4-pyridyl)-
1,3,4-oxadiazole (4-BPO). The genesis for this expectation
arose from the report that oxadiazoles flanked by pyridines
at the the 4-location (4-BPO) complexes with mesitoic acid
to form turn structures that further assemble to triple
helices [4]. These turn structures simply arise as shown in
Fig. 5 by tandem arrangement of mesitoic acid and 4-BPO.
The triple helix formation involves modules as shown
below harboring acids that form salts with the base of the
neighboring strings.
The general profile of salts of MA with organic bases,
as composed of ribbons or layers of MA anions with the
positive counter ion held separately, and in favorable
cases as stacks that could elicit p–p interaction, could be
used in several designs. In an imaginative approach,
endeavors were made to encapsulate stacks of tetra-
thiafulvalene (TTF) radical cation with MA counter ions.
-
2
+ꢀ
Initial efforts produced crystals of MA (TTF ) which,
2
+
ꢀ
having the profile in which stacks of TTF
were
encapsulated in a MA anion helix, pairing interactions
failed to produce the desired magnetic material. Interest-
ingly the salt profile changed when TTF was replaced by
EDTTTF [3].
S
S
S
S
Experimental
S
S
EDTTTF
Materials and Methods
-
2
In this complex, two-dimensional sheets of MA
sandwich stacks of cation layers of the EDTTTF that
Melting points were recorded on a Fischer–John’s appa-
ratus and are uncorrected. Infrared spectra were recorded
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J Chem Crystallogr (2009) 39:201–208
Table 1 Crystallographic data and structure refinement for the
-2
2+
MA –4-BPO complex
Identification
CCDC# 682881
-
2
+2
Empirical formula
Molecular weight
Chemical, m.p., °C
Temperature, K
(C12
H
4
O
12) ꢀ (C12
10
H N
4
O) ꢀ 2.5H
2
O
606.39
[300
293°
˚
Wavelength, A
1.5418
Space group
1
P2 /c
˚
a, A
9.181(1)
9.624(1)
˚
b, A
˚
c, A
29.390(2)
94.63
b, °
Volume, A
3
˚
2588.4(4)
4
Z
3
Density (calc.) (mg/mm ) 1.556
Absorption coefficient, l 1.17
-
1
(
mm )
F(000)
Color
Shape
1,240
Pale yellow
Rods
Crystal size, mm
Limiting indices
0.28 9 0.20 9 0.18
0 B h B 10
-
-
1 B k B 11
30 B l B 33
Fig. 4 Side view of the MA anionic sheets and the EDTTTF cation
layers in the MA EDTTTF salt [3]
Reflections collected
3808
2682
Reflections
observed [4r(F)
Goodness to fit
1.01
Final R indices [I [ 2(I)] 0.063
Extinc. Coeff. 0.0021
Larg. Diff. peak and hole, 0.40/-0.36
3
˚
e/A
Param./Restr./Data
413/0/2682
Fig. 5 Tandem arrangement of mesitoic acid and 4-BPO
Mellitic Acid (MA)–2,5-Bis-(4-pyridyl)-1,3,4-
Oxadiazole (4-BPO) Complex, MA–BPO
on a Thermo Nicolet Nexus 760 spectrophotometer as KBr
-
A solution of MA (0.034 g, 0.1 mmoL) in MeOH (1 mL)
was admixed with a solution of 4-BPO (0.022 g,
0.1 mmoL) in MeOH (2 mL). The resulting solution
immediately deposited small cubic crystals. This solid was
crystallized from hot water to give small rod like crystals
within one day; M.p: [ 300 °C.
1
pellets and prominent peaks expressed in cm
.
2
,5-Bis-(4-pyridyl)-1,3,4-oxadiazole (4-BPO) was pre-
pared by reacting isonicotinic acid with hydrazine
dihydrochloride in the presence of P O , POCl , and
2
5
3
H PO [5]:
3
4
COOH
N
N
H PO
3
4
O
+
H NNH . 2HCl + P O + POCl3
2 2
2 5
N
N
N
70%
°
m.p. 189 C
1
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J Chem Crystallogr (2009) 39:201–208
205
Fig. 6 (a) The primary module
2+
-2
of MA –BPO complex, a
novel and unusual
4
0-membered macrocycle
generated from pairs of MA and
-BPO. The thermal ellipsoids
4
are shown at the 50%
probability. (b) An edge-on
view of the macrocycle shows
that all rings are nearly coplanar
and that many of the CO and
OH bonds in the MA molecules
are directed out of the plane. (c)
A quartet assembly of four basic
units by simple hydrogen
bonding. (d) An edge-on view
of the quartet shown in (c)
The aqueous filtrate on standing for three days deposited
an additional batch of long rod like crystals. The IR
spectrum of the crystals clearly indicated that the desired
salt was formed. One of these crystals was used for X-ray
diffraction analysis.
X-ray Structure Analysis
Single crystal X-ray data were collected at room temper-
ature on a P4 Bruker automated four-circle diffractometer
in the h/2h mode, with a constant speed of 10 deg/min, 1.5°
scan width, and 2hmax & 115° (resolution 0.9 A), using
Cu-Ka radiation (k = 1.54178 A), and a graphite mono-
chromator. Parameters and details are listed in Table 1.
˚
M.p: [ 300 °C; Yield: 0.018 g; IR (KBr): 3422 (s, br),
-
1
˚
1
710 (m), 1636 (s), 1443 (m), 1248 (m), 624 (m) cm
.
The two crops of crystals were identical, except for size.
123

2
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J Chem Crystallogr (2009) 39:201–208
Table 2 Hydrogen bonds
ions neatly integrated. The module shows a unique profile
+
-
of a 40-membered ring held by four strong NH ꢀꢀꢀO –C
˚
D–A (A)
˚
H–A (A)
Donor
Acceptor
D–H–A (°)
hydrogen bonds where the NꢀꢀꢀO distances are only 2.59
N1
O2A
2.595
2.642
2.667
2.531
2.633
2.550
2.904
2.912
2.840
2.75
1.75
1.78
155
160
˚
and 2.64 A, Table 2. An edge-on view of the basic module
a
N4
O5A
shows coplanarity of the 40-membered macrocycle
(Fig. 6b), except for the rotated carboxyl groups in MA.
An analysis of this crystal structure has enabled a better
understanding of the novel and unique properties of the
primary module. The basic module assembles to a quartet
(Fig. 6c) bythe pair of OHꢀꢀꢀO=C bonds connecting carbonyl
groups of MA around a center of symmetry. The distances
O4A
O8A
O10A
O12A
O1S
O1S
O2S
O1S
b
O6A
1.47
1.57
1.53
176
160
174
c
O2S
d
O1A
e
O3A
f
O11A
e
O7A
˚
involving atoms O1A and O12A are 2.55 A. This pair of
0
f
O3S
O1A
hydrogen bonds connects modules A and B and a similar pair
of hydrogen bonds connects modules C and D. To complete
the quartet of modules, the A, B pair is joined to the C, D pair
of modules by only one hydrogen bond, between O8A and
a
b
Symmetry equivalents: -x, 2 - y, -z; -x, -‘ + y, -‘ - z;
c
d
e
f
x, ‘ - y, -‘ + z; 1 - x, -y, -z; -x, 1 - y, -z; x, 1 + y, z
˚
O6AB in Fig. 6c, with an OꢀꢀꢀO distance of 2.53 A. The
The solution of the crystal structure showed the forma-
tion of a 40-membered macrocycle arising from four
+
-
NH ꢀꢀꢀ O–C hydrogen bonds that link pairs of alternating
-
2
2+
units of MA and BPO , Fig. 6a, into discrete modules.
Water molecules O1S within the macrocycle and O2S
outside the macrocycle participate in well-determined
hydrogen bonds, Table 2. Full matrix least-squares yield
Ueq thermal values of 0.026–0.050 for the atoms in the
organic entity and values of 0.06 and 0.05 for O1S and
O2S. However, there is ‘‘empty volume’’ between the
modules for which difference maps indicate a probable
third water molecule O3S that is distributed among several
0
sites. One partially occupied site containing O3S , that is
consistent with a hydrogen bond to atom O1A in the
0
0
module, appears to be stable. Other sites, such as O3S
have not been stable in the least-squares refinement.
The programs used are those in the SHELXTL package
6]. Tables of coordinates, bond lengths and angles,
[
anisotropic thermal parameters, and hydrogen coordinates
are deposited with the Cambridge Crystallographic Data
Centre, CCDC# 682881. Copies of the data can be obtained
free of charge on application to the Director, CCDC, 12
Union Road, Cambridge CB2 1EZ: (fax: +44-1223-336-
0
33; e-mail: deposit@ccdc.cam.ac.uk).
Results and Discussion
As already mentioned, the energetics of the usual organic
salts derived from MA lead to separate cation and anion
assemblies. One of our long standing objectives has been to
discover a system that may overcome this natural tendency
so that an integrated cation–anion module is formed.
Consequently the results obtained from the X-ray crystal
structure of MA–4-BPO are gratifying in that the primary
Fig. 7 An extended packing diagram of the modules that shows the
layer-like arrangements. The unit cell is inscribed with light lines
-
2
2+
module (Fig. 6a) has the acid (MA ) and base (BPO
)
1
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J Chem Crystallogr (2009) 39:201–208
207
Fig. 8 (a) Water molecules
both inside and outside the
macrocycles. (b) One complete
module shown layered between
MA moieties (darkened atoms)
on either side of BPO moieties.
Two water molecules within the
cavity participate in three
hydrogen bonds each. (c) Edge-
on view of (b). The two BPO
moieties are superimposed in
the center of the diagram
listing of hydrogen bonds in Table 2 shows that the
may also be the fact that the initially formed macromolecule
prefers to form multiplexes by hydrogen bonding rather than
having separate identities (vide infra).
NHꢀꢀꢀO=C bonds in the macrocycle and the OHꢀꢀꢀO=C bonds
between modules in the quartet are very strong, 2.53 to
˚
2
.64 A, while the hydrogen bonds involving the H O mol-
2
Of interest is the characterization of the quartet assem-
bly shown in Fig. 6c when viewed edge-on, as in Fig. 6d.
The mean plane of the A, B pair of modules is rotated by
*40° from the C, D pair of modules. The mode of the
macromolecular assembly is layering, as shown in Fig. 7.
The basic modular scaffolds described above are
assembled to tertiary structures by making use of the free
carboxylic groups of MA and water molecules present
inside and outside the macrocycle as shown in Fig. 8a. The
unique pair of carboxylic groups that project into the
module are hydrogen bonded to the water molecules O1S
0
ecules (O1S, O2S, and O3S ) are considerably weaker with
˚
OꢀꢀꢀO values of 2.67–2.91 A. Furthermore, the many O9A
carbonyl oxygens on the periphery of the quartet do not
participate in any hydrogen bonding, thus contributing to the
separation of quartets from each other. There is no center of
symmetry within a quartet. A simple explanation for the
radical change in the structural profile could be that an ini-
tially formed intermediate where MA is linked to two units of
4
4
-BPO at the 1, 3 locations is ideally oriented to form the
0-membered cycle with another unit of MA. Basic to this
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J Chem Crystallogr (2009) 39:201–208
and O1SA inside the ring as shown in Fig. 8b. The process
makes use of all sites available for hydrogen bond forma-
tion except for carbonyl O9. The intricate nature of this
operation is illustrated in Fig. 8b and c. In Fig. 8b extra-
modular MA (shown with darkened atoms above and
below the cavity of the module) also hydrogen bond with
the water O1S and O1SA inside the module. The same
group of atoms is shown in Fig. 8c at right angles to
Fig. 8b. Figure 8c also illustrates the layering of separate
and 4-BPO took place and underwent simple dimer for-
mation that forms the basic 40-membered unit (Fig. 6a),
that further assembled to macrocyles. The differences in
the structural profile of compounds having the common
base 4-BPO but differing acids, mesitoic acid and MA, is
noteworthy. It appears that the extra carboxylic groups in
the latter could provide kinetic advantages for the forma-
tion of the basic module (Fig. 6a).
-
2
2+
Acknowledgments SR and Rajesh are most grateful to the
Department of Biotechnology, New Delhi, for generous financial
assistance. Work performed at the Naval Research Laboratory was
supported by the Office of Naval Research.
modules, in which MA ions alternate with BPO ions,
˚
at distances [3.7 A, a value that does not indicate any
particular attraction. The acceptance of two and only two
water molecules within the basic module opens avenues to
take advantage of the pair of carboxylic groups of the
module that project into the macro-ring that are spaced by
˚
References
1
1.78 A for molecular recognition. Such studies are plan-
1
2
. Karle IL, Gilardi RD, Rao CHC, Muraleedharan KM, Ranganathan
S (2003) J Chem Crystallogr 33:727. doi:10.1023/A:10261512
ned with 1,x-diamines, H N(CH ) NH having n = 7 or 8.
2
2 n
2
The assembly profile of MA and 4-BPO is unique and
should be a harbinger for the design of novel functional
assemblies. The 40-membered module mimics the self-
assemblies of peptides and can be important in the design
of ‘‘Haptens’’ from simple molecules.
2
2486
. Karle IL, Rajesh YBRD, Ranganathan S (2005) J Chem Crystal-
logr 35:835. doi:10.1007/s10870-005-4554-9
. Inabe T (2005) Mater Chem 15:1317. doi:10.1039/b413848a
. Du M, Zhang ZH, Zhao XJ (2005) Cryst Growth Des 5:1247. doi:
10.1021/cg0495680
. Bentiss F, Lagrenee M (1999) J Heterocycl Chem 36:1029
3
4
An analysis of the present results do indeed show that
the expected alternate hydrogen bonding between the acid
5
6. Version SHELXTL 5.1: (1994) Madison, WI: Bruker, ASX, Inc.
1
23