Molecular recognition: Preorganization of a bis(pyrrole) schiff base derivative for tight dimerization by hydrogen bonding

Article abstract of DOI:10.1002/chem.200600403

Multiple techniques have been used to delineate the self-assembly of a bis(pyrrole) Schiff base derivative (compound 4, C₁₆H ₁₄N₄), which forms an unusual dimer through complementary N-H...N=C hydrogen bonds between twisted, C₂-symmetric monomer units. The asymmetric unit of the crystal structure comprises one and a half dimer units, with one dimer exhibiting approximate D₂ point-group symmetry and the other exact D₂ symmetry (space group C2/c). The dimers pack into columns whose axes are collinear with the a axis of the unit cell. The columns assemble into discrete layers with two distinct types of hydrogen-sized voids residing between the layers. Despite the promising architec ture of the voids within the lattice of 4, the absence of genuine channels to interconnect the voids precludes the uptake of hydrogen gas, even at elevated pressures (10 bar). AM1 calculations of the structure of dimeric 4 indicate that self-recognition through hydrogen bonding depends primarily on favorable electrostatic interactions. The potential-energy surface for monomeric 4 mapped by counter-rotation of an adjacent pair of C=C-N=C torsion angles indicates that the X-ray structures of the four monomeric units are global minima with highly nonplanar conformations that are preorganized for self-recognition by hydrogen bonding. The in vacuo enthalpy of association for the dimer was calculated to be significantly exergonic (ΔG_assoc = -21.9 kJ mol^-1, 298 K) and in excellent agreement with that determined by ¹H NMR spectroscopy in CDCl₃ (AG_assoc = -16.6(4) kJ mol ^-1, 298 K). Using population and bond order analyses, in conjunction with the conformation dependence of the frontier MO energies, we have been able to show that π-electron delocalization is only marginally diminished in the nonplanar conformers of 4 and that the electronic structures of the constituent monomers of the dimer are well mixed.

Full text of DOI:10.1002/chem.200600403

FULL PAPER
DOI: 10.1002/chem.200600403
Molecular Recognition: Preorganization of a Bis
A
T
E
N
(pyrrole) Schiff Base
Derivative for Tight Dimerization by Hydrogen Bonding
[
a]
Orde Q. Munro,* Sandra D. Joubert, and Craig D. Grimmer
Abstract: Multiple techniques have
been used to delineate the self-assem-
ture of the voids within the lattice of 4,
the absence of genuine channels to in-
terconnect the voids precludes the
uptake of hydrogen gas, even at elevat-
ed pressures (10bar). AM1 calcula-
tions of the structure of dimeric 4 indi-
cate that self-recognition through hy-
drogen bonding depends primarily on
favorable electrostatic interactions. The
potential-energy surface for monomeric
4 mapped by counter-rotation of an ad-
jacent pair of C=C-N=C torsion angles
indicates that the X-ray structures of
the four monomeric units are global
minima with highly nonplanar confor-
mations that are preorganized for self-
recognition by hydrogen bonding. The
in vacuo enthalpy of association for the
dimer was calculated to be significantly
bly of a bis
A
C
H
T
R
E
U
N
G
(pyrrole) Schiff base deriva-
tive (compound 4, C H N ), which
1
6
14
4
forms an unusual dimer through com-
plementary hydrogen
ꢀ
1
NꢀH···N=C
exergonic
(DGassoc =ꢀ21.9 kJmol ,
bonds between twisted, C -symmetric
298 K) and in excellent agreement with
that determined by H NMR spectro-
2
1
monomer units. The asymmetric unit of
the crystal structure comprises one and
a half dimer units, with one dimer ex-
hibiting approximate D2 point-group
scopy
in
CDCl3
(DGassoc =
ꢀ
1
ꢀ16.6(4) kJmol , 298 K). Using popu-
lation and bond order analyses, in con-
junction with the conformation de-
pendence of the frontier MO energies,
we have been able to show that p-elec-
tron delocalization is only marginally
diminished in the nonplanar conform-
ers of 4 and that the electronic struc-
tures of the constituent monomers of
the dimer are well mixed.
symmetry and the other exact D sym-
2
metry (space group C2/c). The dimers
pack into columns whose axes are col-
linear with the a axis of the unit cell.
The columns assemble into discrete
layers with two distinct types of hydro-
gen-sized voids residing between the
layers. Despite the promising architec-
Keywords: dimerization · hydrogen
bonds
· molecular recognition ·
Schiff bases · self-assembly
II [10]
Introduction
species of the type [M (L) ] are also known for M=Zn ,
2 2
Mn , and Cu
II [6]
II[5]
where L is a derivative of type 1. Indeed,
Bis
A
C
H
T
R
E
U
N
G
(pyrrole) Schiff base derivatives 1 (Scheme 1), where X
by varying the bridging group X it is possible to control the
supramolecular coordination chemistry of such systems. For
example, Wu et al. have shown, using a substituted analogue
is a synthetically variable bridging alkyl or aryl group, have
[1]
been known since the 1960s. Despite their long existence,
however, relatively few crystal structures of metal-free or
metalated tetradentate ligands have been reported. Metal
ions are usually coordinated by 1 as the dianionic conjugate
base (structure type 2, where M is a divalent or trivalent
metal ion). Examples of crystallographically characterized
II
of 1 with Zn , that when the linker is 1,2-, 1,3-, or 1,4-diami-
nobenzene, dinuclear, trinuclear [M (L) ], or porous tetra-
3
3
nuclear complexes [M (L) ], respectively, are synthetically
4
4
[10]
feasible.
To date, studies of the coordination chemistry of ana-
logues of 2 have not been paralleled to the same extent by
structural and spectroscopic studies of the metal-free spe-
II [2]
II [3]
II [4]
complexes of type 2 include chelates of Ru , Pd , Ni ,
II [5]
II [6,7]
II [7]
II [8]
III [9]
Cu , Mn ,
Fe , Sm , and Co . Several dinuclear
[11,12]
cies. However, two independent articles
published in
2
003 showed, in more than passing detail, that the pyrrole-
[
a] Prof. O. Q. Munro, S. D. Joubert, C. D. Grimmer
imine functional group combination in 3 (Scheme 1 is a po-
tentially useful supramolecular synthon comprising a strong
H-bond donor (pyrrole NꢀH group) and a strong H-bond
School of Chemistry, University of KwaZulu-Natal
Private Bag X01, Scottsville 3209, Pietermaritzburg (South Africa)
Fax : (+27)33-260-5009
acceptor (imine nitrogen). Efficient self-recognition or self-
assembly through complementary hydrogen bonding in this
type of system is now known to lead to dimerization (3a)
E-mail: munroo@ukzn.ac.za.
Supporting Information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2006, 12, 7987 – 7999
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7987

sites. Furthermore, the addition of other H-bonding func-
tional groups to such a system enhances the ability of these
compounds to participate in molecular recognition events.
For example, the mono
ACHTREUNG
[
(1E)-1H-pyrrol-2-ylmethylene)]benzene-1,2-diamine
self-assembles by complementary (pyrrole)NꢀH···NH Ar
2
[14]
hydrogen bonding both in solution and in the solid state.
Crystal engineering applications of metal-free, pyrrole-imine
Schiff bases are clearly at a very early stage of development,
but have the potential to yield some useful new supramolec-
ular architectures. Herein, we report the X-ray structural
characterization of 4 (a tight H-bonded dimer), NMR stud-
ies which delineate the process of self-assembly in fluid solu-
tion, and gas-phase AM1 simulations of the electronic struc-
tures of the monomeric and dimeric species. Our data col-
lectively show that complementary electrostatic interactions
and conformational preorganization are two fundamental
parameters that control highly favorable self-assembly in
this system.
Results and Discussion
Scheme 1.
Solid-state molecular structures: The asymmetric unit of 4
comprises three molecules: two fully occupied molecules in
general positions and two symmetry-unique half-molecules.
(For convenience, the four independent structural compo-
nents of the asymmetric unit are labeled A, B, C, and D.)
Compound 4 therefore exists as discrete dimers in the crys-
talline solid state (Figure 1). The two half molecules labeled
C and D are the symmetry-unique components of a dimer
with D2 point-group symmetry paired by complementary
and polymerization (1a) in the case of mono- and bis-
A
C
H
T
R
E
U
N
G
(pyrrole) derivatives, respectively.
For crystal engineering applications, small variations in
the identity of the spacer, such as regioisomerism of the two
amino groups on a diaminobenzene ring, allow one to ele-
gantly control the supramolecular chemistry of the system,
particularly if metal ions are used to facilitate oligomeriza-
[10]
tion. Although the simplest aromatic derivative of 1 with
X=C H4 (1,2-diaminobenzene-based spacer, compound 4;
(pyrrole)NꢀH···N=C
A
T
E
N
(imine) hydrogen bonding, while the
6
Scheme 2) has been synthesized before, no crystal structure
fully occupied molecules A and B (C symmetry) are simi-
1
[3,6]
of the free base has been reported.
Surprisingly, only
larly hydrogen-bonded to form a dimer with only approxi-
three derivatives of 1 have been crystallographically charac-
terized, namely 4,5-dimethyl-N,N’-bis(1H-pyrrol-2-ylmethy-
mate D symmetry (the molecular point group is strictly C ).
2
1
For molecule B, the mean pyrrole a-CꢀN, a-Cꢀb-C and b-
Cꢀb-C bond lengths are 1.369(7), 1.378(6), and 1.414(2) Š,
respectively. The pair of imine C=N bond lengths average
[6]
lene)benzene-1,2-diamine (5), N,N’-bis(1H-pyrrol-2-ylme-
[11]
thylene)propane-1,2-diamine (6), and N,N’-(1,2-cyclohexy-
[3]
lene)bis(1H-pyrrol-2-ylmethyleneamine) (7). Self-assembly
occurs in 5 and 6 through hydrogen bonding, as depicted in
1.278(1) Š, while the mean pyrrole a-Cꢀ
A
T
E
N
(C=N) bond meas-
ures 1.441(4) Š. The mean CꢀC bond length of the phenyl
ring is 1.396(8) Š. The mean bond angles subtended at the
N atoms of 4 are 109.6(6)8 (C-N-C), 124.8(13)8 (H-N-C),
[13]
3/3a (Scheme 1).
The existing evidence suggests that a pyrrole group adja-
cent to an imine group constitutes a powerful molecular rec-
ognition motif with integral H-bond donor and acceptor
and 118.3(6)8 (C=N-CH ). As might be anticipated from a
2
reasonably good data set, these mean distances and angles
compare favorably with those reported for similar deriva-
[3,6,11]
tives of 1.
The structural parameters for all four mole-
cules (A–D) are similar, which obviates the need for further
discussion of the key bond distances and angles for mole-
cules A, C, and D.
Taking molecule B as being representative of each mono-
mer in the asymmetric unit of 4, it is clear that a markedly
non-planar conformation is favored in this system; the dihe-
dral angle between the mean plane of one pyrrole group
and the adjacent pyrrole ring is 35.98(4)8 (see Figure 2 and
Figure S1 in the Supporting Information). The pyrrole rings
themselves are twisted out of the molecular plane and the
Scheme 2.
7988
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
A
H
R
U
G
FULL PAPER
Figure 2. a) Representation of the mean plane passing through the ben-
zene ring of 4 (molecule B); the sharply canted orientations of the pyr-
role rings relative to this plane are clearly evident. b) Depiction of the
perpendicular displacements of all non-hydrogen atoms of compound 4
from the six-atom mean plane of the benzene ring. Atomic displacements
are given in units of 0.01 Š; standard uncertainties range from 0.001 to
Figure 1. Thermal ellipsoid plots of the two independent dimer structures
of 4 at 100(2) K. (Displacement ellipsoids are drawn at the 50% probabil-
ity level; only the isotropically refined hydrogen atoms are shown for
clarity.) Molecules A and B make up the first C -symmetric dimer; the
1
component monomers are designated by lowercase letters a and b on all
atom labels. The second dimer comprises independent half-molecules C
0
.004 Š. c) Least-squares fit of the benzene rings of the X-ray structures
of 4 and 5 (RMSD = 1.81 Š). Compound 4 clearly has the more nonpla-
nar conformation.
2
and D and has exact D symmetry. Hydrogen bonds are shown with
broken lines in both H-bonded complexes.
angle between the mean plane of the first pyrrole ring (con-
taining atom N1b) and the mean plane through the phenyl
ring is 42.70(6)8. This dihedral angle for the second pyrrole
ring (including N4b) is a substantial ꢀ50.52(6)8. As shown
in Figure 2, the perpendicular displacements of the non-hy-
drogen atoms of the structure from the six-atom mean plane
of the central benzene ring range from 0to 1.93(4) Š, thus
highlighting the strikingly nonplanar conformation of the
molecule.
The nonbonded distance between the N atoms of the pyr-
role groups (N1b and N4b) is 5.273(1) Š. The complementa-
ry hydrogen bonds between the pyrrole NH groups of one
molecule and the imine nitrogen atoms of the other (and
vice versa) lock the two C-shaped structures almost perpen-
dicularly together (the dihedral angle between the two 20-
atom mean planes is 83(2)8, Figure 1). The average NꢀH-
A
H
R
U
A
H
R
U
2.04(3) Š (Table 1), which is consistent with moderate to
[15,16]
strong, rather than weak, hydrogen bonding.
The X-ray
data therefore clearly indicate that the pyrrole NꢀH groups
serve as hydrogen-bond donors and the imine groups as hy-
drogen-bond acceptors. Remarkably, complementary Nꢀ
H···NR=CR hydrogen bonding from an adjacent pair of
2
pyrrole-imine functional groups and concomitant formation
of ring motif 3 is, in fact, unusual, having hitherto escaped
[17]
any rigorous statistical scrutiny.
Chem. Eur. J. 2006, 12, 7987 – 7999
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7989

O. Q. Munro et al.
[
a,b]
Table 1. Hydrogen bonding geometries for 4.
An intriguing feature of the X-ray structure of 4 is the
non-coplanar arrangement of the pyrrole groups. At first
glance, this conformation might be explained by the fact
that 4 forms hydrogen-bonded dimers in the crystal lattice.
Optimal binding of the monomers could dictate that each
pyrrole ring twists out of the mean molecular plane, or so it
may seem from the dimeric structure of 4 and the related
4,5-dimethylbenzene derivative 5, which has a similar,
Interaction
DꢀH
H···A
DꢀH···A
D···A
N1a
ꢀ
H1a1···N3b
0.923(16)
0.940(18)
0.904(17)
0.920(17)
0.903(18)
0.940(17)
0.92(1)
2.050(16)
2.018(18)
2.115(17)
2.019(17)
2.035(18)
2.024(17)
2.04(3)
162(1)
159(2)
164(2)
159(2)
158(2)
155(1)
160(3)
2.943(2)
2.916(2)
2.997(2)
2.899(2)
2.892(2)
2.907(2)
2.93(3)
N1bꢀH1b1···N3a
[
c]
N1cꢀH1c1···N2d
N1dꢀH1d1···N2c
N4aꢀH4a1···N2b
N4bꢀH4b1···N2a
average
[
c]
[6]
though slightly less distorted, conformation (Figure 2c).
[
a] Distances in angstroms; angles in degrees. [b] D=donor; A=accept-
or. [c] Symmetry code: ꢀx+1, y, ꢀz+3/2.
However, our AM1 simulation of the lowest-energy confor-
mation of monomeric 4 in the gas phase clearly suggests
that the very notion that this compound should be planar is
strictly incorrect (vide infra). A nonbonded repulsion be-
tween the two pyrrole NꢀH groups in the planar conformer
Just how tight is the complementary hydrogen bonding in
4
? A search of the CSD for derivatives of 3 revealed that,
in the absence of unusual stereochemical constraints or in-
cluded H-bonded solvent species, most of the available
structures self-assemble in the solid state via the archetypal
supramolecular synthon shown schematically in 3a. The hy-
drogen-bonding parameters for seven compounds that show
type 3 molecular recognition are summarized in Table 2.
evidently drives the formation of the strain-relieving twisted
structure for each monomer. Since this conformation differs
insignificantly from that of molecule B in Figure 1, the X-
ray structure of 4 essentially comprises four lowest-energy
conformers of the compound. The twisted conformation of 4
(with exact or approximate D2 point-group symmetry)
therefore distinctly preorganizes the monomer for self-rec-
ognition by complementary intermolecular hydrogen bond-
ing. Interestingly, according to MacGillivrayꢁs classifica-
Table 2. Summary of the mean hydrogen-bonding geometries for deriva-
tives of 1 and 3 (structures are given in Figure S2).
[24]
[
a,b]
tion, both 4 and 5 may be categorized as symmetric U-
shaped bifunctional supramolecular synthons that are funda-
mentally capable of forming homodimers through H-bond-
ing interactions.
[c]
CSD ref. code
Structure
Av. H···A
Av. DꢀH···A
154(3)
166(2)
158
Av. D···A
[
12]
AWIXIN
7, BP
6, BP
9, MP
10, MP
5, BP
11, MP
12, MP
–
2.26(33)
2.066(6)
2.198
2.910(4)
2.942(6)
2.999
[
11]
EMIHEN
EWOLUX
EWOMAE
QOSMAM
SUVMUR
UMUKUI
average
[
d],[21]
[
d],[21]
2.172
171
3.023
Crystal packing: The crystal structure of 4 has a relatively
large unit cell accommodating 24 molecules. Viewing the
unit cell down the a-axis (Figure 3a) is somewhat deceptive
as it suggests that molecular scale cavities (approximately
[
6]
2.10(3)
2.169(7)
2.141
156(1)
166(1)
158
2.93(3)
3.032(9)
3.042
[
d],[22]
[
d],[23]
2.16(6)
161(5)
2.98(5)
3
.6 Š in diameter), created by association of the nonplanar
[
a] Distances in angstroms; angles in degrees. [b] D=donor; A=accept-
monomers into dimeric structures and subsequent ordering
of the dimers into columns along the a axis, might possibly
exist. However, it is important to note that since a plot of
the unit cell contents using van der Waals radii for the
atoms almost completely fills these apparent cavities (Fig-
ure S3), the crystal structure is not truly porous (genuine in-
finite channels are absent). Studies on porous molecular
or. [c] MP=mono
hydrogen bond.
A
C
H
T
R
E
U
N
G
(pyrrole), BP=bis(pyrrole). [d] One symmetry-unique
A
H
R
U
G
[16]
While it is generally recognized that the strength of a hy-
drogen bond is not linearly dependent on the interaction
[18]
distance, we note that the mean hydrogen-bond distance
for 4 is somewhat shorter than the average interaction dis-
crystals (particularly metal–organic frameworks) are cur-
[19]
[25]
tance given in Table 2. This may well reflect the fact that
comprises two molecular recognition synthons 3 and forms
a tightly interlocked dimer. Interestingly, Allen and cowork-
rently highly topical.
Indeed, elegant work by Barbour
[26]
4
and co-workers suggests that seemingly nonporous lattices
with no discernible channels (but discrete cavities or voids)
may behave as porous materials that can reversibly absorb
gases such as methane, halogens, CO , CO, and N .
[
17]
ers have analyzed the distribution of crystallographically
determined distances for NꢀH···N interactions in the CSD
2
2
and have reported that the most frequently observed hydro-
gen-bond distance for this type of interaction ranges from
Given the present global interest in finding molecular ma-
terials suitable for gas storage applications (particularly
[27,28]
2.033–2.066 Š; clearly, compound 4 falls neatly into this
H ),
2
we examined the crystal lattice of 4 a bit more
range with its 2.04(3) Š average. Furthermore, since most
closely. By using a probe radius of 1.2 Š (van der Waals
[29]
[30]
weak hydrogen bonds of the CꢀH···O type have interaction
radius of H) with MSROLL interfaced to X-Seed, we
identified 16 voids belonging to two types (A and B) be-
tween the layers formed by the columns of dimers (Fig-
ure 3b and 3c). The first type of void (type A) has a volume
distances greater than 2.2 Š, we conclude that the X-ray
structure of 4, together with those listed in Table 2, exhibit
structurally tight (i.e., intermediate to strong) hydrogen
[20]
3
bonding. The large association constant measured for 4 in
solution by NMR spectroscopy (vide infra) independently
supports this conclusion.
of 15.3(1) Š and has four sites per layer in the unit cell.
The remaining 12 sites are type B voids that each comprise
two closely spaced (2.22 Š separation) smaller voids of
7990
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Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
A
H
R
U
G
FULL PAPER
Encouraged by the existence of H -shaped cavities in the
2
lattice of 4 (H has a van der Waals volume of about
2
3
[25]
1
3 Š ), we tested the material for H sorption. In a typical
2
experiment, gas uptake was measured volumetrically
[33]
by
monitoring the pressure drop as a function of time in a
closed system containing the host material and the test gas
at a known initial pressure. A pure sample of microcrystal-
line 4 (1.0g) showed no H 2 uptake at an initial hydrogen
pressure of about 1.3 bar. Experiments at higher initial hy-
drogen pressures (10bar) also showed no hydrogen uptake.
These data suggest that: a) the lack of genuine channels in
the lattice inhibits hydrogen diffusion and thus its uptake in
the “tailor-made” voids and/or b) a phase change that could
possibly permit the uptake of H cannot readily occur at am-
2
[
34]
bient temperature, even at elevated hydrogen pressures.
In keeping with the idea that supramolecular aggregates can
be tailored to produce functional materials,
[24,35]
it is foresee-
able that U-shaped aromatic derivatives of 1 with more
widely spaced H-bonding motifs 3 might well produce simi-
lar layers of H-bonded dimers within columnar stacks that
encompass true infinite channels and harbor H -shaped
2
voids in the interlayer sites. Such a material would presuma-
bly have the correct lattice architecture to permit both diffu-
sion and storage of molecular hydrogen.
Despite the fact that solid 4 is not a true porous material,
the packing shown in Figure 3a is nevertheless interesting,
particularly since two layers of molecules exist, each of
which consists of two adjacent rows or columns of stacked
dimers. In the lower left row of molecules, the sequence of
stacked dimers is C···D, A···B, A···B, and C···D. This column
of molecules fits alongside a column of A···B, C···D, and
A···B dimers in the same plane. The right-hand-side column
of dimers is translated along the a axis to half the distance
between any pair of dimers in the left column, thereby ach-
ieving relatively tight “bump-in-hollow” packing within the
same layer. As might be anticipated from the space group
symmetry, the upper layer is the inverse of the lower layer
(
the twofold axis runs co-linear with the a axis in the center
of the unit cell, exactly midway between the two layers). In
the interests of brevity, discussion of the most prominent
short contacts involving dimer A···B and dimer C···D is
given in the Supporting Information (Figure S5).
Figure 3. a) Unit cell contents for 4 viewed approximately down the a
axis (hydrogen atoms have been omitted for clarity). b) Stick plot of the
unit cell contents illustrating the locations of the voids (semi-transparent
surfaces calculated with
a grid point probe radius of 1.2 Š using
[
29]
[30]
MSROLL interfaced to X-Seed ). c) Unit cell contents viewed ap-
proximately down the c axis illustrating the locations and shapes of the
two types of voids.
1
Solution H NMR studies: To be regarded as a well-defined
molecular recognition process, the formation of a hydrogen-
bonded dimer in the solid state should be mirrored by the
same event in fluid solution. One of the most accurate ex-
perimental methods available to delineate hydrogen-bonded
molecular associations in solution is to probe the resonance
frequencies of protons directly involved in the self-recogni-
3
7
.6(0) and 8.3(0) Š . Since these smaller voids are overlap-
ped, we have classified them as belonging to a single site B
3
1
[36]
with a mean volume of around 15 Š . The distinction be-
tion process by high-field H NMR spectroscopy. Indeed,
[20]
tween the sites is clearly evident from the projection of the
unit cell contents down the c axis (Figure 3c) as well as the
b axis (Figure S4). Similar void sites were identified using
Steiner has noted that XꢀH proton chemical shifts for an
H-bond donor typically fall in the range d=14–22 ppm in
strongly H-bonded species and appear around d=14 ppm in
moderately H-bonded species. (These are only approximate
values for the chemical shift ranges as the identities of the
[31,32]
OSCAIL-Xꢁs VOID algorithm,
but since the exact
cavity volumes are not output by the program, it is some-
what less useful than MSROLL.
Chem. Eur. J. 2006, 12, 7987 – 7999
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7991

O. Q. Munro et al.
H-bond donor, the solvent system, and the H-bond acceptor
cannot be ignored.)
Chemical shifts versus concentration: We recorded the
1
H NMR spectrum of 4 as a function of concentration in
CDCl at 258C (Figure 4). The pyrrole NꢀH protons partici-
3
pate directly in the molecular recognition event as the hy-
drogen-bond donors in the dimeric structure of 4 (Figure 1)
and this fact is clearly evident from the NMR spectra in the
d=10–13 ppm chemical shift range. More specifically, the
pyrrole NꢀH proton signal increases in intensity (as expect-
ed) and shifts by 0.7 ppm downfield from d=11.8 ppm to
around d=12.5 ppm with an increase in the concentration
of 4 from 3.3 mm to 847 mm. The simplest model accounting
for the self-assembly of 4 in fluid solution is one based on a
dimerization process involving two monomers (M) combin-
ing to give the hydrogen-bonded dimer (D, Figure 5). If we
assume that the observed chemical shift for the pyrrole Nꢀ
H protons is the equilibrium-weighted average of the chemi-
cal shifts of the monomer and dimer, then a modified form
[14]
of the usual dimerization equation that takes into account
nonspecific changes in the chemical shift with increasing
solute concentration (i.e., perturbations not due to the dime-
rization process itself, such as monotonic changes in the die-
lectric constant of the medium) can be used to fit the con-
centration dependence of the signal (Equation (1)). In this
equation the terms dobs, d , and d are the chemical shifts of
M
D
the equilibrium mixture, monomer, and dimer, respectively,
Ctot is the total concentration of 4, and q=d(d )/dC . The
AHCTREUNG
obs
tot
association (or dimerization) constant, K , is then given by
D
Equation (2), with the fractions of the monomer and dimer
obtained from Equations (3) and (4), respectively.
dobs ¼ dM  fM þ d  f þ q  Ctot
ð1Þ
ð2Þ
ð3Þ
ð4Þ
D
D
2
KD ¼ ½DŠ=½MŠ
fM ¼ 1=ð0:5 þ 0:5f1 þ 8 K C g
1=2
Þ
D
tot
fD ¼ 1ꢀfM
From Figure 4 (middle plot), it is clear that the use of a
linear offset term in Equation (1) (q”C ) is mandatory for
an acceptable fit of the experimental variation of the pyrrole
tot
ꢀ
Figure 4. Top: Selected NMR spectra of 4 in the pyrrole N H proton fre-
quency range as a function of concentration in CDCl
3
at 258C (signal am-
NꢀH proton chemical shifts with increasing concentration of
plitudes are not plotted on the same scale): a) 3.3 mm, b) 21.3 mm, c)
6.5 mm, and d) 368 mm. Middle: fit of the chemical shift of the pyrrole
NꢀH proton resonance as a function of concentration of 4 in CDCl
at
58C. The solid line is a fit to Equation (1) in the text; the dashed line is
9
4
. The origin of this term for the present system will be dis-
3
cussed below. The following parameters were obtained from
the nonlinear least-squares fit of Equation (1) to the data:
2
a fit to Equation (1) without the linear offset term. Bottom: Fit of the
ꢀ
1
d =10.68(7) ppm, d =12.40(2) ppm, K =815(83) m , and
pyrrole NꢀH proton resonance line-width (full width at half maximum)
M
D
1 [37]
D
ꢀ
q=0.18(3) ppmm . The free-energy change for the dime-
as a function of the concentration of 4 using Equation (5).
rization process at 258C in CDCl is thus exergonic and
3
2
98
ꢀ1
highly favorable: DG =ꢀ16.6(4) kJmol . Importantly, the
value of KD is three orders of magnitude higher than that
bonding interaction, b) two molecular recognition motifs (as
opposed to only one) lead to enhanced binding, and c) the
conformation of 4 is in fact preorganized for self-assembly
in this system. No untoward energy penalties (i.e., negative
contributions to DS for the binding process) associated with
[14]
measured for the mono(pyrrole) system 8 under identical
A
H
R
U
G
conditions. Our interpretation of this rather intriguing result
is that a) the basic geometry of the supramolecular synthon
3
is probably near-ideal for a tight two-point hydrogen-
7992
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Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
A
H
R
U
G
FULL PAPER
to that measured from the fit of the concentration depend-
ence of the pyrrole NꢀH proton chemical shift. From the fit
residuals (inset to bottom graph in Figure 4), it is clear that
the constant y allows for the line-width variation at the
highest concentrations of 4 to be properly accounted for
(
Figure S6 gives the fit of the data by Equation (5) without
the linear decay term).
Medium effects: Although the NMR spectroscopic data are
indisputably well modeled by Equations (1)–(5), one con-
cern is whether the linear offset terms are justified. If, as we
suggested above, the term q in Equation (1) takes into ac-
count monotonic changes in the dielectric constant of the
medium with increasing concentration of the Schiff base,
then all protons in the molecule must (to a first approxima-
tion) be similarly perturbed by this external change. Clearly,
if the concentration dependence of the chemical shift for
any magnetically unique protons in the molecule is meas-
ured, then the same value of q should be observed in all
cases. Figure 6 tests this hypothesis. The concentration de-
pendence of the chemical shift for the imine CꢀH protons is
Figure 5. Diagram depicting the equilibrium self-assembly of 4.
conformational reorganization therefore exist before two
monomers of 4 may self-assemble into a dimeric structure
similar (or, more likely, identical) to that of the X-ray struc-
ture (Figure 1). Our claim that 4 is preorganized for dimeri-
zation is based not only on the large value of KD for the
system, but also on the nonplanar conformation of mono-
meric 4 calculated in vacuo at the AM1 level of theory (vide
infra). If the lowest-energy conformer of the molecule hap-
pens to be nonplanar and already of the correct shape to in-
teract perfectly with a second monomer, then such a system
is clearly preorganized for self-recognition.
shown in Figure 6a. These protons are increasingly shielded
upon dimerization of 4 (as evidenced by the negative slope
in the concentration range below 0.1m) prior to experienc-
ing monotonic deshielding in the dimer due to the change in
the dielectric constant of the medium at concentrations
above 0.1m. The fit to Equation (1) is good and is described
by the parameters: d =8.10(1) ppm, d =7.68(1) ppm, K =
Line-width analysis: The pyrrole NꢀH proton line-width
narrows considerably (by an order of magnitude) with in-
creasing concentration (Figure 4, lower plot). The major
(
nonlinear) change clearly occurs in the concentration range
below 0.3m. This marked change in line-width is due primar-
ily to the formation of the hydrogen-bonded dimer. As
M
D
D
ꢀ
1
ꢀ1
821(32) m , and q=0.124(3) ppmm . For the phenyl m-pro-
tons, the data were fit to the first-order polynomial function
dobs =dinit +q”Ctot (Figure 6b). The adjustable parameters
converged to the values dinit =7.087(1) ppm and q=
0.114(3) ppmm . Thus, for chemically (and magnetically)
unique protons in solvent-accessible environments on the
outside perimeter of the dimeric structure of 4, we find that
[14]
noted previously for the mono(pyrrole) derivative 8, hy-
A
H
R
U
G
drogen-bond formation in the dimeric structure localizes the
pyrrole NꢀH protons and diminishes their exchange rate
ꢀ
1
until, on the NMR timescale, the slow exchange limit is
reached. At concentrations higher than 0.3m, it is evident
that further more-gradual narrowing of the line-width
occurs with a constant slope. This post-dimerization change
in the pyrrole NꢀH proton line-width probably reflects the
ꢀ
1
q is indeed constant, at about 0.11(1) ppmm , and may cor-
rectly be attributed to concentration-dependent changes in
the medium. Finally, the self-association constant KD meas-
ured from the fit of the data for the imine CꢀH proton reso-
changing dielectric constant of the medium with increasing
solute concentration and its indirect effect on the relaxation
rate of the pyrrole NꢀH protons. As with Equation (1), a
nance (Figure 6a) is experimentally equivalent to that meas-
model was derived to fit the concentration dependence of
ured from the concentration dependence of the pyrrole Nꢀ
the line-width (full width at half maximum, Dn ) that spe-
H resonance, thus implying an internally consistent method
for quantifying the self-association constant in this system.
1
/2
cifically includes both the effect of dimerization on the line-
width and the changing relaxation rate [Eq. (5)].
Molecular simulations: Semi-empirical quantum mechanics
simulations using methods such as AM1 are not only com-
putationally efficient, but are widely recognized as being
sufficiently accurate for simulations on medium to large hy-
Dn1=2 ¼ Dn1=2M  fM þ Dn1=2D  fD þ y  Ctot
ð5Þ
The fractions of the monomer and dimer in solution, fM
and f , are given by Equations (3) and (4), respectively. The
drogen-bonded
supramolecular
species
with
both
D
[11,14,38]
[39,40]
intrinsic pyrrole NꢀH proton line-widths of the monomer
strong
and weak
hydrogen bonds. Using this
and dimer are given by the terms Dn
and Dn , while
method, our computational objectives were to: 1) fully map
the region of conformational space encompassing the X-ray
conformations for 4 in an effort to further understand the
marked nonplanarity of each monomer conformation ob-
served in the crystal lattice, 2) determine the structures and
energies of the global and local minima accessible to 4, 3)
determine the in vacuo enthalpy of association of the dimer-
1
/2M
1/2D
ꢀ
1
the constant y (in units of Hzm ) quantifies the medium-in-
duced change in the pyrrole NꢀH proton relaxation rate
with increasing concentration. The following parameters
were obtained for the fit of Equation (5) to the data: Dn
A
H
R
U
G
1/
ꢀ
1
=
1261(35) Hz, Dn1/2D =34(6) Hz, K =815(56) m , and
D
2M
y=ꢀ31(13) Hz. Importantly, the value of KD is equivalent
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7993

O. Q. Munro et al.
Figure 6. a) Fit of the concentration dependence of the chemical shift of
to Equation (1). b) Fit of the
concentration dependence of the benzene m-protons at 258C in CDCl to
3
Figure 7. a) Three-dimensional plot of the variation in the relative heat
of formation, DE, of 4 as a function of the torsion angles f and f . The
1 2
the imine CꢀH protons at 258C in CDCl
3
data were calculated at the AM1 level of theory (gas phase). b) Two-di-
mensional contour map of the PES showing the locations of the global
energy minimum X, the local energy minimum Y, and the global energy
maximum, Z. Inversion-related conformers have been given primed
labels; torsion angles f and f are defined in Figure 8.
a first-order polynomial function.
ic structure of 4, and 4) delineate the electrostatics of the
monomeric and dimeric forms of the compound that stabi-
lize self-association as well as some aspects of the crystal
packing between adjacent dimers in the solid state.
1
2
formational adjustment and that the lowest-energy confor-
mation has the correct geometry for self-assembly by hydro-
gen-bond formation into the experimentally observed dimer-
ic structure. Together with the X-ray data, our AM1 simula-
tions therefore indicate that 4X is conformationally preor-
ganized for this particular molecular recognition event.
Several other interesting conformations are energetically
feasible for 4. Thus, a local minimum with a nonplanar
domed conformation (both pyrrole NꢀH groups pointing
Low-energy conformations: Figure 7a shows a three-dimen-
sional plot of the potential energy surface (PES) that spans
the conformational space incorporating the most relevant
conformers of 4 (the torsion angles f and f are defined
1
2
graphically in Figure 8). From the contour map of the sur-
face (Figure 7b), a center of inversion exists at the coordi-
nate f , f =08. This corresponds to the global maximum
1
2
(
4Z, Figure 8) with a heat of formation some 2.86(2) kcal
above or below the molecular mean plane) was located by
ꢀ
1
mol higher than that of the lowest energy conformer (4X)
found at f , f =ꢀ49.88. Importantly, conformer 4X has a
the grid search of conformational space (4Y). This confor-
ꢀ
1
mation is 0.83 kcalmol higher in energy than the global
1
2
ꢀ1
highly nonplanar, twisted architecture that is remarkably
similar in geometry to the independent monomers found in
the X-ray structure of 4 (Figure 9a). This strongly suggests
that dimerization of 4 does not require a pronounced con-
minimum. The transition state (DE=1.5 kcalmol ) con-
necting minima 4X and 4Y corresponds to a structure in
which one pyrrole ring is canted out of the mean molecular
plane (f =ꢀ498) while the other remains coplanar with re-
1
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Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
A
H
R
U
G
FULL PAPER
Figure 8. Structures and relative heats of formation of the C
conformations 4X and 4Z and the C -symmetric conformer 4Y taken
from the AM1-calculated potential energy surface for monomeric 4
shown in Figure 8. The torsion angles f and f are defined using 4X for
illustration.
2
-symmetric
1
Figure 9. a) Root-mean-square fit of the X-ray structure of 4 (molecule
B) to the AM1-calculated conformation 4X (in vacuo) of the monomeric
Schiff base derivative. b) Root-mean-square fit of the X-ray structure of
1
2
4
(molecules A and B) to the AM1-calculated structure of the dimer in
the gas phase. All atoms were included in the least-squares fitting proce-
dure in both cases.
spect to the benzene ring (f =08). The low barrier for the
Theoretical versus experimental structures: As shown in
Figure 9, the AM1-calculated structures of monomeric and
dimeric 4 are fundamentally good when compared with the
relevant X-ray structures using least-squares fitting techni-
ques. If we take into account the fact that the simulations in-
clude only the valence electrons and operate in vacuo (local
distortions of the experimental conformers caused by crystal
packing interactions, such as those illustrated in Figure 4,
are thus excluded), then the fact that the differences be-
tween the experimental and theoretical structures amount to
less than 1 Š for all atoms in each case is remarkable. Fur-
thermore, if we consider some key intermolecular interac-
tions, we find that the mean NꢀH···N and Ndonor···Nacceptor hy-
2
transition state (saddle-point) reflects the fact that the most
strained conformation of the compound has the two pyrrole
NꢀH groups pointing directly at one another (4Z). As soon
as one pyrrole ring flips out of the mean molecular plane,
steric strain is partly relieved. Full relief of the steric strain
engendered by nonbonded repulsion between the pyrrole
NꢀH groups occurs if both pyrrole rings are canted out of
plane and in opposite directions (conformer 4Z ! 4X). In-
terestingly, our AM1 simulations suggest that the bond
order for the central CꢀN bond of the torsion angles f and
1
f is much closer to one than two. Specifically, the Wiberg
2
[41]
bond order
calculated for 4X (1.04) is only marginally
less than that calculated for 4Z (1.06), thus suggesting that
the barrier to rotation about f and f should be close to
drogen-bond distances in the calculated structure of the
dimer (Figure 9b) are 2.56 and 3.47 Š, respectively, and thus
compare reasonably well with the analogous values deter-
mined crystallographically (2.04(3) and 2.93(3) Š). Together
with the acceptable conformation calculated for the dimeric
structure of 4, we conclude that AM1 provides a practical
and computationally efficient method for analyzing the con-
formational structures, most probably the relative energies,
and possibly some of the fundamentals of the H-bonding in-
1
2
that for a normal CꢀN single bond. A further indication of
the low CꢀN bond order is the fact that the energy of the
conformation calculated with f =f =908 is only around
1
2
ꢀ
1
0
.6 kcalmol (Figure 7). For a strongly delocalized structure
with a bond order closer to two, such a conformation would
be expected to have one of the highest energies for the
system, not one of the lowest.
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7995

O. Q. Munro et al.
teractions in this rather complex experimental system. It is
worth noting that the calculation of the PES for 4 (with 19
well known and is paralleled by similar, though smaller,
over-estimations of calculated vibrational frequencies by
2
[45]
conformers, Figure 7) would be prohibitively costly in both
computational time and machine infrastructure, with no
more rigorous ab initio methods.
Notwithstanding this,
the simulations still afford a qualitatively correct measure of
the electronic structure perturbations brought about by di-
merization in this system.
[42]
guarantee of improved structural accuracy, for any HF or
[43]
DFT methods with basis sets ꢁ 3-21G in size.
[11,14]
Electrostatics: Previous work by our group
has shown
Self-assembly thermodynamics: The dimerization of 4 meas-
that complementary electrostatic interactions are probably
the key driving force for the self-assembly of pyrrole-imine
systems 3 both in the solid state and in solution. The Mullik-
ured by NMR spectroscopy in CDCl solution is clearly ex-
3
ergonic (DG<0, vide supra). For credibility, any theoretical
simulation of this system would need to give a comparable
result. To compute the Gibbs energy change and enthalpy
change for self-assembly of 4, we first calculated the struc-
ture of the dimer using the X-ray coordinates as input. We
then moved the constituent monomers apart to a distance
greater than 11 Š and recalculated the geometries of the
noninteracting molecules. A full frequency analysis of each
system was employed to evaluate the thermochemical pa-
rameters at 298 K. The enthalpy of association, DHassoc, was
[44]
en populations
(partial charges) computed at the AM1
level of theory for the monomeric and dimeric forms of 4
confirm this notion (Figure 10). Specifically, the pyrrole Nꢀ
calculated from Equation (6), where DHf(dimer) is the heat
A
H
R
N
#
of formation at 298 K of the dimer and DHf is the heat of
formation of the noninteracting system.
#
DHassoc ¼ DH ðdimerÞꢀDHf
ð6Þ
f
A similar equation was used to evaluate the Gibbs func-
tion for self-assembly in the gas phase. In effect, Equa-
tion (6) is equivalent to applying a counterpoise correc-
[46]
tion for the basis set superposition error that typically af-
fects the calculated binding energies of dimers in all-elec-
Figure 10. Symmetry-unique Mulliken partial-charge distributions (in
tron basis set simulation methods. From the thermodynamic
electron units) calculated at the AM1 level of theory for the D
2
-symmet-
ꢀ1
data listed in Table 3, we calculate DH
=ꢀ29.2 kJmol ,
assoc
2
ric dimeric structure of 4 (italics font, left half of molecule) and the C -
symmetric monomer (right half of molecule).
ꢀ
1
ꢀ1
ꢀ1
DGassoc =ꢀ21.9 kJmol , and DS
=ꢀ24.3 JK mol
at
assoc
H hydrogen partial charge (+0.263) complements the parti-
al charge of the imine C=N nitrogen (ꢀ0.163) in the mono-
mer. Dimer formation clearly also favors polarization of
these key functional groups, particularly the imine C=N
Table 3. AM1-calculated conformational and frontier MO energies (at
298 K) for various structural forms of 4.
[
a]
[a]
[b]
[b]
[b,c]
Conformation
DHf
DGf
EHOMO
ELUMO
DEHL
twisted, 4X
domed, 4Y
flat, 4Z
154.04
154.87
156.91
302.71
309.68
298.33
299.21
304.00
605.96
611.20
ꢀ8.327
ꢀ8.272
ꢀ8.136
ꢀ8.245
ꢀ8.272
ꢀ0.3810
ꢀ0.4626
ꢀ0.7619
ꢀ0.5987
ꢀ0.5170
7.946
7.810
7.374
7.647
7.755
0
.025
unit, where the charge separation increases from C
=
ꢀ
0.163
0.038
ꢀ0.193
N
in the monomer to C =N
in the hydrogen-
2
D dimer
bonded dimer. As might be expected, the calculated Wiberg
[d]
4
X, 4X
[41]
bond orders for the C=N and pyrrole NꢀH bonds confirm
ꢀ
1
[
a] Energy in kcalmol . [b] Energy in eV. [c] ELUMOꢀEHOMO. [d] Two
the above polarization effects resulting from hydrogen-bond
formation. Thus, the C=N bond order decreases from 1.84 in
the monomer to 1.82 in the dimer, while the NꢀH bond
twisted monomers separated by 11 Š.
order decreases from 0.882 in the monomer to 0.873 in the
dimer. These changes are mirrored by red shifts in the calcu-
lated vibrational frequencies of these bonds. Specifically, di-
merization favors a decrease in the intense antisymmetric
298 K. The negative entropy term is not only of a sensible
magnitude but indeed perfectly correct for a system in
which two reactant species associate to form a single prod-
uct. Remarkably, the gas-phase free-energy change calculat-
ed for self-assembly of 4 is in very good agreement with the
ꢀ1
pyrrole NꢀH stretching vibration from 3512 cm in the
ꢀ
1
monomer to 3479 cm in the dimer. The antisymmetric C=
ꢀ
1
N stretching mode is similarly shifted from 1921 cm in the
value measured by NMR spectroscopy (DGassoc
=
ꢀ
1
ꢀ1
monomer to 1909 cm in the dimer. While the calculated vi-
brational frequencies are not particularly accurate and differ
ꢀ16.6(4) kJmol ). This confirms the suitability of AM1 for
[
38]
such calculations, in agreement with our previous findings,
ꢀ1
by as much as 300 cm from the experimental values (Sup-
porting Information), this limitation of the AM1 method is
and probably reflects the fact that the dielectric constant of
CDCl (4.81 D) is not overly different from the gas-phase di-
3
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Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
A
H
R
U
G
FULL PAPER
electric constant (1.0D). Importantly, our finding that the
experimental value of DGassoc is only slightly less than that
calculated for 4 in the absence of solvent suggests that solva-
tion of the dimer by a non hydrogen-bonding solvent might
marginally weaken the molecular recognition interactions
that stabilize the supramolecular structure. Since CDCl has
3
a dipole moment, this subtle effect may derive from pertur-
bation of the complementary electrostatics that seemingly
govern hydrogen bonding in this system. Alternatively, an
entropy penalty related to desolvation of the monomers
upon dimerization in the experimental system, which is ob-
viously unaccounted for in the gas phase simulation, might
be at work.
Molecular orbitals: The MO energies listed in Table 3 for
different monomer conformations of 4 as well as the hydro-
gen-bonded dimer suggest that the electronic structure of
the system is fairly sensitive to both structural distortion and
to dimer formation. The twisted, highly nonplanar lowest
energy conformer of the Schiff base 4X has the largest
HOMO–LUMO energy gap. The frontier MO splitting,
DEHL, for 4X is seen to be larger than that for 4Z (planar
conformation) by more than 0.5 eV. For the series of con-
formers 4X, 4Y, and 4Z, the HOMO energy systematically
increases while the LUMO energy systematically decreases.
Clearly, the conformation-dependence of DEHL reflects
modulation of the p-electron delocalization with the degree
of distortion of the structure. A convenient way to further
analyze this trend is to evaluate how bond orders for key
bonds in the structure change when the conformation dis-
torts from planarity. Thus, we found that the calculated C=N
bond orders were 1.841, 1.833, and 1.814 for conformers
Figure 11. a) HOMO for the AM1-calculated C
2
-symmetric monomeric
structure 4X. b) HOMO for the D -symmetric dimer.
2
Conclusion
We have obtained novel X-ray structural data for a bis-
(pyrrole) Schiff base derivative synthesized by the condensa-
AHCTREUNG
4
X, 4Y, and 4Z. The slight decrease in C=N bond order
tion of 1,2-diaminobenzene and pyrrole-2-carboxaldehyde
(compound 4). The crystal structure shows that dimers are
formed through complementary sets of hydrogen bonds be-
tween the pyrrole NꢀH donor groups and imine N=C ac-
with increasing planarity of the conformation is consistent
with increased p-electron delocalization. However, it is
noteworthy that even the nonplanar conformer 4X exhibits
extensive p-electron delocalization, as evidenced by the
HOMO, which spans the entire structure (Figure 11a).
Finally, an important question is how tightly mingled are
the electronic structures of the monomers that make up the
dimer in this hydrogen-bonded system? Previous calcula-
tions on more weakly hydrogen-bonded dimers suggest that
considerable mixing occurs. In the present system, Figur-
e 11b clearly shows that the dimer of 4 has an electronic
structure that is not merely the sum of the two independent
monomers. If this were the case, the HOMO would reside
entirely on one monomer component of the dimer and the
HOMOꢀ1 (not shown) on the other. The fact that the
HOMO is fully delocalized over both monomers within the
dimer (other filled p MOs behave similarly) indicates that
the interlocked Schiff base units become electronically
mixed upon dimer formation. Considering the fact that the
mean plane of one monomer unit is almost orthogonal to
that of the other (86.08) and, furthermore, that the mono-
mers are linked by noncovalent bonds, this level of p-orbital
mixing (and thus p-electron delocalization) is quite remark-
able.
ceptor groups of the interacting monomers. The crystal lat-
tice exhibits an unusual packing pattern for the dimers,
which assemble into layers of columns whose axes are col-
linear with the crystallographic a axis. We have established
that this intriguing packing leaves small H -sized voids (with
2
two geometries) between the layers of dimers. However, the
absence of bona fide channels within the lattice probably
prevents hydrogen gas uptake (sorption) by the microcrys-
talline solid, despite the use of hydrogen pressures up to
10bar.
[14]
From the concentration dependence of key resonances in
1
the H NMR spectrum of 4, we have used nonlinear curve-
fitting methods to delineate the self-assembly process for 4
in fluid solution and have established that dimer formation
ꢀ
1
is highly exergonic (DGassoc =ꢀ16.6 kJmol ). Semiempirical
MO calculations at the AM1 level of theory indicate that
complementary hydrogen bonding (molecular recognition)
in this system is driven by favorable electrostatic interac-
tions. Thermochemical analysis of the self-assembly process
for 4 in vacuo using AM1 affords a remarkably good predic-
ꢀ
1
tion of DGassoc for the reaction (ꢀ21.9 kJmol ). Part of the
Chem. Eur. J. 2006, 12, 7987 – 7999
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7997

O. Q. Munro et al.
success of the in vacuo AM1 simulation may be due to the
fortuitously small contribution that solvation makes to the
thermodynamics of the process in the experimental system.
Finally, our AM1 simulations of the potential energy surface
for monomeric 4 indicate that the lowest energy conformer
has a twisted nonplanar structure that is clearly preorgan-
ized for self-assembly into a dimeric supramolecular struc-
ture.
over activated neutral alumina. Standard pulse sequences were used (128
scans, spectral width=12604.38 Hz, spectral resolution=0.264265 Hz).
An exponential line-broadening factor of 1.061 was used during Fourier
[51]
transformation of the data with the program SpinWorks 2.5.1. The pyr-
role N H signal (at about d=12 ppm) was fit to a Voigt line-shape func-
ꢀ
[
52]
tion in each case and the resonant frequency, intensity, and line width
determined accurately by nonlinear least-squares regression using the
[53]
program PEAKFIT v4.0(Table S2).
[
54]
Molecular simulations: AM1 geometry optimization calculations were
[
55]
[56]
carried out with ArgusLab 4.0.1 and Gaussian 03W using the X-ray
coordinates of 4 as input. Spin-restricted wave functions were used on
the lowest-lying doublet states of the X-ray structures (monomer and H-
bonded dimer), which were analyzed by single-point calculations as well
as full geometry optimizations with the default convergence criteria. Fre-
quency calculations (298.15 K) were performed on each optimized struc-
Experimental Section
General details and synthesis: Hexane and dichloromethane (BDH)
were distilled from sodium metal and calcium hydride, respectively,
before use. Ethanol (96%, BDH), pyrrole-2-carboxaldehyde, and 1,2-
phenylenediamine (both from Aldrich) were used as received. Electronic
spectra were recorded with a Perkin–Elmer Lambda 45 double beam
2
ture. No imaginary vibrational modes were found for the nonplanar C -
symmetric conformation of 4, thus confirming the fact that this conform-
er is a true minimum on the potential energy surface. In contrast, the
2
planar C -symmetric conformation yielded one imaginary frequency.
A relaxed scan of the potential energy surface (PES) was performed at
the AM1 level of theory for monomeric 4 by counter-rotating the pyr-
2 2
spectrophotometer using CH Cl solutions in 1.0cm path length cuvettes.
Samples for IR spectroscopy were KBr mulls of polycrystalline material.
FT-IR spectra were recorded with a Perkin–Elmer Spectrum One spec-
role-imine units from ꢀ90to 90 8 in 108 increments, producing a total of
2
ꢀ1
19 starting conformations for refinement. The torsion angles f and f
trometer (four scans; spectral resolution: 1.0cm ). Compound 4 was
1
2
were defined as the adjacent pair of C=CꢀC=N angles with the C=C
synthesized from 1,2-phenylenediamine (1.600 g, 15.0 mmol) and pyrrole-
bond not common to both (e.g., C6bꢀC7b and C11bꢀC10b in molecules
2
-carboxaldehyde (2.853 g, 30.0 mmol) in refluxing ethanol (15 mL) fol-
[
47]
A and B of the X-ray structure). A maximum of 2000 least-squares
lowing the literature method of Jones. Single crystals of 4 suitable for
cycles with
a
root-mean-square gradient termination cutoff of
X-ray diffraction studies were grown by slow diffusion of hexane into a
ꢀ
1
ꢀ1
0
.01 kcalŠ mol was used for geometry optimization with the Polak–
dichloromethane solution of 4, or by slow evaporation of the solvent
[
57]
1
Ribiere conjugate gradient algorithm in HyperChem 6.03. The three-
dimensional grid of enthalpy of formation data was analyzed in relative
energy format, DE, using the global energy minimum as the zero refer-
ence. The program KyPlot 3.0 was used with a thin plate smoothing
spline regression to fit the 3D data (a second-order penalty derivative
and equivalent bandwidth, i.e., smoothing parameter, of 0.1 were em-
ployed with a calculation step set at 90x and y grid divisions).
(
ethanol). H NMR spectroscopic data for 4 were consistent with those
[
6]
reported in the literature (Supporting Information).
X-ray crystallography: X-ray diffraction data for a pale-yellow rectangu-
[
58]
3
lar block with the approximate dimensions 0.4”0.6”0.7 mm were col-
lected with an Oxford Diffraction Xcalibur2 CCD four-circle diffractom-
eter equipped with an Oxford Instruments Cryojet operating at 100(2) K.
The data were collected at a crystal-to-detector distance of 60mm using
omega scans at q=29.3278 with 30s exposures taken at 2.20kW X-ray
power with 0.608 frame widths. The data were reduced with the program
[
48]
CrysAlis RED
using outlier rejection, scan speed scaling, as well as
standard Lorentz and polarization correction factors. A total of 65453 re-
flections were merged to give 40466 unique data with an average redun-
2
2
dancy of 1.6 and a mean F /sF of 14.61. The internal R index for the
data set after reduction was 0.03(3) and the resolution of the data was to
Acknowledgments
0
.72 Š. The structure was solved in the monoclinic space group C2/c
[
49]
[50]
We gratefully acknowledge financial support from the University of Kwa-
Zulu-Natal, SASOL, and the National Research Foundation (NRF, Pre-
toria). Any opinion, findings and conclusions or recommendations ex-
pressed in this paper are those of the authors and therefore the NRF
does not accept any liability in regard thereto. The authors also wish to
thank Prof. Len Barbour and Gareth Lloyd of the University of Stellen-
using direct methods in WinGXꢁs
All non-H atoms were located in the electron density map and were re-
implementation of SHELXS-97.
[
50]
fined anisotropically with SHELXL-97. The data set was of sufficiently
high quality that all H atoms were located in the final difference Fourier
synthesis cycle. The coordinates of the hydrogen atoms attached to the
pyrrole nitrogen atoms of 4 were refined isotropically without con-
straints; however, the isotropic Uij values were fixed at 1.2-times the Ueq
values of the nitrogen atoms. All other H atoms were calculated using
the standard riding model of SHELXL-97 (HFIX 43 instruction).
Table S1 lists the full crystal and data collection parameters for 4.
2
bosch for assaying the H sorption behavior of 4.
[
[
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CCDC-601917 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Crystal data: C16
14 4
H N , M=262.31 gmol , T=100(2) K, l=0.71073 Š,
monoclinic, C2/c, a=34.778(10), b=17.018(11), c=14.094(4) Š, b=
9
flections collected=31465, unique reflections=10365, observed reflec-
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3
ꢀ3
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4.40(2)8, V=8317(6) Š , Z=24, 1calcd =1.257 gcm , m=0.08 mm , re-
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=0.044 (F >
[
[
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s(F )), wR =0.113 (F ), largest difference peak and hole=0.28 and
2
ꢀ
3
ꢀ
0.21 eŠ .
Dimerization of 4 studied by NMR spectroscopy: NMR spectra for 4
were recorded as a function of concentration in CDCl
Varian Unity Inova 500 MHz spectrometer operating at a transmitter fre-
quency of 499.983 MHz. Solutions were prepared by dissolving from
3
at 258C with a
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.5 mg up to 130 mg of polycrystalline material in 600 mL of CDCl dried
7998
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7987 – 7999

Preorganization of a Bis(pyrrole) Schiff Base Derivative
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Received: March 22, 2006
Revised: June 12, 2006
1
986.
Published online: September 8, 2006
Chem. Eur. J. 2006, 12, 7987 – 7999
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7999