Salts of 4-aminobutyric acid and 6-aminohexanoic acid behaving as molecular Velcro

Article abstract of DOI:10.1039/c7ce01597f

The crystal structures of eight novel carboxyalkylammonium salts, (⁺H₃N(CH₂)nCOOH)X^-, are reported, with n = 4 and X = Cl, Br and I in structures 1, 2 and 3, respectively, and n = 6 and X = Cl, Br·0.5H₂O, Cl·0.5H₂O, NO₃ and ClO₄ in structures 4, 5, 6, 7 and 8. The members of this family of compounds were found to display significant structural diversity, and a careful analysis of the structures employing the principles of crystal engineering was done to explain the observed trends and differences, specifically also the interdigitation or non-interdigitation of alkyl chains. It was found that a primary hydrogen bonding network formed between the ammonium groups and halide or oxo-anions, which plays a major structure-directing role. The structures may be likened to molecular Velcro, in which secondary hydrogen bonding interactions involving the carboxylic acid groups act as "hooks" to link primary networks.

Full text of DOI:10.1039/c7ce01597f

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Salts of 4-aminobutyric acid and 6-aminohexanoic
acid behaving as molecular Velcro†
Cite this: DOI: 10.1039/c7ce01597f
*
M. Rademeyer
and B. van der Westhuizen
The crystal structures of eight novel carboxyalkylammonium salts, (+H3NIJCH2)nCOOH)X−, are reported,
with n = 4 and X = Cl, Br and I in structures 1, 2 and 3, respectively, and n = 6 and X = Cl, Br·0.5H2O,
Cl·0.5H2O, NO3 and ClO4 in structures 4, 5, 6, 7 and 8. The members of this family of compounds were
found to display significant structural diversity, and a careful analysis of the structures employing the princi-
ples of crystal engineering was done to explain the observed trends and differences, specifically also the
interdigitation or non-interdigitation of alkyl chains. It was found that a primary hydrogen bonding network
formed between the ammonium groups and halide or oxo-anions, which plays a major structure-directing
role. The structures may be likened to molecular Velcro, in which secondary hydrogen bonding interac-
tions involving the carboxylic acid groups act as “hooks” to link primary networks.
Received 4th September 2017,
Accepted 30th October 2017
DOI: 10.1039/c7ce01597f
rsc.li/crystengcomm
mono-n-alkylammonium halide monohydrates (CSD refcodes:
Introduction
HUZBOT,10 KUTSAU,11 QUMWOL,12 QUMWUR,12 QUMXAY,12
Long chain n-alkane molecules typically crystallise in layered
structures,1 with the cohesion of the alkyl chains achieved by
van der Waals interactions. The introduction of a terminal
functional group to the alkyl chain may potentially affect the
ideal close packing of the alkyl chains. Due to the conforma-
tional flexibility of the alkyl chain, deviations of molecular
conformations from the ideal all-trans conformation, and
gauche bonds, are possible. Depending on the size of the ter-
minal functional group, the chains may pack to form a bi-
layer, or the alkyl chains may interdigitate.2
In the case of primary long chain n-alkylammonium salts,
a counter anion is incorporated into the structure to ensure
charge neutrality, in addition to the terminal ammonium
head group. The resulting structure balances the strong ionic
interactions and hydrogen bonding between the charged am-
monium groups and anions, and the van der Waals interac-
tions between the alkyl chains, in addition to close packing
requirements.
QUMXEC,12 QUMXIG,12 TABLAJ,13 ULIJAB14) have been
reported.
Both the anhydrous and the monohydrate salts typically
form layered, interdigitated structures in which the alkyl
chains do not contain any gauche bonds. No structures of
primary, mono-n-alkylammonium nitrates or -perchlorates
could be located in the CSD.
In the reported primary n-alkylammonium halide struc-
tures, a hydrogen bonding network is formed between the
ammonium group and the hydrogen bond accepting anion,
X−. Bond15 classified the hydrogen bonding networks of these
structures according to the principles of ring-stacking and
ring-laddering.
In the current study, the effect of the introduction of a ter-
minal carboxylic functional group at the opposite end of the
ammonium group in a primary mono-n-alkylammonium cat-
ion, to form a carboxyalkylammonium cation, (+H3NIJCH2)-
nCOOH), and the structures of the salts obtained, are investi-
gated. This introduces further hydrogen bonding capability
compared to the n-alkylammonium cation. In these salts, the
carboxylic acid functional group can act as both a hydrogen
bond donor or acceptor, resulting in two hydrogen bonding
donors (the ammonium group and the carboxylic acid group)
and two hydrogen bonding acceptors (the anion and the car-
boxylic acid group). If the carboxyalkylammonium salt is hy-
drated, water molecules may act as both hydrogen bonding
donors or acceptors. In the case of the anhydrous carboxy-
alkylammonium salts, a hydrogen bonding network that com-
bines all the hydrogen bonding donors and acceptors in a sin-
gle hydrogen bonding network may theoretically be formed.
A search of the Cambridge Crystallographic Database3
(CSD, version 5.38, May 2017 update) reveals that a number
of structures of primary, mono-n-alkylammonium halides
(CSD refcodes: DEAMMC01-02,4,5 DODAMB,6 KAKSIA,7
ZZZLWK02,5 ZZZLWK03,8 ZZZLWK04 (ref. 9)) and primary
Department of Chemistry, University of Pretoria, cnr Lynnwood Road &, Roper
Street, Hatfield, Pretoria 0002, South Africa. E-mail: melanie.rademeyer@up.ac.za
† Electronic supplementary information (ESI) available. CCDC 1571889–1571896.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c7ce01597f
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Etter16 noted that the strongest hydrogen bonding donor of-
ten interacts with the strongest hydrogen bonding acceptor. If
this approach is applied to the carboxyalkylammonium salts,
the strongest hydrogen bonding donor, the charged ammo-
nium group, and the strongest hydrogen bond acceptor, the
charged anion, are expected to interact via hydrogen bonding,
while the second strongest donor and acceptor, both carbox-
ylic acid groups, will form hydrogen bonds.
Scheme 1 Novel structures determined in the current investigation.
Scheme 1. The salts under investigation will be abbreviated
CnX for the anhydrous salts, or CnX·0.5H2O for the hemihy-
drate salts, where n indicates the number of carbon atoms in
Here we report the structural characteristics and hydrogen
bonding interactions in a series of carboxyalkylammonium
salts, (+H3NIJCH2)nCOOH)X− where X− = Cl−, Br−, I−, NO3 and
the cation and X indicates the anion (X = Cl−, Br−, I−, NO3 or
−
−
ClO4− and n = 4 or 6. A minimum of four carbon atoms in the
alkyl chain allows van der Waals interactions between the
n-alkyl portions in the cations. By restricting the number of
carbon atoms in the chain to the even numbers 4 and 6, the
well-known odd–even effect, often observed in compounds
containing alkyl portions,17 is expected to be negated.
Salt formation is achieved via the protonation of the
amine group of 4-aminobutyric acid (also known as
γ-aminobutyric acid or GABA), and the longer chain
6-aminohexanoic acid, with a strong acid, HX. GABA is a com-
mercially available supplement against anxiety,18 while
6-aminohexanoic acid is prescribed as a treatment for bleed-
ing disorders.19 Many drugs used today are marketed in the
form of a salt,20 with the active ingredient as cation or anion,
due to potentially improved properties like solubility and
chemical stability of the salt compared to the neutral com-
pound. Considering these potential improvements, the inves-
tigation of salt formation of pharmaceutically important com-
pounds is also of interest.
ClO4 ).
−
Results
Crystallographic discussion of structures
The crystallographic parameters of structures 1 to 8 are listed
in Table 1, their asymmetric units are illustrated in Fig. 1
and strong hydrogen bonding interactions are given in
Table 2.
One carboxybutylammonium cation and one chloride an-
ion comprise the asymmetric unit of 1, C4Cl, and there are
two asymmetric units in the unit cell. The whole cation, in-
cluding the carboxylic acid group, lies on a mirror plane, and
the alkyl portion adopts the low energy, all-trans conforma-
tion, with torsion angles close to 180°. A layered structure is
formed parallel to the ab-plane, with the cations packing in
an interdigitated fashion, as shown in Fig. 2(a). The ammo-
nium groups, chloride anions and carboxylic acid groups
comprise the inorganic layer, while the parallel alkyl and car-
boxylic acid portions of the cation form the organic layer.
When viewed down the b-axis, the cations in a layer are paral-
lel and tilted at an angle of 62.6IJ1)° relative to the layer plane,
as shown in Fig. 2(a).
In the inorganic layer, the ammonium groups, chloride
anions and carboxylic acid groups all interact through hydro-
gen bonding to form a single, two-dimensional hydrogen
bonded network. However, even though only one hydrogen
bonding network is present, this network can be divided into
two parts, namely a two-dimensional primary hydrogen bond-
ing network, consisting of charge-assisted hydrogen bonds
between the strongest hydrogen bonding donor, the ammo-
nium group, and the strongest hydrogen bonding acceptor,
the chloride anion, and a secondary hydrogen bonding net-
work, involving hydrogen bonds which anchor the carboxylic
acid groups of the interdigitated cations to the primary hy-
drogen bonding network.
When the active pharmaceutical ingredient is a cation, in-
organic anions like chloride and phosphate are commonly
employed in salt formation because of their abundant occur-
rence in the body.20 Bromide and nitrate anions are used to a
lesser extent due to the respective risks of bromism and ni-
trosamine formation.20 At the same time iodide anions may
lead to iodism.21 In the current study, the pharmaceutically
important chloride, bromide, iodide and nitrate salts are con-
sidered, and even though the perchlorate anion is not used
in salt formation in the pharmaceutical industry, perchlorate
salts were included here due to their hydrogen bonding
capability.
Two salt structures related to those in the current study
have been reported in the literature, and these structures will
be included in the current comparison. Firstly, the crystal
structure of 4-aminobutyric acid hydrochloride, has been
reported twice (CSD refcodes: GAMBAC01,22 GAMBAC10 (ref.
23)), but additional symmetry was observed for this structure
in the current study. Previously the space group was reported
as P21, while in this study we found it to be P21/m, with the
cation lying on a mirror plane. This warrants the inclusion of
structure 1 here. The structure of the bromide salt of the
much longer chain 11-aminoundecanoic acid, a hemihydrate,
was reported by Sim24 (CSD refcode: AUNDBH).
In the primary hydrogen bonding network, each ammo-
nium group interacts with three chloride anions through
three classic, charge-assisted N+–H⋯Cl− hydrogen bonds,
while each chloride anion, in turn, is hydrogen bonded to
three ammonium groups. Employing the description of
Bond,15 the hydrogen bonding interactions in the primary hy-
drogen bonding network result in the formation of a one-
dimensional transoid hydrogen bonded ladder, as illustrated
in Fig. 2(b), with both the ladder sides and rungs formed by
In the current study, eight novel carboxyalkylammonium
salt structures have been determined, as illustrated in
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Table 1 Crystal data for structures 1 to 8
1
2
3
4
Empirical formula
Abbreviation
HOOC(CH2)3NH3+Cl−
HOOC(CH2)3NH3+Br−
HOOC(CH2)3NH3+I−
HOOC(CH2)5NH3+Cl−
C4Cl
C4Br
C4I
C6Cl
M (g mol−1
)
139.58
Monoclinic
P21/m
184.04
Orthorhombic
Pbca
231.03
Orthorhombic
Pnma
167.63
Monoclinic
P21/c
Crystal system
Space group (no.)
T (K)
a/Å
b/Å
c/Å
150(2)
5.9059(3)
6.3964(3)
8.9893(4)
90
150(2)
150(2)
9.5887(4)
6.0522(3)
12.6513(6)
90
150(2)
13.3778IJ13)
6.4784(6)
15.7657IJ15)
90
11.2287(6)
8.5257(4)
9.1381(5)
90
α/°
β/°
100.064(2)
90
334.36(3)
2
1.386
0.487
90
90
1366.4(2)
8
1.789
90
90
734.19(6)
4
2.090
101.510(2)
90
857.22(8)
4
1.299
0.383
γ/°
V/Å3
Z
D (calc)/g cm−3
μ/mm−1
5.935
4.286
FIJ000)
148
736
440
0.392
Scan range (θ)/°
Total reflections
Unique reflections
[RIJint)]
Parameters
R1 [I > 2σ(I)]
wR2 (all data)
2.301–33.303
16 556
1386
0.0441
71
2.584–27.216
36 170
1521
0.0660
114
0.0152
0.0365
2.665–28.398
21 535
1010
0.0329
72
3.023–27.194
24 417
1897
0.0383
107
0.0244
0.0638
0.0288
0.0781
0.0110
0.0252
5
6
7
8
−
−
Empirical formula
Abbreviation
HOOC(CH2)5NH3+Br−·0.5H2O
HOOC(CH2)5NH3+I−·0.5H2O
HOOC(CH2)5NH3+NO3
C6NO3
194.19
Monoclinic
P21/c
HOOC(CH2)5NH3+ClO4
C6ClO4
231.63
Triclinic
C6Br·0.5H2O
442.20
Monoclinic
C2/c
C6Br·0.5H2O
536.18
Monoclinic
C2/c
M (g mol−1
)
Crystal system
Space group (no.)
¯
P1
T (K)
a/Å
b/Å
c/Å
α/°
β/°
150(2)
150(2)
30.237(2)
5.0915(3)
12.8358(9)
90
93.163(2)
90
1973.1(2)
4
150(2)
150(2)
29.6835IJ16)
4.9623(3)
12.5219(6)
90
92.194(2)
90
1843.10IJ17)
4
1.594
4.8399(5)
8.3511(7)
23.167(2)
90
91.273(4)
90
936.14(15)
4
1.378
5.2863(3)
5.6138(3)
17.4559(9)
82.962(2)
86.746(2)
88.924(2)
513.26(5)
2
γ/°
V/Å3
Z
D (calc)/g cm−3
1.805
3.207
1.499
0.378
μ/mm−1
4.418
0.119
FIJ000)
904
1048
416
244
Scan range (θ)/°
Total reflections
Unique reflections
[RIJint)]
Parameters
R1 [I > 2σ(I)]
wR2 (all data)
2.747–27.157
25 382
2047
0.0447
155
0.0166
0.0407
2.699–27.301
24 581
2222
0.0369
155
2.593–27.519
24 903
2150
0.0813
116
0.1366
0.4188
2.355–27.264
13 688
2284
0.0298
184
0.0286
0.0726
0.0132
0.0324
N+–H⋯Cl− hydrogen bonds. Neighbouring ladders are
connected via a N+⋯Cl− close contact to form a corrugated,
two-dimensional 44 net,15 as illustrated in Fig. 2(c).
The same hydrogen bonding network has been reported
by Bond15 for primary alkyl- and arylammonium chloride and
bromide salts where the hydrocarbon parts of the cations
comprise alkyl chains or small aromatic moieties. In this net,
the hydrocarbon parts of the cations across the net diagonal
are in a transoid arrangement while those lying along the
N⋯X net directions are in a cisoid arrangement relative to
each other.15
In structure 1, carboxylic acid groups hydrogen bond to
the primary hydrogen bonded sheet from above and below
via an O–H⋯Cl− hydrogen bonding interaction to the chlo-
ride anions in the primary network, to form an interdigitated
structure. Here the –OH moiety of the carboxylic acid group
hydrogen bonds to a chloride anion at the apex of the saw-
tooth geometry on each side of the primary hydrogen bond-
ing network, as shown in Fig. 2(a). The resulting overall hy-
drogen bonding network comprises the strong charge-
assisted interactions between the ammonium groups and
chloride anions in the primary network as well as the weaker
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Fig. 1 Asymmetric units of structures 1 to 8, illustrating the atomic numbering scheme. Ellipsoids are drawn at the 50% probability level.
O–H⋯Cl− interactions anchoring the carboxylic acid groups
to the primary network.
shown in Fig. 2(e). Neighbouring ladders are linked via a close
N+⋯Br− contact to form a 44 net,15 shown in Fig. 2(f).
The asymmetric unit of structure 2, C4Br, contains one
carboxybutylammonium cation and one isolated bromide an-
ion, with eight asymmetric units in the unit cell, and this
structure is not isostructural to structure 1. The cation does
not exhibit the low energy, all-trans geometry, instead the
C(2)–C(3)–C(4)–NIJ1) section adopts a gauche conformation
with a torsion angle of −61.5IJ3)°, as shown in Fig. 2(d). The
C(1)–C(2)–C(3)–C(4) portion of the cation has a torsion angle
of −162.5IJ2)°, indicating a much smaller deviation from the
all-trans geometry compared to the C(2) to N(1) portion.
The layered packing of 2, parallel to the ab-plane, is illus-
trated in Fig. 2(d). The ammonium groups, bromide anions
and carboxylic acid functional groups all comprise an inor-
ganic layer, while the alkyl portions and carboxylic acid
groups form the organic layer. When viewed down the b-axis,
pairs of cations pointing in the same direction alternate with
pairs of cations adopting an opposite orientation, as illus-
trated in Fig. 2(d).
The ammonium groups, bromide anions and carboxylic
acid groups interact via hydrogen bonds to form a single hy-
drogen bonding network, but this network can again be di-
vided into a two-dimensional primary hydrogen bonding net-
work consisting of charge-assisted hydrogen bonds between
ammonium groups and bromide anions, and a secondary hy-
drogen bonding network in which the carboxylic acid groups
hydrogen bond to the primary hydrogen bonding network
from above and below. In the primary hydrogen bonding net-
work, each ammonium group interacts with three bromide an-
ions, through three conventional, charge-assisted N+–H⋯Br−
hydrogen bonds to form a transoid hydrogen bonded ladder,
The alkyl chains of the cations across the net diagonal in
a ladder adopt a transoid arrangement, and those along the
N+⋯Br− net directions a cisoid arrangement similar to what
was found in structure 1, but due to the pairwise packing of
cations, the cations across the net diagonal between ladders
are cisoid relative to each other, and the primary hydrogen
bonded network exhibits a sinusoidal conformation rather
than the saw-tooth conformation seen in structure 1.
Carboxylic acid functional groups are hydrogen bonded to
the primary network via hydrogen bonds, but unlike struc-
ture 1, where only the –OH portion of the carboxylic acid
group hydrogen bonds to the primary network, in structure 2
both the –OH group and the O group of the carboxylic acid
functional group anchor the carboxylic acid group of the cat-
ion to the primary hydrogen bonding network, with a bro-
mide anion and an ammonium group acting as a hydrogen
bond acceptor and donor to the –COOH group, respectively,
as shown in Fig. 2(d). This means that the bromide anion
and the ammonium group in the primary hydrogen bonding
network are suitably positioned for hydrogen bonding to and
from the carboxylic acid group, allowing the –COOH group to
straddle the species in the primary network. Anchoring oc-
curs to an ammonium group and a bromide anion that be-
long to neighbouring ladders, hence the hydrogen bonds in-
volving the carboxylic acid group further link the transoid
ladders defined earlier. The combination of the primary hy-
drogen bonded network with the hydrogen bonding interac-
tions involving the terminal carboxylic acid groups results in
a two-dimensional hydrogen bonded sheet parallel to the
ab-plane in which pairs of cations linked through their
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Table 2 Strong hydrogen bonding parameters [Å, °] for compounds 1 to 8
Structure
D–H⋯A (Å)
dIJD–H) (Å)
dIJH⋯A) (Å)
dIJD⋯A) (Å)
∠ (DHA) (°)
Symmetry operator
1
OIJ1)–HIJ1)⋯ClIJ1)
0.85(3)
0.87(2)
0.879(16)
0.77(2)
0.87(2)
0.84(2)
0.84(2)
0.95(2)
0.95(2)
0.79(3)
0.86(3)
0.89(2)
0.818(18)
0.893(17)
0.911(17)
0.933(17)
0.75(2)
0.89(2)
0.90(2)
0.90(2)
0.91(2)
0.68(2)
0.90(2)
0.87(2)
0.90(2)
0.78(8)
0.91
2.25(3)
2.29(2)
2.508(16)
2.54(2)
2.48(2)
2.91(2)
2.19(2)
2.62(2)
2.91(2)
2.79(3)
2.11(3)
2.77(2)
2.255(18)
2.399(17)
2.535(17)
2.265(17)
1.93(2)
2.02(2)
2.80(2)
2.77(2)
2.44(2)
2.00(2)
2.03(2)
2.96(2)
2.64(2)
1.85(9)
2.1
3.0820(11)
3.1521(12)
3.2790(3)
3.2977(12)
3.3337(14)
3.5729(15)
2.7680(18)
3.3315(14)
3.5453(15)
3.4476(14)
2.961(2)
3.6295(10)
3.0589(9)
3.2678(11)
3.2312(11)
3.1932(11)
2.6749(15)
2.8939(18)
3.4437(16)
3.4483(15)
3.3422(14)
2.6822(17)
2.9026(18)
3.6265(16)
3.5460(16)
2.626(10)
2.823(8)
167(2)
NIJ1)–HIJ1A)⋯ClIJ1)#1
NIJ1)–HIJ1B)⋯ClIJ1)#2
OIJ1)–HIJ1)⋯BrIJ1)
169.5(18)
146.9(13)
169(2)
164.5(17)
137.0(18)
125.8(19)
132.6(17)
125.2(17)
142(3)
#1 x − 1, y, z + 1
#2 –x + 1, −y + 2, −z + 1
2
NIJ1)–HIJ1A)⋯BrIJ1)#1
NIJ1)–HIJ1B)⋯BrIJ1)#2
NIJ1)–HIJ1B)⋯OIJ2)#3
NIJ1)–HIJ1C)⋯BrIJ1)#4
NIJ1)–HIJ1C)⋯BrIJ1)#3
OIJ1)–HIJ1)⋯IIJ1)
#1 –x + 3/2, −y, z − 1/2
#2 x − 1/2, y, −z + 1/2
#3 x, −y + 1/2, z − 1/2
#4 –x + 3/2, −y + 1, z − 1/2
3
4
NIJ1)–HIJ1A)⋯OIJ2)#1
NIJ1)–HIJ1B)⋯IIJ1)#2
OIJ1)–HIJ1)⋯ClIJ1)
173(2)
#1 x + 1/2, y, −z + 3/2
164.7(14)
167.9(16)
164.2(13)
133.6(13)
173.7(13)
175(2)
166.2(18)
129.7(16)
133.2(17)
174.3(17)
177(3)
162.5(19)
135.0(17)
176.3(19)
173(7)
135.1
131.5
#2 –x + 1, −y + 2, −z + 1
NIJ1)–HIJ1A)⋯ClIJ1)#1
NIJ1)–HIJ1B)⋯ClIJ1)#2
NIJ1)–HIJ1C)⋯ClIJ1)#3
OIJ1)–HIJ1)⋯OIJ2)#1
NIJ1)–HIJ1A)⋯OIJ3)
NIJ1)–HIJ1B)⋯BrIJ1)#2
NIJ1)–HIJ1B)⋯BrIJ1)#3
NIJ1)–HIJ1C)⋯BrIJ1)#4
OIJ1)–HIJ1)⋯OIJ2)#1
NIJ1)–HIJ1A)⋯OIJ3)
NIJ1)–HIJ1B)⋯IIJ1)#2
NIJ1)–HIJ1C)⋯IIJ1)#3
OIJ1)–HIJ1)⋯OIJ2)#1
NIJ1)–HIJ1A)⋯OIJ5)#2
NIJ1)–HIJ1B)⋯OIJ4A)
NIJ1)–HIJ1C)⋯OIJ3A)#3
NIJ1)–HIJ1C)⋯OIJ4A)#3
OIJ1)–HIJ1)⋯OIJ2)#1
NIJ1)–HIJ1A)⋯OIJ5)#2
NIJ1)–HIJ1B)⋯OIJ4)#4
NIJ1)–HIJ1C)⋯OIJ4)#5
NIJ1)–HIJ1C)⋯OIJ5)#5
#1 –x + 1, −y + 1, −z + 1
#2 x − 1, −y + 3/2, z + 1/2
#3 x − 1, y, z
5
#1 –x + 3/2, −y + 5/2, −z + 1
#2
−x, −1 + y, 1/2 − z
#3 x, 1− y, −1/2 + z
#4 –x + 1, −y + 1, −z
6
7
#1 –x + 3/2, −y + 5/2, −z + 1
#2 x, −y, −1/2 + z
#3 –x + 1, −y + 1, −z
#1 –x + 2, −y, −z + 1
#2 x + 1, y, z
0.91
0.91
0.91
0.75(2)
0.89(2)
0.83(2)
0.81(2)
0.81(2)
2.14
2.15
2.14
1.91(2)
2.28(2)
2.22(2)
2.32(2)
2.52(3)
2.829(7)
3.011(8)
2.798(6)
2.6515(16)
3.0245(17)
3.0091(17)
2.9824(17)
3.2755(18)
157.7
128.5
176(2)
141.4(18)
159(2)
#3 –x + 1, y − 1/2, −z + 1/2
8
#1 –x − 1, −y + 1, −z + 1
#2 x, y + 1, z
#4 x − 1, y, z
140(2)
157(2)
#5 x − 1, y + 1, z
Hydrogen bonding definition: strong hydrogen bonding donors and acceptors, dminIJD⋯A) = RIJD) + RIJA) − 0.50 Å; dmaxIJD⋯A) = RIJD) + RIJA), D–
H⋯A > 120.0°.
carboxylic acid functional groups to the primary hydrogen
bonded sheet alternate with pairs of cations that form part of
the primary hydrogen bonding sheet, on both sides of the
layer, as shown in Fig. 2(d).
The asymmetric unit of structure C4I, 3, contains one cat-
ion and one isolated iodide anion. The cation adopts the low
energy, all-trans conformation, with all torsion angles close
to 180°, and lies on a mirror plane.
As illustrated in Fig. 2(g) to (i), the layered type packing ob-
served for structures 1 and 2 is not exhibited by this structure.
Instead rows of iodide anions pack in a channel formed by six
cations, in the b-direction. Each ammonium group acts as hy-
drogen bond donor to two iodide anions, thereby anchoring
the iodide ions in the channel. The ammonium group also in-
teracts with the O atom on the carboxylic acid group, a hy-
drogen bonding interaction which connects the cations
forming the channel. An additional hydrogen bonding interac-
tion with the O atom on the carboxylic acid group as the do-
nor anchors the iodide anion inside the channel, thus each io-
dide anion accepts three hydrogen bonds from groups on the
surface of the channel. The combination of these hydrogen
bonding interactions results in a three-dimensional hydrogen
bonding network, involving all the hydrogen bonding donors
and acceptors, which extends throughout the structure.
One isolated chloride anion and one carboxy-
pentylammonium cation comprise the asymmetric unit of 4,
C6Cl, with four asymmetric units in the unit cell. This struc-
ture is not homologous to the other chloride salt structure,
structure 1, or to structures 2 or 3. The cation adopts the low
energy, all-trans conformation with the carbon atoms approx-
imately planar, as shown in Fig. 2(j). The ammonium group
and carboxylic acid group, however, deviate slightly from the
plane formed by the C(3)–C(6) atoms.
A structure consisting of layers parallel to the bc-plane is
formed with the alkyl parts of the cation all packing parallel
in an organic layer, while the hydrogen bonded ammonium
groups, carboxylic acid groups and chloride anions comprise
the inorganic layer, as illustrated in Fig. 2(j). When viewed
down the c-axis, the chloride anions pack in layers,
surrounded by layers of carboxylic acid and ammonium
groups. The carbon zig-zag plane through atoms C(1)–C(6) of
the cation makes an angle of 65.3IJ2)° with the layer plane.
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Fig. 2 (a) Interdigitated, layered packing in C4Cl, 1. (b) Transoid ladder and primary hydrogen bonded layer viewed down the a-axis. (c) 44 net in 1.
(d) Layered packing in C4Br, 2. (e) Transoid ladder viewed down the a-axis. (f) 44 net in 2. (g). Hydrogen bonding in C4I, 3. (h) Packing in 3. (i) Iodide
anions packing in the channel formed by the cations. (j) Layered packing in C6Cl, 4. (k) Hydrogen bonded ladder in C6Cl, 4. (l) 44 net in 4. In all fig-
ures, hydrogen bonds are shown as dotted lines.
In the inorganic layer, the ammonium groups, chloride
anions and carboxylic acid groups interact through hydrogen
bonding to form a single hydrogen bonding network, but as
done previously for structures 1 and 2, this network can be
divided into a primary network comprising the ammonium
groups and chloride anions, and a secondary network that
links the carboxylic acid groups to the primary network.
In the primary network, each ammonium group forms
three strong, charge-assisted N+–H⋯Cl− hydrogen bonds to
three Cl− hydrogen bonding acceptors to form a transoid hy-
drogen bonded ladder, as shown in Fig. 2(k). Neighbouring
ladders are connected through N+⋯Cl− close contacts to form
a 44 net,15 as illustrated in Fig. 2(l). This is the same net as
that formed for structure 1, except that it does not adopt a
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saw-tooth conformation due to the non-planarity of the hy-
drogen bonded ladder.
shown in Fig. 3(b). This ladder differs from the hydrogen
bonded ladders described for structures 1, 2 and 4 where all
three hydrogen atoms of the ammonium group are involved
in the hydrogen bonding interactions forming the ladder,
since in structures 5 and 6 only two ammonium hydrogen
atoms participate in hydrogen bonding interactions to form
the ladder, requiring one of the interactions to be a bifur-
cated hydrogen bond. The third hydrogen atom of each am-
monium group forms a hydrogen bond to the oxygen atom of
a water molecule, and is thus not available to participate in
ladder formation. The water molecule links neighbouring
ladders by accepting a hydrogen bond from an ammonium
group in a neighbouring ladder, and by making a hydrogen
bond to a halide anion in a neighbouring ladder, as shown
in Fig. 3(c). A two-dimensional hydrogen bonding network
parallel to the ab-plane is formed.
The –OH group of the carboxylic acid group forms a hy-
drogen bond to a chloride anion in the primary hydrogen
bonding network, and at the same time, the O group ac-
cepts a hydrogen bond from an ammonium group in the pri-
mary network, thus, the carboxylic acid group straddles an
ammonium group and a chloride ion in a ladder. In contrast
to what was observed in structure 2, where the carboxylic acid
group straddles groups across ladder rungs, in this structure,
the orientation of carboxylic acid groups alternates by approx-
imately 90° as they alternately bridge ammonium and chlo-
ride groups across the ladder rung, then across the ladder
rail, on the same side of the ladder. Neighbouring ladders
are straddled by the carboxylic acid groups from opposite
sides of the primary network, as shown in Fig. 2(j).
Structures 5, C6Br·0.5H2O, and 6, C6I·0.5H2O, are iso-
structural, with the unit cell of 6 slightly larger than that of
structure 5, due to the larger size of the iodide anion com-
pared to the bromide anion, and these structures will be
discussed together. Even though water molecules were avail-
able as the solvent during the crystallisation of all the com-
pounds, water molecules are only incorporated in structures 5
and 6. The asymmetric unit consists of one carboxy-
pentylammonium cation, one halide anion and half a water
molecule, with the oxygen atom of the water molecule lying
on a two-fold rotation axis. In both structures, the C(3)–NIJ1)
portion of the cation adopts an all-trans conformation, but the
C(2)–C(3)–C(4)–C(5) torsion angles display values of 71.4IJ2)°
and 70.1IJ3)° in structures 5 and 6, respectively, indicating a
gauche bond, hence a deviation from the all-trans geometry in
this part of the alkyl chain. A layered structure is displayed by
compounds 5 and 6, parallel to the bc-plane, but a different
type of structure is formed compared to the other layered
structures 1, 2 and 4 discussed previously. In structures 5 and
6, the packing is such that the carboxylic acid groups pack in
a layer, which is separated from a layer containing the ammo-
nium groups, halide anions and water molecules, by alkyl
chains, as shown in Fig. 3(a). This means that the cation
chains are not interdigitated, as was observed in structures 1,
2 and 4. Structures 5 and 6 can be considered to consist of
two layers, an inorganic layer containing the ammonium
groups, halide anions and water molecules and an organic
layer comprising the alkyl chains and carboxylic acid groups.
In structures 5 and 6, the trans-part of the alkyl chains is tilted
by 64.4° and 68.3°, respectively, relative to the layer plane.
While a single hydrogen bonding network is formed in
structures 1, 2 and 4, hydrogen bonding occurs in two sepa-
rate regions of the structure in 5 and 6, due to the non-
interdigitation of the cation chains, with a two-dimensional
hydrogen bonding network involving the ammonium groups,
water molecules and halide anions present in the inorganic
layer, and a second zero-dimensional network comprising
carboxylic acid dimers in the organic layer.
The same hydrogen bonding network is observed in the
homologous structure 11-aminoundecanoic acid bromide
hemihydrate24 (CSD refcode: AUNDBH). However, in AUNDBH,
the alkyl chains do not exhibit the gauche bond observed in
structures 5 and 6. Interestingly, the same hydrogen bonding
network is also displayed di-n-alkylammonium salt structures,
including 1,8-diaminooctane dihydrochloride monohydrate25
(CSD refcode: GINJUJ) and 1,12-diaminododecane dihydro-
chloride monohydrate26 (CSD refcode: BENTET01).
This means that in structures 5, 6 and AUNBDH, the car-
boxylic acid hydrogen bonding dimers can be considered to
link two carboxyalkylammonium cations into a larger “supra-
molecular cation”, which effectively has two terminal ammo-
nium groups, similar to the di-alkylammonium cations in the
BENTET01 and GINJUJ structures.
Another interesting feature of structures 5 and 6, as well
as the literature structures AUNBDH, BENTET01 and GINJUJ,
which all display the same hydrogen bonding network, is that
the alkyl chains in the organic layer pack with crossed alkyl
chains. Thus, it seems to imply that this specific type of hy-
drogen bonding network requires the alkyl chains to adopt a
crossed chain packing. Pascher et al.2 commented that the
energetics driving crossed alkyl chain packing is not well
understood.
One carboxypentylammonium cation and one nitrate an-
ion comprise the asymmetric unit of C6NO3, structure 7.
The nitrate anion was found to be disordered over two po-
sitions, with occupancies of 0.58 and 0.42, respectively. The
hydrogen bonding analysis was performed by considering
only the anion with the highest occupancy. The cation
adopts the all-trans conformation, with torsion angle values
close to 180°, and the nitrate anion geometry is trigonal
planar. Similar to structures 5 and 6, a non-interdigitated
layered structure is formed. The inorganic layer containing
the ammonium groups and nitrate anions is separated
from the carboxylic acid groups by alkyl chains, with the al-
kyl chains and carboxylic acid groups forming the organic
layer. Carboxylic acid hydrogen bonded dimers link two cat-
ions to form an extended di-n-alkylammonium-like supramo-
lecular dication, which is tilted by approximately 29°
In the inorganic layer, a transoid hydrogen bonded ladder
is formed between ammonium groups and halide anions, as
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Fig. 3 (a) Layered packing in C6Br·0.5H2O, 5 (also representative of C6I·0.5H2O, 6). (b) Hydrogen bonded ladder in 5. (c) Hydrogen bonds
involving water molecules in 5. (d) Layered packing in C6NO3, 7. (e) Two-dimensional hydrogen bonding network in 7. (f) Hydrogen bonding inter-
actions between ammonium groups and nitrate anions in 7. (g) Layered packing in C6ClO4, 8. (h) Hydrogen bonding between ammonium groups
and perchlorate anions in 8.
relative to the layer plane. In neighbouring layers, the su-
pramolecular cations alternate in tilted-orientation, as
shown in Fig. 3(d).
m-nitroanilinium nitrate (PAJFEM30) and adamantine-
ammonium nitrate (ELIMIV31).
The asymmetric unit of 8, C6ClO4, contains one carboxy-
pentylammonium cation and one tetrahedral perchloride an-
ion. The NIJ1)–C(6)–C(5)–C(4)–C(3) portion of the cation
adopts the planar, all-trans conformation, with torsion angles
close to 180°, while the OIJ1)–C(1)–C(2)–C(3)–C(4) section
forms a planar, all-trans section. However, the planes through
the two trans sections are at an angle of 58.4IJ2)°, which is
expressed as a gauche C(2)–C(3)–C(4)–C(5) torsion angle of
66.0IJ4)°, indicating a kinked conformation.
Strong, charge-assisted hydrogen bonds between the am-
monium groups and nitrate anions in the inorganic layer re-
sult in a corrugated, two-dimensional hydrogen bonded sheet
parallel to the ab-plane, as illustrated in Fig. 3(e). In this
sheet, each ammonium group forms three hydrogen bonds
to three different nitrate anions, of which two are bifurcated
and one is a classical hydrogen bond, as shown in Fig. 3(f).
Each nitrate anion is hydrogen bonded to three different am-
monium groups. The same hydrogen bonding network is ob-
served in p-toluidinium nitrate (CSD refcode: FUGTOR,27
FUGTOR01 (ref. 28)), m-toluidinium nitrate (QUZHOJ29),
Similar to what was observed in structures 5–7, two types
of layers, parallel to the ab-plane, are formed, as shown in
Fig. 3(g). Perchlorate anions and ammonium groups pack in
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the inorganic layer, and the alkyl chains and carboxylic acid
groups form the organic layer. In the organic layer, hydrogen
bonds link the carboxylic acid groups into zero-dimensional
carboxylic acid dimers, effectively linking the cations to form
an extended supramolecular di-n-alkylammonium-like cation,
with a tilt angle of approximately 56° relative to the layer
plane. Alkyl chains in neighbouring layers display the same
orientation, as shown in Fig. 3(g).
In all the layered structures, a primary hydrogen bonding
network containing the strongest hydrogen bonding donors
and acceptors (the ammonium groups and anions, with the
possible inclusion of water molecules into this network) can
be identified. This underlines the statement by Etter16 that
the strongest hydrogen bonding donors and acceptors are
likely to be involved in hydrogen bonding to each other. The
weaker carboxylic acid hydrogen bonding groups may either
anchor to the primary network resulting in interdigitation of
the alkyl chains, as is observed in structures 1, 2 and 4, or
form hydrogen bonded carboxylic acid dimers, separated
from the primary network by alkyl chains, as seen in struc-
tures 5 to 8.
In the case of the halide anion containing structures, the
primary networks correspond to networks previously reported
for arylammonium halides,15 n-alkylammonium halides15 and
di-n-alkylammonium halides,25,26 indicating the important
structure-directing role of the strong, charge-assisted N+–
H⋯X− hydrogen bonding interactions. The fact that the same
hydrogen bonding networks are formed, even though an addi-
tional hydrogen bonding capability is present in the carboxy-
alkylammonium halides compared to n-dialkylammonium
and arylammonium halides, highlights the degree of molecu-
lar recognition taking place between the ammonium groups
and halide anions, as well as the stability of the observed
charge-assisted hydrogen bonding networks and the robust-
ness of the hydrogen bonding synthons comprising these hy-
drogen bonding networks.
In the inorganic layer, strong, charge-assisted N–H+⋯−O–
Cl hydrogen bonds link each ammonium group to four differ-
ent perchlorate anions through one classical and two bifur-
cated hydrogen bonds, to form a two-dimensional hydrogen
bonded sheet parallel to the ab-plane, as illustrated in
Fig. 3(h). Two of these sheets are present in the inorganic
layer, as shown in Fig. 3(g), with the ammonium groups of
one sheet stacking on top of the perchloride groups in the sec-
ond sheet, thus interacting through electrostatic interactions.
The same hydrogen bonding network is observed in the
structure of 1,4-diammoniumbutane bis (perchlorate) (CSD
refcode: URAKEE32), which again illustrates the similarity be-
tween the hydrogen bonding network in
a carboxy-
alkylammonium salt structure and an alkyldiammonium salt
structure, and the role of the carboxylic acid dimer hydrogen
bonds that connect the carboxyalkylammonium cations into
a supramolecular cation that resembles a alkyldiammonium
cation.
Structural comparison
Interdigitation of alkyl chains. One of the most striking
differences between the structures in the series is the fact
that in certain structures (1, 2 and 4, all containing halide an-
ions, but no water molecules) the alkyl chains are interdigi-
tated, with the carboxylic acid group anchoring to the pri-
mary hydrogen bonding network, while structures 5 to
8 (containing either halide anions and water molecules or
larger oxo-anions) are non-interdigitated, with hydrogen
bonded dimers forming between carboxylic acid groups, sep-
arate from the primary hydrogen bonding network. Bond15
showed that in related n-alkylammonium halides, the small
diameter of the n-alkylammonium cation does not affect the
hydrogen bonding in the primary hydrogen bonding network
on interdigitation, thus interdigitation can easily occur with-
out disruption of the primary hydrogen bonding network. In
analogy, in the current family of structures, the small cross
section of the carboxyalkylammonium cations should still al-
low interdigitation to occur in all the structures.
The question why interdigitation of the alkyl chains can
now be asked, and thus anchoring of the carboxylic group to
the primary network to form a single hydrogen bonding net-
work occurs in structures 1, 2 and 4, but not in structures 5
to 8.
In structure 1, the all-trans alkyl chains alternate above
and below the primary network, as shown in
Fig. 2(a) and (b), and this leaves the halide anions open to ac-
cept additional hydrogen bonds, which allows a carboxylic
acid group from a neighbouring primary network to anchor
All the compounds except compound 3, C4I, the only anhy-
drous iodide salt, form structures in which the alkyl chains
pack in layers distinct from layers containing the ammonium
groups, anions and water molecules where present.
A comparison of the layered structures 1, 2 and 4 to 8 can
thus be made. Of interest is the fact that only structures 5
and 6 are isostructural, even though long chain compounds
are known to often form homologous series in which the
members with an even or odd number of carbon atoms in
the chain exhibit similar structures, the only differences be-
ing those required by the increase in the carbon chain
length. In the current series, the structures C4Cl, 1, and
C6Cl, 4, are not homologous. This observation may be attrib-
uted to the fact that, unlike in long chain compounds that do
not contain head groups and counter ions, where van der
Waals interactions are the major intermolecular interactions
between the alkyl chains, both hydrogen bonding and van
der Waals interactions are structure-directing in the current
family of structures, and the final structure obtained repre-
sents a balance between the two. The fact that more than one
stable hydrogen bonding network containing the strong hy-
drogen bond donors and acceptors in the current family of
structures can be obtained, may thus contribute to the forma-
tion of non-homologous structures.
Water molecules are incorporated into only two of the
structures, 5 and 6, despite water being available as solvent
in all cases.
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to the primary network, and thus interdigitation of the alkyl
chains. In structure 2, even though the kinked alkyl chain
has a larger “average cross section” than that of an all-trans
alkyl chain, and is thus expected to inhibit access of a
neighbouring carboxylic acid group to the primary network,
the fact that the alkyl chains alternate above and below the
primary network in pairs, as shown in Fig. 2(d) and (e),
means that again the halide anions are accessible to the
neighbouring carboxylic acid groups, and alkyl chain inter-
digitation occurs. Alternation of the all-trans cations above
and below the primary network is also observed in structure
4, making the chloride anions accessible, and allowing inter-
digitation, as illustrated in Fig. 2(j) and (k). The primary hy-
drogen bonding network formed in structures 5 and 6 does
not show alternation of the cations above and below the pri-
mary hydrogen bonding network, as illustrated in
Fig. 3(a) and (b). Instead, in these structures, all the positions
above and below the primary hydrogen bonding network are
occupied by alkyl chains, effectively blocking access to the
halide anion. Hence, the formation of carboxylic acid dimers
in a second hydrogen bonding layer occurs, which is the only
other route available to satisfy the hydrogen bonding capabil-
ity of all the functional groups. Even though alternation of
the alkyl chains above and below the primary network occurs
in structure 7, as shown in Fig. 3(d) and (e), the corrugation
of the primary hydrogen bonding network, as well as the
large tilt angle of the cations, prevents access of
neighbouring carboxylic acid groups to the nitrate anions in
the primary network, and a non-interdigitated structure is
formed. The fact that alkyl chains occupy all positions above
and below the primary hydrogen bonding network, shown in
Fig. 3(g), explains the non-interdigitation of alkyl chains in
structure 8.
structure-directing role of the strong, charge-assisted hydro-
gen bonding species in the current family of structures, not
only on the primary hydrogen bonding network formed, but
also on the type of layered structure that ultimately results.
The two types of structures, interdigitated and non-inter-
digitated, may be viewed as two different types of “molecular
Velcro”, where the primary hydrogen bonded layer represents
the nylon Velcro strip. In the case of the interdigitated struc-
tures, the carboxylic acid “hooks” of a primary layer anchor it
onto
a
neighbouring primary layer, as shown in
Fig. 4(a) and (b), through interdigitation of the layers. When
interdigitation does not occur, the carboxylic acid groups
“hook” together, and zipper the layers together, forming a
non-interdigitated structure, as shown in Fig. 4(c) and (d).
Cation geometry and tilt angle. The final structure
obtained has to allow optimal electrostatic interactions be-
tween the charged anions and ammonium groups, as well as
appropriate interactions of the alkyl chains through van der
Waals interactions, and secondary hydrogen bonding interac-
tions involving the carboxylic acid groups, with a balance be-
ing achieved between these driving forces. Strong, charge-
assisted hydrogen bonds anchor the ammonium head groups
of the cation in the primary network, and determine the posi-
tions of the ammonium groups in the structure. The alkyl
chains then adapt their geometry to obtain the best close
packing via van der Waals interactions, while also satisfying
the hydrogen bonding requirements of the carboxylic acid
functional groups at the other end of the cation. Since the al-
kyl chains, ammonium groups and carboxylic acid groups all
form a part of the same cation, optimum packing may often
only be achieved via distortion of the cation geometry from
the ideal, low energy all-trans geometry, or through tilting of
the cation relative to the layer plane, or both. Thus, the na-
ture of the primary network not only dictates the
In the interdigitated structures, one may imagine the pri-
mary network being formed via strong, charge-assisted hydro-
gen bonds, and the alkyl chains of one such a network slot-
ting into the spaces between the alkyl chains of
a
neighbouring network, with a good fit between the chains.
The carboxylic acid groups then anchor the two networks
together.
In the case of the non-interdigitated structures, no space
is available for the slotting of the alkyl chains of
neighbouring primary networks to occur, preventing interdig-
itation, but since the terminal ends of the chains contain the
carboxylic acid groups, hydrogen bonded dimers are formed.
The type of primary hydrogen bonding network formed
thus determines if alternation of alkyl chains above and be-
low the primary layer occurs or not, and this determines the
accessibility of a hydrogen bond acceptor in the primary net-
work to accept a hydrogen bond from a neighbouring carbox-
ylic acid group, which in turn determines the interdigitation,
or not, of the alkyl chains. However, even if alternation of al-
kyl chains above and below the primary hydrogen bonding
network occurs, corrugation of the primary network and/or a
large alkyl chain tilt angle may prevent chain interdigitation,
as is seen in structure 7. This again emphasises the
Fig. 4 “Molecular Velcro”: (a) schematic of interdigitated structures,
(b) space-fill depiction of structure C4Br, 2, showing two primary
layers and the carboxylic acid hydrogen bonds acting as “hooks”, (c)
schematic of non-interdigitated structures, and (d) space-fill depiction
of structure C6ClO4, 8, showing two primary layers and the carboxylic
acid hydrogen bonds acting as “hooks”.
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interdigitation or non-interdigitation of the alkyl chains as
described previously, it also affects the geometry and/or tilt
angle of the alkyl chains relative to the layer plane in the lay-
ered structures.
networks. As such, the distances between the carboxylic acid
groups are similar to the distances between the halide anions
in the primary network, allowing the alkyl chains to slot be-
tween each other (interdigitate) and anchor to the primary
network. This means that the halide anions in the primary
network have a structure-directing effect, as hydrogen bond-
ing acceptors, and force the cation to adopt a geometry which
allows the correct positioning of carboxylic acid group for hy-
drogen bonding.
In structure 1, the carboxylic acid groups of the cations
can be correctly positioned for hydrogen bonding to the
neighbouring inorganic layers by adopting a tilted position
relative to the zig-zag primary layer, while maintaining the
low energy, all-trans cation geometry, as shown in
Fig. 5(a) and (b), which illustrate how the cation “stretches”
in the direction of the chloride anion it is hydrogen bonded
to in the neighbouring primary layer. The reduced tilt angle,
and the fact that interdigitation occurs between the chains of
two neighbouring layers, results in an ideal packing of alkyl
chains in structure 1. The corrugation of the primary network
also makes the chloride anion accessible to accept a hydro-
gen bond from the carboxylic acid group.
Because the ammonium ends of the cations form part of
the primary hydrogen bonding network, the distances be-
tween these ends of the cations, and thus the alkyl chains
bonded to the ammonium groups, are fixed by the relative
positions of ammonium groups, anions and possibly water
molecules in the primary network. If the primary networks
were planar, and the alkyl chains packed perpendicular to
this network, the alkyl chain cross section would exceed the
ideal cross-sectional area of 18–20 Å2,33 which corresponds to
ideal close packing of alkyl chains.
However, there are different ways to bring the alkyl chains
closer together to obtain a better close packing of chains,
and improve the van der Waals interactions between the
chains. The first is to reduce the tilt angle of the alkyl chains
relative to the layer plane to a value smaller than 90°, which
brings the alkyl chains closer together. The effective diameter
of an alkyl chain can be increased by the introduction of a
gauche bond in the alkyl chain. Interdigitation of the chains
of a primary layer with the chains of a neighbouring primary
layer also results in a closer packing of alkyl chains, provided
interdigitation is possible. None of the above impacts on the
primary hydrogen bonding network, and involves only the
packing and/or geometry of the cation. A structure may ex-
hibit more than one of these features to improve close pack-
ing of the alkyl chains when the cross-sectional area of the
primary network, as defined by the placement of the ammo-
nium groups in the primary network, exceeds the ideal alkyl
chain cross-sectional area. In addition, when the ammonium
group anchors a cation to the primary hydrogen bonding net-
work, the cation geometry may also be distorted in order to
correctly position the carboxylic acid group of the cation to
form a hydrogen bond, either to a neighbouring primary net-
work or to the carboxylic acid group of a cation bonded to a
neighbouring primary network.
It should be noted that corrugation of the primary net-
work also brings the alkyl chains closer together compared to
a planar primary network, by shortening the distance be-
tween ammonium groups, and thus also decreasing the dis-
tance between the alkyl chains. As discussed in the following
section, the novel layered structures reported here show a
number of the features listed above, with the final structure
obtained the result of a delicate balance between strong and
weaker hydrogen bonding interactions, van der Waals inter-
actions, and close packing of the species.
In all the interdigitated structures in the series (structures
1, 2 and 4), the packing is such that the anions and ammo-
nium groups in the inorganic layer pack approximately above
their counterparts in successive inorganic layers. Thus, they
roughly overlay when viewed perpendicular to the layer plane.
The carboxyalkylammonium cation then adopts the required
geometry to position the carboxylic acid groups correctly to
hydrogen bond to the halide anions in neighbouring primary
A gauche bond is required to position the carboxylic acid
group in the correct position to hydrogen bond to the bro-
mide anion in a neighbouring inorganic layer in structure 2,
as shown in Fig. 5(c) and (d). In this structure, the hydrogen
bonded layer is slightly corrugated, and the alkyl chains are
tilted relative to the layer plane.
The cations in structure 4 maintain the all-trans geometry
while hydrogen bonding to the chloride anion in
a
neighbouring layer (Fig. 5(e)). However, the carboxylic acid
group is twisted out of the carbon zig-zag plane to allow hy-
drogen bonding, as illustrated in Fig. 5(f). The primary net-
work is corrugated in structure 4, making the chloride anion
more accessible to the carboxylic acid group.
Cation geometries observed in the non-interdigitated
structures can be explained in the same way, but here a su-
pramolecular cation formed via the carboxylic acid dimer,
which results in an “n-alkyldiammonium-type supra-
molecule”, is considered. The ammonium groups of the
“supramolecule” have to be positioned in such a way to fit
into two primary hydrogen bonding networks, while
maintaining the carboxylic acid dimers and close packing be-
tween the alkyl chains. This can be achieved by adopting the
correct tilt angle, or the introduction of a gauche bond in the
alkyl chain, or both. In structures 5 and 6, the cations are
tilted relative to the layer plane, and a gauche bond is intro-
duced to achieve the correct positioning of the hydrogen
bonding groups of the supramolecular cation in consecutive
inorganic layers, as well as close packing of the alkyl chains
(Fig. 6(a)). Note that in structures 5 and 6, the cation
“stretches” across a water molecule in the primary network to
reach a halide anion in a neighbouring primary network, as
shown in Fig. 6(b). When projecting this stretch on the lower
primary network, the cation stretch corresponds to a “long”
ammonium⋯halide distance, as shown in Fig. 6(b).
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Fig. 5 (a) Tilted, all-trans cations and zig-zag primary layer in C4Cl, 1. (b) Tilted cation “stretching” to reach a hydrogen bonding acceptor in C4Cl,
1. (c) Kinked cations hydrogen bonding to bromide acceptors in C4Br, 2. (d) Kinked cations bonding to bromide anions, viewed normal to a layer
plane in C4Br, 2. (e) Tilted, all-trans cation and primary network in C6Cl, 4. (f) Cations hydrogen bonding to chloride anions in a neighbouring pri-
mary layer in C6Cl, 4, viewed normal to the layer plane.
In structure 7, the supramolecular cation displays a high
tilt angle (Fig. 6(c)), and corrugation is observed in the pri-
mary network, both structural features which bring the alkyl
chains closer together. It this structure, the cation stretches
over a “trough” in the corrugated primary network (Fig. 6(c)),
thus also a region with a long ammonium⋯anion distance,
as was observed in structures 5 and 6.
A gauche bond is also observed in structure 8 (Fig. 6(e)).
However, here the tilt angle is smaller than in structures 5
and 6. The primary network (Fig. 6(f)) is not corrugated.
It is interesting to note the position of the gauche bond in
the carboxyalkylammonium cations. A gauche bond is ob-
served in structures 2, 5, 6 and 7, and in all these structures
the gauche bond involves the C(2)–C(3)–C(4)–C(5)/NIJ1) atoms,
with atom C(1) being the carboxylic acid group carbon atom.
This means that the distortion from the ideal all-trans geom-
etry occurs close to the carboxylic acid group, while the por-
tion of the cation closer to the ammonium group retains its
all-trans geometry better, at least in the case of the longer
chain salts.
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Fig. 6 (a) Kinked cation forming a “supramolecular diammonium cation” in C6Br·0.5H2O, 5 (also representative of structure C6I·0.5H2O, 6). (b)
Kinked cations stretching across a water molecule to hydrogen bond to a bromide anion in a neighbouring primary layer in structure C6Br·0.5H2O,
5, viewed normal to the layer plane. (c) Tilted “supramolecular diammonium cation” in structure C6NO3, 7. (d) Cation hydrogen bonded to nitrate
anions in a neighbouring primary layer in structure C6NO3, 7, viewed normal to the layer plane. (e) Tilted “supramolecular diammonium cation” in
structure C6ClO4, 8. (f) Cation stretching to hydrogen bond to a perchlorate anion in structure C6ClO4, 8, viewed normal to the layer plane.
Conclusions
the fact that a number of the networks observed in the cur-
rent study correspond to networks reported for primary alkyl-
and arylammonium halide and nitrate structures in the liter-
ature, as well as for n-alkyl-diammonium salts. Secondary hy-
drogen bonding interactions involving the carboxylic acid
groups link neighbouring primary networks, either through
the formation of carboxylic acid dimers in non-interdigitated
In summary, a two-dimensional primary hydrogen bonding
network involving the strongest hydrogen bonding donors
and acceptors, namely the ammonium groups and halide/
oxo-anions, is formed in all the layered structures 1, 2, 4 and
5 to 8. The robustness of the primary network is shown by
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structures, or through hydrogen bonding of the carboxylic
acid group to a primary network in interdigitated structures.
The type of primary hydrogen bonding network is pivotal
in determining whether or not interdigitation occurs between
neighbouring layers, with one important feature of the net-
work being whether the alkyl chains alternate above and be-
low the primary network or not. Various factors affect the
conformation adopted by the cation, and in the end, the final
structure obtained represents a delicate balance between
strong and weak hydrogen bonds, van der Waals interactions
and close packing effects.
Synthesis of C6Cl, 4. 6-Aminohexanoic acid (1.0099 g,
7.699 mmol) was dissolved in 50 ml distilled water in a 250
ml beaker, and 1.3 ml of HCl (15.08 mmol) was added. The
solution was left to evaporate at room temperature, and crys-
tals of 4 were filtered off from the mother liquor. Yield:
31.7%. Elemental analysis: calculated: C: 42.99%, H: 8.42%,
N: 8.36%; found: C: 43.17%, H: 8.46%, N: 8.34%.
Synthesis of C6Br·0.5H2O, 5. 6-Aminohexanoic acid (0.9960
g, 7.593 mmol) was dissolved in 50 ml water in a 250 ml bea-
ker. To this solution, 1.7 ml (15.1 mmol) HBr was added. The
solution was left open to the atmosphere. Colourless crystals
of 5 formed on partial evaporation of the solvent, and were
filtered off from the mother liquor. Yield: 64.6%. Elemental
analysis: calculated: C: 32.59%, H: 6.84%, N: 6.34%; found:
C: 32.75%, H: 6.87%, N: 6.36%.
Experimental
Chemicals and reagents
All chemicals were used as-purchased without further purifi-
cation: 4-aminobutyric acid (Sigma, 99%), 6-aminohexanoic
acid (Fluka, ≥98.5%), HCl (Sigma-Aldrich, 37%), HBr (Sigma-
Aldrich, 48%), HI (Sigma-Aldrich, 57%), HNO3 (Promark
Chemicals, 55%), HClO4 (Sigma-Aldrich, 70%) and chloro-
form (Sigma-Aldrich, ≥99.8%).
Synthesis of C6I·0.5H2O, 6. 6-Aminohexanoic acid (1.0091
g, 7.693 mmol) was dissolved in a 250 ml beaker in 20 ml dis-
tilled water. To this solution 1.1 ml of HI (8.327 mmol) was
added. The solution was left open to air, at room tempera-
ture. A cream coloured product crystallised, and was filtered
off. Re-crystallisation of the product from distilled water at
room temperature yielded crystals suitable for single crystal
X-ray diffraction. Yield: 88.2%. Elemental analysis: calculated:
C: 26.88%, H: 5.64%, N: 5.22%; found: C: 26.85%, H: 5.68%,
N: 5.19%.
Synthesis of C6NO3, 7. 6-Aminohexanoic acid (0.9902 g,
7.5489 mmol) was dissolved in 20 ml distilled water in a 50
ml beaker. To this solution, 1.0 ml HNO3 (16.0 mmol) was
added. The solution was left open to the atmosphere. On par-
tial evaporation of the solvent, colourless crystals of 7
formed. The crystals were filtered off from the mother liquor.
Yield: 47.6%.
Synthesis
No attempts were made to optimise the yields of the reac-
tions. Due to risk of explosion, elemental analysis determina-
tions were not performed for the perchlorate and nitrate
salts, 7 and 8. The calculated and experimental powder X-ray
diffraction powder patterns are compared in the ESI.†
Synthesis of C4Cl, 1. 4-Aminobutyric acid (1.0052 g, 9.747
mmol) was dissolved in a 250 ml beaker in 40 ml distilled
water. To this solution, 1.7 ml HCl (19.49 mmol) was added.
The solution was left open to the atmosphere, at room tem-
perature, until colourless crystals of the product were formed.
The crystals were filtered off from the mother liquor. Yield:
98.1%. Elemental analysis: calculated: C: 34.42%, H: 7.22%,
N: 10.03%; found: C: 34.30%, H: 7.16%, N: 10.02%.
Synthesis of C4Br, 2. 4-Aminobutyric acid (0.9817 g, 9.520
mmol) was dissolved in 40 ml chloroform in a 250 ml beaker.
To this solution, 2.2 ml (19.55 mmol) HBr was added. The so-
lution was left open to the atmosphere. Colourless crystals of
2 formed on partial evaporation of the solvent, and were fil-
tered off from the mother liquor. Better quality crystals were
obtained on crystallisation of the product from water. Yield:
57.9%. Elemental analysis: calculated: C: 26.11%, H: 5.48%,
N: 7.61%; found: C: 26.11%, H: 5.51%, N: 7.58%.
Synthesis of C4I, 3. 4-Aminobutyric acid (0.5052 g, 4.899
mmol) was dissolved in 10 ml water in a 50 ml beaker. 0.65
ml HI (4.921 mmol) was added to this solution, and the bea-
ker was heated on a hot plate at 60 °C to reduce the solution
volume to approximately 4 ml. The solution was removed
from the heat, and a white product crystallised on cooling.
Crystals of 3 suitable for single crystal X-ray diffraction were
obtained by re-crystallisation of the product from distilled
water at room temperature. Yield: 95.2%. Elemental analysis:
calculated: C: 20.79%, H: 4.36%, N: 6.06%; found: C: 20.76%,
H: 4.38%, N: 6.04%.
Synthesis of C6ClO4, 8. 6-Aminohexanoic acid (0.9951 g,
7.5863 mmol) was dissolved in 20 ml water in a 50 ml beaker.
To this solution, 1.3 ml of HClO4 (15.1 mmol) was added.
The solution was left open to the atmosphere. Colourless
crystals of 8 formed on partial evaporation of the solvent,
and were filtered off. Yield: 37.7%.
Crystallographic studies
X-ray structure analysis. The X-ray diffraction data for all
compounds were collected using a Bruker D8 Venture diffrac-
tometer, with a Photon 100 CMOS detector, at 150(2) K,
employing a combination of ϕ and ω scans. Monochromatic
MoKα radiation with a wavelength λ of 0.71073 Å, from an IμS
source, was used as the irradiation source. Data reduction
and absorption corrections were performed using SAINT+34
and SADABS35 as part of the APEXII36 suite. The structures
were solved by direct methods using SHELXS37 as part of the
WinGX38 suite. Structure refinements were carried out using
SHELXL39 in WinGX38 as GUI. In structures 1, 2, 3, 5, 6 and 8,
non-hydrogen atoms were refined anisotropically, and hydro-
gen atoms were placed as observed in the difference map and
refined isotropically. Hydrogen atoms in structure 3 involved
in hydrogen bonding, were refined isotropically, while the rest
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of the hydrogen atoms were placed geometrically, and non-
hydrogen atoms refined fully. For structure 7, all hydrogens
atoms were placed geometrically, except the hydroxide hydro-
gen atom, while non-hydrogen atoms were refined anisotropi-
cally, and the nitrate anion was modelled to be disordered
over two positions. Graphics were generated using Mercury
3.9.40 Even though structure 7, C6NO3, is of a poorer quality
than the rest due to the disorder displayed by the nitrate an-
ion, it adds value to the paper, and the authors felt that it
should be included for comparative purposes, especially since
the cation shows no disorder, and its conformation is clear.
Single crystal X-ray diffraction analysis of a number of crystals
of compound 7 was carried out, but improved data could not
be obtained, indicating that the disorder is the cause of the
lower R value.
8 J. Silver, S. Martin, P. J. Marsh and C. S. Frampton, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1995, 51,
2432.
9 Y.-X. Kong, Y.-Y. Di, Y.-Q. Zhang, W.-W. Yang and Z.-C. Tan,
Thermochim. Acta, 2009, 33, 495.
10 G. J. Kruger, M. Rademeyer and D. G. Billing, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2003, 59, o480.
11 W. Dan, Y. Di, D. He, W. Yang and Y. Kong, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o910.
12 M. Rademeyer, G. J. Kruger and D. G. Billing,
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13 J. Silver, S. Martin, P. J. Marsh and C. S. Frampton, Acta
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14 L. Zhang, Y. Di and W. Dan, Acta Crystallogr., Sect. E: Struct.
Rep. Online, 2011, 67, o717.
Powder X-ray diffraction. Powder X-ray diffraction patterns
were measured on a Bruker D2 Phaser powder diffractometer
employing a Si low-background sample holder, and experi-
mental powder patterns were compared with powder patterns
calculated from single crystal structure data using the soft-
ware DiffractWD.41
15 A. D. Bond, Cryst. Growth Des., 2005, 5(2), 755.
16 M. C. Etter, Acc. Chem. Res., 1990, 23, 120.
17 See, among others: R. Boese, H.-C. Weiss and D. Bläser,
Angew. Chem., Int. Ed., 1999, 38(7), 988; V. R. Thalladi, R.
Boese and H.-C. Weiss, Angew. Chem., Int. Ed., 2000, 39(5),
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Gatta, D. D'Angelo, B. Brunetti and Z. Rećková, J. Chem.
Thermodyn., 2006, 38, 1546.
Conflicts of interest
18 A. M. Abdou, S. Higashiguchi, K. Horie, K. Mujo, H. Hatta
and H. Yokogoshi, BioFactors, 2006, 26, 201.
19 D. C. Thomas and P. J. Wormald, Am. J. Rhinol., 2008, 22,
188.
20 P. H. Stahl and C. G. Wermuth, Handbook of Pharmaceutical
Salts: Properties, Selection, and Use, Wiley-VCH Verlag,
Weinheim, 2002.
There are no conflicts to declare.
Acknowledgements
The authors would like to thank Dave Liles and Frikkie Malan
for single crystal X-ray diffraction data collection. MR ac-
knowledges financial support from the National Research
Foundation (Grant No. 87659).
21 S. M. Berge, L. D. Bighley and D. C. Monkhouse, J. Pharm.
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23 K. Tomita, Joken Hansha, 1965, 61, 1.
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