Synthesis, intermolecular interactions and biological activities of two new organic-inorganic hybrids C6H10N2,2Br and C6H10N2,2Cl·H2O

Article abstract of DOI:10.1039/c9ra09294c

A slow evaporation method has permitted the crystallization of two novel crystals of (2-aminomethyl)pyridindiumdihalide C₆H₁₀N₂,2Br (1) and C₆H₁₀N₂,2Cl·H₂O (2). The structures of the prepared compounds (1) and (2) were elucidated by single-crystal X-ray diffraction which revealed that they crystallize, respectively, with triclinic and monoclinic symmetries. Their crystal packing was stabilized by non-covalent interactions, including N-H?Br, C-H?Br, N-H?Cl, O-H?Cl and N-H?O hydrogen bonds. 3-D Hirshfeld surface analysis followed by 2-D fingerprint schemes gives insights into the intermolecular interactions in the crystalline structure. Furthermore, the FT-IR spectroscopy of these two compounds was carried out. The synthesized products were also screened for in vitro antioxidant and antimicrobial activities, which reveals their favourable antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as the discolouration of β-carotene.

Full text of DOI:10.1039/c9ra09294c

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Synthesis, intermolecular interactions and
biological activities of two new organic–inorganic
hybrids C6H10N2,2Br and C6H10N2,2Cl$H2O†
Cite this: RSC Adv., 2020, 10, 5864
b
c
d
Intissar Hamdi,a Intidhar Bkhairia,
Andreas Roodt,
Thierry Roisnel,
*
b
a
*
Moncef Nasri and Houcine Naıli
¨
A slow evaporation method has permitted the crystallization of two novel crystals of (2-aminomethyl)
pyridindiumdihalide C6H10N2,2Br (1) and C6H10N2,2Cl$H2O (2). The structures of the prepared
compounds (1) and (2) were elucidated by single-crystal X-ray diffraction which revealed that they
crystallize, respectively, with triclinic and monoclinic symmetries. Their crystal packing was stabilized by
non-covalent interactions, including N–H/Br, C–H/Br, N–H/Cl, O–H/Cl and N–H/O hydrogen
bonds. 3-D Hirshfeld surface analysis followed by 2-D fingerprint schemes gives insights into the
intermolecular interactions in the crystalline structure. Furthermore, the FT-IR spectroscopy of these two
compounds was carried out. The synthesized products were also screened for in vitro antioxidant and
antimicrobial activities, which reveals their favourable antioxidant activities against 1,1-diphenyl-2-
picrylhydrazyl (DPPH) as well as the discolouration of b-carotene.
Received 8th November 2019
Accepted 10th January 2020
DOI: 10.1039/c9ra09294c
rsc.li/rsc-advances
investigate the inuence of hydrogen bonds on the structural
features, we aimed to use the amine 2-(aminomethyl)pyridine
1. Introduction
(amp) also commonly known as 2-picolylamine (pic) a clear
yellowish liquid used as an intermediate in the pharmaceutical
industry17–21 for obtaining two new amine halide salts
C6H10N2,2Br and C6H10N2,2Cl$H2O which are expected to
possess notable chemical and biological activities.
In the last twenty years, studies on the self-assembly of molec-
ular salts as well as their hydrogen-bond interactions in the
solid-state have evoked a multitude of interest among chemists
owing to their intriguing structural diversities and potential
applications.1 Weak intermolecular interactions which are
important in the elds of physical, chemical and life sciences
represent the backbone of self-assembly processes and supra-
molecular architectures and exert directional and saturation
effects.2–5 The hydrogen bond, which is the most common
among weak interactions, remains the most important and
reliable means of enforcing molecular organization in the solid-
state,6–13 plays a critical role in many chemical and biological
processes, and has been a subject of research interest.14–16 To
enrich the varieties in such kinds of hybrid compounds and to
2. Experimental
2.1. Materials
All the employed chemicals, hydrochloric acid (HCl; 37%),
hydrobromic acid (HBr; 48%) and 2-aminomethyl pyridine (2-
picolylamine (C6H8N2); 99%) were commercial products (Sigma-
Aldrich), which were used without further purication.
2.2. Synthesis
aLaboratory of Physico-chemical of the Solid State, Department of Chemistry, Faculty of
Compounds (1) and (2) were prepared by mixing 2-picolylamine
(1 mmol; 0.108 g) and 10 mL of distilled water. The resulting
solutions were acidied with concentrated hydrobromic acid
(1 mmol; 5 drops) for (1) and hydrochloric acid (1 mmol; 5
drops) for (2). The two mixture were stirred magnetically for
´
Sciences of Sfax, Universite de Sfax, BP 1171, 3000 Sfax, Tunisia. E-mail:
houcine_naili@yahoo.com; Fax: +216 74 274 437; Tel: +216 98 660 026
bLaboratory of Enzyme Engineering and Microbiology, University of Sfax, National
School of Engineering of Sfax (ENIS), B.P. 1173-3038 Sfax, Tunisia. E-mail:
ibkhairia@yahoo.com
cDepartment of Chemistry, University of the Free State, P.O. Box 339, Bloemfontein 10 min at room temperature resulting in the formation of
9300, South Africa
homogeneous solutions. The two resulting solutions were
slowly evaporated to dryness for a week. Some single crystals
with suitable dimensions for crystallographic study were
collected. The synthesis is reproducible and crystals prepared in
dUniversity of Rennes, CNRS, ISCR (Institute of Chemical Sciences of Rennes) – UMR
6226, F-35000 Rennes, France
† Electronic supplementary information (ESI) available. CCDC 1919004 and
1919003 contain the supplementary crystallographic data for (1) and (2),
this way are stable for a long time under normal conditions of
temperature and humidity.
respectively. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c9ra09294c
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crystal structure was solved in the monoclinic symmetry, space
group P21/c and according to the automated search for space group
available in WingX,24 which incorporates SHELXL.25 In the struc-
ture renement, all hydrogen atoms were added in calculated
positions and treated as riding on the atom to which they are
attached. All non-hydrogen atoms were rened with anisotropic
displacement parameters. The hydrogen atoms were positioned
geometrically and rened, utilizing a riding model xed C–H
2.3. Infrared spectroscopy
IR absorption spectra of the title compounds were measured
with a PerkinElmer BX FT-IR spectrometer, in the 400–
4000 cmꢀ1 region at ambient temperature with KBr pellets.
2.4. Single-crystal X-ray data collection and structure
determination
˚
distance of 0.93 A (CH) for aromatic hydrogen, and methylene H-
Crystal data, data collection and structure renement details for (1)
and (2) are summarized in Table 1. Data for crystals (1), were
collected on a Bruker D8 VENTURE AXS diffractometer using Mo-
Ka radiation. The structure was solved by the dual-space algorithm
using the SHELXT program22 and then rened with full-matrix
least-squares methods based on F2(SHELXL).23 All non-hydrogen
atoms were rened with anisotropic atomic displacement param-
eters. Except nitrogen linked hydrogen atoms that were introduced
˚
atoms xed at 0.97 A (CH). Bond distances and angles calculated
from the nal atomic coordinates, as well as probable hydrogen
bonds, are listed in Tables 2 and 3. The drawings were made with
Diamond program.26
2.5. Hirshfeld surface analyses
in the structural model through Fourier difference maps analysis, The intermolecular interactions ensuring the structure cohe-
H atoms were nally included in their calculated positions. A nal sion are visualized by Hirshfeld surface analysis and the 2-D
renement on F2 with 2065 unique intensities and 104 parameters ngerprint plots which identify each type of intermolecular
converged at uR(F2) ¼ 0.046 (R(F) ¼ 0.019) for 1928 observed interactions. The Hirshfeld surfaces and 2-D ngerprint plots
reections with I > 2s(I). The reection data for (2) was collected on were prepared in this paper by means of Crystal Explorer
APEX II area detector 4-circles diffractometer using graphite (Version 3.1)27 based on the structure of the CIF le. The
˚
monochromated Mo-Ka radiation (l ¼ 0.71073 A), with u- and 4- Hirshfeld surface is set using (dnorm). The measured connection
scans at 100(2) K, through the Bruker AXS APEX2 soware. The distance (dnorm) is determined on the basis of de and di by,
Table 1 Crystallographic data for C6H10N2,2Br and C6H10N2,2Cl$H2O
Empirical formula
Formula weight (g molꢀ1
Temperature (K)
C6H10N2,2Br
269.98
150
0.71073
Triclinic
ꢀ
P1
6.6560 (9)
7.7563 (10)
9.1524 (12)
76.320 (4)
80.652 (4)
82.187 (5)
450.65 (10)
2
C6H10N2,2Cl$H2O
199.08
293
0.71073
Monoclinic
P21/c
16.678 (5)
7.107 (5)
15.865 (5)
90
97.397 (5)
90
1864.8 (15)
8
1.418
0.65
)
˚
Wavelength (A)
Crystal system
Space group
˚
a (A)
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
g (ꢁ)
3
˚
V (A )
Z
Calculated density (mg mꢀ3
)
1.990
8.93
Absorption coefficient (mmꢀ1
)
F(000)
260
832
Crystal size (mm3)
Habit-color
qmin ꢀ qmax (ꢁ)
Rint
0.33 ꢂ 0.27 ꢂ 0.16
Plate-colourless
3.1–27.5
0.33 ꢂ 0.27 ꢂ 0.16
Block-yellow
1.2–28.4
0.041
0.041
Tmin
0.103
0.811
Tmax
0.240
0.902
Index ranges
ꢀ8 # h # 8
ꢀ10 # k # 10
ꢀ11 # l # 11
Full-matrix least-squares on F2
0.020
ꢀ22 # h # 20
ꢀ9 # k # 7
ꢀ21 # l # 20
Renement method
R1
Full-matrix least-squares on F2
0.025
wR2
0.046
1.05
0.092
1.19
4666/0/215
0.066 (5)
ꢀ0.40
0.39
Goodness-of-t on F2
Data/restraints/parameters
2065/0/104
0.075 (3)
ꢀ0.75
Extinctionꢀc3oefficient
˚
Drmin (e Aꢀ3
)
˚
Drmax (e A
)
0.65
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Table 2 Selected bond distances (A˚) and angles (ꢁ) for (1) and (2)
bi-directional de ꢀ di and di ꢀ de measures. The graph shows
that the areas visible in the ngerprint correspond to a single
molecule, such as de > di and the other di > de. The 2-D nger-
print segment provides quantitative analysis of the molecular
interconnections found in the molecule and presents this
information in a plot of color.30
C6H10N2,2Br
N1–C5
1.343 (3)
C2–C3
1.383 (3)
N1–C1
1.344 (3)
C5–C4
1.384 (3)
N2–C6
1.492 (3)
C5–C6
1.505 (3)
C2–C1
1.376 (3)
C4–C3
1.387 (3)
C5–N1–C1
C1–C2–C3
N1–C5–C4
N1–C5–C6
C4–C5–C6
123.64 (17)
119.14 (19)
118.67 (17)
116.61 (17)
124.71 (18)
C5–C4–C3
C2–C3–C4
N1–C1–C2
N2–C6–C5
119.14 (19)
120.29 (19)
119.11 (19)
111.10 (16)
2.6. Antioxidant and antibacterial activities
2.6.1. Antioxidant activities
2.6.1.1. ABTS radical scavenging activity. According to the
method of Wang et al.31 ABTS radical scavenging activity of
C6H10N2,2Br and C6H10N2,2Cl$H2O was determined. This
method is based on the ability of the compounds to trap the
ABTS+c radical cation. 1 mL of test compounds, at different
concentrations (0.5 to 2 mg mLꢀ1 dissolved in dimethylsulph-
oxide (DMSO)), were as mixed with 1 mL the preformed radical
(ABTS) and then kept in obscurity at room temperature, the
residual absorbance of the ABTS+c radical is measured at
734 nm. In the presence of antioxidant compounds (1 and 2),
the nitrogen radical concerned scavenge an Hc, leading to
ABTSH+, which causes the formation of a precipitate and
discoloration of the solution.
C6H10N2,2Cl$H2O
N3–C7
N3–C1
N4–C11
N4–C2
N5–C10
N6–C12
C1–C3
C1–C12
C7–N3–C1
C11–N4–C2
N3–C1–C3
N3–C1–C12
C3–C1–C12
N4–C2–C4
N4–C2–C10
C4–C2–C10
C1–C3–C5
1.3431 (17)
1.3471 (16)
1.3431 (17)
1.3483 (16)
1.4745 (17)
1.4777 (18)
1.3856 (18)
1.5089 (17)
123.10 (11)
123.18 (11)
118.64 (11)
116.49 (11)
124.82 (12)
118.49 (11)
115.00 (11)
126.46 (12)
119.65 (12)
C2–C4
C2–C10
C3–C5
C4–C9
C4–C9
C6–C11
C6–C9
C7–C8
C2–C4–C9
C3–C5–C8
C11–C6–C9
N3–C7–C8
C7–C8–C5
C6–C9–C4
N5–C10–C2
N4–C11–C6
N6–C12–C1
1.3805 (18)
1.5054 (17)
1.3914 (18)
1.3967 (18)
1.3967 (18)
1.376 (2)
1.3898 (19)
1.3780 (19)
119.67 (12)
119.86 (12)
118.46 (12)
120.09 (12)
118.64 (12)
119.97 (12)
112.67 (11)
120.22 (12)
111.65 (11)
The ABTS scavenging activity was calculated by the following
formula:
Acontrol ꢀ Asample
ABTS scavenging activityð%Þ ¼
ꢂ 100 (1)
Acontrol
where Acontrol is the absorbance control and Asample is the
absorbance of C6H10N2,2Br and C6H10N2,2Cl$H2O sample.
2.6.1.2. b-Carotene-linoleic-acid assay. The ability of
C6H10N2,2Br (1) and C6H10N2,2Cl$H2O (2) to prevent bleaching
of b-carotene was assessed as described by Koleva et al.32 A stock
solution of b-carotene/linoleic acid mixture was freshly
prepared before each experiment. 2.5 mL of the emulsion of b-
carotene/linoleic acid were transferred to test tubes containing
two crystals concentrations. The tubes were immediately placed
in water bath and incubated at 50 ꢁC for 2 h. The absorbance of
each hybrid compound was measured at 470 nm. The same
di ꢀ rvi dW de ꢀ rvedW
dnorm
¼
þ
rvi dW
rvedW
where rvidW and revdW are the van der Waals radii of the atoms. di
and de are the distance from Hirshfeld surface to nearest
nucleus inside and to nearest nucleus outside, respectively. The
dnorm value can be negative or positive. The dnorm values are set
using a red-white-blue color scheme.28,29 The short contact is
red, the white indicates the contact around vdW, and the blue is
for longer contact. Fingerprint areas represent a combination of
Fig. 1 IR spectra of C6H10N2,2Br (a), and C6H10N2,2Cl$H2O (b).
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procedure was repeated with butylated hydroxyanisole (BHA) as v)) solution. The reaction tubes were incubated for 20 min at
positive control. A blank consisted of 0.5 mL of distilled water 50 ꢁC. Aer incubation, 2.5 mL of trichloroacetic acid (TCA, 10%
instead of sample. Antioxidant activity in b-carotene bleaching (w/v)) was added and the reactions mixtures were then centri-
model in percentage was calculated with the following fuged for 10 min at 10 000 ꢂ g. 2.5 mL of supernatant, from
equation:
each hybrid compound mixture, was mixed with distilled water
(2.5 mL) and ferric chloride (0.5 mL of 0.1% (w/v)) solution. The
absorbance of the resulting solutions was measured at 700 nm.
2.6.1.4. DPPH assay. The DPPH radical-scavenging activity
of the two crystals was determined according to the method of
Bersuder et al.34 Briey, 0.5 mL of each hybrid compound at
2
3
ðA0 ꢀ AtÞ
4
5
ꢀ
ꢁ
b-Carotene-bleaching inhibitionð%Þ ¼ 1 ꢀ
ꢂ 100
A00 ꢀ A0t
(2)
where A0 and A00 are the absorbance of the sample and the different concentrations (0.5–2 mg mLꢀ1) was added to
control, respectively, measured at time zero, and At and A0 are 0.375 mL of ethanol and 0.125 mL of a DPPH solution prepared
t
the absorbance of the sample and the control, respectively, in ethanol (0.02% (w/v)). The reaction solutions were incubated
measured aer 2 h.
in the dark at room temperature for 60 min. Scavenging capacity
2.6.1.3. Ferric ion reducing antioxidant power (FRAP). The was measured spectrophotometrically at 517 nm. DPPH radical-
reducing power was performed according to the method of Xie scavenging activity was calculated as follows:
et al.33 1 mL of each crystal sample at different concentrations
DPPH radical scavenging activityð%Þ
(0.5–2 mg mLꢀ1) was mixed with 1.25 mL of phosphate buffer
(pH ¼ 6.6; 0.2 M) and 2.5 mL of potassium ferricyanide (1% (w/
Acontrol þ Ablank ꢀ Asample
¼
(3)
Acontrol
Fig. 2 (A) The asymmetric unit of compound (1), showing the atom-labeling scheme. Displacement ellipsoids are drawn at 50% probability level.
The dashed line represents the possible hydrogen bond. (B) The crystal packing of the title salt (1) projected onto bc plane. The N–H/Br and C–
H/Br hydrogen bonds are shown as dashed lines. (C) The asymmetric unit of compound (2), showing the atom-labeling scheme. Displacement
ellipsoids are drawn at 50% probability level. The dashed lines represent the possible hydrogen bonds. (D) A view of the three-dimensional
supramolecular architecture of (2), formed by N–H/Cl, O–H/Cl and N–H/O hydrogen bond interactions.
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where Acontrol is the absorbance of the control reaction, Ablank is Pasteur pipettes and 50 mL of the hybrid compound (20 mg
the absorbance of the blank and Asample is the absorbance of the mLꢀ1) was added to each well. Gentamicin and bacitracin (150
sample with DPPH solution. BHA was used as a positive control. mg mLꢀ1) was used as positive control to determine the sensi-
2.6.2. Antibacterial activities
tivity of each bacterial strain. To permit the diffusion of the
2.6.2.1. Microorganisms. Antibacterial activities of the hybrid compound and standards onto agar, the plate was
synthesized compounds were tested against Gram+ and Gramꢀ allowed to stand for 4 h at 4 C. Aer that, the plate was incu-
ꢁ
bacterial strains. Bacteria used were Bacillus cereus (ATCC bated at 37 ꢁC for 24 h. The antimicrobial activity was evaluated
11778), Staphylococcus aureus (ATCC 25923), Enterococcus fae- by determination of the inhibition zone diameters (IZD).
calis (ATCC 29212), Salmonella enterica (ATCC 43972), Micro-
coccus luteus (ATCC 4698), and Klebsiella pneumoniae (ATCC
13883).
2.6.2.2. Agar-well diffusion method. The antibacterial
3. Results and discussion
3.1. Infrared spectroscopy
potential was essayed by agar-well diffusion method as In both IR spectra (Fig. 1a and b for 1 and 2, respectively), the
described by Tagg and McGiven.35 200 mL of freshly cell presence of the 2-aminomethyl pyridindium was checked,
suspension adjusted to 106 cfu mLꢀ1 for bacteria were speared indeed the bands appearing around 1500 and 3110 cmꢀ1 on
onto the surface of agar. Aer incubation, wells (6 mm in each IR spectrum are assigned, respectively, to the deformation
+
diameter) were punched in the agar medium with sterile and elongation vibrations of the NH3 group. In addition, the
Fig. 3 (A) Hirshfeld surface mapped over dnorm (a) of the asymmetric unit and 2D fingerprint plots (b) of the C6H10N2,2Br compound. (B) Hirshfeld
surface mapped over dnorm (a) of the asymmetric unit and 2D fingerprint plots (b) of the C6H10N2,2Cl$H2O compound.
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Fig. 4 (A) 2D fingerprint plots of the C6H10N2,2Br compound. (B) 2D fingerprint plots of the C6H10N2,2Cl$H2O compound.
Fig. 5 (A) ABTS radical scavenging of compounds (1) and (2) at different concentration. (B) Reducing power of the synthesized compounds (1)
and (2) at different concentrations. C) b-Carotene bleaching inhibition activity of the synthesized compounds (1) and (2) at different concen-
trations. (D) DPPH free radical-scavenging activity of compounds (1) and (2) at different concentrations.
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bands around 1635 and 3071 cmꢀ1 can be assigned, respec- dnorm surface, the large circular depressions (deep red) are the
tively, to the NH+ deformation and elongation vibrations which indicators of hydrogen bonding contacts whereas other visible
corroborate the protonation of the 2-picolylamine molecule. spots are due to H/H contacts (Fig. 3(A) and (B)). As expected,
The bands with different intensities between 500 and drawing 2D ngerprint plots from the surface of the analysis
1400 cmꢀ1 are due to the vibrations of the amine cycle. The IR presented in Fig. 4(A) and (B), the 2D ngerprint plots from
spectrum of compound (2) shows a large band around Hirshfeld surface analysis allows quantitative data to be ob-
3353 cmꢀ1 which can be attributed to the vibrations of the water tained on percentage of element contribution interactions in
molecule.
the molecule. H/Br/Br/H for compound (1) and H/Cl/Cl/H
for compound (2) corresponds to 56.3% and 43.8% of the total
surface structure provided by the important role of hydrogen
bonds in creating strong cohesion between molecules. In
addition, the decomposition of ngerprint plots H/H reaction
is widespread in the two compounds (1 and 2) and constitutes
respectively 33.1% and 36.7% of the total area of Hirshfeld
surface. Moreover, a signicant H/C/C/H interactions are
reected in the distribution of scattered points in the nger-
print plots, which covers 9% and 6% of the total Hirshfeld
surface area for the two compounds (1) and (2), respectively. In
addition, O/H/H/O interaction constitutes 4.2% of the total
area of Hirshfeld surface of the C6H10N2,2Cl$H2O compound.
3.2. Structural commentary
ꢀ
The structure of (1) is solved in the triclinic space group P1
(Table 1) with an asymmetric unit consisting of two bromide
anions and one diprotonated 2-aminomethyl pyridine cation,
which are connected together via N–H/Br and C–H/Br
hydrogen bonds as shown in Fig. 2(A). Selected bond lengths,
angles, and supramolecular interactions are listed in Tables 2
and 3, respectively. The cohesion is ensured by hydrogen bonds
between the cationic groups and the bromide atoms. The
resulting H-bonding networks can be described by three-
dimensional supramolecular frameworks, thus forming chan-
nels in which the diprotonated amine plays a templating role.
The structure can be also described as an alternation of anionic
3.4. Biological properties
ꢀ
and cationic layers along the [011] direction (Fig. 2(B)). The
3.4.1. Antioxidant activities. Antioxidants are important
compounds that reduce or neutralize free radicals, thus pro-
tecting the cells from oxidative injury.36 Therefore, considerable
research has been directed towards the identication of new
antioxidants to prevent radical-induced damage. Due to various
types of radicals and different sites of action, several methods
structure cohesion and stability is further assured by two types
of hydrogen bonds, N–H/Br and C–H/Br. Compound (2)
displays monoclinic symmetry, space group P21/c (Table 1) with
an asymmetric unit consisting of two 2(-amino methyl)pyr-
idinium cations, four chloride anions and two water molecules
as shown in Fig. 2(C). The crystal packing of the title salt, pro-
jected in the ac plane (Fig. 2(D)), shows that the organic mole-
cule is connected with chloride anions and water molecules by
N–H/Cl and N–H/O hydrogen bonds via nitrogen atoms. The
water molecules participate in two types of hydrogen bonds O–
H/Cl and N–H/O as donor or acceptor, respectively, playing
a subordinative role in the stabilization of the crystal structure.
All these entities form three-dimensional supramolecular
frameworks and assure the stability of the structure of
a
Table 3 Hydrogen bonding geometry (A˚, ꢁ
)
˚
˚
˚
D–H (A)
H/A (A)
D/A (A)
D–H/A (ꢁ)
C6H10N2,2Br
N1–H1/Br2a
N2–H2A/Br1b
N2–H2B/Br1c
0.86
0.89
0.89
0.89
2.39
2.50
2.54
2.62
3.2397 (17)
3.2808 (17)
3.2378 (18)
3.3393 (17)
170
146
135
138
compound (2). In both title crystals, the organic cations are N2–H2C/Br2
interlayered within the inorganic framework to compensate for
the negative charge of the inorganic part. The organic parts are
formed by the diprotonated amines 2-aminomethyl pyridin-
C6H10N2,2Cl$H2O
N3–H3/Cl2
0.86
0.86
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.84 (3)
0.86 (3)
2.17
2.17
2.38
2.96
2.36
2.60
2.38
2.38
2.38
2.38
2.38
2.46
2.48
2.39 (3)
2.35 (3)
3.0296 (13)
3.0241 (13)
3.1809 (15)
3.3897 (15)
3.147 (2)
3.0603 (19)
3.1705 (17)
3.1913 (15)
2.9383 (18)
3.2826 (18)
3.118 (2)
172
177
150
112
148
113
148
151
121
132
158
173 (3)
163 (3)
168 (2)
166 (3)
N4–H4/Cl3
ꢁ
˚
ꢁ
N5–H5A/Cl1d
dium cations (C–N–C ¼ 123.64 , C–C ¼ 1.376 to 1.505 A, N–C ¼
1.343 to 1.492 A) for (1) and (C–N–C ¼ (123.10–123.18 ), C–C ¼ N5–H5A/Cl3e
˚
N5–H5B/Cl2f
˚
˚
1.376 to 1.5089 A, N–C ¼ 1.3431 to 1.477 A) for (2).
N5–H5B/O55
N5–H5C/Cl4
N6–H6A/Cl4g
N6–H6B/O56
N6–H6B/Cl1
The most interesting feature of the crystal structure of the
two new compounds is the intermolecular hydrogen-bonding
interactions and the effect of the water molecule to increase
ꢀ
the symmetry from P1 to P21/c.
N6–H6C/Cl3h
O56–H118/Cl1i
O55–H120/Cl4g
O56–H119/Cl1j
O55–H121/Cl4k
3.1999 (15)
3.2039 (16)
3.212 (3)
3.3. Molecular Hirshfeld surfaces calculations
Hirshfeld surfaces and their associated 2D ngerprint plots
were used to clarify the nature of the intermolecular interac-
tions in C6H10N2,2Br as well as C6H10N2,2Cl$H2O. The Hirshfeld
surfaces have been mapped over a dnorm, shape-index, de and
curvedness. The dnorm surface reveals the contacts of hydrogen
bond donors and acceptors along with other close contacts. In
3.190 (2)
a
Symmetry codes: (a) ꢀx + 2, ꢀy + 1, ꢀz + 1; (b) ꢀx + 2, ꢀy, ꢀz + 1; (c) x +
1, y, z; (d) ꢀx + 1, y + 1/2, ꢀz ꢀ 1/2; (e) x, ꢀy + 1/2, z ꢀ 1/2; (f) ꢀx + 1, ꢀy,
ꢀz; (g) ꢀx + 1, y ꢀ 1/2, ꢀz ꢀ 1/2; (h) ꢀx + 1, ꢀy + 1, ꢀz; (i) ꢀx + 2, y + 1/2,
ꢀz ꢀ 1/2; (j) x, y + 1, z; (k) x, y ꢀ 1, z.
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Table 4 Antibacterial activity of the synthesized compounds (1) and (2) using agar disc diffusion
Micrococcus
luteus
Salmonella
enterica
Staphylococcus
aureus
Bacillus
cereus
Klebsiella
pneumonia
IZD (1)
IZD (2)
IZD (bacitracin)
IZD (gentamicin)
16
26
19
14
10
18
—
20
10
16
25
18
22
30
22
16
20
22
9
14
(with their peculiarities) are available and have been used to compounds (1 and 2) against the bacterium B. cereus with
assess the antioxidant potential of the synthesized compounds. a zone of inhibition 22 mm and 30 mm, respectively. The
The antioxidant properties of the synthesized compounds (1 synthesized compounds (1 and 2) exhibited strong antibacterial
and 2) were evaluated by four different methods in vitro: ferric activity against M. luteus with a zone of inhibition 16 mm and 26
ion reducing antioxidant power (FRAP), b-carotene bleaching mm, respectively, and K. pneumonia with a zone of inhibition
inhibition, DPPH (1,1-diphenyl-2-picryl-hydrazyl) and ABTS+ 20 mm and 22 mm, respectively. However moderate activities
2,20-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical were noted by other microbial strains with a zone of inhibition
scavenging ability (Fig. 5(A), (B), (C) and (D)). According to Li ranging between 10 mm and 18 mm. Our results have been
et al.,37 reactive oxygen species ROS can induce cell death shown that the synthesized compounds (1 and 2) displayed
through mechanisms such as lipid peroxidation, alteration of varying degrees of antimicrobial activity against Gram-positive
cellular proteins and initiation of diverse stress-signalling and Gram-negative bacteria in vitro.
pathways. Hence, to prevent free radical damage in the body,
it is important to administer drugs that may be rich in antiox-
idants. As can be seen in the previous gures, the antioxidant
activity of the synthesized compounds (1 and 2) increased in
4. Conclusion
In summary, the synthesis of two new semi-organic compounds
has been demonstrated. The crystal structure and biological
activities have been accomplished. Our results showed that
highly stable crystals were successfully prepared from an
aqueous solution of (2-aminomethyl)pyridine and hydrobromic
or hydrochloric acid. A meaningful structural characterization
reveals that the two compounds crystallize in two centrosym-
a concentration-dependent manner. However, the synthesized
compounds showed lower antioxidant activity than did BHA
and a-tocopherol, as standard, at the same concentrations.
Compounds exhibited moderate antioxidant activities, they
possess an almost equal potential, but the potential of the
synthesized compound (1) was observed to be a little higher
than its corresponding compound (2) by 53.16% (b-carotene
bleaching test) and 54.23% (ABTs radical scavenging activity)
and 41.46% (DPPH scavenging activity). Results of ABTS radical
scavenging activity are in accordance with those of DPPH assay.
At present, there is no evidence to support a mechanism for the
phenomenon in the case of chloride and bromide. Therefore, it
is tempting to hypothesize that the slight hight antioxidant
potential of compound (2) is might may be hinge around the
balance between reduction of metal ions to more reactive
reduced forms for mediating Fenton chemistry (as is the case
with some other antioxidants) and by the importance of radical-
scavenging activity (antioxidant). These results obtained by
preliminary screening of antioxidant activity suggested that the
synthesized salts might serve as interesting compounds for the
development of new antioxidant agents by synthesis of some
new derivatives with these structures. Overall, compounds (1
and 2) displayed an important antioxidant activity. Neverthe-
less, they showed lower antioxidant potential than standards at
the same concentration.
metric space groups with different arrangements.
A 3D
hydrogen-bonded system is built up by cationic (2-picolyl-
amine)2+ entities as donor, Cl/Br ions and H2O molecules as
acceptors. The biological activities of the prepared compounds
have been investigated. They were screened for in vitro antiox-
idant and antimicrobial activities. They have shown favourable
antioxidant activities against DPPH as well as their ability to
discolour the b-carotene. However, one cannot draw accurate
correlations between centrosymmetric and biological activities
of these materials, considering the examples presented in this
paper and many more cases in literature.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
3.4.2. Antibacterial activity. Antibacterial activity of the
synthesized compounds (1 and 2) was assessed against ve
strains. The result was compared with those of the standards
(bacitracin and gentamicin) and the mean diameters of inhi-
bition zones were shown in Table 4. From Table 4, it can be seen
that the highest antibacterial activity of the synthesized
´
Grateful thanks are expressed to Dr T. Roisnel (Universite de
Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Ren-
nes) – UMR 6226, F-35000 Rennes, France) and Dr A. Roodt
(Department of Chemistry, University of the Orange Free State
Bloemfontein 9300, South Africa) for the X-ray data collection.
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13 A. Karthikeyan, R. Swinton Darious, P. Thomas Muthiah and
F. Perdih, Supramolecular hydrogen-bonding patterns in
two cocrystals of the N(7)–H tautomeric form of N6-
benzoyladenine: N6-benzoyladenine–3-hydroxypyridinium-
2-carboxylate (1/1) and N6-benzoyladenine–DL-tartaric acid
(1/1), Acta Crystallogr., Sect. C: Struct. Chem., 2015, 71(11),
985–990.
14 T. V. Sundar, V. Parthasarathi, B. Sridhar, P. Venkatesan and
M. Nallu, 2-Amino-1-(4-nitrobenzyl)pyridinium bromide,
Acta Crystallogr., Sect. E: Struct. Rep. Online, 2006, 62(1),
o74–o76.
References
1 R. Swinton Darious, P. Thomas Muthiah and F. Perdih,
Supramolecular hydrogen-bonding patterns in a 1 : 1 co-
crystal of the N(7)–H tautomeric form of N6-
benzoyladenine
Crystallogr., Sect. E: Crystallogr. Commun., 2017, 73(3), 383–
386.
with
4-hydroxybenzoic
acid,
Acta
2 K. C. Hunter, L. R. Rutledge and S. D. Wetmore, The
Hydrogen
Bonding
Properties
of
Cytosine:
A
Computational Study of Cytosine Complexed with
Hydrogen Fluoride, Water, and Ammonia, J. Phys. Chem. A,
2005, 109(42), 9554–9562.
˜
15 P. S. Pereira Silva, M. Ramos Silva, J. A. Paixao and A. Matos
Beja, bromide, Acta
N,N0,N00-Triphenylguanidinium
Crystallogr., Sect. E: Struct. Rep. Online, 2007, 63(5), o2524–
o2526.
16 S. M. Fellows and T. J. Prior, Crystal structure of 4-
carbamoylpyridinium chloride, Acta Crystallogr., Sect. E:
Crystallogr. Commun., 2016, 72(4), 436–439.
17 R. G. Lacoste and A. E. Marttel, New Multidentate Ligands. I.
Coordinating Tendencies of Polyamines Contaimng a-
Pyridyl Groups with Divalent Metal Ions, Inorg. Chem.,
1964, 3(6), 881–884.
18 T.-M. Hseu, Y.-H. Tsai and C.-W. Cheng, Spectrophotometric
Studies of Nickel(II) Chelate of 2-Picolylamine, J. Chin. Chem.
Soc., 1975, 22(4), 299–308.
3 P. C. Singh and G. Naresh Patwari, Theoretical investigation
of C–H/H–B dihydrogen bonded complexes of acetylenes
with borane-trimethylamine, Chem. Phys. Lett., 2006, 419(1–
3), 5–9.
4 S. R. Choudhury, P. Gamez, A. Robertazzi, C.-Y. Chen,
H. M. Lee and S. Mukhopadhyay, Experimental
Observation
of
Supramolecular
Carbonyl–p/p–p/p–
Carbonyl and Carbonyl–p/p–p/p–Anion Assemblies
Supported by Theoretical Studies, Cryst. Growth Des., 2008,
8(10), 3773–3784.
5 M. Lozynski, Liquid water: The helical perspective of
structure, Chem. Phys., 2015, 455, 1–6.
6 B.-S. Zhang and Y.-Q. Zheng, Crystal structure of 4,40-
bipyridinumdibromide, (C10H10N2)Br2, Z. Kristallogr. - New
Cryst. Struct., 2003, 218.
7 T. V. Sundar, V. Parthasarathi, K. Sarkunam, M. Nallu,
B. Walfort and H. Lang, 1-[(4-Chlorobenzoyl)methyl]-4-(N,N-
dimethylamino)pyridinium bromide sesquihydrate and 1-
[(4-bromobenzoyl)methyl]-4-(N,N-dimethylamino)
pyridinium bromide sesquihydrate, Acta Crystallogr., Sect. C:
Cryst. Struct. Commun., 2004, 60(7), o464–o466.
8 T. V. Sundar, V. Parthasarathi, K. Sarkunam, M. Nallu,
B. Walfort and H. Lang, 1-[(2,4-Dichlorobenzoyl)methyl]-4-
(N,N-dimethylamino)pyridinium bromide, Acta Crystallogr.,
Sect. E: Struct. Rep. Online, 2004, 60(12), o2345–o2346.
9 T. V. Sundar, V. Parthasarathi, K. Sarkunam, M. Nallu,
B. Walfort and H. Lang, 1-[2-(Biphenyl-4-yl)-2-oxoethyl]-4-
(N,N-dimethylamino)pyridinium bromide hemihydrate,
Acta Crystallogr., Sect. E: Struct. Rep. Online, 2005, 61(4),
o889–o891.
19 S. Utsuno and K. Sone, Spectrophotometric Studies of the
Metallic Chelates of 2-Picolylamine. I. The Electronic
Absorption Spectra of Some Nickel, Copper(II) and
Cobalt(III) Chelates, Bull. Chem. Soc. Jpn., 1964, 37(7), 1038–
1043.
20 R. P. Feazell, C. E. Carson and K. K. Klausmeyer, Variability
in the Structures of Luminescent [2-(Aminomethyl)pyridine]
silver(I) Complexes: Effect of Ligand Ratio, Anion, Hydrogen
Bonding, and p-Stacking, Eur. J. Inorg. Chem., 2005,
2005(16), 3287–3297.
¨
21 K. W. Tornroos, M. Hostettler, D. Chernyshov, B. Vangdal
¨
and H.-B. Burgi, Interplay of Spin Conversion and
Structural Phase Transformations: Re-Entrant Phase
Transitions in the 2-Propanol Solvate of Tris(2-
picolylamine)iron(II) Dichloride, Chem.–Eur. J., 2006,
12(24), 6207–6215.
22 G. M. Sheldrick, Crystal structure renement with SHELXL,
Acta Crystallogr., Sect. C: Struct. Chem., 2015, 71(1), 3–8.
23 G. M. Sheldrick, SHELXT – Integrated space-group and
crystal-structure determination, Acta Crystallogr., Sect. A:
Found. Adv., 2015, 71(1), 3–8.
24 L. J. Farrugia, WinGX and ORTEP for Windows: an update, J.
Appl. Crystallogr., 2012, 45(4), 849–854.
25 G. M. Sheldrick, A short history of SHELX, Acta Crystallogr.,
Sect. A: Found. Crystallogr., 2008, 64(1), 112–122.
26 K. Brandenburg, Diamond Version 3.2i, Crystal Impact GbR,
Bonn, Germany, 2012.
27 J. J. McKinnon, D. Jayatilaka and M. A. Spackman, Towards
quantitative analysis of intermolecular interactions with
Hirshfeld surfaces, Chem. Commun., 2007, 3814.
28 M. A. Spackman and D. Jayatilaka, Hirshfeld surface
analysis, CrystEngComm, 2009, 11(1), 19–32.
10 K. B. Kim, S. M. Yu, C. Kim and Y. Kim, 5-Carbamoyl-2-
methyl-1-(2-methyl-benz-yl)pyridinium
bromide,
Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2012, 68(Pt 6),
o1609–o1610.
11 P. Venkatesan, V. Rajakannan and S. Thamotharan, Crystal
structure of 3-amino-1-propylpyridinium bromide, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2014, 70(12), 580–
583.
12 R. Anitha, S. Athimoolam and M. Gunasekaran, A strong
NH/Br vibrational behaviour studied through X-ray,
vibrational spectra and quantum chemical studies in an
isomorphous
crystal:
2-Nitroanilinium
bromide,
Spectrochim. Acta, Part A, 2015, 138, 753–762.
5872 | RSC Adv., 2020, 10, 5864–5873
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View Article Online
Paper
RSC Advances
29 M. A. Spackman and P. G. Byrom, A novel denition of 33 Z. Xie, J. Huang, X. Xu and Z. Jin, Antioxidant activity of
a molecule in a crystal, Chem. Phys. Lett., 1997, 267(3–4),
215–220.
peptides isolated from alfalfa leaf protein hydrolysate,
Food Chem., 2008, 111(2), 370–376.
30 R. R. Ternavisk, A. J. Camargo, F. B. C. Machado, 34 P. Bersuder, M. Hole and G. Smith, Antioxidants from
J. A. F. F. Rocco, G. L. B. Aquino, V. H. C. Silva, et al.,
Synthesis, characterization, and computational study of
a new dimethoxy-chalcone, J. Mol. Model., 2014, 20(12), 2526.
31 B. Wang, Z.-R. Li, C.-F. Chi, Q.-H. Zhang and H.-Y. Luo,
a heated histidine-glucose model system. I: Investigation
of the antioxidant role of histidine and isolation of
antioxidants by high-performance liquid chromatography,
J. Am. Oil Chem. Soc., 1998, 75(2), 181–187.
Preparation and evaluation of antioxidant peptides from 35 J. R. Tagg and A. R. McGiven, Assay System for Bacteriocins,
ethanol-soluble proteins hydrolysate of Sphyrna lewini
muscle, Peptides, 2012, 36(2), 240–250.
32 I. I. Koleva, T. A. van Beek, J. P. H. Linssen, A. de Groot and
L. N. Evstatieva, Screening of plant extracts for antioxidant
Appl. Microbiol., 1971, 21(5), 943.
36 S. Farooq and F. Azam, The use of cell membrane stability
(CMS) technique to screen for salt tolerant wheat varieties,
J. Plant Physiol., 2006, 163(6), 629–637.
activity: a comparative study on three testing methods, 37 S. Li, X. Li and G. J. Rozanski, Regulation of glutathione in
Phytochem. Anal., 2002, 13(1), 8–17.
cardiac myocytes, J. Mol. Cell. Cardiol., 2003, 35(9), 1145–
1152.
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