Synthesis, spectroscopic characterization, crystal structure, Hirshfeld surface analysis and antimicrobial activities of two triazole Schiff bases and their silver complexes

Article abstract of DOI:10.1016/j.ica.2018.05.028

The present work describes the synthesis, structural characterization, Hirshfeld analysis, and antibacterial assays of two hydroxy Schiff bases with triazole moiety: N-[(E)-(3-hydroxy)methylidene]-4H-1-2-4 triazol-4-amine (L1) and N-[(E)-(2,4-dihydroxy)me

Full text of DOI:10.1016/j.ica.2018.05.028

Accepted Manuscript
Research paper
Synthesis, spectroscopic characterization, crystal structure, Hirshfeld surface
analysis and antimicrobial activities of two triazole Schiff bases and their silver
complexes
Zakaria Bouhidel, Aouatef Cherouana, Pierrick Durand, Abdelatif Doudouh,
Filippo Morini, Benoit Guillot, Slimane Dahaoui
PII:
S0020-1693(17)31761-9
https://doi.org/10.1016/j.ica.2018.05.028
ICA 18279
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
15 November 2017
8 April 2018
21 May 2018
Please cite this article as: Z. Bouhidel, A. Cherouana, P. Durand, A. Doudouh, F. Morini, B. Guillot, S. Dahaoui,
Synthesis, spectroscopic characterization, crystal structure, Hirshfeld surface analysis and antimicrobial activities
of two triazole Schiff bases and their silver complexes, Inorganica Chimica Acta (2018), doi: https://doi.org/
10.1016/j.ica.2018.05.028
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Synthesis, spectroscopic characterization, crystal structure,
Hirshfeld surface analysis and antimicrobial activities of two
triazole Schiff bases and their silver complexes
Zakaria Bouhidela, Aouatef Cherouanaa*, Pierrick Durandb, Abdelatif Doudouhb, Filippo
Morinib,c, Benoit Guillotb and Slimane Dahaouib*,
a
Unité de Recherche de Chimie de l’Environnement et Moléculaire Structurale (CHEMS),
Département de Chimie, Université des frères Mentouri-Constantine 1, 25000 Constantine,
Algeria.
b CRM2 (UMR UL-CNRS 7036). Faculté des Sciences et Technologies, Université de
Lorraine. BP 70239, Boulevard des Aiguillettes. 54506 Vandoeuvre-lès-Nancy CEDEX.
c
Center of Molecular and Materials Modelling, Hasselt University, Agoralaan Gebouw D, B-
3590 Diepenbeek, Belgium.
Abstract
The present work describes the synthesis, structural characterization, Hirshfeld analysis, and
antibacterial assays of two hydroxy Schiff bases with triazole moiety: N-[(E)-(3-
hydroxy)methylidene]-4H-1-2-4
triazol-4-amine
(L1)
and
N-[(E)-(2,4-
dihydroxy)methylidene]-4H-1-2-4 triazol-4-amine (L2). The interaction of these two Schiff
bases with AgNO3 leads to Ag(I) dimer [Ag(L1)](NO3) in the case of the first ligand (L1) and
polymer [Ag(L2)]n(NO3)n(H2O) for (L2). Crystal structure determination and Hirshfeld
analysis reveal the presence of two important hydrogen bond interactions in the four
compounds, O…H and H…N, involving nitrogen atoms of triazole ring. Contribution of these
two types of hydrogen bonds evolves inversely from (L1) which contains one –OH, to (L2)
containing two –OH, then to [Ag(L1)](NO3) dimer and finally to [Ag(L2)]n(NO3)n(H2O)
polymer. Indeed, we observed an increase of the percentage to the Hirshfeld surfaces of O…H
contribution from (L1) to [Ag(L2)]n(NO3)n(H2O) passing by (L2) and [Ag(L1)](NO3), while
the percentage of N…H decrease in the same way. Antibacterial activity of the free ligands
(L1), (L2) and their silver complexes [Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O) were
evaluated against four Gram-negative (E. coli, Salmonella typhimurium, Klebsiella
1

pneumoniae and serratia marcescens) and two Gram-positive (Staphylococcus aureus,
streptococcus) bacteria strains, using the standard antibiotics, Colistin, Fosfomycin,
Gentamycin, Erythromycin, Rifampicin, Amikacin, Ofloxacin and Amoxicillin as positive
controls. AgNO3 salt was also used as second control test. The results of this evaluation reveal
that, while the two Schiff bases inhibit the growth of the Serratia Marcescens bacterium only,
the two Ag(I) complexes are active for all bacteria, with activities comparable to the ones of
silver nitrate. However, [Ag(L2)]n(NO3)n(H2O) complex appears significantly more efficient
than the AgNO3 salt against Klebsiella Pneumoniae.
Keywords
Schiff bases; silver complexes; hydrogen bonding; Hirshfeld surfaces; antimicrobial activity
1. Introduction
Schiff bases i.e. R2C=NR’ (R and R’≠H), are an important class of organic compounds
reported for the first time in 1864 by Hugo Schiff [1]. This family of compounds is used as
starting materials in the synthesis of important drugs, such as antibiotics and antitumor
substances [2-4]. A number of these bases have been reported to possess antioxidant, [5-9]
anticonvulscent, [10] analgesic, [11] antituberclotic, [12] and diuretic [13] activities. Schiff
bases have often been used as chelating ligands in the field of coordination chemistry for
obtaining metal-based supramolecular assemblies, with a large number of potential
applications such as catalysis, [14-15] photochemistry, [16] luminescence, [17] sensing, [18]
magnetism, [19-20] gas storage, [21-23] gas purification, [24-25] and medicine [26-30].
Our interests have been in the synthesis, the characterization and the biological properties of
heterocyclic Schiff bases and their Ag(I) complexes, where heterocycles are chosen as 1-2-4
triazole groups. Triazole moieties are indeed known as important polar pharmacophore able to
act either as hydrogen bond donor or acceptor, and thus ready to interact with a variety of
partners in biological systems. Triazole heterocyclic rings are thus considered as
pharmacologically important scaffolds and are indeed used in many drugs associated to
diverse biological activities [31, 32]. On the other hand, ionic silver is known for its
antimicrobial properties for many centuries. Even if the precise mechanisms by which it is
able to inhibit bacterial growth is still studied nowadays, it is commonly admitted that silver
can kill bacteria by entering cells through impairment of enzymes binding Ag(I) ions on the
surface of cell wall. Once inside the cell, proposed mechanisms range from the deactivation or
2

the denaturation of essential enzymes by interaction between silver and sulfhydryl-containing
molecules, to DNA denaturation by intercalation between base pairs. In any case, these
mechanisms lead to a deep disruption of the cell metabolism and, finally, to cell death [33,
34]. Despite the historical knowledge of the antimicrobial properties of silver ions, the
discovery and the development of antibiotics significantly reduced the search of new silver-
based bactericidal agents and, overall, the use of silver in medicine. Nowadays the use of
silver in medicine is in practice limited to burns treatment with silver sulfadiazine and wound
management, for instance using dressings or medicinal devices coated with silver
nanoparticles [35]. However, the emergence of antibiotic resistant bacteria strains and of
multidrug-resistant organisms quite recently changed the situation and prompted the search of
new antimicrobial drugs relying on the well-known properties of silver, such as silver
coordination compounds. For instance, the literature is abundant concerning the development
of silver complexes with N-heterocycles (including triazoles), or N-heterocyclic carbenes
[36], and the evaluation of their antibiotic properties. In addition to the evaluation of
biological activities of our triazole substituted Schiff bases and their Ag(I) complexes, this
study can be a plus for the construction of metal-organic frameworks (MOFs) with novel
topology and for the crystal engineering of molecular architectures organized by coordination
bonds and supramolecular contacts (such as hydrogen bonding, π-π interactions). Indeed,
Ag(I) is a favourable building block for constructing MOFs because of its flexible
coordination numbers and weak metal-metal or metal-ligand interactions [37-38].
2. Experimental
2.1. Reagents and measurements
All reagents were commercially available, purchased from Sigma-Aldrich, and used without
further purification. The IR spectra were recorded on a Nicolet 5700 FT-IR Thermo Scientific
spectrophotometer using powder in mixed KBr pellets in the range of 400-4000 cm-1. The
UV-Vis spectra were recorded at room temperature in the range of 100-900 nm, on a Cary
4000 Varian UV-Visible spectrophotometer by dissolving the compounds in DMSO.
2.2. Procedure of synthesis of the two Schiff bases and their silver complexes
2.2.1. Synthesis of N-[(E)-(3-hydroxyphenyl)methylidene]-4H-1-2-4 triazol-4-amine.
(L1):
3-Hydroxybenzaldehyde (0.244 g, 2 mmol), was added to an ethanolic solution (15 ml) of 4-
amino-4H-1,2,4-triazole (0.161 g, 2 mmol) containing few drops of glacial acetic acid. The
reaction mixture was stirred for 6h under reflux at 75°. The resulting yellow solution was
3

cooled in an ice bath. The crystalline powder obtained was filtered off, washed with ethanol
and dried under vacuum. Pure colourless crystals for (L1) diffraction were obtained by
1
recrystallization in acetonitrile/H2O. H NMR (250 MHz, [D6] DMSO, 300K): =9.04 (2H,
s, H1, H2), 8.85 (1H, s, H3), 7.36 (1H, m, H8), 7.31 (1H, m, H5), 7.26 (1H, m, H7), 6.89 (1H,
m, H9) ppm. 13C NMR (250 MHz, [D6] DMSO, 300K) = 159.76 (C6), 158.27 (C3), 140.09
(C1-C2), 134.00 (C8), 131.50 (C9), 121.69 (C5), 120.83 (C7), 115.07 (C4) ppm. (supp.1).
C9H8N4O (188.19): calcd. C 57.44, H 4.28, N 29.77, O 8.50; found C 57.54, H 4.35, N 29.90,
O 8.55.
2.2.2. Synthesis of N-[(E)-(2,4-dihydroxyphenyl)methylidene]-4H-1-2-4 triazol-4-amine.
(L2) :
The pure crystals of second Schiff base (L2) was synthesized by the same procedure used for
(L1). However, in this case, we use 2,4-dihydroxybenzaldehyde (0.276 g, 2 mmol) instead of
1
3-hydroxybenzaldehyde. H NMR (250 MHz, [D6] DMSO, 300 K): = 8.98 (2H, s, H1, H2),
8.89 (1H, s, H3), 7.56 (1H, d, j=8.6 Hz, H9), 6.41 (1H, dd, j= 8.6 Hz, 2.0 Hz, H8), 6.34 (1H, d,
13
j=2.0 Hz, H6) ppm. . C NMR (250 MHz, [D6] DMSO, 300K) = 163.80 (C5), 161.12 (C7),
158.43 (C3), 139.90 (C1-C2), 132.37 (C9), 110.57 (C6), 109.75 (C8), 103.57 (C4) ppm.
(supp.2). C9H8N4O2 (188.19): calcd. C 52.89, H 3.92, N 27.43, O 15.67; found C 53.00, H
3.99, N 27.44, O 15.80.
2.2.3. Synthesis of [Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O) :
Complexes [Ag(L1)](NO3) and [Ag(L2) ](NO3)(H2O) were prepared by the reaction of (L1)
and (L2) respectively with AgNO3 (0.3:0.3 mmol) in 14 ml of H2O/CH3CN (1:1) solution.
After stirring for about 30 min at 50 °C, the resulting solutions were filtered. Colourless
single crystals suitable for X-ray diffraction were obtained by slow evaporation of the two
solutions after few days. For [Ag(L1)](NO3): AgC18H16N9O5 (546.27): Ag 19.75 C 39.54, H
2.93, N 23.06, O 14.64; found Ag 19.90 C 39.54, H 3.05, N 23.09, O 14.70. For [Ag(L2)
](NO3)(H2O): AgC9H10N5O6 (392.09): Ag 27.51 C 27.54, H 2.55, N 17.85, O 24.48; found
Ag 27.60 C 27.56, H 2.80, N 17.95, O 24.67.
2.3. X-ray crystallography
A suitable crystal of each compound was glued to a glass fibber mounted on dual source
supernova with the large area Atlas CCD detector. Diffraction data were collected using the
Mo-Kα radiation at 100 K. Correction for Lorentz-polarization effect, peak integration and
4

reduction were carried out with CrysAlisPro package [39]. The structures were solved by
direct methods and refined by full-matrix least squares method using SHELX programs [40].
All non-hydrogen atoms are placed appropriately and refined anisotropically. All H atoms
were located in difference electron-density maps and were treated as riding on their parent
atoms, with C-H = 0.93Å, N-H = 0.85 Å, O-H = 0.84 Å and Uiso(H) = -1.2Ueq(X) (X = C and
N) and -1.5 Ueq(O).
The crystallographic data for the structures reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publications no. CCDC
1582965 - 1582968. Copies of available material can be obtained, free of charge, on
application to the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, fax: +44
(0)1223 336033 or Email: deposit@ccdc.cam.ac.uk. Relevant crystal data are listed in table 1
together with refinement detail.
Table 1. Crystal data, data collection and structure refinement for the four title
compounds
Crystal data
Chemical formula
Mr
(L1)
C9H8N4O
188.19
(L2)
[Ag(L1)](NO3)
[Ag(L2) ](NO3)(H2O)
C9H8AgN4O2. NO3.
H2O
C9H8N4O2
C18H16AgN8O2. NO3
204.19
Monoclinic,
P21/n
546.27
392.09
Cell setting, space
group
Orthorhombic,
Triclinic,
Monoclinic,
Pna21
P21/n
P
1
Temperature (K)
100 (2)
100 (2)
100 (2)
100 (2)
a = 22.7284(5) Å
b = 9.8594(2) Å
c = 3.7808(1) Å
α = 90°
a = 5.8440(5) Å
b = 21.118(2) Å
c = 7.5764(8) Å
α = 90°
a = 8.751(5) Å
b = 9.625(5) Å
c = 12.313(5) Å
α = 90.081(5)°
β = 97.473(5)°
γ = 99.838(5)°
a = 12.5270(4) Å
b = 8.2643(3) Å
c = 12.5996(3) Å
α = 90°
Unit cell parameters
β = 107.094(5)°
β = 90°
γ = 90°
β = 103.151(3)°
γ = 90°
γ = 90°
V (Å3)
Z
847.23(3)
4
893.74(15)
4
1012.9(9)
2
1270.16(7)
4
Dx (Mg m–3)
Radiation type
µ (mm–1)
1.475
Cu Kα
0.86
1.518
Mo Kα
0.11
1.791
2.050
Mo Kα
Mo Kα
1.05
1.63
Crystal form, colour Prism, colourless Prism, colourless
Crystal size (mm) 0.15 × 0.10 × 0.09 0.20 × 0.10 × 0.10
Prism, colourless
0.10 × 0.10 × 0.08
Prism, colourless
0.20 × 0.10 × 0.10
5

Agilent SuperNova Agilent SuperNova Agilent SuperNova Agilent SuperNova
CCD diffractometer CCD diffractometer CCD diffractometer CCD diffractometer
Diffractometer
Data collection
method
ω-scans
ω-scans
ω-scans
ω-scans
Absorption
correction
Integration
Integration
Integration
Integration
Tmin, Tmax
0.908, 0.938
0.889, 0.940
0.708, 0.750
0.896, 0.946
No. of measured,
independent and
observed reflections
(I > 2σ(I))
15602, 1787, 1574 8605, 2267, 1440
21173, 6041, 4082
32791, 6508, 4856
a
Rint
0.059
76.5
F2
0.049
28.6
F2
0.037
30.5
F2
0.036
37.7
F2
θmax (°)
Refinement on
R[F2 > 2σ(F2)]b,
wR(F2)c, Sd
0.053, 0.135, 1.04 0.057, 0.200, 1.08
0.041, 0.164, 1.09
0.029, 0.070, 1.05
No. of relections
No. of parameters
(∆/σ)max
1663 reflections
127
2267 reflections
136
6041 reflections
298
2815 reflections
167
< 0.01
< 0.01
0.001
0.001
∆ρmax, ∆ρmin (e Å–3)
0.60, –0.32
0.42, –0.37
0.63, -0.93
0.75, –0.83
a
2
2
2
Rint = Σ(F – <F >)] /Σ(F
)
o
o
o
b
c
2
2 2
2 2 1/2
R(F2) = Σ||F |–|F || /Σ|F |. wR(F2) = [Σw(F –F ) ] /[Σw(F ) ]
.
o
c
o
o
c
o
d
2
2 2
1/2
Goodness-of-fit S = [Σw(F − F ) /(n − p)] , where n is the number of reflections and p the number of
o
c
parameters.
2.4. Hirshfeld surface analysis
In order to have a better understanding of the intermolecular interactions within the crystal
structure, Hirshfeld surface analysis [41] has been undertaken. It consists in partitioning the
crystal electron density into molecular fragments. Thus, the Hirshfeld surface can be defined
as the border between regions where promolecule electron density surpasses that from all
neighbouring molecules over the rest of the crystal. The Hirshfeld surface, which envelops the
molecule, is defined as an iso-surface of w(r) = 0.5, where w(r) is a molecular weight function
derived from the spherically averaged atomic electron densities ρi (r) [42]:
6

ꢄ
i ∈ moleculeꢅꢆꢇꢁrꢃ
ꢁ ꢃ
ꢁ ꢃ
ꢀ ꢂ =
ꢄ
i ∈ crystalꢅꢆꢇ r
The normalized contact distance dnorm is the sum of the distances of any surface point to the
nearest interior (di) and exterior (de) atom, normalized by the van der Waals radii of the
atoms, Spackman et al. [43]. The Hirshfeld surfaces were computed to explore the
contributions of non-covalent interactions in the crystal structures using Crystal Explorer 3.1
software [44].
3. Results and discussion
FT-IR spectroscopy:
The spectrum of the triazole Schiff bases, (L1) and (L2), exhibit remarkable bands at 1611
and 1605 cm-1 respectively due to the formation of the imine group (C=N) [45-46], supp.3
(supplementary materials). Furthermore, the ν(O-H) bands of the weak intensity were
observed in the range 3100-3150 cm-1. These bands do not shift to lower wave number in the
spectra of the complexes indicating the non-participation of the imine nitrogen and the
hydroxyl group in coordination to the metal ion [47]. In addition, the bands detected in the
range of 1300-1500 cm-1 is due to the ν(N-N) stretching vibration of the triazole moiety. This
band is shifted to higher wave number in the complex spectra suggesting the participation of
the two nitrogen atoms N1 and N2 of triazole in coordination to the metal ion [48].
UV-visible spectroscopy:
The UV-visible absorption of the four compounds display two bands observed in DMSO in
the range of 260-400 nm. The first band observed around 320 nm is owing to the low energy
π –π* transition of the imine group. The second band detected around 280 nm was assigned as
a moderate π –π* transition of the aromatic ring table S1 and supp.4 (supplementary
materials). These bands undergo a hypsochromic shift due to the coordination of the free
ligand with the metal ion.
X-ray structure analysis.
Crystal structure of (L1) and (L2)
The crystal structure of ligand (L2) has been reported by François Safin and co-workers [49],
however, the data collection was done at room temperature on a twinned crystal, with
7

insufficient data to have a good refinement of the structure (Ratio NO/NV: 6.8). These
constraints affected the accuracy of the values of distances and angles.
The molecular structures of the two free ligands (L1) and (L2) are depicted in Fig.1. The two
compounds crystallize in the orthorhombic group space Pna21 for (L1) and in the monoclinic
group space P21/n for (L2) with four molecules in the unit cell for each compound. The two
Schiff bases (L1) and (L2) differ only by the positions and the nature of the substitutions on
the six-membered aromatic ring: (L1) bears a single hydroxyl group at the C(6A) meta
position while (L2) presents two hydroxyl substituent at the ortho and para positions. Both
(L1) and (L2) are in their enolimine form, confirmed by the lengths of C-O bonds (1.368(3),
1.366(3) and 1.348(8) Å), and of C-C single bonds (1.469(3) and 1.451(3) Å) and C=N imine
bond (1.278(3) and 1.279(3) Å) (Fig.1). The two molecules have an almost planar E
configuration with respect to the imine C=N double bond, as indicated by the value of -
177.1(2)° for (L1) and 177.21(17)° for (L2) of the N(3A)-N(4A)-C(3A)-C(4A) torsion angle.
The dihedral angles between aromatic rings in both ligands are comparable: 17.16° for (L1)
and 19.51° (L2). The bond angles and distances in (L1) and (L2) are in agreement with
similar compounds [50-52].
(a)
8

(b)
Fig.1: ORTEP of the two ligands (L1) and (L2) with thermal displacement ellipsoids drawn
at the 50% probability level. (a) (L1) and (b) (L2).
In the crystal structures formed by (L1) and (L2), the nitrogen atoms of triazole moieties
interact with hydroxyl group through intermolecular O-H…N hydrogen bonds. In the case of
(L1), the single hydroxyl group is hydrogen bonded to N(1A) allowing to form infinite chains
along a axis with a C(10) graph set motif [53-54]. The presence of the second OH in the case
of (L2) has drastic consequences for the crystal packing. It leads indeed to the formation of
another O-H…N hydrogen bond involving the second triazole nitrogen atom, transforming
4
the infinite chain observed in the case of (L1) into R4 (29) rings, generating two-dimensional
layers developing parallel to the (101) plane (Fig.2) and (table S2 in supplementary
materials). These hydrogen bonds replace the intramolecular ones between ο-OH and imine
nitrogen atom which are broken by the rotation of the phenolic ring [55].
(a)
9

(b)
Fig.2: O-H…N hydrogen bonds. (a) Infinite chains in (L1) and 2D layers (b) in (L2)
In (L1), the azomethine nitrogen (N4A), which is not involved in O-H…N interaction, acts
nevertheless as acceptor in a C4A-H4A…N4A hydrogen bond along b axis, giving rise to 2D
6
3
layers built on the basis of alternating R6 (33) and R3 (18) rings, (Fig.3a). Moreover, along
the third direction (c axis), C1A-H1…O1A bonds between triazole and hydroxyl, and C2A-
H2A…N1A bond between two triazole moieties ensure the supramolecular cohesion of the
2D layers, (Fig.3b). The same C-H…O hydrogen bond links the 2D layers in (L2) along the
b axis and leads to a three dimensional structure. In both crystal structures, π…π interactions
coexist with hydrogen bonding and participate in the final stability of the molecular
assemblies. As shown in Fig.4, in the case of (L1), the crystal packing presents clear triazole
… triazole and phenyl…phenyl π…π interactions. In the case of (L2), a single weaker π…π
stacking appears to form partially between the phenyl ring of a molecule and both the triazole
moiety and the imine double bond of the symmetry equivalent molecule obtained by
translation along the a axis. ꢀ
10

(a)
(b)
Fig 3: C-H…N and C-H…O hydrogen bonds in (L1). (a) 2D layers generated by interactions
involving azomethine nitrogen atoms. (b) Supramolecular structure of (L1).
11

(a)
(b)
Fig.4: π…π interactions.
(a) phenyl…phenyl and triazole…triazole in (L1). (b) phenyl…triazole in (L2)
Crystal structure of the silver complexes [Ag(L1) ](NO3) and [Ag(L2)]n(NO3)n(H2O)
Reaction of AgNO3 with (L1) and (L2) yield a Ag(I) dimer for the first ligand and a polymer
for the second one. As observed in the crystal structures of the isolated ligands, the presence
of an extra hydroxyl group in (L2) compared to (L1) led to very different crystal structures of
their corresponding silver complexes. The structure of the dimer issued by (L1) contains a
dinuclear cation formed by two-symmetry related Ag(I) coordinated to four (L1) ligands,
-
[Ag2(L1)4], and uncoordinated NO3 anions, Fig.5. Each Ag(I) ion adopts a trigonal
environment and the sum of angles around it, equal to 360.0°, indicates planarity of its
geometry [56-57]. Ag(I) and Ag(I)(i) [(i) 2-x, 1-y, 1-z] are bridged by two ligands, hereafter
noted A and B, to form a six-membered ring {Ag N } The Ag(I)…Ag(I) separation is 3.917
.
4
2
Å, which is significantly longer than the sum of the van der Waals radii of two Ag(I) cations
(3.44 Å) [58]. The Ag-N separations (2.1812(12) Å and 2.1919(12) Å) are very similar in
structures with such coordination bonds [59]. The ligand A is bitopic with the two nitrogen
atoms N(1A) and N(2A), however, ligand B interacts with Ag(I) by only one nitrogen atom
(N1B). The dihedral angles formed between the aromatic and triazole rings are 4.63° for A
and 7.65° for B, much less than the 17.16° observed for the free ligand (L1), which indicate
that they are nearly coplanar in the silver complex. In [Ag(L1)](NO3), the O-H…N
interaction, between two ligands, organizes the dimers into polymeric chains, built on the
2
succession of R2 (32) rings and developing in the [110] direction, Fig.6. O-H…O and C-
H…O hydrogen bonds between ligands and nitrate anion organize these chains into 3D
supramolecular network. In addition, π…π and Ag…π interactions in conjunction with all
hydrogen bonds contribute to the stability of the structure.
12

In the crystal structure of the second complex, [Ag(L2)]n(NO3)n(H2O), the coordination
geometry of Ag(I) ion is square pyramidal with a basal plane constituted by N(1A) and N(2A)
-
triazole nitrogen atoms in two (L2) molecules and by oxygen atoms of two NO3 anions. The
apical direction of the square pyramid is defined by the O(1A) atom of the phenyl hydroxyl
group located at ortho position. Ag(I) ions, being coordinated by the nitrogen atoms of
−Ag(1)−N(2A) of 179.31(5)°).
triazole moiety, is found in distorted linear geometry (N(1A)
This slight deviation from perfect linear geometry, is essentially due to the weak Ag…O
interactions between Ag(I) and nitrate anion on one side and hydroxyl group on the other side
(2.6892(12) Å and 2.7181(14) Å respectively). In the Cambridge Structural Database (CSD-
2017, update Feb 2017), only two structures are reported considering these two weak
interactions as Ag-O bond [60]. Ag(I) ions are connected via bridging ligand molecules to
form polymeric chains along b axis Fig.7. The dihedral angle between triazole and phenyl
rings in the bitopic ligand (L2) in this polymer is the same as found for the free one (19.52°).
Fig.5: ORTEP representation of the dimer of [Ag(L1) ](NO3) with thermal displacement
ellipsoids drawn at the 50% probability level. (i) 2-x, 1-y, 1-z
13

Fig.6: Interligand O-H…N hydrogen bond connecting dimers
Fig.7: Polymeric chains of [Ag(L2)]n(NO3)n(H2O) developing along b axis
Interestingly, unlike in the free (L2) ligand, in the polymer [Ag(L2)]n(NO3)n(H2O), one S(6)
intra-ligand O-H…N hydrogen bond is observed between the o-OH group of the phenyl ring and
the azomethine nitrogen atom, Fig.8. O-H…O hydroxyl-water hydrogen bonds connect polymeric
chains in 2D sheets parallel to (bc) plane C-H…O ligand-nitrate anion and π…π interactions
reinforce the crystal structure and contribute to the construction of 3D supramolecular network. In
the structure of [Ag(L2)]n(NO3)n(H2O), the presence of a structured water molecule is
14

-
noteworthy. This water molecule fills a void formed by five (L2) molecules and a NO3 ion and is
-
involved in three hydrogen bonds: two as donor to oxygen atoms of a NO3 ion and of a hydroxyl
group of the ligand, and one as acceptor of hydrogen atom of the same hydroxyl group located in a
symmetry related molecule (Fig.8). This water molecule has probably a significant impact on the
packing stability as the hydrogen bonds in which it is involved are among the shortest in the
crystal structure, with oxygen-oxygen distances of 2.617(2) and 2.812(2) Å (see Table S3 in
supplementary materials).
Fig.8: 2D Sheets built on the basis of O-H…O and O-H…N hydrogen bonds in
[Ag(L2)]n(NO3)n(H2O)
Hirshfeld surfaces analyses of (L1), (L2):
The intermolecular interactions within the crystal structures of the ligands (L1) and (L2), and
of their silver complexes were analysed by combining 3D Hirshfeld surface and 2D
fingerprint plots. A better understanding of the molecular structure requires quantitative
insights into the relative contributions of intermolecular interactions within the crystal [61].
For that purpose, Hirshfeld surfaces of the title compounds have been generated, and mapped
over dnorm value (Fig. 9). The red hot spots on the surface indicate the presence of atoms in
very close proximity to the outside of the Hirshfeld surface. The white surface means that the
15

atoms are in medium proximity, while the blue surface shows little proximity of outside
atoms.
Fig. 9: Hirshfeld surfaces of the title compounds mapped with ꢅ
ꢈꢇ ꢍ ꢂꢎꢏꢐ ꢈꢒ ꢍ ꢂꢎꢏꢐ
ꢒ
ꢇ
ꢈꢉꢊꢋꢌ
=
ꢑ
ꢂꢎꢏꢐ
ꢂꢎꢏꢐ
ꢒ
ꢇ
Recently, these type of triazole compounds have been studied by Safin et al. [49]. In this
paper we have used the Hirshfeld surfaces and 2D fingerprint plots analyses to perform a
comparative study of the intermolecular interactions in two different families, the free ligands
and their silver complexes. From the combination of the 3D Hirshfeld surface and 2D
fingerprint plots of the (L1) and (L2) compounds, we notice that the intermolecular H…H
contacts have the main contribution, corresponding to 31.3% and 29.5% of the total Hirshfeld
surfaces areas (supp.5). For (L1) we observe the presence of short intermolecular H…H
contact where de = di ≈ 1.13 Å. Two red spots are depicted on the dnorm surfaces, Fig.10. On
the other hand, the intermolecular H...H contacts for (L2) are bit longer in the vicinity of 2.65
and 2.86 Å, these contacts are manifested as white spots on dnorm which are considered as weak
interaction.

Fig. 10: Hirshfeld surfaces mapped with dnorm for (L1) and (L2)
showing H…H contacts
As shown previously, the stabilization of the crystal structure is provided for the two
structures by hydrogen bonds. In the fingerprint plots of both (L1) and (L2), N...H contacts
are depicted in supp.5 (supplementary materials), as a pair of sharp spikes at de + di ≈ 1.8 Å.
These contacts in the two structures (L1) and (L2) have considerable contribution on
Hirshfeld surface of 27.3% and 23.3%, respectively (Fig. 12).
The red spots on the dnorm surfaces in Fig.11 are due to the HC…N and HO…N contacts
corresponding to C-H..N and O-H…N hydrogen bonds, respectively. Thus, in the dnorm suface
of (L1) and (L2); the red spots of HO..N appear larger than HC..N, which is related to the
hydrogen bonds interaction distances, and hence to their strength.
Fig.11: Hirshfeld surfaces mapped with dnorm for (L1) and (L2) showing O-H…N and C-
H…N hydrogen bonds
The ligand (L2) contains an extra OH function in the phenolic part of the molecule compared
to (L1). As expected, this function increases the proportion of O...H contacts, and decreases
the C…H ones, on Hirshfeld surface in (L2). The O...H contacts show up as a sharp spike in
the fingerprint plots of the molecules at de + di ≈ 2.4 Å. The packing cohesion of the two
structures is also provided by C...H interactions, representing 16.4% and 11.3% of the total
surface area for (L1) and (L2), respectively, (supp.5 and supp.6). As stated in the previous
section, π…π stacking interactions also contribute to the cohesion of the crystal packing. Such
interactions appear on Hirshfeld surfaces as C…C and C…N intermolecular contacts.
However, these contacts in the two structures represent a small proportion of the total
17

Hirshfeld surface areas. The fingerprint plots show the C…N interactions as a region of
blue/green colour on the diagonal at de ≈ di ≈ 1.80 Å (supp.5 and supp.6).
In the study by Safin et al. [49] the same molecule (L2) had different fingerprint plots (Fig
.12), reflecting differences in the structures due to the way the X-ray data were collected. The
fingerprint plot is highly sensitive to the environment surrounding the molecule, and unique
for each molecule in a particular polymorphic form [42]. The distinction can be observed in
the contribution of each intermolecular contacts and in the sum of de, di. Furthermore, the area
and the volume closed by Hirshfeld surfaces (223.56 Å2, 218.04 Å3) for (L2) and (222.81 Å2,
216.60 Å3) for the same one previously reported by Safin and co-workers, named in this work
(L2bis), show this distinction [49]. The packing energy (PE) is one of the most important
property which can be calculated to characterize the crystal packing cohesion. Using the
dispersive-repulsive forces only, the packing energy can be approximated by the empirical
formula developed by Gavezzotti and Filippini studying the geometry of intermolecular X-
H…Y (X, Y = N,O) hydrogen bond and the calibration of its empirical potentials [62]:
ꢕ ꢄ ꢄ
ꢞꢟ
ꢓꢔ = ꢖ
ꢔꢅꢁꢗꢇꢘꢃ where ꢔꢙꢗꢇꢘꢚ = ꢛ expꢙꢍꢜꢗꢇꢘꢚ ꢍ ꢝꢗꢇꢘ
Using this potential as implement in the software « Mercury CSD 2.0 - New Features for the
Visualization and Investigation of Crystal Structures » [63], the packing energies of (L1) and
(L2) crystal structures are -153.4 kJ/mol and -191.4 kJ/mol, respectivly. The fact that the
crystal structure of ligand (L2) appears more stable than the one of (L1) can be explained by
the extra OH function which gives more stability to the crystal packing, and by the presence
of the water molecule mediating intermolecular interactions by strong O-H…O hydrogen
bonds [64].
Fig.12: 2D Fingerprint plot of (L2, this work) and (L2bis, Safin et al. [49])
18

Hirshfeld surfaces analyses of [Ag (L1)] (NO3) and [Ag (L2)]n(NO3)n(H2O):
The fingerprint plots of the silver complexes are drastically different from the ones obtained
from the crystal structures of the free ligands.
The main share of total Hirshfeld surface for the complexes [Ag(L1)](NO3),
[Ag(L2)]n(NO3)n(H2O) is attributed to O…H interactions with 21.4% and 25.8% of the total
surfaces, respectively. O…H interactions appear as two sharp spikes in the fingerprint plots of
the two complexes (supp.5). The upper spike in bottom left (donor) region of the fingerprint
plot where (de = 1.19, Å di =0.83 Å) for [Ag(L1)](NO3) and (de = 1 Å, di = 0.65 Å) for
[Ag(L2)]n(NO3)n(H2O) involves 17.5% and 19.9% of the total surface, respectively. The
lower spike which correspond to the hydrogen-bond acceptor in the region (de = 1.1 Å, di =
1.4 Å) for [Ag(L1)](NO3) and (de = 0.7 Å, di = 1.1 Å) for [Ag(L2)]n(NO3)n(H2O) corresponds
to 4% and 5.9% of the total surface, respectively. With a comparable proportion than for
O…H interactions, H…H contacts account for the quarter of the total Hirshfeld surfaces area
of each complex. These contacts are showed in the middle of scattered points in the
fingerprint plots (supp.5). Furthermore, in the [Ag(L1)](NO3) structure N...H contacts play
the main role in the stabilization of crystal packing. The N…H contact are observable as a
very sharp spike (de = 0.9 Å, di = 1.19 Å) (Supp.5). Interestingly, these contacts represent
16.9% of the total surface, while only 7.2% for [Ag(L2)]n(NO3)n(H2O). The π…π stacking
(C...C) contacts is manifested in the 2D fingerprint plot, (Supp.5), as a region of blue/green
colour (de = di ≈ 1.65 Å) corresponding to an interlayer distance of 3.3 Å for [Ag(L1)](NO3).
For [Ag(L2)]n(NO3)n(H2O) the π…π stacking are visible in the fingerprint plot where (de = di
≈ 1.8 Å) corresponding to an interlayer distance of 3.6 Å. The pattern of red and blue triangles
on the Hirshfeld surface coloured by the shape index value is characteristic of π…π stacking
(Fig.13).
19

Fig.13 : Hirshfeld surfaces mapped with shape index (front and back views) for
[Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O).
The C…H interactions appear as wings in fingerprint plot for both structures [Ag (L1)] (NO3)
and [Ag (L2)]n(NO3)n(H2O). These contacts occupy 12% and 9.2% of the total Hirshfeld
surface area, respectively.
-
The counter-ion NO3 contribute in the cohesion of the crystal packing. Its oxygen atoms are
involved in C-H…O and O-H…O hydrogen bonds in both structures, (Fig.14). The Hirshfeld
surface around the counter-ion in [Ag(L2)]n(NO3)n(H2O) shows the interactions between
oxygen and Ag(I) cations which represent 15.7% of the total surface (Fig. 15(c-d)).
-
Fig.14: Hirshfeld surfaces mapped with dnorm for NO3 in the [Ag (L1)] (NO3)
(a,b) and [Ag (L2)]n(NO3)n(H2O) (c,d) crystal structures. The surfaces are shown
in two different orientations
In order to acquire a better understanding of the silver contribution in the crystal lattice
cohesion, the atomic Hirshfeld surface analysis has been undertaken. The Hirshfeld surface
20

around Ag(I) mapped over curvedness (Fig.15), is introduced to understand the coordination
and the chemical interactions in the two complexes [Ag(L1)](NO3) and [Ag
(L2)]n(NO3)n(H2O).
Fig.15 : Curvedness plotted on the atomic Hirshfeld surface is mapped from -1,4 (flat; red) to
-0,3 (sphere-like, blue).(a): [Ag (L1)] (NO3) and (b): [Ag (L2)]n(NO3)n(H2O)
The Hirshfeld surface was divided into a set of patches, where each patch represents a
different interaction[8]. The shape of the surface indicates the regions of interactions, which
varies from high curvature (blue) to low curvature (red), (Fig.15). Curvedness plotted on the
Hirshfeld surface reflects closer contacts between adjacent atoms [62] and allows also to
estimate the coordination number of the metal [65-66]. The flat regions on the Hirshfeld
surface around Ag(I) ion in both structures [Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O),
reveal the number and the nature of the interatomic interaction. The large flat regions are
related to the strong interaction [60]. These regions on the surface around Ag(I) cation in the
[Ag(L1)](NO3) dimer is related to the covalent bonds Ag-N, Where the metal is
tricoordinated by three nitrogens of triazole rings. The remaining small flat regions on the
surface refer to the medium and weak interactions Ag…π and Ag…O, respectively. In the
[Ag(L2)]n(NO3)n(H2O) polymer structure, the Hirshfeld surface around the Ag(I) cation
shows two large flat regions related to the covalent bonds Ag-N, which refer to coordination
number 2 (linear structure). Besides, the small flat regions denote medium and weak
interactions Ag…O and Ag…π, respectively. The atomic Hirshfeld volumes have been
calculated for the Ag(I) cation in both structure to be 27.03 Å3 for the dimer and 22.95Å3 for
the polymer. Due to the coordination number of the silver in the two structures, the Hirshfeld
volume of the Ag(I) cation in the dimer is a bit larger than that one of the same atom in the
polymer structure.
21

Antibacterial studies:
Antibacterial activity of the free ligands (L1), (L2) and of their silver complexes
[Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O) has been evaluated using the well-diffusion
method [67] at 20 mg.ml-1 concentration in DMSO against four Gram-negative (E. coli,
Salmonella typhimurium, Klebsiella pneumoniae and serratia marcescens) and two Gram-
positive (Staphylococcus aureus, streptococcus) bacteria strains. The standard antibiotics,
Colistin, Fosfomycin, Gentamycin, Erythromycin, Rifampicin, Amikacin, Ofloxacin and
Amoxicillin have been used as positive controls against some of the tested bacteria. Solvent
control test was also carried out to study the DMSO effect on the bacteria growth. Similarly,
in an attempt to dissociate the inhibitory and antimicrobial effects of ionic silver from the one
of the silver complexes described in this study, AgNO3 salt was also used as second control
test. The antibacterial activity results of these compounds are listed table S4 in supplementary
materials, and represented in Fig.16, as averages of four measurements.
It was observed that the DMSO alone did not inhibit the growth of these bacteria while, as
expected, the silver nitrate exhibits significant antibacterial activity. Indeed, even if the
precise antimicrobial mechanism of ionic silver is not totally elucidated, several plausible
mechanisms have been described in the literature. It is thought that silver ions can kill bacteria
by entering the cell through interactions with enzymes present on cell surface, and once inside
the cell can bind sulphur-containing groups such as thiol in proteins, leading to the
deactivation or the denaturation of enzymes essential for the cell metabolism [68]. Moreover,
TEM imaging of bacteria exposed to silver nitrate showed phenomenon of DNA
condensation, leading to the loss of its replication ability, along with deep structural damage
of cell membranes [34]. Also, the antibacterial activity of silver may be due to its binding to
the surface of the cell membrane disrupting the permeability and the respiration [69, 70].
In our experiments, the antibacterial activity of silver nitrate was especially strong against
staphylococcus aureus, with a diameter of inhibition zone of 22.0(6.7) mm, significantly
larger than the one of Rifampicin (d = 13 mm), a drug used generally as an adjunctive in the
treatment of staphylococcus aureus infections [71].
Experiments performed using the free ligands indicated that they do not display any
measurable antibacterial activity, excepted against Serratia Marcescens for which inhibition
zones of 13.8(1.7) mm and 9.5(1.7) mm diameters were observed for (L1) and (L2) ligands,
respectively. These clearance zones diameters compare, for (L1), with the one of silver nitrate
(d = 15.0(1.1) mm), but is significantly smaller in the case of (L2). Nevertheless, this is
22

especially remarkable that the standard antibiotic Gentamycin did not lead to any measurable
inhibition zone in the case of the Serratia strain tested in this study. Even if the precise
mechanism of action of these ligands on Serratia Marcescens is unknown, the fact that they
are active against a Gram-negative bacteria indicate that the lipophilicity of (L1) and (L2)
molecules allows them to cross, or at least to interfere with their outer phospholipidic
membrane. The outer membrane permeability barrier has indeed a big impact on the
susceptibility of the microorganism to antibiotics [72-73].
Antimicrobial activity measurements were also performed to test the metal complexes
described in this study. In the case of Gram-positive bacteria, Fig. 16 shows that the
complexes [Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O) display clearance zones of
respectively 19(1) mm /17.3(1.3) mm diameters for Staphylococcus aureus and 16.0(2.5) mm
/15.0(1.1) mm for Steptococcus. These antimicrobial activities are however comparable to the
ones obtained, under the same experimental conditions, with silver nitrate alone (d = 22(7)
mm for Staphylococcus and 15.3(1.3) mm for Steptococcus). Hence, given that the parent
ligands alone did not display any measurable activity for these bacteria strains, these results
indicate that the antimicrobial effect of the [Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O)
complexes cannot reliably be distinguished from the one of ionic silver.
Experiments performed to test the silver complexes against Gram-negative bacteria led to
variable outcomes. At first, it appears for Salmonella typhimurim that the clearance zones
obtained for both complexes, accounting for standard errors, compare with the one of the
silver nitrate alone (d = 16.3(1.3) mm, 15.3(1.3) mm and 16.5(8) mm for [Ag(L1)](NO3),
[Ag(L2)]n(NO3)n(H2O) and AgNO3, respectively, (Fig. 16), leading to inconclusive results
concerning a possible antimicrobial activity of the silver complexes in this case. For Serratia
Marcescens, both (L1) and (L2) ligands displayed moderate antimicrobial activities,
comparable or lower than the one of silver nitrate. When these ligands are being tested in their
silver complex form, diameters of inhibition zones, again, are comparable to the ones
obtained with silver nitrate (Fig. 16). Besides, the most significant results were obtained for
antimicrobial activities of the complexes against E. Coli and Klebsiella Pneumoniae. Indeed,
for the first bacterium, E. Coli, both Ag(I) complexes exhibit more efficient antibacterial
activity than AgNO3 (d = 11.0(1.1) mm), and the polymer [Ag(L2)]n(NO3)n(H2O) (d =
17.8(1.7) mm) has a better activity than the dimer [Ag(L1)](NO3) (d = 14(0) mm). For the
second bacterium, Klebsiella pneumoniae, only the polymer based on (L2) ligand exhibits a
significantly better activity (d = 26.0(2.5) mm) than AgNO3 (d = 14.5(1.8) mm). This result is
especially remarkable as the isolated ligand (L2) seemed inactive against Klebsiella
23

Pneumoniae, and the antibacterial activity of the corresponding complex compare with the
one obtained for the standard antibiotic Gentamycin tested in the experiments (d = 29 mm).
Even if the elucidation of a precise molecular mechanism of the bactericidal effect of
[Ag(L2)]n(NO3)n(H2O) against Klebsiella pneumoniae is beyond the scope of this study,
plausible explanations can nevertheless be proposed. At first, the lipophilicity of the ligand
(L2), which has been shown able to be moderately active against the Gram-negative bacteria
Serratia Marcescens, can be enhanced upon complexation with Ag(I) [74], allowing the
[Ag(L2)]n(NO3)n(H2O) complex to cross the phospholipidic membrane of Klebsiella
pneumoniae. Once inside the cell, assuming a favourable kinetic of de-ligation reaction, and
given that the ligand (L2) possesses a triazole group known to be a strong nitrogen donor
toward transition metals, the chelation theory may explain the measured activity. Indeed,
chelating agents are able to disturb the metal metabolism of microorganisms by interfering
with metal acquisition needed for crucial reactions, or by inhibiting the biological role of
metal-dependent proteins [75]. In this scenario, the observed activity of
[Ag(L2)]n(NO3)n(H2O) is thus interpreted as a synergetic effect of the chelating properties of
the ligand (L2) and the known antimicrobial activity of ionic silver, in conjunction with an
enhanced lipophilicity of the ligand upon formation of the silver complex. This may explain
why the isolated (L2) ligand does not seem to be active and why the silver complex based on
(L2) appears significantly more active than the silver nitrate control.

Fig.16: Antimicrobial activity of the four title compounds. Error bars correspond to 95%
confidence intervals using a student t-distribution based on quadruplicate measurements.
Conclusion:
Two hydroxy Schiff bases have been synthesized by condensation of 4-amino-4H-1,2,4-
triazole with 3-hydroxybenzaldehyde for the first ligand (L1) and 2,4-dihydroxybenzaldehyde
for the second one (L2). The preliminary IR spectroscopy study of these two ligands has
highlighted the formation of imine bond –C=N characteristic of Schiff base compounds (band
around 1600 cm-1). The two compounds differ by the presence of an additional –OH in the
second Schiff base (L2). This difference influences directly the hydrogen bond network
involving the two ligands. Infinite chains formed by O-H…N hydrogen bonds in (L1) are
indeed transformed into 2D layers in (L2). Three dimensional supramolecular assemblies of
(L1) and (L2) in their respective crystal structures is then ensured by C-H…N hydrogen
bonds, and π…π stacking interactions.
The reaction of these two Schiff bases with AgNO3 leads to the formation of Ag(I) dimer
[Ag(L1)](NO3) with (L1) and polymer [Ag(L2)]n(NO3)n(H2O) with (L2) which includes a
water solvent molecule. Ag adopts a trigonal geometry in the dimer and a square pyramidal
one in the polymer. This polymer expands on 1D direction and the O-H…O hydroxyl-water
hydrogen bonds connect the polymeric chains in 2D sheets parallel to (bc) plane. C-H…N, C-
H…O and π…π stacking reinforce the crystal structure of the two compounds and ensure the
three dimensionality of their networks. Analyse based on Hirshfeld surfaces confirm the
presence of these interactions and reveals that N…H and O…H interactions evolve inversely
in the way (L1), (L2), Ag(L1)](NO3) and [Ag(L2)]n(NO3)n(H2O). The percentage of O…H
interaction increases in this way while the one of N…H contacts decreases, and it is probably
due to the presence of additional –OH in the second ligand (L2), and of a water molecule in
the polymer [Ag(L2)]n(NO3)n(H2O). Antimicrobial activity of the four compounds confirms
also the importance of Ag(I) in bacteria inhibition, indeed, while the free ligands are only
active for one bacterium (Serratia Marcescens), the silver (I) dimer and polymer inhibit the
growth of all bacteria strains tested in this study. However, activities of the complexes are
generally comparable to the ones of the silver nitrate tested alone, except in the case of the
polymer [Ag(L2)]n(NO3)n(H2O) which has been shown to be significantly more active than
ionic silver against Klebsiella pneumoniae.
Acknowledgments:
25

-
-
Institut Jean Barriol X-ray diffraction facility. Dr. E. Wenger.
Pr. Foudil Khelifa, Director of "Laboratoire d’hygiène de la Wilaya de Constantine.
Algérie" for antimicrobial facility.
-
Biologists: Zine Faiza, Haifi Maya and Belhaffaf Mouni for their help.
References:
[1] Schiff, H. Ann. Chem. 1864, 131, 118-119.
[2] Barton, D. & Ollis, W. D. 1979, Comprehensive Organic Chemistry, vol 2. Oxford:
Pergamon.
[3] Ingold, C. K. 1969, Structure and Mechanism in Organic Chemistry, 2nd
ed. Ithaca: Cornell University Press.ꢀ
[4] Layer, R. W. Chem. Rev. 1963, 63, 489–510.ꢀ
[5] Anouar, E.H.; Raweh, S.; Bayach, I.; Taha, M.; Baharudin, M.S.; Meo, F.D.; Hasan,
M.H.; Adam, A.; Ismail, N.H.; Weber, J.F. J. Comput. Aided Mol. Des. 2013, 27, 951–964. ꢀ
[6] Taha, M.; Ismail, N.H.; Jamil, W.; Yousuf, S.; Jaafar, F.M.; Ali, M.I.; Kashif, S.M.;
Hussain, E. Molecules, 2013, 18, 10912–10929. ꢀ
[7] Khan, K.M.; Shah, Z.; Ahmad, V.U.; Khan, M.; Taha, M.; Ali, S.; Perveen, S.;
Choudhary, M.I.; Voelter, W. Med. Chem. 2012, 8, 452–461. ꢀ
[8] Khan, K.M.; Taha, M.; Naz, F.; Ali, S.; Perveen, S.; Choudhary, M.I. Med. Chem. 2012,
8, 705–710.
[9] Aziz, A.N.; Taha, M.; Ismail, N.H.; Anouar, E.H.; Yousuf, S.; Jamil, W.; Awang, K.;
Ahmat, N.; Khan, K.M. and Kashif, S.M. Molecules, 2014, 19, 8414-8433.
[10] Jain, J.S.; Srivastava, R.S.; Aggarwal, N.; Sinha, R. Med. Chem. 2007, 7, 200–204. ꢀ
[11] Chinnasamy, R.P.; Sundararagan, R.; Govindaraj, S. Soc. Pharm. Edu. Res. 2010, 1,
342–347. ꢀ
[12] Pandey, A.; Dewangan, D.; Verma, S.; Mishra, A.; Dubey, R.D. Int. J. Chem. Tech. Res.
2011, 3, 178–184. ꢀ
[13] Mishra, P.; Gupta, P.N.; Shakya, A.K.; Shukla, R.; Srimal, R.C. Indian J. Physiol.
Pharmacol. 1995, 39, 169–172. ꢀ
[14] Hasegawa, S.; Horike, S.; Matsuda, R.; Furukawa, S.; Mochizuki, K.; Kinoshita, Y.;
Kitagawa, S. J. Am. Chem. Soc. 2007, 129, 2607− 2614.
26

[15] Kajiwara, T.; Fujii, M.; Tsujimoto, M.; Kobayashi, K.; Higuchi, M.; Tanaka, K.;
Kitagawa, S. Angew. Chem., Int. Ed. 2016, 55, 2697− 2700.
[16] Flynn, D. C.; Ramakrishna, G.; Yang, H.; Northrop, B. H.; Stang, P. J.; Goodson, T., III
J. Am. Chem. Soc. 2010, 132, 1348−1358.
−1162.
[17] Cui, Y.; Yue, Y.; Qian, G.; Chen, B. Chem. Rev. 2012, 112, 1126
ꢀ
[18] Xie, Z.; Ma, L.; de Krafft, K. E.; Jin, A.; Lin, W. J. Am. Chem. Soc. 2010, 132,
−923.
922
[19] Zhang, Q.; Li, B.; Chen, L. Inorg. Chem. 2013, 52, 9356−9362.
−1195.
ꢀ
[20] Zhang, W.; Xiong, R. Chem. Rev. 2012, 112, 1163
[21] Gygi, D.; Bloch, E. D.; Mason, J. A.; Hudson, M. R.; Gonzalez, M. I.; Siegelman, R. L.;
Darwish, T. A.; Queen, W. L.; Brown, C. M.; Long, R. Chem. Mater. 2016, 28, 1128−1138.
[22] Gańdara,F.;Furukawa,H.;Lee,S.;Yaghi,O.M.J.Am.Chem. Soc. 2014, 136, 5271−5274.
[23] Ma, S.; Zhou, H. Chem. Commun. 2010, 46, 44−53.
−5430.
[24] Barea, E.; Montoro, C.; Navarro, J. A. R. Chem. Soc. Rev. 2014, 43, 5419
[25] Bloch, D. E.; Queen, W. L.; Krishna, R.; Zadrozny, J. M.; Brown, C. M.; Long, J. R.
−1611.
Science 2012, 335, 1606
[26] Ünaleroğlu and C.; Hökelek, T. Spectrosc. Lett. 2002, 35, 317 ꢀ
[27] Thangadurai, T. D.; Gawri, M.; Natarajan, K. Synth. React. Inorg. Met.-Org. Chem.
2002, 32, 329.
[28] Salib, K. A. R.; Stefan, S. L.; Abu El-Wafa, S. M.; El-Shafiy, H. F. Synth. React. Inorg.
Met.-Org. Chem. 2001, 31, 895.ꢀ
[29] Fan, Y.H.; Bi, C.F.; Li, J.Y. Synth. React. Inorg. Met.-Org. Chem. 2003, 33, 137.
[30] Serron, S.A.; Haar, C.M.; Nolan, S.P.; Brammer, L. J. Organomet. Chem. 1997, 16,
5120.
[31] Ferreira, V.F.; da Rocha, D.; da Silva, F.; Ferreira, P.G.; Boechat, N.A.; Magalhães, J.L.
Expert Opinion on Therapeutic Patents, 2013, 23, 319-331. ꢀ
[32] Kharb, R.; Sharma, P.C.; Yar, M.S. J. Enzyme Inhib. Med. Chem., 2011, 26, 1-21.
[33] Percival, S.L.; Bowler, P.G.; Russell, D. J Hosp Infect, 2005, 60, 1-7.
[34] Feng, Q.L.; Wu, J.; Chen, G.Q.; Cui, F.Z.; Kim, T.N.; Kim, J.O. Journal of Biomedical
Materials Research Part A, 2000, 52(4), 662-668.ꢀ
[35] Rai, M.; Yadav, A.; Gade, A., Biotechnology advances, 2009, 27, 76-83.
[36] Medici, S.; Peana, M.; Crisponi, G.; Nurchi, V.M.; Lachowicz, J.I.; Remelli, R.;
Zoroddu, M.A. Coordination Chemistry Reviews, 2016, 349-359.
27

[37] Wilkinson, G. Comprehensive Coordination Chemistry; Pergamon Press: New York,
1987.
[38] Wang, Y.; Yi, L.; Yang, X.; Ding, B.; Cheng, P.; Liao, D.-Z.; Yan, S.-P. Inorg. Chem.
2006, 45, 5822.
[39] Oxford Diffraction 2008. CrysAlis CCD and CrysAlis RED. Versions 1.171.32.21.
Oxford Diffraction, Wroclaw, Poland.
[40] Sheldrick, G. M. Acta Cryst. 2015, C71, 3-8.
[41] Jelsch, C.; Ejsmont, K.; Huder, L. IUCr. 2014, 1, 119-128.
[42] Spackman, M. A. and Jayatilaka D. CrystEngComm, 2009, 11, 19.
[43] Spackman, M.A. and McKinnon, J.J. CrystEngComm. 2002, 4, 378–392
[44] Wolff, S. K.; Grimwood, D. J.; McKinnon, J. J.; Turner, M. J.; Jayatilaka, D. &
Spackman, M. A. Crystal Explorer, 2012, the University of Western Australia.
[45] Agarwal, R.K.; Prakash, B.; Kumar, V. and Khan, A.A. Journal of the Iranian Chemical
Society, 2007, 4, 114-125.
[46] Mapari, A.K. and Mangaonka, K.V. International Journal of ChemTech Research, 2011,
3, 477-482.
[47] Abu-Khadra, A.S.; Farag, R.S.; Mokhtar Abdel-Hady, A.E.D. American Journal of
Analytical Chemistry, 2016, 7, 233-245.
[48] (a) Matulkova, I. ; Nemec, I.; Teubner, K.; Nemec, P.; Micka, Z. Journal of molecular
structure, 2008, 873, 46-60. (b) Hanif, M.; Chohan, Z. H. Spectrochimica Acta Part A:
Molecular and Biomolecular Spectroscopy, 2013, 104, 468-476.
[49] Safin, D.A.; Robeyns, K. and Garcia,Y. CrystEngComm. 2016, 18, 7284-7296.
[50] F.H. Allen, O. Kennard, D.G. Watson, L. Brammer, A.G. Orpen, R. Taylor, J. Chem.
Soc. Perkin Trans. 1987, 2, 1-19.ꢀ
[51] Kwiecien, A., Barys, M. and Ciunik, Z. molecules, 2014, 19, 11160-11177.
[52] Wajda-Hermanowicz, K.; Pieniazczak, D.; Zatajska, A.; Wrobel, R.; Drabent, K. and
Ciunik, Z. molecules, 2015, 20, 17109- 17131.
[53] Etter, M. C. Acc. Chem. Res. 1990, 23, 120–126.
[54] Bernstein, J.; Davis, R. E.; Shimoni, L. and Chang, N. L. Angew. Chem. Int. Ed. Engl.
1995, 34, 1555–1573.
[55] (a) Labisbal, E.; Rodriguez, L.; Vizoso, A.; Alonso, M.; Romero, J.; Garcia-Vazquez,
J.A.; Sousa-Pedrares, A. and Sousa, A. Z. Anorg. Allg. Chem. 2005, 631, 2107-2114
28

(b) Cinarli, A.; Gurbuz, D.; Tavman, A.; Birteksoz, A.S. Chin. J. Chem. 2012, 30, 449-459
(c) Zhang, Y.; Chen, S.; Fan, G.; Zhao, Z.; Gao, S. Chin. J. Chem., 2009, 27, 1697-1702
(d) Yu, H.-X.; Ma, J.-F.; Xu, G.-H.; Li, S.-L.; Yang, J.; Liu, Y.-Y. and Chen, Y.-X. Journal of
Organometallic Chemistry, 2006, 691, 3531–3539
[56] (a) Kennedy, A.R.; Brown, K.G.; Graham, D.; Kirkhouse, J.B.; Kittner, M.; Major, C.;
McHugh, C.J.; Murdoc, P. and Smith, W.E. New J. Chem. 2005, 29, 826; (b) Catalano, V.J.;
Malwitz, M.A.; Etogo, A.O. Inorg. Chem. 2004, 43, 5714; (c) Zheng, Y.; Li, J.R.; Du, M.;
Zou, R.Q.; Bu, X.H. Cryst. Growth Des. 2005, 5, 215.
[57] Sang, R.L. and Xu, L. Eur. J. Inorg. Chem. 2006, 1260.
[58] Wilkinson, G. Comprehensive Coordination Chemistry; Pergamon Press: New York,
1987. (b) Wang, Y.; Yi, L.; Yang, X.; Ding, B.; Cheng, P.; Liao, D.-Z.; Yan, S.-P. Inorg.
Chem. 2006, 45, 5822-5829.
[59] Wang, Y.; Ding, B.; Cheng, P, Liao, D.-Z.; and Yan, S.-P. Inorg. Chem. 2007, 46, 2002-
2010.
[60] (a) Deng, Z.-P.; Zhu, L.-N.; Gao, S.; Huo, L.-H. and Weng Ng, S. Crystal Growth &
Design. 2008, Vol. 8, No. 9, 3277-3284 ; (b) Medishetty, R.; Sahoo, S.C.; Mulijanto, C.E.;
−1829.
Naumov, P. and Jagadese J. Vittal Chem. Mater. 2015, 27, 1821
[61] Nbili, W.; Kaabi, K.; Ferenc, W.; Cristovao, B.; Lefebvre, F.; Jelsch, C.; Ben Nasr, C. J.
mol.struct. 2017, 1130, 114-121.
[62] Gavezzotti, A.; Filippini, G. J. Phys. Chem. 1994, 98, 4831-4837.
[63] Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington, P. R.; McCabe, P.; Pidcock, E.;
Rodriguez-Monge, L.; Taylor, R.; van de Streek J.; and Wood, P. A.; J. Appl. Cryst., 2008,
41, 466-470,
[64] Nouri, K.; Jemmali, M.; Walha, S.; Zehani, K.; Ben Salah, A. and Bessais, L. Journal of
Alloys and Compounds, 2016, doi: 10.1016/j.jallcom.2016.02.142.
[65] Skovsen, I.; Christensen, M.; Clausen, H.F.; Overgaard, J.; Stiewe, C.; Desgupta, T.;
Mueller, E.; Spackman, M.A.; Iversen, B.B. Inorg. Chem. 2010, 49, 9343-9348.
[66] Smol'yakov, A.F.; Korlyukov, A.A.; Dolgushin, F.M.; Balagurova, E.V.; Chizhevsky,
I.T.; Vologzhanina, A.V. Eur. J. Inorg. Chem. 2015, 5847-5855.
[67] (a) Heatley, N.G. Biochem. J. 1944, 38, 61-65; (b) CLSI, Performance standards for
antimicrobial disk susceptibility tests, approved standards, 7th ed., CLSI document M02-A11.
Clinical and laboratory standards institute, 950 west valley road, suite 2500, Wayne,
Pennsylvania 19087, USA, 2012.
[68] Li, X.; Gong, Y.; Zhao, H. and Wang, R. Inorg. Chem., 2014, 53 (22), 12127–12134.
29