Bidentate ligands and their Cu(II) complexes: Structural characterization, electrochemical properties and biological evaluation

Article abstract of DOI:10.1016/j.molstruc.2019.127059

In this manuscript, three bidentate ligands 2-[(2-methoxybenzylidene)amino]phenol (HA¹), 2-[(3,4,5-trimethoxybenzylidene) amino]phenol (HA²) and 2-[(2,3,4-trimethoxybenzylidene) amino]phenol (HA³) were synthesized from the

Full text of DOI:10.1016/j.molstruc.2019.127059

Journal of Molecular Structure 1199 (2020) 127059
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Bidentate ligands and their Cu(II) complexes: Structural
characterization, electrochemical properties and biological evaluation
a
a
a
b
€
€
Ferhan Tümer , Seyit Ali Güngor , Muhammet Kose , Feridun Koçer ,
Mehmet Tümer a
,
*
a Chemistry Department, K.Maras Sütcü Imam University, 46100, K.Maras, Turkey
b Bioengineering Sciences, K.Maras Sütcü Imam University, 46100, K.Maras, Turkey
a r t i c l e i n f o
a b s t r a c t
In this manuscript, three bidentate ligands 2-[(2-methoxybenzylidene)amino]phenol (HA1), 2-[(3,4,5-
trimethoxybenzylidene) amino]phenol (HA2) and 2-[(2,3,4-trimethoxybenzylidene) amino]phenol
(HA3) were synthesized from the reaction of the 2-aminophenol and methoxy benzaldehyde derivatives
in MeOH solution. The Cu2þ metal complexes of these ligands were obtained in the 1:1 (M:L) ratio. All
the compounds were characterized by the micro analytical and spectroscopic techniques. The single
crystals of the bidentate ligands (HA2 and HA3) were obtained from the recrystallization from the MeOH
solution and their structural characterizations were conducted by the X-ray diffraction method. Anti-
microbial activity studies of the bidentate ligands and their Cu2þ metal complexes were tested towards
S. aureus, E. coli, B. cereus, B. subtilis, S. typhimurium as bacteria and C. albicans as fungi and the complex
Cu2þ of the ligand HA2 showed the highest activity against to the S. aureus. While the ligands HA2 and
HA3 do not show the activity against the bacteria and fungi, the ligand HA1 has the activity against to the
S. typhimurium, S. aureus and C. albicans. Electrochemical behaviours of all compounds have been
investigated in DMF solution and it was found that the cathodic and anodic values of the [CuA3(Cl)H2O]
complex shifted to the more positive regions owing to the positions of the methoxy groups on the
benzaldehyde ring.
Article history:
Received 25 June 2019
Received in revised form
9 September 2019
Accepted 10 September 2019
Available online 11 September 2019
Keywords:
Schiff base
X-ray
Electrochemistry
Thermal
Bidentate
Biological activity
© 2019 Elsevier B.V. All rights reserved.
1. Introduction
advanced in coordination with metal ions. The transition metal
complexes of the imine ligands are usually shown more biological
Due to their ease of synthesis and high yields, organic com-
pounds called Schiff bases have been widely used as ligands [1,2].
When Schiff base ligands (also known as imines) have additional
donor atoms such as O and N, and they can form a chelate ring
forming stable metal complexes. The versatile properties of these
compounds have led them to be used in several research areas
including the medicine [3], pharmaceutical [4], electronics [5],
dyestuffs [6], catalysis [7] and interesting antimicrobial activity [8]
studies. Schiff bases, an important class of organic compounds,
attract a lot of attention since they are used as models for many
biological systems. Biological activity of these compounds is not
only dependent on the molecular structure of the compounds.
Transition metal complexes of imin ligands sare also very specific
because the applications of the organic imine ligands have
activity than the corresponding Schiff bases [9].
In the previous studies, the ligands 2-[(2,3,4-trimethoxybenzy
lidene)amino]phenol and 2-[(3,4,5-trimethoxybenzylidene) ami
no]phenol were synthesized and characterized by the instrumental
methods [10,11]. The cyclometallated complexes were obtained
from the reaction of the aromatic imine ligand and Pd(CH3COO)2 in
the toluene solution. The mononuclear [Pd{2,3,4-(MeO)3C6HC(H)]
N[2-(O)C6H4]}(PPh3)] complex has been obtained from the reaction
of the cyclometallated Pd-complex with P(PH3)3. On the other
hand, the compound (2) was synthesized as a resveratrol derivative
and its biological properties was investigated. In this study, all
synthesized molecules, resveratrol and its analogues, offered a
distinct photoprotection for a single UV-filter substance. E. Tauer
and co-workers have reported the photochemical and thermal
properties of the aromatic imine ligands obtained from o-amino-
phenol and the carbonyl compounds (aldehydes and/or ketones)
[12].
* Corresponding author.
E-mail address: mtumer@ksu.edu.tr (M. Tümer).
https://doi.org/10.1016/j.molstruc.2019.127059
0022-2860/© 2019 Elsevier B.V. All rights reserved.

2
F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
In this study, we obtained three Schiff bases (HA1-HA3) from the
82e85 ꢁC. Elemental analysis; found (calcd.) %; C, 66.94 (66.89); H,
6.11 (5.96); N, 4.94 (4.88). 1H NMR (
, CDCl3), 8.63 (s, 1H, CH]N),
7.93e6.66 (m, 6H, aromatic rings-H), 3.98 (s, 3H, ortho-OCH3), 3.85
(s, 3H, meta-OCH3), 3.94 (s, 3H, para-OCH3). 13CNMR (
, CDCl3)
o-aminophenol and aldehydes (2-methoxy benzaldehyde, 2,3,4-
trimethoxy benzaldehyde and 3,4,5- trimethoxy benzaldehyde)
and characterized by the spectroscopic and analytical techniques.
The Cu2þ metal complexes of the ligands were synthesized. The
single crystals of the ligands HA2 and HA3 were obtained from
MeOH solution by the slow evaporation at room temperature and
their molecular structures have been examined by the X-ray
diffraction method. The electrochemical, thermal and antimicrobial
properties of all compounds have been investigated.
d
d
166.15 (CH]N), 159.72e110.44 (aromatic rings C-atoms), 61.50
(ortho-OCH3-C atom), 59.10 (meta-OCH3-C atom), 57.15 (para-
OCH3-C atom). Mass spectrum (ESI/MS, m/z): Calcd.: 287.31, found:
288 [M]þ; calcd.: 101.10, found: 101 [C7H3N]þ. FTIR (KBr,
n
, cmꢀ1):
3376
1286
350, 290, 239.
n
(OeH), 2936
n
(CeH)aliph, 1620
n
(C]N), 1485
n
(C]C)aromatic
,
n
(CeO)phenolic. UVevis (DMF, lmax, 1.0 ꢂ 10ꢀ3 M): 386, 366,
2. Methods and materials
2.1. General
2.3. Preparation of the Cu2þ complexes of the bidentate ligands
HA1-HA3
All reagents and solvents were of reagent-grade quality and
obtained from commercial suppliers (Aldrich or Merck) and used as
received, unless otherwise noted. Elemental analyses (C, H, N) were
performed using a Costech ECS 4010 (CHN). Infrared spectra were
obtained using KBr disc (4000-400 cmꢀ1) on a PerkinElmer Spec-
trum 100 FT-IR. The electronic spectra in the 200e900 nm range
were obtained on a PerkinElmer Lambda 45 spectrophotometer. 1H
and 13C NMR spectra were recorded on a Bruker 400 MHz instru-
ment and TMS was used as an internal standard TMS. Mass spectra
of the ligands and their Cu2þ metal complexes have recorded on a
LC/MS APCI AGILENT 1100 MSD spectrophotometer. Cyclic vol-
The ligands HA1-HA3 (1 mmol, 0.227 g for HA1; 1 mmol, 0.288 g
for HA2 and HA3) have dissolved in MeOH (20 mL). The CuCl2$2H2O
(1 mmol, 0.171 g) dissolved in the MeOH (20 mL) was added to the
ligand solution and resulting solution was refluxed for 5e6 h. The
reaction solution was cooled to the room temperature and the dark
colored precipitates were filtered off, washed with the cold MeOH
and finally dried in a desiccator.
[CuA1(Cl)(H2O)]: C15H16ClCuNO4. Yield: 75%, color: Dark green,
melting point: >250 ꢁC. Elemental analysis; found (calcd.) %; C,
49.02 (48.99); H, 4.15 (4.11); N, 4.12 (4.08). Mass spectrum (ESI/MS,
m/z): Calcd.: 373.29, found: 373 [M]þ; calcd.: 355.27, found: 356.15
tammograms were recorded on
a Iviumstat Electrochemical
workstation equipped with a low current module (BAS PAe1)
recorder.
[M ꢀ H2O]þ. FTIR (KBr,
n
, cmꢀ1): 3342
(CeH)aliph
(C]C)aromatic, 1243 n(CeO)phenolic, 542
n(OeH)H2O, 2948
n
,
1596
n
(C]N), 1475
n
n
(CueO), 478
n
(CueN). UVevis (DMF, lmax, 1.0 ꢂ 10ꢀ3 M): 505, 440,
2.2. Preparation of the 2-aminophenol based Schiff base ligands
(HA1-HA3)
334, 291, 276.
[CuA2(Cl)(H2O)]: C16H18ClCuNO5. Yield: 73%, color: Dark green,
melting point: >250 ꢁC. Elemental analysis; found (calcd.) %; C,
47.72 (47.65); H, 4.56 (4.50); N, 3.53 (3.47). Mass spectrum (ESI/MS,
m/z): Calcd.: 403.31, found: 404 [M]þ; calcd.: 349.84, found: 350
2-Aminophenol (1 mmol, 0.109 g) was dissolved gently in MeOH
(25 mL) and then the solution of the aromatic carbonyl compounds
(1 mmol, 0.136 g for 2-methoxybenzaldehyde; 1 mmol, 0.196 g for
2,3,4-trimethoxybenzaldehyde or 3,4,5-trimethoxybenzaldehyde)
in MeOH (15 mL) were added to the aminophenol solution with
stirring. The solution was refluxed for 2 h at 65 ꢁC. The reaction
solution was then allowed to cool to the room temperature. The
precipitates were filtered and recrystallized from MeOH and dried
in a desiccator.
[MeH2OeCl]þ. FTIR (KBr,
(CeH)aliph, 1600 (C]N), 1500
519 (CueO), 444
440, 413, 325, 276.
n
,
cmꢀ1): 3321
n
(OeH)H2O
,
2935
n
n
n
(C]C)aromatic, 1232
n
(CeO)phenolic
,
n
n
(CueN). UVevis (DMF, lmax, 1.0 ꢂ 10ꢀ3 M): 507,
[CuA3(Cl)(H2O)]: C16H18ClCuNO5. Yield: 73%, color: Dark green,
melting point: >250 ꢁC. Elemental analysis; found (calcd.) %; C,
47.69 (47.65); H, 4.56 (4.50); N, 3.55 (3.47). Mass spectrum (ESI/MS,
m/z): Calcd.: 373.29, found: 373 [M]þ; calcd.: 319.82, found: 320.44
HA1: C14H13NO2. Yield: 90%, color: Dark red, melting point:
102e105 ꢁC. Elemental analysis; found (calcd.) %; C, 74.05 (73.99);
[MeH2OeCl]þ. FTIR (KBr,
(CeH)aliph, 1598 (C]N), 1482
535 (CueO), 447
441, 415, 379, 276.
n
,
cmꢀ1): 3320
n
(OeH)H2O
,
2942
H, 5.82 (5.77); N, 6.21 (6.16). 1HNMR (
d
, CDCl3) 8.58 (s, 1H, CH]N),
7.72e6.28 (m, 8H, aromatic rings-H), 3.90 (s, 3H, ortho-OCH3).
13CNMR (
, CDCl3) 164.55 (CH]N), 152.20e108.40 (aromatic rings
n
n
n
(C]C)aromatic, 1287
n
(CeO)phenolic,
n
n
(CueN). UVevis (DMF, lmax, 1.0 ꢂ 10ꢀ3 M): 503,
d
C-atoms), 56.45 (ortho-OCH3-C atom). Mass spectrum (ESI/MS, m/
z): Calcd.: 227.25, found: 228 [M]þ; calcd.: 110.13, found: 110
[C6H8NO]þ. FTIR (KBr,
n
, cmꢀ1): 3375
n
(OeH), 2937
n(CeH)aliph,1616
n
(C]N), 1486
n
(C]C)aromatic, 1290
n
(CeO)phenolic. UVevis (DMF,
2.4. X-ray crystallography
lmax, 1.0 ꢂ 10ꢀ3 M): 389, 366, 352, 265, 230.
HA2: C16H17NO4. Yield: 81%, color: Dark red, melting point:
112e115 ꢁC. Elemental analysis; found (calcd.) %; C, 66.93 (66.89);
Bruker D8 QUEST diffractometer using Mo-Ka radiation
(
l
¼ 0.71073 Å) was used to collect X-ray crystallographic data for
H, 5.98 (5.96); N, 4.93 (4.88). 1H NMR (
d
, CDCl3), 8.66 (s, 1H, CH]N),
8.02e6.37 (m, 6H, aromatic rings-H), 3.75 (s, 3H, meta-OCH3), 3.82
(s, 3H, para-OCH3), 3.75 (s, 3H, meta’-OCH3). 13CNMR (
, CDCl3)
bidentate ligands (HA2 and HA3) [13]. The reflection data were
collected at 273 K. The structures of the compounds were solved by
the direct method SHELXS97 and refined against F2 using full-
matrix least-squares refinement using SHELX2014/6 [14,15]. All
atoms except hydrogens were refined using anisotropic atomic
displacement parameters. Hydrogen atoms bonded to carbon and
oxygen atoms were located at calculated positions using a riding
model and refined with temperature factors riding on the carrying
atoms. The crystallographic data for bidentate ligands (HA2 and
HA3) are presented in Table 1. Bond lengths and angles are given in
the supplementary documents (Table S1&S2).
d
167.80 (CH]N), 158.40e109.15 (aromatic rings C-atoms), 57.55
(meta-OCH3-C atom), 58.10 (para-OCH3-C atom), 57.55 (meta’-
OCH3-C atom). Mass spectrum (ESI/MS, m/z): Calcd.: 287.31, found:
288 [M]þ; calcd.: 101.10, found: 101 [C7H3N]þ. FTIR (KBr,
n
, cmꢀ1):
3350
1286
343, 290, 230.
n
(OeH), 2940
n
(CeH)aliph, 1624
n
(C]N), 1485
n
(C]C)aromatic,
n
(CeO)phenolic. UVevis (DMF, lmax, 1.0 ꢂ 10ꢀ3 M): 380, 358,
HA3: C16H17NO4. Yield: 84%, color: Dark red, melting point:

F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
3
Table 1
Crystallographic data for the complexes.
Identification code
HA2
HA3
Empirical formula
Formula weight
Crystal system
Space group
C16H17NO4
287.30
Monoclinic
I2
C16H17NO4
287.30
Tetragonal
P41212
Unit cell
a (Å)
10.7746(6)
25.4384(15)
11.3786(6)
90
104.928(4)
90
96.500(6)
8
1.232
6.7446(2)
6.7446(2)
64.410(3)
90
90
90
2930.0(2)
8
1.303
b (Å)
c (Å)
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
Volume (Å3)
Z
Calculated density (mg/cm3)
Abs. coeff. (mmꢀ1
)
0.089
0.094
Refl. collected
8979
4489
Ind. Refl. [Rint
]
6054 [0.0289]
99.6%
0.0601, 0.0858
0.1272, 0.1147
0.965
2861 [0.0662]
97.9%
0.1290, 0.3009
0.1518, 0.3166
1.095
Comp. to W ¼ 25.242ꢁ
R1, wR2 [I > 2
s
(I)]
R1, wR2 (all data)
Goodness-of-fit on F2
CCDC number
1919490
1919491
2.5. Preparation of microbial culture
positive bacteria), Escherichia coli ATCC-8739, Salmonella typhimu-
rium (as Gram-negative bacteria) and Candida albicans ATCC-90028
(fungi) by agar-well diffusion. In the antimicrobial activity studies,
Müller Hilton Agar (MHA) for bacteria was used as a stock medium
and Malt Extract Agar (MEA) for the yeast strain. The antimicrobial
activity studies were carried out according to a known method [16].
The Schiff base ligands and their Cu2þ metal complexes were
evaluated in vitro antibacterial and antifungal activity against the
Staphylococcus aureus Rosenbach ATCC-6538, Bacillus subtilis
Ehrenberg ATCC-14028 and Bacillus cereus ATCC 7064 (as Gram-
Fig. 1. Synthesis route of the bidentate Schiff base ligands and their Cu(II) transition metal complexes.

4
F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
Fig. 2. The UVevis spectra of the ligands and their Cu2þ metal complexes in the 1.0 ꢂ 10ꢀ3 M DMF solution.
Compounds (20
mL) in DMSO/H2O (1:9) were pipetted into the
3. Results and discussion
hollow agar at concentration 12.5 mg/mL. The petri dishes were left
at 4 ꢁC for 2 h and then the plates were incubated at 37 1 ꢁC for
bacterium and 25 1 ꢁC fungi (18e24 h). At the end of this period,
inhibition zones formed on the medium were determined as mil-
In this study, we prepared three aromatic imine ligands (HA1-
HA3) from the reaction of the o-aminophenol and methoxy benz-
aldehyde derivatives (Fig. 1). The ligands have been characterized
by using the analytical and spectroscopic methods. Since the li-
gands have a polar character, they are readily soluble in polar
organic solvents. In addition, they can be stored at the 25 ꢁC for a
long time without degradation. The Cu2þ complexes of the ligands
were prepared in 1:1 M ratio. In addition, the ligands and their Cu2þ
complexes were found to be non-hygroscopic. This situation was
confirmed by analytical and spectroscopic data. It was also
confirmed by the results of thermal analysis that the ligands do not
have hygroscopic property. Since all ligands have the bidentate
character, when they interact with copper ions in the methanol
solution, they form complexes in the 1: 1 M ratio.
limeters (mm). The disc containing DMSO, Amikacin (AK: 30
and Gentamicin (CN: 10 g) were used for control.
mg)
m
Minimal inhibitory concentrations (MIC) of the ligands and their
Cu(II) complexes were obtained by using the serial dilution tech-
nique [16]. Prior to this study, compounds were dissolved in DMSO/
H2O (1:9) to make a 12.5 mg/mL stock and then diluted to 1.25 and
0.125 mg/mL. The results were expressed in milligrams per milli-
liter. The minimum inhibition concentration (MIC) values for the
ligands (HA1-HA3) and their Cu2þ metal complexes are given in the
supplementary file.

F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
5
Fig. 3. Molecular structures of HA2 and HA3 with atom numbering.
3.1. Spectroscopic characterization of the bidentate ligands and
their Cu2þ complexes
complexes, there is H2O molecule that coordinated to the metal ion.
The azomethine group (CH]N) of the imine ligands were observed
in the 1624-1616 cmꢀ1 range. Since the nitrogen atom of the azo-
methine group has a donor property, during the complexation, as
the nitrogen atom coordinates to the Cu2þ ion, the azomethine
group stretchings shifted to the lower wavenumbers (1600-
1596 cmꢀ1). In the spectra of the complexes, the bands in the
So as to characterize the 2-aminophenol based imine ligands
and their Cu2þ complexes, their FTIR spectral properties were
investigated and obtained spectral properties were given in the
experimental section. The FTIR spectra of the HA3 and its
[CuA3(Cl)(H2O)] complex are given in the supplementary file
(Fig. S1). In the spectra of the ligands, the stretching vibrations in
542e519 and 478-444 cmꢀ1 range can be attributed to the
and (CueN), respectively.
n(CueO)
n
the 3376-3350 cmꢀ1 range refer to the
complexation, this band became a wide band and observed in the
range of 3342e3320 cmꢀ1
Because, in the structure of the
n
(OeH) group. After
The electronic spectral properties of the bidentate ligands and
their Cu2þ complexes were studied DMF (1.0 ꢂ 10ꢀ3 M) and the
spectral results are given in the experimental section. The UVevis
.
Fig. 4. Fingerprint plots of HA2 and HA3. Spikes indexed as (1) and (2) show H$$$$O/O$$$$H and H$$$$H, respectively.

6
F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
retained in the resulting ligands. In the 1H NMR spectra of the li-
gands, the signal for the phenolic hydroxy proton of the ligands
appears to be a weak and broad singlet around 9.5 ppm. The signals
in the 8.66e8.56 ppm range may be arised from the hydrogen atom
of the azomethine group (CH]N). In the structure of the ligands,
there are two aromatic rings. These are phenol and phenyl rings.
The multiplets belonging to the aromatic rings hydrogen atoms are
shown in the 8.02e6.28 ppm range. The hydrogen atoms of the
eOCH3 group of the ligand HA1 are shown at 3.90 ppm as a singlet.
In the ligand HA2, the hydrogen atoms of the methoxy groups were
observed at 3.75 and 3.82 ppm because they had an equivalent
environment. But, the ligand HA3, the hydrogen atoms of the
methoxy groups are in the 3.98e3.85 ppm range.
The 13C NMR spectra for the ligands have also been investigated.
The signals belonging to the carbon atom of the azomethine group
in the ligands were seen in the 167.80e164.55 ppm range. The ar-
omatic ring carbon atoms of the ligands were observed in the range
of 159.72e108.40 ppm. The methoxy group carbon atoms in the
ligands were seen in 61.50e56.45 ppm range.
Fig. 5. Hydrogen bonded tetramer in the structure of HA2. Hydrogen bonds are shown
as dashed lines.
3.2. Molecular structures of HA2 and HA3
spectra of all compounds are presented in Fig. 2. In the UVevis
spectra of the ligands, the absorption bands in the 389-343 nm
range come from the n-p* transitions. The p-p* and p-d* transi-
Molecular structures of the HA2 and HA3 were further charac-
terized by X-ray diffraction studies. The structures of HA2 and HA3
were depicted in Fig. 3. The asymmetric unit of HA2 contains two
crystallographically independent ligand molecules with similar
bond lengths and angles. Molecular structures of the ligands are
broadly similar differing in the position of methoxy groups and
hydrogen bond interactions within the structures. In the structure
of both ligands, the imine bond distances are within the range of
the carbon nitrogen double bond (C]N) distances. The indepen-
dent molecules in the asymmetric unit of HA2 differ from the
dihedral angles between the phenyl and phenol rings. The phenyl
(C1/C6) and phenol rings (C8/C13) are tilted at 21.424(15)ꢁ for HA2
and 21.424(15)ꢁ for HA3. This may be due to the different inter-
molecular interactions within structures.
tions are shown in the 290-230 nm range. As different from the
electronic properties of the ligands, the Cu2þ complexes show the
d-d transitions in the 507-503 nm range. The absorption bands at
440 nm may be assigned to the charge transfer band (M/ L or
L/M). Upon complexation with Cu2þ, the n-
p
* transitions shifted
to the lower wavelength (379-325 nm range). On the other hand,
the * and * transitions in the spectra of the complexes were
p-p
p-d
seen at the 276 and 271 nm, respectively.
The mass spectra of the complexes were obtained and the data
are given in the experimental section. The ESI mass spectra of the
ligands were given in the Supplementary documents (Fig. S2). In
the mass spectra of all compounds, the molecular ion peaks [M]þ
were observed. All compounds suffer from mass loss on a regular
basis and they have similar fragmentation ions.
Although the structures of HA2 and HA3 are similar, packing of
molecules are widely different due to the different hydrogen bond
interactions within each structure. In order to investigate the
intermolecular contacts between neighbouring molecules, Hirsh-
feld surfaces for both ligands were drawn. The 2D fingerprint plots
of ligands HA2 and HA3 are not similar due to different intermo-
lecular contacts between the ligand molecules (Fig. 4). Both com-
pounds show an expected phenol-imine hydrogen bond
(OH$$$$$N) forming a S(5) hydrogen bond motif. In the structure of
HA2, the phenolic group (O1) also involves in intermolecular
The 1He13C NMR spectra of the ligands were recorded in CDCl3
and TMS as internal standard and obtained spectral data were given
in the experimental section. While the 3,4,5-trimethoxy benzal-
dehyde, which is one of the carbonyl compounds used to synthesize
the ligands, has a symmetrical, the hydrogen atoms of the other
carbonyl compounds (2-methoxy and 2,3,4-trimethoxy benzalde-
hyde) are asymmetric nature. That is, these structural features are
Fig. 6. Packing diagram of HA3 showing CH$$$$O contacts.

F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
7
hydrogen bonding with the phenolic oxygen atom (OH$$$$O) of an
adjacent molecule. The HA2 molecules form a tetramer connected
by OeH$$$O hydrogen bonds between phenolic groups producing a
R44(8) motif (Fig. 5). Hydrogen bond parameters for HA2 and HA3 are
given in the supplementary documents (Table S3&S4). In the 2D
fingerprint plot of HA2 (Fig. 4), the hydrogen bond contacts
(OH$$$$O) are seen as two sharp spikes (1). The spiked indexed as
(2) is due to the H/H contacts. Moreover, these hydrogen bond
contacts between the phenolic groups are observed in the dn sur-
face as intense red spots (Fig. S3). HA2 molecules are further linked
by CH$$$$O contacts. In the structure of HA3, there is no intermo-
lecular hydrogen bond contacts between the phenolic group of
adjacent molecules. Molecules are linked by CHphenyl$$$$O in-
teractions as shown in Fig. 6. The relatively close H$$$$O in-
teractions are seen as red spots in the dn surface and two broad
spikes in the 2D finger print plot (Fig. 4). In structure of both
compounds, phenyl-phenyl stacking interactions were not
observed.
the same experimental conditions. All of aldehyde compounds
showed similar redox behavior. In the ꢀ2.0 - (þ) 2.0 V range
cathodic and anodic scaning area, the starting compounds have two
anodic and two cathodic peak potentials. The cathodic and anodic
redox couples have similar values in positive and negative regions.
The cathodic values in the negative region are in the ꢀ0.47-(-0.34)
V range. In addition, positive cathodic values are in the range of
0.53e0.33 V. On the other hand, in the anodic region, while the
negative anodic values are in the ꢀ0.12-(-0.34) V range, the positive
values are in the 0.05e0.26 V range. While the cathodic peak po-
tentials shift to the more positive region due to increased scanning
speed, the anodic peak potentials shifted to the negative regions.
All redox processes of the starting materials are irreversible.
The ligand HA1 has two cathodic and two anodic peak potentials
in the ꢀ0.54-0.15 and ꢀ0.38-0.28 V range, respectively. The redox
processes are irreversible at all scan rates and the electrochemical
values have shifted to the more negative regions than the 2-
methoxy benzaldehyde (starting material). However, the ligands
HA2 and HA3 have three cathodic peaks in the ꢀ0.55-(þ0.84) V
range and there are two anodic peaks in the ꢀ0.42-(þ0.19) V range
and all redox couples are irreversible. In the cyclic voltammetry
sudies of the Cu2þ complexes, in the forward scan (cathodic scan),
cathodic values for the [CuA1(Cl)(H2O)] and [CuA2(Cl)(H2O)] show
one cathodic and two anodic peaks in the 0.75e0.62 and ꢀ0.41-
0.27 V range, respectively. The complex [CuA3(Cl)(H2O)] has three
anodic and two cathodic peaks in the ꢀ0.55-0.84 and ꢀ0.34-0.22 V
range, respectively. In the [CuA3(Cl)(H2O)], the cathodic and anodic
values shifted to the more positive regions owing to the positions of
the methoxy groups on the phenyl ring. The obtained results offer a
strong interaction between Cu(II) and ligands. In the complexes,
redox processes are the metal centred. In the consecutive redox
couple of Cu(II)/Cu(0), the cathodic peak results from the reduction
of Cu(II) to Cu(0) and the anodic peak is for the oxidation of Cu(0) to
3.3. The electrochemical of the ligands and their metal complexes
The redox properties of the organic ligands and their Cu2þ metal
complexes have been identified in the 1.0 ꢂ 10ꢀ3 M DMF solution
and obtained electrochemical data are given in Table 2. The redox
properties of the compounds were studied in the ꢀ2.0 e (þ2.0) V
range and 100e1000 mV/s scan rate. The glassy carbon electrode
was used as the working electrode during the electrochemical
study, on the other hand, Agþ/AgCl was used as the reference
electrode and Pt was used as the counter electrode. The cyclic
voltammograms of the ligands HA1-HA3 have given in Fig. 7. To
understand the redox properties of the ligands and Cu(II) com-
plexes, the electrochemical properties of the starting compounds
(Fig. S4), the methoxy aldehyde derivatives, were examined under
Table 2
Electrochemical data of the ligands HA1-HA3 and their Cu2þ complexes in the 1.0 ꢂ 10ꢀ3 M DMF solution.
Compound
HA1
Scanrate (mV/s)
Epc(V)
Epa(V)
Epa/Epc
E1/2(V)
DEp(V)
100
250
500
750
1000
100
250
500
750
1000
100
250
500
750
1000
100
250
500
750
1000
100
250
500
750
1000
100
250
500
750
1000
0.05
0.28, ꢀ0.07
0.17, ꢀ0.21
0.09, ꢀ0.30
0.04, ꢀ0.35
0.01, ꢀ0.38
0.27, ꢀ0.17
0.23, ꢀ0.23
0.16, ꢀ0.28
0.13, ꢀ0.32
0.10, ꢀ0.33
0.16, ꢀ0.23
0.09, ꢀ0.30
0.10, ꢀ0.35
0.11, ꢀ0.39
0.07, ꢀ0.42
0.27, ꢀ0.19
0.21, ꢀ0.28
0.16, ꢀ0.33
0.12, ꢀ0.36
0.07, ꢀ0.41
0.19, ꢀ0.20
0.14, ꢀ0.25
0.10, ꢀ0.27
0.08, ꢀ0.31
0.04, ꢀ0.33
0.22, ꢀ0.32
0.17, ꢀ0.30
0.14, ꢀ0.31
0.10, ꢀ0.34
0.10, ꢀ0.32
5.60
1.70
0.75
0.68
0.70
0.43
0.35
0.23
0.18
0.13
1.60
0.60
0.52
0.47
0.89
0.42
0.31
0.22
0.12
0.09
0.39
0.51
0.58
0.57
0.71
0.70
0.57
0.69
0.64
0.58
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
0.23
0.07
ꢀ0.45, 0.10
ꢀ0.49, 0.12
ꢀ0.51, 0.14
ꢀ0.54, 0.15,
0.62
0.64
0.68
0.70
0.74
ꢀ0.55, 0.10, 0.75
ꢀ0.50, 0.16, 0.73
ꢀ0.47, 0.19, 0.69
ꢀ0.45, 0.23, 0.62
ꢀ0.47, 0.25, 0.58
0.64
0.67
0.71
0.73
0.75
ꢀ0.51, 0.07, 0.52
ꢀ0.49, 0.09, 0.57
ꢀ0.46, 0.13, 0.61
ꢀ0.45, 0.14, 0.63
ꢀ0.46, 0.16, 0.65
ꢀ0.55, 0.31, 0.81
ꢀ0.53, 0.32, 0.82
ꢀ0.49, 0.33, 0.84
ꢀ0.53, 0.34, 0.75
ꢀ0.55, 0.35, 0.77
ꢀ0.03
ꢀ0.10
ꢀ0.14
ꢀ0.35
0.41
ꢀ0.52
ꢀ0.57
ꢀ0.64
0.06
ꢀ0.07
ꢀ0.09
ꢀ0.03
0.05
ꢀ0.37
ꢀ0.46
ꢀ0.55
ꢀ0.61
ꢀ0.68
0.12
[CuA1(Cl)(H2O)]
HA2
[CuA2(Cl)(H2O)]
HA3
0.05
ꢀ0.03
ꢀ0.06
0.13
ꢀ0.09
ꢀ0.14
0.18
[CuA3(Cl)(H2O)]
0.19
0.23
All the potentials are referenced to Agþ/AgCl; where Epa and Epc are anodic and cathodic potentials, respectively. Ep ¼ EpaꢀEpc. E1/2 ¼ 0.5 x (Epa þ Epc). Concentration: 1.0
D
x 10-3 M DMF.

8
F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
Fig. 7. The cyclic voltammograms of the ligands in the 1.0 ꢂ 10ꢀ3 M DMF solution and 100-1000 mVsꢀ1 scan rates.
Cu(II).
ligands. At the second step, the remaining part of the decomposi-
tion of the ligands is completely degraded to CO2, H2O and NxOy
gases. In the DTA curves of the ligands, the degradation of the li-
gands corresponds to the strong endothermic peaks. In the TGA
curves of the Cu2þ complexes, thermal decomposition process
takes place in four steps. At the first step, the coordinated water
molecules to the Cu2þ ions move away from the complexes in the
110e130 ꢁC temperature range. At the second step, the coordinated
Clꢀ ion to the metal ions is lost at about 218 ꢁC temperature. At the
third and fourth steps, the organic parts of the remaining residues
start the decomposition at about 350 ꢁC and the decomposition
process continues up to the 800 ꢁC temperature. The final product
obtained by degradation of the complexes is metal oxide (CuO).
3.4. The thermal properties of the ligands and their metal
complexes
Thermal properties of the compounds were investigated in the
20e800 ꢁC temperature range. Thermal decomposition curves of
the ligands HA1-HA3 and their [CuAn(Cl)H2O] (n: 1, 2, 3) complexes
in the 20e900 ꢁC temperature range are shown in Fig. 8. Thermal
degradation curves show that the ligands and their metal com-
plexes do not contain adsorbed water molecules. The TGA curves of
the ligands and their metal complexes show the similar decom-
position processes. The ligands are stable up to 210 ꢁC. The ligands
decompose at two steps. The process of degradation of the ligands
begins at about 213 ꢁC. At first step, a large proportion of the masses
of ligands have lost. As can be seen also from the thermal degra-
dation curves, the ligand HA1 is more unstable than the other li-
gands. Thermal stability of the ligand HA2 is higher than the other
3.5. The biological activity properties of the ligands and their metal
complexes
Fungicidal and bactericidal activities of the bidentate Schiff base

F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
9
Fig. 8. Thermal curves of the ligands and their Cu2þ complexes in the 20e800 ꢁC temperature range.
ligands (HA1-HA3) and their Cu2þ complexes against photogenic
bacteria and fungi were given in Table 3. Comparison of the anti-
microbial activity properties of the bidentate ligands and their Cu2þ
transition metal complexes is shown in Fig. S5. In the antimicrobial
activity studies, we used the Staphylococcus aureus, Bacillus subtilis
and Bacillus cereus as the gram positive; Escherichia coli and Sal-
monella typhimurium as the gram negative and Candida albicans as
the fungi. Gentamicin and amikacin antibiotics were used as posi-
tive control groups. The sensitivity of a microorganism to antibi-
otics and other antimicrobial agents was determined by the assay
plates which were incubated at 25 ꢁC for three days for yeasts and
at 37 ꢁC for 18e24 h for bacteria. Some of the tested compounds
showed a remarkable biological activity against different types of
Gram-positive and Gram-negative bacteria. The ligands containing
the nitrogen (N) and oxygen (O) donor atoms have the power to
inhibit enzyme production. Because enzymes need free hydroxy
groups for their activity seem to the particularly susceptible to
deactivation by the metal ions existed in the complexes. The di-
versity in the impressiveness of various biocidal drugs against
different organisms [17] has attached to the impermeability of the
cell. The organic compounds behave as a lipophilic group [18] to
take out the compound through the semipermeable membrane of
the cell. The synthesized ligands have the ability to form chelates
between the azomethine nitrogen atom and the phenolic hydroxyl
groups. In the ligands, there are
p-electron delocalization
throughtout the molecules. The donor groups (such as methoxy
groups) on the benzene rings give the electron to the rings.
Therefore, the chelate forming in the molecule diminishes the po-
larity of the central ion. This chelation enhances the lipophilic
structure of the central atom that allows the membrane to pass
through the lipid layer.
It has been determined that the complexes have different anti-
microbial activity on microorganism strains. While the gram-
positive, gram-negative and yeast strains generally had
a

10
F. Tümer et al. / Journal of Molecular Structure 1199 (2020) 127059
Table 3
typhimurium as bacteria and C. albicans as fungi and the complex
Cu2þ of the ligand HA2 showed the highest activity against to the
S. aureus. While the ligands HA2 and HA3 do not show the activity
versus to the bacteria and fungi, the ligand HA1 has the activity
against to the S. typhimurium, S. aureus and C. albicans.
Antimicrobial activity values of the bacteria and fungi (mm).
Gram (-) bacteria
Gram (þ) bacteria
E. coli S. typhimurium S. aureus B.cereus C. albicans
Fungi
Compounds
HA1*
e
8
12
e
12
14
e
e
8
[CuA1(Cl)(H2O)] 12
12
e
e
e
8
HA2
[CuA2(Cl)(H2O)] 10
HA3
[CuA3(Cl)(H2O)] 12
e
Appendix A. Supplementary data
18
e
20
e
16
e
e
e
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molstruc.2019.127059.
16
18
18
e
18
18
18
e
18
22
16
e
8
Amikacin
Gentamicin
DMSO
16
12
e
e
e
e
References
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the hollow agar at concentration 12.5 mg/mL.
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