Ball milling approach to prepare new Cd(II) and Zn(II) complexes; characterization, crystal packing, cyclic voltammetry and MOE-docking agrees with biological assay

Article abstract of DOI:10.1016/j.molstruc.2020.128473

A simple green strategy was efficiently used for quantitative solvent-free synthesis of Cd (II) and Zn (II) complexes by using ball milling technique. The produced complexes were illustrated by using various spectroscopic (¹H &¹³C NM

Full text of DOI:10.1016/j.molstruc.2020.128473

Journal of Molecular Structure 1218 (2020) 128473
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Ball milling approach to prepare new Cd(II) and Zn(II) complexes;
characterization, crystal packing, cyclic voltammetry and
MOE-docking agrees with biological assay
Seraj Alzahrani a, Moataz Morad b, Abrar Bayazeed b, Meshari M. Aljohani c,
Fatmah Alkhatib b, Reem Shah b, Hanadi Katouah b, Hana M. Abumelha d,
, e, *
Isamil Althagafi b, Rania Zaky e, Nashwa M. El-Metwaly b
a Department of Chemistry, College of Science, Taibah University, Saudi Arabia
b Department of Chemistry, Faculty of applied Science, Umm-Al-Qura University, Makkah, Saudi Arabia
c Depertment of Chemistry, Faculty of Science, Tabuk University, Tabuk-71491, Saudi Arabia
d Department of Chemistry, Faculty of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
e Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple green strategy was efficiently used for quantitative solvent-free synthesis of Cd (II) and Zn (II)
complexes by using ball milling technique. The produced complexes were illustrated by using various
spectroscopic (1H &13C NMR, IR, EDX, TEM, SEM) and analytical techniques. The octahedral geometry was
proposed for such diamagnetic complexes having 1:2 (M:L) molar ratio through mono-negative tri-
dentate binding mode. Conformational study was carried out by applying DFT, to predict the optimized
configuration for the tested compounds. Surface properties were studied by using Crystal explorer 3.1
software as well as VESTA package. The molecular packing was appeared strong and closely contact
within the ligand and Zn(II) complex crystals. The 2D-fingerprint plots displayed the favourable
contribution of carbon and oxygen atoms in packing systems. Moreover, the in-vitro antimicrobial assay
via MIC technique revealed the moderate or ineffective behaviour predominantly. Such was confirmed
through docking simulation approach. The antioxidant assay displayed a promising behaviour in scav-
enging free radicals that appeared obviously with the two complexes. Also, antitumor assay towards
HCT-116 cell line reveals the effectiveness of the two complexes. Finally, the kinetic parameters for Zn (II)
were evaluated by applying cyclic voltammetry technique in the absence/presence of ligand using a
glassy carbon electrode.
Received 18 April 2020
Received in revised form
9 May 2020
Accepted 15 May 2020
Available online 23 May 2020
Keywords:
Ball milling
Crystal properties
DFT
MOE-Docking
Bioactivity
Cyclic voltammetry
© 2020 Elsevier B.V. All rights reserved.
1. Introduction
crossing point between building structure of biological systems and
chemistry, supplies us with the majority of creative resources for
Anchored on the interface between molecular bioinorganic
chemistry as well as biological systems, building structure of co-
ordination complexes have extensive interest. These complexes
may treat cellular growth and biological properties of many types
of microorganisms and tumours. It was known that, developing of
targeted drugs stimulated from their cytotoxicity, which work on
definite cellular targets [1e3]. But, major aim remains, and the
improving unique bioactive agents [4e7]. Accordingly, transition
metal ion complexes in nano-particle scale have high biological
efficiency, especially that prepared by efficient and
environmentally-friend way. Such way in which the reactors grind
by using ball milling technique (Scheme 1S) as a green approach
[8,9]. This approach is known by, low coast, solvent-less, highly
yielded product, non-hazardous, clean and environmental friend-
liness. While, the current advance in nanotechnology led to
improve new metallic nano-particles that eventually increase the
environmental hazards. So, the main aim in this study is to syn-
thesize new metallic complexes under minimum hazard condi-
tions. A green approach for synthesis will be implemented to
* Corresponding author. Department of Chemistry, Faculty of applied Science,
Umm-Al-Qura University, Makkah, Saudi Arabia.
E-mail address: n_elmetwaly00@yahoo.com (N.M. El-Metwaly).
https://doi.org/10.1016/j.molstruc.2020.128473
0022-2860/© 2020 Elsevier B.V. All rights reserved.

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S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
Scheme 1. The outline of the synthesis of H2BHNH and its Cd(II) and Zn(II) complexes.
prepare zinc (II) and cadmium (II) complexes from new Schiff base
derivative. Characterizing new compounds will be done firstly by
using possible analytical, spectral and conformational techniques.
Moreover, other computerized special studies will be considered to
depth the research. Finally, the biological screening will be done to
assess antioxidant, antimicrobial and antitumor efficiency for the
new compounds in comparing to reference drugs.
2.4. Modelling simulation protocol
Docking process was executed by applying a progressive simu-
lation module called Molecular Operating Environment (Vs. 2015).
Two functional proteins chosen for this study were the PDB co-
crystal that belong to aspergillus flavus (6dtc) and bacillus sub-
tilis (3vzx). Before starting computational process, several steps
must be done over the tested compound (guest) as well as the
handled protein (host). The guest compound faced optimization to
minimize energy content, followed by render atomic charges and
potential energy [13]. In addition to, other important parameters
must be regulated by MMFF94x force field. Consequently, the
hosted-compound is ready for the process after building new data
base as MDB format. On the other hand, the host-protein also faced
orientation stages by adding H-atoms on receptors, connecting
receptors and followed by fixing potential energy [14]. Then site-
finder was proceeded to adapt the receptor sites followed by
dummies regulation. Each docking process are running over 30
poses and consumed variable times. Some poses are unsuitable,
which clash by unfavourable way with protein receptors. So, the
true poses were already adjusted by London dG-scoring function
that truly advanced twice times by triangle-matcher. Real docking
paths, which have bond lengths of ꢀ3.5 Å, were interested to rank
inhibition effectiveness based on exported interaction data.
2. Material and methods
2.1. Apparatus
As shown in Scheme 1S, the devices used for analysis and
characterization were photographically presented. Also, the
analytical restrictions were mostly written in the scheme, or in
discussion part.
2.2. Synthesis procedure
Benzaldehyde and 3-hydroxy-2-naphthohydrazide were used to
synthesize Schiff base ligand (H2BHNH) by a simple condensation
reaction (Scheme 1). Sequentially, equi-molar ratio from the ligand
and each metal salt were grinded together in ball milling till
complete complexation which confirmed after analyses.
2.3. Computational simulation
2.5. Biological evolution
The computational simulation was carried out by using DFT
theory in electronic program DMOL3 [10] by applying Mulliken
population analysis in Material Studio 7.0 software [11]. DMOl3
permits analysis for energetic and electronic structures of tested
compounds [12].
2.5.1. Antimicrobial and antioxidant evaluation
MIC for tested compounds were assessed by agar-streak dilution
technique [15] as displayed (Scheme 2S). Concentrated stock so-
lutions were prepared by100
mg/ml in DMSO solvent from each
tested compound. A referenced ABTS method was used to measure

S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
3
the magnitude of antioxidant feature for all compounds (Scheme
3.2. Vibrational and 1H &13C NMR analyses
3S). The preference for this method is due to giving a consistent
color for a suitable time (1 h) that sufficient for accurate spectros-
copy [16].
IR spectrum for Schiff base ligand (H2BHNH) exhibited func-
tional vibrations for (OH), (OH), (C]O), (C]N), (NeN) and
y
y
y
y
y
y
(CeO)naphthoic bands (Table 2). Such vibrations were appeared at
3449, 3271, 1646, 1622, 1063 and1268 cmꢁ1, respectively [19]. The
2.5.2. Cytotoxic activity
ligand formula was confirmed firstly by 1H NMR spectrum
Antitumor activity was estimated for all compounds versus
colorectal carcinoma cell line (HCT-116), which taken from ATCC by
Holding company for biological products and vaccines in Cairo-
Egypt. The reagents used were 5-fluorouracil (reference drug),
MTT, RPMI-1640 medium and DMSO, which taken from Sigma &
Aldrich. As shown in 4S-scheme and applying MTT examination,
the inhibition efficiency for the tested compounds versus cell
growth, was known [17]. The change in tetrazolium bromide (MTT)
color (yellow) to formazan derivative by mitochondrial succinate
dehydrogenase (purple) in viable cells, was colorimetrically
monitored. The cells (HCT-116) were cultured in RPMI-1640 me-
dium with fetal bovine serum (10%).
(DMSO‑d6, Fig.1), which displayed signals at
d
(ppm) ¼ 11.98 (s, OH),
11.30 (s, NH), 7.34e8.47(m, AreH), 3.40 (DMSO) and 2.45 (s, CH2).
The downfield shift for OH and NH signals denote the presence of
intra-ligand hydrogen bonding, which supported by broadness at
1900 cmꢁ1 in IR spectrum. This indicates that the two groups (OH &
NH) have the same efficiency in susceptibility to hydrogen loss
(ionization), which obviously happened in the complexes. Sec-
ondly, its 13C NMR spectrum (Fig. 2) strictly asserted the ligand
formula through the signals assigned for all carbon-skeleton (see
the figure).
The IR spectrum for Zn(II) complex displayed disappearance for
y(OH)
vibration in addition to lower shift for
y(C]O) and
naphthoic
y(C]N) bands. This feature points to mono-negative tri-dentate
2.6. Cyclic voltammetry
mode of bonding within the complex after ionizing OH-group.
Moreover, the y(ZneN) and y(ZneO) vibrations were assigned at
416 and 508 cmꢁ1, respectively. Such behaviour further supported
Cyclic voltammograms were performed for Zn(II) ion either in
absence or in presence of Schiff base ligand. The used cell consists
of three types of electrodes that connected with multichannel
potentiostat DY 2000. The first one was known by a reference
electrode (Ag/AgCl) that filled with a saturated KCl solution. The
second one was known by a glassy carbon electrode (GCE), which
polished by fine-powdered Al2O3 that placed over a clean piece of
wool. The third one was a platinum wire that known by auxiliary
electrode (AE), which protects glassy carbon electrode from
destroying. The electrochemical cycles were conducted under inert
atmosphere by using nitrogen flow. Within the cell, the electrodes
were deliberately immersed in 0.1 M Na2SO4 (30 mL), the system
was adapted at potential range of 1.0 Ve1.5 V and the scan rate was
0.1 v/s (at 297.15 K).
firstly by its 1H NMR spectrum, which exhibited disappearance for
OH signal beside the downfield shift for NH signal (
d
¼ 12 ppm)
(Fig. 1). Secondly, its 13C NMR spectrum (Fig. 2) displayed high-field
shift for CeN and CeO signals that confirm their coordination to-
wards Zn(II) centre, while the other carbon-signals not clearly
affected.
On the other side, the IR spectrum of Cd(II) complex displayed
disappearance for
instantaneous appearance for
Furthermore, the lower shift for
y
(C]O) and
(CeO) and
(C]N) and
y
(NH) vibrations beside the
(C]N*) bands [20].
(OH)naphthoic bands,
y
y
y
y
was recorded. This feature points to mono-negative tri-dentate
binding mode within Cd(II) complex after enolization for C]O
group. Moreover, the
y(CdeN) and y(CdeO) vibrations were
assigned at 516 and 440 cmꢁ1, respectively. Such behaviour further
supported firstly by its 1H NMR spectrum (Fig. 1), which exhibited
disappearance for NH signal due to enolization for C]O, while the
OH signal still appeared (Fig. 1). Secondly, its 13C NMR spectrum
(Fig. 2) displayed also the high-field shift for CeN and CeO signals
in agreement with Zn(II) complex.
3. Results and discussion
3.1. General characteristics
The two complexes were proposed having 1:2 M ratio (M:L)
based on analytical data (Table 1). Their non-conducting behaviour
was recorded for 1 mmol according to bases previously reported
[18].
Table 1
Analytical and physical data of H2BHNH, Zn(II) and Cd(II) complexes.
a
No.
Compound
(E. F.)
(F. Wt.)
M.P. (ꢂC)
260
C
H
M
Lm
1
H2BHNH
C18H14O2N2 (290.324)
74.41 (74.46)
4.91 (4.86)
e
e
e
2
3
[Zn(HBHNH)2]·H2O
[Cd(HBHNH)2]
ZnC36H28O5N2 (662.018)
CdC36H26O2N2 (691.032)
293
>300
65.33 (65.31)
62.55 (62.57)
4.30 (4.26)
3.91 (3.79)
9.79 (9.87)
16.30 (16.26)
4
4
a
In DMSO (ohmꢁ1cm2molꢁ1).
Table 2
Most important IR spectral bands of H2BHNH, Zn(II) and Cd(II) compounds.
Compound
y(OH)naphthoic
y
(NH)
y(C]O)
y(C]N)
y
(C]N*)
y
(CeO)naphthoic
y(CeO)enolic
1
2
3
3449
e
3271
3115
e
1646
1634
e
1622
1605
1602
e
1268
1282
1261
e
e
e
3354
1630
1168
C¼N* is a new band after enolozation

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S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
Fig. 1. 1H NMR spectrum of H2BHNH in DMSO‑d6 and its (A) Cd(II) and (B) Zn(II) complexes.
3.3. EDX, SEM and TEM analyses
emitted X-ray energy and number were measured by energy-
dispersive X-ray microanalysis (EDX) technique for the two com-
plexes. The patterns (Fig. 3) displayed different peaks assign for
elemental composition, the presence of Cd or Zn verifies the
complexation. Moreover, the weight percentage of elemental
composition was estimated within the primary formula of each
complex.
To stimulate X-ray emission to characterize definite sample, X-
ray beam must directed to focus on studied sample. The charac-
terization potential is basically depends on principle called that
each element has a unique atomic configuration that permit a
single set of peaks in its emission spectrum. Consequently, the

S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
5
Fig. 2. 13C NMR spectrum of H2BHNH and its (A) Cd(II) and (B) Zn(II) complexes.
SEM analysis, which performed by using a beam of energetic
electrons scanning the surface, to know morphological feature and
particulate distribution. The micrograph of Cd(II) and Zn(II) com-
plexes (Fig. 1S) showed irregular broken rocky-like sheets
accompanied by fine micrometer-sized granules. For sure, the TEM
images were obtained to detect the particulate-size for materials.
The image of Zn(II) complex, exhibited particle sizes in
32.88e40.09 nm range while, in Cd(II) complex the particle sizes

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S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
Fig. 3. EDX views of (A) Zn(II) and (B) Cd(II) complexes.
fall in 28.53e39.35 nm range.
the positive of
iii) Increasing values of
D
H, reflect nonspontaneous endothermic process.
G from step to another, reflects the ease of
D
decomposition for the complex than the yielded fragment from
each step.
3.4. TGA and kinetics for Zn (II) complex
TGA curve of Zn(II) complex (Fig. 2S) showed three decompo-
sition stages starting from z55 to 590 ꢂC. The hypothesis thermal
degradation way (Scheme 5S) was proposed starting with removal
of crystal water followed by successive degradation till reach to ZnO
residue (Table 1S) [21].
3.5. Hirshfeld crystal surface properties and XRD
Through Crystal explorer 3.1 software [25], the mapping of
normalized contact distance (d norm) and the coloured patches
(fragment) on Hirshfeld surface, were obtained (Fig. 4& 4S; A, B).
This usage was done over all compounds after orientation by VESTA
software [26]. Also, the unit cell was established over VESTA screen
according to simple monoclinic unit (C). So, the molecular contact
The kinetic features of thermal behaviour of the complex were
obtained over DTA curve (Table 2S) by using Coats-Redfern [22] and
Horowitz-Metzger [23] methods, for assertion. The plots between
ln (-ln (1-
slope is E/R and the intercept is the pre-exponential factor (A)
a
)/T2 and 1/T in accordance to Coats-Redfern method, the
strength can be imagined from d
model (A) through three
norm
(Fig. 3S). While, the plots between Log [log (wa/wg)] and
q
in
supporting colours (red, blue and white). According to van der
Waals radii, shorter (˂0, strong), moderate and long (weak) contact
lengths were indicated by red, white and blue spots. Based on that,
the strength of molecular contact in packing systems was arranged
by L (ꢁ0.517 Å) ˃ Zd (II) complex (ꢁ0.45 Å) ˃ Cd(II) complex
(ꢁ0.429 Å) in accordance with contact lengths. Also, the coloured
mapping in fragment patches (B) differentiates the degree of
closeness with other adjacent molecule. It facilitates to identify the
most suitable way for connection to the nearest molecules and
hence the contribution percentages. This feature was further
confirmed by some characteristics (Table 3) as asphericity, glob-
ularity and surface area, which displayed the priority of the ligand
accordance to Horowitz-Metzger method, the slope equal Ea/RTs2.
By the way and after knowing Ea, A can be estimated from this
relation; E*/RTs2 ¼ A/[
f
exp (-E*/RTs)], where,
q
¼ T- Ts, wg ¼ wa-w,
wa ¼ mass loss at the end of reaction; w ¼ mass loss at each time t.
Also depending on the above, thermodynamic parameters as
H and G were calculated from these relations; S ¼ R
H ¼ E-RT,
ln hA/KBTs and H-T S [24]. Where, KB is the constant of
DS,
D
D
D
D
DG ¼
D
D
Boltzmann, h is the constant of Plank and Ts is the peak midpoint-
temperature. The aggregated information about parameters esti-
mated are; i) low activation energy of first stage reflects the ease of
losing crystal water molecule. ii) The negative values of
DS beside

S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
7
Fig. 4. 3D models of Hirshfeld surface as d
(A), fragment patch (B) and unit-cell (C) of H2BHNH ligand.
norm
complex, which appeared cover the whole molecule. Whiles, the
LUMO levels appeared extended over the free ligand only but
concentrated on definite organic moiety in the two complexes with
absence for the two metals.
Also, important energy indices and dipole moment values were
calculated and displayed (Table 3S), for investigation. The structural
activity relationships can be predicated based on such data calcu-
lated. The lower dipole moment values for the ligand and its
complexes point to lipophilic feature of them, which is promising
for biological efficiency. Regarding the two complexes, the reduced
energy values of binding, spin polarization, exchange-correlation,
electrostatic and kinetic, signify the high stability of complexes.
3.6.2. Electrostatic potential map (MEP)
This maps (MEP) were used to discriminate electrophilic and
nucelophilic attack sites in structural forms of investigated com-
pounds. The maps of all compounds were built and shown (Fig. 9S)
three indicating colours. The blue area mentioned to electron-poor
region that obvious for reagents have nucelophilic attack ability. On
the other hand, the red area mentioned to electron rich region that
obvious for reagents have electrophilic attack ability. In addition to,
the green area specified to neutral electrostatic potential region
[30].
Fig. 5. Theoretical XRD pattern for H2BHNH ligand.
in its features. This has been enhanced by 2D-fingerprint plots
(Fig. 5S), which displayed the elemental contribution in surface
contact, separately [27]. As typed on the figures, the significant
contribution was recorded from carbon (8.7, 9.6%) and oxygen
(3.2e3.7%) atoms in three packing systems.
XRD patterns were computationally drawn for the ligand and its
complexes by using Crystal Maker 6.8 software (Figs. 5 & 6S), for
comparison. The ligand pattern appeared distinctly different from
that of two complexes, while the complexes appeared quietly
compatible. Miller indices (hkl) were estimated as 001(ligand), 010
(Zn (II) complex) and 100 (Cd (II) complex). Also, the d-spacing
were 17.61, 18.02 and 17.30 Å, respectively. Practical XRD patterns
couldn’t executed due to unavailability of technique, so the com-
parison is completely missing.
3.7. Biological efficiency
MIC was evaluated for three compounds towards different mi-
croorganisms in comparing to certified antibacterial drug (cipro-
floxacin) and other antifungal drug (fluconazole). The data obtained
(Table 4S) reflect the high efficiency of the ligand towards all mi-
crobes, while Zn(II) complex displayed a sufficient inhibition to-
wards B. subtilis and A. flavus. It was known that, the mild inhibition
of complexes are preferable than the high efficiency of pure organic
ligands in agreement with chelation theory [31]. Antioxidant
behaviour for the tested compounds were assessed by credible and
precise method (ABTS) [32]. The data obtained (Table 5S) reflect the
successful antioxidant behaviour of all tested compounds particu-
larly the complexes. The two complexes displayed a compatible
results with reference used (ascorbic acid). Furthermore, the
cytotoxic behaviour was also evaluated versus colorectal carcinoma
cell line (HCT-116) (Table 6S) in parallel with 5-fluorouracil drug (5-
FU). Highly reduced IC50 values recorded, particularly with Cd(II)
3.6. Computational studies
3.6.1. Conformational studies
Using DFT method on DMOL3 module, the structural optimi-
zation was executed for the ligand and its complexes (Fig. 7S). The
exported files displayed various significances among that, the bond
angles which compared between ligand and complexes, to support
complex geometries. The following angles C (8)-N (7)-C (4), O (12)-
C (8)-N (7), O (12)-C (8)-C (9), N (13)-C (10)-C (11), C (15)-N (14)-N
(13), H (34)-N (14)-N (13) O (23)-C (18)-C (16) and O (23)- C (18)eC
(19) " were monitored after complexation. A confidential changes
were observed with such angles in two complexes in agreement
with octahedral configuration (sp3d2 hybridization) [28]. In addi-
tion to, the bonds of C (4)eN (7), N (7)eC (8), N (14)eC (15), N (13)e
N (14) and C (18)eO (23) suffer elongation within two complexes
[29]. Whereas, HOMO and LUMO maps were established on opti-
mized structures and exhibited (Fig. 8S). The HOMO levels were
mainly focused on definite organic moiety except with Zn(II)
complex (3.16 mg/mL), which denote a promising antitumor feature
of such compounds.
3.8. Inhibitory simulation
Using MOE module (Vs. 2015) behaviour of the ligand and its
complexes was deliberately monitored by using this advanced
program. Two microorganism’s proteins were chosen for this

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S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
Fig. 6. Interaction patterns (A &B) for tested compounds and Fluconazole against A. flavus protein kinase.
simulation, aspergillus flavus (6dtc) and bacillus subtilis (3vzx). The
selected bacterium and fungus were taken as example on behalf the
others. This because the compounds exhibited a lower efficiency as
antimicrobial agents as reported in the part of in-vitro study, while
the only affected microbes by a little extent were that selected for
this simulation. After executing the docking, all exported interac-
tion parameters (Table 4) as well as the docking maps (Figs. 6 and
10S), were displayed. These data offer a well opportunity to know
what happen inside the cell after treatment [13]. Many important
information has been collected and are as follows;
the following information in the parallel way with that from
interaction data;
1 The receptor exposure surface was extended than the ligand
one, particularly in the maps of ligand-6dtc and Fluconazole-
6dtc.
2 A broad proximity contour was appeared with the reported two
maps, while suffered shrinkage in the other maps
3 Greasy receptors with backbone donor, polar receptors with
side chain acceptor and acidic receptors with side chain donor,
were the binding types displayed [14].
1 A shortage in contributing sites, it was limited on O12 & N15
2 The only receptors were Glutamate, Lysine and Tryptophan
3 Two interaction types were recorded as H-acceptor and H-donor
4 A significant interaction was appeared with H2BHNH-6dtc,
Zn(II)complex-6dtc and Fluconazole-6dtc as well as Zn(II)
complex-3vzx. The scoring energy values of such docking
complexes were enough to expect their significant inhibition
5 The other docking paths although they showed high scoring
energy (Kcal/mol) as Cd(II) but the features of interaction are not
known
3.9. Redox reaction of ZnSO4 depositing ZnO
The voltammogram have two anodic peaks at about (0.8 V &
0.3 V) vs. (Ag/AgCl/sat. KCl) electrode resulting in the deposition of
ZnO on a glassy carbon working electrode. The electro-reduction of
the formed ZnO from the dissolution of ZnSO4 in 0.1 M Na2SO4 was
displayed in Fig. 7. The outcomes data of the concentration effect for
the first and second couple of waves was shown in Tables 5 and 7S.
The peak current was given by applying Randles-Sevcik equa-
tion (1) [33].
On the other hand, the docking maps (Figs. 6 and 10S) displayed

S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
9
Fig. 6. (continued).
DEp ¼ Ep;a ꢁ Ep;c
(2)
The charge transfer coefficient of electrons was calculated by
applying equation (3)
a
na ¼ 1:857 RT = ðEpc ꢁ Epc=2Þ F
(3)
The surface concentration of the redox ion in (mol.cmꢁ2) was
estimated by the use of relation (4)
G
¼ ip 4RT =n2 F2
A
n
(4)
The quantity of charge consumed during the redox reaction of
MnO2 adsorbed layer was evaluated by applying equation (5) [35]:
Q ¼ n FA
G
(5)
Fig. 7. Cyclic Voltammetry of ZnSO4 at 0.1 scan rate at 297.15 K.
The heterogeneous charge transfer rate constant (ks) can be
calculated by the use of equation (6)
ks ¼ 2:18*½Dcana
F
n
=RTꢃ1=2*exp½
a
2nF ðEp;c ꢁ Ep; aÞ=RTꢃ
Ip ¼ ð2:69x105Þ n3=2A C
n
1=2D1=2
(1)
(6)
Ip The measured current in Ampere.
AThe surface electrode area (cm2).
DThe diffusion coefficient in (cm2/s).
Ep,a:The anodic wave potential.
p,a:The anodic peak current.
I
n
The scan rate in (volts/sec).
Da:The anodic diffusion coefficient
ks:The electron rate constant.
Ga:The anodic surface coverage.
CThe molar concentration of metal ion (mol/cm3) Equation (2)
was used for calculating the potential difference [34]:

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S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
Fig. 8. v^1/2 vs Ip for of ZnSO4 at 297.15 K.
electrochemical interaction between ZnSO4 and H2BHNH in the
range between 1.5V and -1.0 V vs. Ag/AgCl/Sat.KCl electrode. The
electrochemical voltammograms displayed (Fig. 11S are like for
ZnSO4 in the absence of H2BHNH and no new peaks were detected.
The current peak potentials for the detected redox peaks in the
existence of H2BHNH are increased by increasing the concentration
of ligand favoring weaker bonds between zinc ions and H2BHNH
than in the absence of it. The outcomes results showed (Tables 6 &
8S) explain the various analytical results obtained from the effect of
Table 3
Hirshfeld crystal surface properties of the ligand and its complexes.
Properties
H2BHNH
Cd(II)complex
Zn(II)complex
Volume (Å3)
Area (Å2)
Globularity
Asphericity
3068.62
1381.49
0.739
4557.55
1919.54
0.693
5034.96
2007.46
0.708
0.130
0.052
0.056
H2BHNH on ZnSO4 peaks. The complexation stability constant (bc)
for interaction of ZnSO4 and H2BHNH was estimated by using
relation (8) [36]:
Qa:The anodic quantity of electricity.
The anodic peaks are increase with increasing the concentration
of ZnSO4 in 0.1 M Na2SO4. Also, the same behaviour was observed
for cathodic peak. Moreover, the standard potential (Eꢂ) are
increased also by increasing the concentration of ZnSO4 favoring
diffusion processes.
(E1/2)C - (E1/2)M ¼ 2.303 (RT/nF) * 2.303 (RT/nF) log CL (8).
(E1/2)M:The half-wave potential for Zn(II) in absence of H2BHNH
(E1/2)C:The half-wave potential of complex formed.
CL:The concentration of ligand.
Gibbs free energy for complexation between ZnSO4 and
3.9.1. Redox reaction of ZnSO4 in presence of H2BHNH
H2BHNH was estimated by using relation (9) [37]:
DG ¼ ꢁ2.303 RT
Cyclic voltammetry technique was used to study
Table 4
Interaction parameters against two selected proteins.
Compounds
Proteins
Ligand
Receptor
Interaction
Distance(Å)
E (Kcal/mol)
S (energy score)
H2BHNH
6dtc
3vzx
6dtc
3vzx
6dtc
3vzx
3vzx
6dtc
O12
e
OH TYR 162 (A)
e
H-acceptor
e
3.00
e
ꢁ1.7
e
ꢁ6.5229
ꢁ4.3744
ꢁ5.0763
ꢁ4.8885
ꢁ6.8204
ꢁ8.0720
ꢁ4.7330
ꢁ6.2708
Zn(II) complex
Cd(II) complex
N15
O12
e
O GLU 122 (A)
OD2 ASP 18 (A)
H-donor
H-donor
3.01
2.54
e
ꢁ5.6
ꢁ10.6
e
e
e
e
e
e
e
e
Ciprofloxacin
Fluconazole
e
e
e
e
e
O12
O LYS 156 (A)
H-donor
2.77
ꢁ1.8
Table 5
Cyclic voltammetric data of Zn(II) at 297.15 K and 0.1 scan rate for wave 2.
Mx106 (mol/ Ep,a
Ep,c
DEp
-Ip,a x105
Ip,c x105
(Amp)
Ip,a/Ipc
(Amp)
Eꢂ
Dax105
(cm2/s)
Dc x106
(cm2/s)
a
na Ks (cm/
sec)
G
cx109 (mol/ þQc
G
ax109 (mol/ - Qa
cm3)
(volt) (volt) (volt) (Amp)
cm2)
x105
cm2)
x105
0.66
1.32
1.96
2.60
0.295 0.041 0.254 2.61
0.146
1.05
3.30
3.32
17.91
6.172
3.943
4.105
0.168 2.719
0.164 4.296
0.183 7.703
0.201 4.823
0.085
1.13
4.95
2.86
1.64 0.23
1.06 0.97
0.57 4.22
0.55 8.32
0.123
0.892
2.787
2.807
0.08
0.54
1.69
1.70
2.206
5.509
10.99
11.52
1.34
3.34
6.66
6.98
0.3
0.346 0.02
0.389 0.013 0.376 13.6
0.027 0.273 6.52
0.326 13.0

S. Alzahrani et al. / Journal of Molecular Structure 1218 (2020) 128473
11
Table 6
Cyclic voltammetric data of Zn(II) in the presence of H2BHNH at 297.15 K for wave 1.
M x106 L x106 -Ip,a x105 Ip,c x105 Ip,a/Ipc
Ep,a Ep,c Ep
D
Eꢂ Da x105
(cm2/s)
Dc x106
(cm2/s)
a
na Ks
G
c x109
þQc
G
a x109
- Qa
(mol/cm3) (mol/cm3) (volt) (volt) (volt) (Amp)
(Amp)
(Amp)
(cm/s) (mol/cm2)
x105 (mol/cm2)
x105
2.59
2.58
2.57
2.56
2.56
2.55
2.54
2.53
0.32
0.65
0.97
1.28
1.60
1.91
2.22
2.53
1.07
1.04
1.03
1.02
1.01
1
0.85
0.84
0.84
0.83
0.83
0.82
0.82
0.82
0.218 14.8
0.199 12.5
0.194 11.8
0.187 10.7
0.184 9.46
0.178 8.69
0.172 8.57
0.165 6.98
8.77
9.06
7.57
6.85
5.44
5.46
4.80
4.16
1.69
1.38
1.56
1.56
1.74
1.59
1.79
1.68
0.96 5.73
0.94 4.11
0.93 3.67
0.93 3.05
0.92 2.40
0.91 2.04
0.90 2.00
0.89 1.33
2.16
2.01
1.52
1.25
0.79
0.80
0.62
0.47
0.72 1.16 7.41
0.76 0.85 7.66
0.76 0.64 6.40
0.87 0.55 5.79
0.85 0.41 4.60
0.82 0.36 4.62
0.78 0.27 4.05
0.85 0.22 3.52
4.49 12.5
4.64 10.6
3.88 9.96
3.51 9.05
2.79 8.01
2.80 7.34
2.46 7.25
2.13 5.90
7.58
6.40
6.03
5.48
4.85
4.45
4.39
3.37
0.99
0.98
Table 7
Effect of different scan rate of ZnSO4 [2.60 ꢄ 10ꢁ6 M] at 297.15 K for wave 1.
ʋ
Ep,a
(volt)
Ep,c
(volt)
D
(volt)
Ep
-Ip,a x105
(Amp)
Ip,c x105
(Amp)
Ip,a/Ipc
(Amp)
Eꢂ
Da x105
(cm2/s)
Dc x105
a
na Ks (cm/
s)
G
cx109 (mol/ þQc
G
a x109 (mol/ - Qa
(cm2/s)
cm2)
x105
cm2)
x105
0.1 1.06
0.05 1.016
0.02 0.996
0.01 0.989
0.815
0.896
0.902
0.908
0.245
0.12
0.094
0.081
17.2
12.0
8.00
5.41
6.43
4.68
2.51
1.40
2.667
2.558
3.184
3.856
0.938 7.64
0.956 7.43
0.949 8.30
0.949 7.58
1.074
1.136
0.819
0.510
0.347 0.995 5.437
0.881 0.1 7.908
1.034 0.035 0.106
1.285 0.017 0.118
3.29
4.79
6.43
7.18
14.50
20.23
33.81
45.68
8.79
12.3
20.5
27.7
Table 8
Stability constant for MnSO4 in presence of H2BHNH at 297.15 K for wave 2.
M x106 (mol/cm3)
L x106 (mol/cm3)
Eꢂ
M
Eꢂ
C
DE (mv)
j
Log
bj
DG (KJ/mol)
2.59
2.58
2.57
2.56
2.56
2.55
2.54
2.53
0.324
0.645
0.965
1.28
1.60
1.91
0.201
0.201
0.201
0.201
0.201
0.201
0.201
0.201
0.091
0.091
0.080
0.083
0.079
0.089
0.091
0.092
0.111
0.110
0.121
0.119
0.122
0.113
0.111
0.109
0.125
0.250
0.375
0.500
0.625
0.750
0.875
1
4.559
5.278
6.380
6.965
7.744
8.092
8.670
9.257
ꢁ25.94
ꢁ30.03
ꢁ36.09
ꢁ39.62
ꢁ44.06
ꢁ46.19
ꢁ49.66
ꢁ53.20
2.22
2.53
log bc (9).
executed in details for Zn(II) in presence or absence of the ligand to
investigate the electrochemical behaviour.
The obtained Figs.12S & 13S correspond to the effect of scan rate
on cyclic voltammograms of ZnSO4 in the absence/presence of
H2BHNH. The outcomes results showed in Table 7& 9Se11S illus-
trate the effect of scan rate on the anodic as well as cathodic cur-
rents for both couple of peaks.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
The calculated thermodynamic parameters (bc
& DG) for the
interaction of ZnSO4 with H2BHNH were tabulated in Table 8 &
12Se14S The outcomes results for 1:1 stoichiometric complex
indicated that the thermodynamic parameter, stability and Gibbs
free energies of complexation increase by increasing H2BHNH
concentration, which indicating more complexation manner. The
relation between Ip versus v^1/2 displayed (Figs. 8 & 14S straight
lines for both cathodic as well as anodic Zn(II) waves in absence/
presence of H2BHNH, which indicating diffusion-controlled
reactions.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molstruc.2020.128473.
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