Synthesis, structural investigations, DFT, molecular docking and antifungal studies of transition metal complexes with benzothiazole based Schiff base ligands

Article abstract of DOI:10.1016/j.molstruc.2018.10.070

A novel series of complexes of the type, [ML₂].nH₂O, [where L = 2-(α-methyl salicylidene–2′-imino) aminobenzo thiazole (HMAB), 2-(α-phenyl salicylidene–2′-imino) aminobenzo thiazole (HPAB), 2-(o-Vanillidene–2′-imino) amino benzothiazole (HVAB)] have been reported. These Schiff bases and their transition metal complexes were fully characterized by several physico-chemical and spectral techniques, which revealed the tridentate chelation of ligand. The DFT calculations of these reported compounds were made to obtain bonding inside the structure by GAUSSIAN 03 programme platforms. The QSAR study was performed by HyperChem Professional 8.0.3 software to explain the biological effeteness of the ligands. A docking analysis using the AutoDock Vina software was carried out to understand the binding pattern of the investigated compounds towards target proteins CYP121 and CYP51 from Mycobacterium tuberculosis. Furthermore, all the compounds have been reported to exhibit significant antifungal activity when tested against Aspergillus flavus and Aspergillus niger.

Full text of DOI:10.1016/j.molstruc.2018.10.070

Accepted Manuscript
Synthesis, structural investigations, DFT, molecular docking and antifungal studies
of transition metal complexes with benzothiazole based Schiff base ligands
Ranjan K. Mohapatra, Ashish K. Sarangi, Mohammad Azam, Marei M. El-ajaily,
Md. Kudrat-E-Zahan, Suyanbhu B. Patjoshi, Dhruba C. Dash
PII:
S0022-2860(18)31265-1
10.1016/j.molstruc.2018.10.070
MOLSTR 25799
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
15 August 2018
22 October 2018
Please cite this article as: Ranjan K. Mohapatra, Ashish K. Sarangi, Mohammad Azam, Marei M. El-
ajaily, Md. Kudrat-E-Zahan, Suyanbhu B. Patjoshi, Dhruba C. Dash, Synthesis, structural
investigations, DFT, molecular docking and antifungal studies of transition metal complexes with
benzothiazole based Schiff base ligands, Journal of Molecular Structure (2018), doi: 10.1016/j.
molstruc.2018.10.070
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ACCEPTED MANUSCRIPT
Synthesis, structural investigations, DFT, molecular docking and
antifungal studies of transition metal complexes with benzothiazole
based Schiff base ligands
Ranjan K. Mohapatra1, Ashish K. Sarangi1*, Mohammad Azam2, Marei M. El-
ajaily3, Md. Kudrat-E-Zahan4, Suyanbhu B. Patjoshi5, Dhruba C. Dash5
1Department of Chemistry, Government College of Engineering, Keonjhar-758002, Odisha, India
2Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
3Chemistry Department, Faculty of Science, Benghazi University, Benghazi, Libya
4Department of Chemistry, Rajshahi University, Rajshahi-6205, Bangladesh
5School of Chemistry, Sambalpur University, Jyoti Vihar, Sambalpur-768019, Odisha, India
* Author for correspondence, e-mail: ashishsbp_2008@yahoo.com
Abstract
A novel series of complexes of the type, [ML2].nH2O, [where L = 2-(α-methyl salicylidene–2'-
imino) aminobenzo thiazole (HMAB), 2-(α-phenyl salicylidene–2'-imino) aminobenzo
thiazole (HPAB), 2-(o-Vanillidene–2'-imino) amino benzothiazole (HVAB)] have been
reported. These Schiff bases and their transition metal complexes were fully characterized
by several physico-chemical and spectral techniques, which revealed the tridentate chelation of
ligand. The DFT calculations of these reported compounds were made to obtain bonding inside
the structure by GAUSSIAN 03 programme platforms. The QSAR study was performed by
HyperChem Professional 8.0.3 software to explain the biological effeteness of the ligands. A
docking analysis using the AutoDock Vina software was carried out to understand the binding
pattern of the investigated compounds towards target proteins CYP121 and CYP51 from
Mycobacterium tuberculosis. Furthermore, all the compounds have been reported to exhibit
significant antifungal activity when tested against Aspergillus flavus and Aspergillus niger.
Keywords: Schiff Base; Complexes; DFT; Molecular Docking; Antifungal Studies
1. INTRODUCTION
Coordination chemistry provides us large number of interesting and useful complexes by the
use of organic ligands containing hetero atoms as coordination sites. Furthermore, the ligands

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with more than one donor hetero atoms have received worldwide attention in coordination
chemistry because of their strong chelating ability to form mono-, di- or multinuclear complexes
[1,2]. In addition, the lone pair of electrons available on hetero atoms participates strongly in the
formation of metal-ligand bonds.
Over the years, heterocyclic ligands with ‘NOS’ donor atoms especially benzothiazoles
have received significant attention due to their unique complex forming ability and huge
applications in analytical chemistry as spectrometric and gravimetric reagents.
Benzothiazole, a sulphur isostere of benzimidazole, is a well-known heterocyclic moiety
with remarkable physical and biological properties. Furthermore, benzothiazoles and its
derivatives find extensive role in medicinal chemistry such as antimicrobial [3,4], antitumor [5],
anthelmintic [6], anticancer [7], antifungal [8,9], anti-HIV [10] and antitubercular agent [11]. In
addition, benzothiazole and its derivatives are also reported showing luminescence properties
[12] and have been used as anti-diabetes agent and central muscle relaxants [13].
Furthermore, it is reported that the activity of such compounds is increased when administered as
metal complexes.
In continuation of our ongoing interest on coordination chemistry [14,15], we are
reporting some benzothiazole derived Schiff bases with –OH, -OCH3 functional groups vicinal
to condensation site and their complexes with metals ions of first transition series. In addition, to
obtain insight into the structure of the ligands and their metal complexes, DFT calculations have
been carried out. Furthermore, the bio-potency of these compounds has been examined against A.
flavus and A. niger.
2. EXPERIMENTAL
2.1 Material

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All chemicals and reagents including 2-mercepto benzothiazole, hydrazine hydrate, o-
hydroxy acetophenone, o-hydroxy benzophenone, o-vanillin and the metal salts were of
Sigma Aldrich and used without further purification.
2.2 Procedure for the synthesis of 2-hydrazinobenzothiazole
2 ml hydrazine hydrate was added to a hot ethanolic (30 mL) solution of 2-
mercepto benzothiazole (1.67gm, 50 mmol). The reaction mixture was refluxed for
around 4 hours until H2S gas ceased to evolve. It was cooled at room temperature, and
left for evaporation. After few days, white needle shaped crysatalline material is
obtained.
N
N
+
NH2
H2S
+
SH
NH
NH2
H2N
S
S
(2-mercepto benzothiazole)
(2-hydrazinobenzothiazole)
2.3 Procedure for the synthesis of Schiff base ligands (HMAB, HPAB and HVAB)
Various ligands were prepared by condensing 2-hydrazinobenzothiazole with
respective aldehyde and ketone as follows.
2-hydrazinobenzothiazole (0.01 mol) in absolute ethanol (20 mL) was added to an
ethanolic (20 mL) solution of o-hydroxyacetophenone/ o-hydroxybenzophenone/ o-vanillin
(0.01 mol), followed by addition of 2 drops of acetic acid therein. The resulting solution
was heated for 3h on a water bath. The colored and clear solution was allowed to
evaporate at room temperature and washed with diethyl ether and finally, recrystallized in

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ethanol. Some microcrystalline product was obtained. Unfortunately, we didn’t find
anyone of them suitable for diffraction.
2.4 Procedure for the synthesis of metal complexes
The hydrated metal (II) chloride (0.01 mol) in absolute ethanol (20 mL) was treated with
ethanolic (20 mL) solution of Schiff base ligand (0.02 mol) in 1:2 molar ratio. The pH of
the resulting mixture was adjusted to 7.5 to 8.0 by adding solid NaOH. It was refluxed for
about 2 hours leading to the formation of precipitate. Then filtered, washed with ether
and finally dried in vacuo over fused CaCl2. The re-crystallization process is carried out at
room temperature for few days with a mixture of solvents by slow evaporation. But
unfortunately, we didn’t find crystals suitable for diffraction.

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Scheme of the reaction for the formation of complexes:
M= Co (II), Ni (II), Cu (II) and Zn (II)
X = -H, -CH3, -C6H5 , Y = -H, -OCH3 ,
n = 1 or 2

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2.5 Analysis and Physical measurements
The metal contents were determined gravimetrically [16]. Conductivity measurements were
recorded using Toshniwal Conductivity Bridge (model CL-01-06). The room temperature
magnetic susceptibility measurements were recorded by Guoy method. Microanalyses (C, H, N)
were executed by using a MLW-CHN micro analyzer. The electronic spectra were obtained in
DMSO from a Perkin-Elmer spectrophotometer. FTIR spectra as KBr pellets were recorded
using Varian FTIR spectrophotometer, Australia. Thermo gravimetric analysis was executed by
1
using Netzch-429 thermo analyzer. H NMR and C13 NMR spectra were collected from JEOL
GSX-400 model equipment in DMSO-d6 medium. The ESR spectra were obtained from a varian
E-112 ESR Spectrophotometer.
2.6 DFT studies
Schiff base ligands and its CuII and ZnII complexes were optimized and analyze with Gauss View
5.0.8 programme [17]. The GAUSSIAN 03 programme platforms [18-24] were used for DFT
calculations with LANL2DZ basic set. The Cu(II) and Zn(II) metal were use LANL2DZ basic
set in gas phase and 6-31 G (d, p) basic set are used for rest of the atoms.
2.7 Molecular docking studies
Molecular docking is one of the important drug design tools to understand the binding pattern of
investigated compounds toward target proteins CYP121 and Cytochrome P450 14 alpha-sterol
demethylase (CYP51) from Mycobacterium tuberculosis. The docking study was analyzed by
using AutoDock Vina software. Crystallographic structures of CYP121 (PDB: 2IJ7) and CYP51
(PDB: 1EA1) proteins [25] were brought from Protein Data Bank (http://www.pdb.org). The
proteins were freed from inbound ligand (fluconazole) by Discovery Studio 3.5 Visualizer [26].
Then polar hydrogen atoms and Kolhman charges were added to the proteins by using the

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AutoDock Tools (ADT). The grid box was selected for proteins centred at the crystal structure of
the corresponding inbound ligand. The grid dimensions were kept with a spacing of 1 Å. On the
other hand, the ligand structures were prepared by adding polar hydrogen atoms, Gasteiger
partial charges, and the torsions were allowed to rotate. The docked poses were visualized by
using the PyMOL software [27].
2.8 Antifungal assay
The in vitro antifungal activities of the compounds were examined at 100, 150, 200 µg mL-1
concentrations by Agar Well Diffusion Technique [28] against A. flavus and A. niger. Solutions
of the compounds in DMSO were plated onto the cultured agar medium and incubated for a
period of 48h at 28 . The results were measured in terms of zone of inhibition (in cm). Negative
℃
control used was DMSO. For comparison, the standard drug gentamycin is also screened under
identical conditions.
3. Results and Discussion
The analytical data and physical properties of the compounds are listed in Table-1, which
are in good agreement with the calculated values. These reported metal complexes are coloured,
non hygroscopic in nature and soluble in DMSO and DMF.
3.1 IR Spectra
The most significant changes in the IR spectra of the condensation
products of 2-hydrazinobenzothiazole with o-hydroxy acetophenone, o-hydroxy
benzophenone or o-vanillin is the disappearance of the -NH2 stretching and bending
vibration. A new band assignable to C=N (azomethine) appears at ~1560 cm-1 resulting
from condensation of the precursor with above aldehyde or ketones. Besides, all these

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ligands exhibit a broad and strong band in the region ~3300 cm-1 attributed to phenolic
–OH stretching vibration [29].
In the metal complexes (Table 2), band at ~ 3300 cm-1 due to phenolic -OH
stretching vibration disappears, there by indicating it’s deprotonation and coordination
to the metal ions through oxygen [30]. This is further supported by the hypsochromic
shift of phenolic C-O mode around ~ 1280 cm-1 of the free ligand by 10–20 cm-1 [31].
Moreover, the position of band due to N-H and C-N remain unaltered indicating non-
involvement of imino nitrogen in coordination.
The characteristic bands at ~ 1540, ~ 1313 and ~ 845 cm-1 can tentatively be
assigned to C=N (cyclic), C-N (cyclic) and C-S-C mode of vibration respectively. In the
spectra of complexes former two bands do not change, indicating nonparticipation of
ring nitrogen atom in coordination. However the later band shifts to lower frequency by
10–20 cm-1 in all complexes showing coordination of ring sulphur to the metal ions.
Besides this, the bands due to C=N (azomethine) and N-N vibration shift their position
in the metal complexes. The former band shifts to lower frequency by 10–20 cm-1 in all
complexes which implies coordination of a azomethine nitrogen atom [32,33].
Occurrence of N-N band at higher frequency region suggest a reduction in repulsion
between the lone pair of nitrogen atom due to electron drainage to metal ion as a result
of coordination via azomethine nitrogen.
All the metal complexes have a pair of sharp bands with moderate intensity around ~
550 and ~ 462 cm-1 attributed to M-N and M-O vibrations respectively. Besides these, the band
appearing at ~ 2567 cm-1 in the IR spectra of the ligand HVAB may be assigned to stretching
vibration of – OCH3

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Group [34]. The position of this band remains unchanged showing non-coordination of –OCH3
group most probably due to steric reason. In addition, the IR spectra of all the complexes show
the presence of lattice water which is further proved by thermal study. Hence the ligands act as
monobasic tridentate donors coordinating through azomethine nitrogen, ring sulphur and
deprotonated phenolic oxygen to yield metal complexes of the composition ML2.nH2O. The
representative IR spectrum of [Cu(MAB)2 2H2O] is shown in (Graph 1).
3.2 Thermal analysis
The metal complexes follow similar pattern of thermal decomposition. All the metal
complexes lose water below 100
indicating to be lattice water [35]. The anhydrous
℃
complexes again start decomposing rapidly around ~ 300
due to decomposition of
℃
organic constituents in the complexes. Decomposition continues up to ~ 700
and
℃
produces their stable oxides. Thermal data of these complexes are enlisted in (Table 3).
The thermal stability can be summarized as follows.
MAB complexes: Co (II) < Ni (II) < Zn (II) < Cu (II)
PAB complexes: Ni (II) < Co (II) < Cu (II) < Zn (II)
VAB complexes: Ni (II) < Co (II) < Zn (II) < Cu (II)
3.3 Electronic spectra and magnetic properties
The electronic spectra of Co(II) complexes in DMSO contain two main bands, a
very broad and a strong band around ~10,500 cm-1 (952 nm) and ~22,000 cm-1 (454 nm)
4
respectively. The former band can be attributed to T1g(F)4T2g(F) (1) and the later to
4
4T1g(F) T1g (P) () transitions respectively. Besides these the spectra also has two

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shoulders at ~19,500-21,500 cm-1 (512-465 nm) and ~16,000-17,000 cm-1 (625-590 nm)
region. The magnetic moment values of Co(II) complexes lie in the range normally seen
for octahedral Co(II) species.
The electronic spectra of Ni(II) complexes are found to possess a split band
system followed by two main bands. The main bands observed at ~15,000 cm-1 (667
3
nm) and ~24,500 cm-1 (417 nm) may safely be attributed to A2g(F)3T2g(F),( 2) and
3A2g(F)3T1g(P) (3) transitions respectively under octahedral symmetry. However, the
value of transition energy ratio  observed for these complexes are lower than the
usual range (~1.7) for octahedral Ni(II) species. This decrease in value might be due to
some distortion from octahedral geometry. The split band at ~8,600 cm-1 (1163 nm) and
~10,200 cm-1 (980 nm) might be due to splitting of 1 band under D4h symmetry and can
3
3
3
be attributed to B1g 3Eg and B1g B2g transitions respectively. The amount of
splitting of 1 band is taken as a measure of degree of distortion. The eff values of
Ni(II) complexes lie in the range expected for either octahedral or pseudo-octahedral
Ni(II) species.
The electronic spectra of all these Cu(II) complexes (Graph 2) are similar in
nature. Here the spectra is characterized by two bands at ~14,200 cm-1 (704 nm) and
2
2
~16,810 cm-1 (594 nm) which may be attributed to B1g2B2g ( and B1g2Eg (
transitions, suggesting there by a distorted octahedral geometry for these complexes like
2
the previous case. In this case also the band due to B1g2A1g is not observed most
probably due to superimposition by  band owing to its broadness. Like our previous
discussion here also no band occurs below ~10,000 cm-1 there by ruling out possibility

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of tetrahedral or pseudo-tetrahedral geometry. The eff values of Cu(II) complexes lie in
the range 1.79-1.90 B.M. which is normal for hexa coordinated Cu(II) complexes.
3.4 NMR spectra
1
The H NMR spectrum of the compounds display a multiplet in the region δ 7.2-7.9 ppm
corresponding to 8/13/7 aromatic protons, while the signals due to exocyclic –NH-N= proton
appear at δ 9.1 ppm. A signal is also observed at δ 2.4 ppm due to –CH3 protons in case of ligand
HMAB. In addition, signals due to azomethine (-N=CH-) and -OCH3 protons observed at δ 8.7
ppm and δ 4.3 ppm respectively. The disappearance of the phenolic OH proton signal and the
downfield signal due to the azomethine protons, indicate the co-ordination of above groups to the
13
metal ion. This was also confirmed from IR study. The C NMR spectrum of the synthesized
compounds explains the electronic environment of different kind of carbon atoms present. In the
13C NMR spectrum, signals appeared in the region 105.4 to 153.2 are due to aromatic carbons.
The signals at 176.4, 169.1 and 18.3 are assigned to C=N (azomethine), C=N (benzothiazole
moiety) and CH3 respectively. The representative 1H NMR and 13C NMR spectra of [Zn(MAB)2
H2O] are shown in (Graph 3 and Graph 4) respectively.
3.5 ESR spectra
The ESR spectra of Cu(II) complexes were recorded in DMSO at 300 K, which exhibits a well
resolved four line spectrum for mononuclear nature. There was no features characteristic for a
binuclear complex. This is also supported by the magnetic moment values. The spin Hamiltonian
parameters were calculated from the spectrum. The observed order (g11 = 2.26 > g┴ = 2.07 >
2.0023) indicates that the complex has octahedral geometry [36]. This also suggests that the
2
2
unpaired electron exists in dx -y orbital [37], as evident from exchange interaction term G (G =

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3.8 < 4.0). Here, g11 < 2.3 explains the covalent nature of the M→L bonding [38]. The covalency
parameter α2 is also calculated, which suggests the covalent nature of the copper complexes
(Graph 5).
3.6 Powder X-ray diffraction
The X-ray diffraction (powder pattern) for [Co(MAB)2] H2O complex is analyzed through
Phillips X’Pert High score software. The prominent diffraction peaks were indexed and analyzed
by using LSUCRPC programme package [39] (Graph 6). The lattice constant such as (a =
9.566Å, b = 11.143Å , c = 6.751Å, α = 104.980, β = 101.650 , γ = 75.310 , Volume = 665.23,
Density = 1.688 g / cm3. For the confirmation of diffraction pattern a comparison was made
between detected and evaluated 2θ values which are supports from the figure of merit value (7.3)
as proposed by de-Woulff [40]. Standard floatation techniques was used to determine the density
( ) of the cobalt complex. The number of unit cell (n) is evaluated from the following equation
휌
훒푵푽
n =
푴
The number of unit cell ‘n’ is establish to be 1.5 that concur well with the proposed triclinic
crystal shape of the cobalt complex. Average particle dimension of the cobalt complex can be
calculated by using the following Debye Scherrer equation
푲
ƛ
푫 =
훃 퐂퐨퐬 훉
After calculation it is found that the particle size of [Co(MAB)2] H2O complex is 5.6nm [41].
3.7 Molecular Modelling Studies (Geometrical optimization and DFT computation)
Three ligands HMAB (L1), HPAB (L2), HVAB (L3) and its Zn complexes (Figure 1 – 6) were
optimized with the help of B3LYP/ 6-31G (d, p) and B3LYP/LANL2DZ basic sets for there

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configurational stable geometry. The observation have been found for the bond lengths and the
bond angles of ligands varies in comparison with metal complexes mentioned in (Table 4 and
Table 5) that indicate the mode of bonding between ligand donor atoms with the metal ions
[42,43].
The calculation of dipole moment and single point energy value of the ligands HMAB (L1),
HPAB (L2), HVAB (L3) and [Zn(MAB)2] H2O, [Zn(PAB)2] H2O [Zn(VAB)2] H2O , [Cu(MAB)2]
2H2O, [Cu(PAB)2] 2H2O, [Cu(VAB)2] 2H2O complexes are evaluated by DFT/B3LYP 6-31G (d,
p) and DFT/B3LYP LANL2DZ basic sets (Table 6). In comparison among all three ligands
single point energy of HPAB (L2) is possesses less energy which indicates greater stability.
Similarly comparison made with metal complexes of all the ligands [Cu(PAB)2] 2H2O and
[Zn(PAB)2] H2O complexes possesses less energy and having greater stability [44]. In both the
basic set of all the Cu complexes possesses higher dipole moment value in comparison with all
the Zn complexes. This clearly indicates all the Cu complexes have stronger dipole-dipole
interaction.
3.8 QSAR Studies
The QSAR study of the ligands was made by using HyperChem Professional 8.0.3 software. All
the structures of the ligands are optimized by applying molecular mechanics force field (MM+)
followed by semi-empirical PM3 methods. The minimization of energy was done by applying
Fletcher-Reeves conjugate gradient algorithm. The calculated Partition coefficient log P of the
ligands (HL1 = 3.83, HL2 = 5.07 and HL3 = 3.59) respectively. The log P values explain the
biological effectiveness of the ligands. The major role is the permeability of the used compounds

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into the cell membrane [45]. Other essential parameters also calculated after completion of
optimization (Table 7).
3.9 Molecular docking studies
To identify how these molecules (L1, L2 and L3) can bind to CYP121 (PDB: 2IJ7) and CYP51
(PDB: 1EA1) proteins, molecular docking studies were carried out (Figure 7 and Figure 8). The
docking protocol verified by re-docking the fluconazole into the active site of CYP121 (PDB:
2IJ7) and CYP51 (PDB: 1EA1) proteins. From the docking study, it was found that the ligand L2
shows the best affinity towards both of the proteins [46]. An overview of the receptor–inhibitor
binding interaction is shown in Figure 9 (a), (b) and Figure 10. Further, the L2 in complexed
with various ions (Cu, Co, Ni, Zn) were docked to understand the binding with CYP51 (PDB:
1EA1) (Figure 11 & 12).
3.10 Antifungal activity
The in vitro antifungal activities of these compounds were examined at different
concentrations by using Agar Well Diffusion Technique. The results of the study are given in
(Table 8). It is observed that the metal complexes exhibit greater activity than the free ligands.
This may be explained on the basis of chelation theory. It is also observed that, the activities of
the synthesized metal complexes increase with increase in the concentration of the test solution.
It is because the concentration plays a vital role in increasing the degree of inhibition of
antifungal growth. In addition, many other factors like nature of the ligand, solubility, dipole
moment, conductivity and geometry may be responsible for the higher activity [47, 48]. The
comparative antifungal activities of complexes with HMAB, HPAB and HVAB against two
stains of fungi such as A. flavus and A. niger are shown in (Graph 7 and Graph 8).

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Conclusion
The present study revealed that all these metal complexes are neutral in nature which is evident
from their extremely low values of conductivity. All the metal complexes contain water
molecules in their lattice, which certainly do not participate in coordination to the central metal
ions as indicated from their thermal behavior. They are removed at a much lower temperature
than the coordinated molecules. This is further corroborated from IR spectral investigations. The
octahedral geometry of all the complexes are established with tridentate chelation of ligand.
From the powder XRD pattern shows that the cobalt complex is triclinic crystal system. The
molecular modeling study supports experimental findings of the bonding sites of the ligands,
symmetry and stability of the complexes. The QSAR study of the ligands shows all the
functional parameters of ligand HPAB is grater, so it is more potent among all the ligands.
Molecular docking study was also carried out to explain the binding pattern of reported
compounds toward target proteins CYP121 and CYP51. The study revealed that the ligand L2
shows the best affinity towards both of the proteins. Furthermore, the metal complexes have
greater antifungal activity as compared to the free ligands. This may be explained due to
enhanced lipophilic property of the central metal ion as a result of chelation with the ligand
moieties. Hence, this study will help the researchers to develop new antifungal agents with
higher potency.

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Acknowledgement
The authors (RKM & AKS) are grateful to the Principal, Government College of
Engineering, Keonjhar for providing necessary facilities and support. The authors are also
thankful to Sk. Abdul Amin, Natural Science Laboratory, Department of Pharmaceutical
Technology, Jadavpur University, Kolkata (WB), for doing the molecular docking study.
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Caption for Figures & Graphs
Graph 1 Infrared spectrum of [Cu(MAB)2] 2H2O
Graph 2 Electronic spectrum of [Cu(MAB)2] 2H2O
Graph 3 1H NMR spectrum of [Zn(MAB)2] H2O
Graph 4 13C NMR spectrum of [Zn(MAB)2] H2O
Graph 5 ESR spectrum of [Cu(PAB)2] 2H2O
Graph 6 XRD Graph of [Co(MAB)2] H2O
Graph 7 Effect of the ligands and complexes on the growth of Aspergillus flavous
Graph 8 Effect of the ligands and complexes on the growth of Aspergillus niger
Figure 1 Optimized geometry of the ligand HMAB (L1)
Figure 2 Optimized geometry of the ligand HPAB (L2)
Figure 3 Optimized geometry of the ligand HVAB (L3)
Figure 4 Optimized geometry of the complex [Zn(MAB)2] H2O
Figure 5 Optimized geometry of the complex [Zn(PAB)2] H2O
Figure 6 Optimized geometry of the complex [Zn(VAB)2] H2O
Figure 7 Docking conformation for the compounds (L1-L3, in wire form) at the CYP51 (PDB:
1EA1) binding site (Protoporphyrin molecule is shown in red stick).
Figure 8 Docking conformation for the compounds (L1-L3, in wire form) at the CYP121
(PDB:2IJ7) binding site (Protoporphyrin molecule is shown in red stick).
Figure 9 (a) CYP51 (PDB: 1EA1) and ligand (L2) 3D-interactions: The binding residues and
hydrogen bonding are represented as constructed in Discovery Studio Visualizer 3.5 (Accelrys,
Biovia, USA) (Protoporphyrin molecule is shown in green wire).

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Figure 9 (b) CYP51 (PDB: 1EA1) and ligand (L2) 2D-interactions: The binding residues and
hydrogen bondings are represented as constructed in Discovery Studio Visualizer 3.5 (Accelrys,
Biovia, USA) (Protoporphyrin molecule is shown in green wire).
Figure 10 CYP121 (PDB: 2IJ7) and ligand (L2) interactions: The binding residues and hydrogen
bonding are represented as constructed in Discovery Studio Visualizer 3.5 (Accelrys, Biovia,
USA) (Protoporphyrin molecule is shown in green wire).
Figure 11 Comparison of (A) L series ligands (L1, L2 and L3 in wire form) and (B) L2 in
complexed with various ions (Cu, Co, Ni, Zn) with CYP51 (PDB: 1EA1). (Protoporphyrin
molecule is shown in red stick).
Figure 12 CYP51 (PDB: 1EA1) and ligand complex (A) L2-Co, (B) L2-Cu, (A) L2-Ni, (B) L2-
Zn interactions: (Protoporphyrin molecule is shown in green stick).

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HIGHLIGHTS
 Schiff base ligands are prepared by the condensation of 2-hydrazinobenzothiazole
with o-hydroxy acetophenone/ o-hydroxy benzophenone/ o-vanillin.
 The metal complexes are synthesized and characterised by spectroscopic, thermal and
X.R.D. powder pattern.
 Molecular modelling of the ligands and their Cu & Zn complexes are made to
understand the mode of bonding.
 Molecular docking, QSAR and antifungal study were ascertained to verify the bio-
potency of the compounds.