Spectral and computational chemistry studies for the optimization of geometry of dioxomolybdenum(VI) complexes of some unsymmetrical Schiff bases as antimicrobial agent

Article abstract of DOI:10.1080/00958972.2018.1533125

This analysis highlights the design, spectroscopic characterization and quantum mechanical calculation of some new dioxomolybdenum(VI) complexes of some dibasic tetradentate Schiff bases. Ligands were derived from mono 5-bromosalicylaldehyde-orthophenylen

Full text of DOI:10.1080/00958972.2018.1533125

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Spectral and computational chemistry
studies for the optimization of geometry of
dioxomolybdenum(VI) complexes of some
unsymmetrical Schiff bases as antimicrobial agent
Mohammad Nasir Uddin, D.A. Chowdhury, Nobuyuki Mase, Mohammad
Fazlur Rashid, Moniruz Zaman, Amrin Ahsan & Noor Mostaq Shah
To cite this article: Mohammad Nasir Uddin, D.A. Chowdhury, Nobuyuki Mase, Mohammad Fazlur
Rashid, Moniruz Zaman, Amrin Ahsan & Noor Mostaq Shah (2018): Spectral and computational
chemistry studies for the optimization of geometry of dioxomolybdenum(VI) complexes of some
unsymmetrical Schiff bases as antimicrobial agent, Journal of Coordination Chemistry, DOI:
10.1080/00958972.2018.1533125
To link to this article: https://doi.org/10.1080/00958972.2018.1533125
Accepted author version posted online: 06
Oct 2018.
Submit your article to this journal
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gcoo20

Spectral and computational chemistry studies for the optimization of
geometry of dioxomolybdenum(VI) complexes of some unsymmetrical
Schiff bases as antimicrobial agent
MOHAMMAD NASIR UDDIN*†, D.A. CHOWDHURY†, NOBUYUKI MASE‡,
MOHAMMAD FAZLUR RASHID†, MONIRUZZAMAN†‡, AMRIN AHSAN† and NOOR MOSTAQ SHAH†
†Department of Chemistry, University of Chittagong, Chittagong-4331, Bangladesh
‡Department of Applied Chemistry and Biochemical Engineering, Shizuoka University, 3-5-1, Johoku,
Hamamatsu 432-8011, Japan
This analysis highlights the design, spectroscopic characterization and quantum mechanical
calculation of some new dioxomolybdenum(VI) complexes of some dibasic tetradentate Schiff
bases. Ligands were derived from mono 5-bromosalicylaldehyde-orthophenylenediamine
(BrSal-OPD) and different 2-hydroxyketone derivatives. The characterization was performed by
1
elemental analysis, FTIR, electronic, H NMR and mass spectra, magnetic and molar
conductance studies. Structure of the ligands and complexes were designed depending on
experimental data and computational studies. According to all data, distorted octahedral
geometry was proposed where oxygen atoms are in cis position. Prepared complexes exhibit
moderate antimicrobial properties when evaluated against some pathogenic bacteria and fungi.
Pharmacokinetic parameters were calculated to search their biological action, e.g. absorption,
distribution, metabolism, excretion and toxicity.
Keywords: Dioxomolybdenum(VI); Dibasic tetradentate Schiff bases; Distorted octahedral
geometry; Computational chemistry; pharmacokinetics
1. Introduction
The chemistry of transition metal complexes of Schiff bases has attracted interest in the field of
bioinorganic and coordination chemistry [1]. Schiff bases containing imine group (-RC=N-) are
usually formed by the condensation of primary amine or diamine with an active carbonyl
compound. Every year a number of reports are published on preparation of such compounds and
their applications [2-6].
*Corresponding author. Emails: nasircu72@gmail.com, mnuchem@cu.ac.bd

Schiff bases are generally bi-, tri- or tetradentate ligands capable of forming very stable
complexes with transition metals [7]. Tetradentate Schiff bases with N2O2-donor atom set are
well known to coordinate with various metal ions and this has attracted many reports [8]. Many
symmetrical tetradentate bis-Schiff bases of 1,2-diamines with o-hydroxy aldehyde/ketone have
been prepared and studied intensively. Keto-enol isomerism of the Schiff
base N,N′-bis(salicylidene)-o-phenylenediamine derived by the condensation of salicylaldehyde
with o-phenylenediamine was studied [9]. Transition metal complexes of N,N′-bis[4-
(benzeneazo)salicylaldehyde]4-methyl-1,2-phenylenediamine
characterized [10]. Nickel, copper and zinc complexes of tetradentate ligands,
N,N-bis(salicylaldehyde)-o-phenylenediamine, N,N-bis(2-hydroxy-1-naphthaldehyde)-o-
were
synthesized
and
phenylene diamine and N,N-bis(o-hydroxyacetophenone)-o-phenylenediamine have been formed
[11]. Mixed-ligand complexes of the transition metal ions Ni(II), Cu(II), Co(II), Fe(II), Mn(II),
and Zn(II) with bis(4-methoxybenzylidene)-o-phenylinediamine (MeBen-opd) have been
synthesized [12].
Less attention has been focused on unsymmetrical tetradentate Schiff bases. In particular,
those derived from 1,2-diamines and different aldehydes/ketones [5, 7, 8]. Prasad et al. reported
the synthesis of unsymmetrical Schiff base ligand from acetyl acetone with o-phenylenediamine
as well as salicylaldehyde and their copper complexes [13]. Metal [Cu(II), Ni(II), Zn(II), Mn(II)
and Co(II)] complexes of unsymmetrical tetradentate Schiff base ligand derived 5-chloro-2-
hydroxybenzophenone, o-phenylenediamine, and salicylaldehyde have been prepared and
characterized by Bi and Fan [14].
The coordination chemistry of molybdenum has assumed special importance because of
its biochemical significance due to a large number of stable and accessible oxidation states
[15, 16] as well as for the involvement of Mo(VI) compounds as catalysts in several industrial
processes such as amoxidation of propene, epoxidation of olefins, olefin metathesis and
isomerization of alicyclic alcohols [17].
This manuscript focused on Mo(IV) complexes with some unsymmetrical Schiff bases
prepared from o-phenylinediamine and different aldehydes/ketones. Ligands and complexes are
1
characterized with conventional methods, elemental analysis, FTIR, electronic, H NMR and
mass spectra, magnetic and conductance studies. Antimicrobial properties of prepared ligands

and complexes have been investigated. Molecular modeling of the ligands and complexes has
been performed by using different quantum mechanical (QM) calculations.
2. Experimental
2.1. Materials and methods
The diamines and sodium molybdate dehydrate were obtained from M/S E. Merck and BDH
Chemicals, respectively, where others were collected from Aldrich Chemical Co. Ltd. Melting
points of ligands and complexes were obtained with an electrothermal melting point apparatus.
Infrared spectra on KBr pellets were recorded on a Shimadzu Infrared Spectrophotometer
(model-470). Electronic spectra were run on a Shimadzu UV-Visible Spectrometer (model-1800)
using 1 cm cell. 1H NMR of Schiff base ligands and their Mo(VI) complexes were recorded by a
BRUKER NMR Spectrometer from Wazed Miah Science Research Center (WMSRC),
Jahangirnagar University, Savar, Dhaka, Bangladesh, by dissolving samples in CDCl3 or DMSO,
respectively, and accordingly. Mass spectrum of several Schiff base ligands and their complexes
of Mo(VI) were recorded by the process “MS Scan‘ through Agilent 6460 Triple Quad LC/MS‘
by dissolving samples in DMSO and accordingly from UL Bangladesh Ltd., Dhaka, Bangladesh.
Conductivity was measured in DMF (10-3 M) solution with a Philips Conductivity Meter (model-
9501). Magnetic moment was determined at room temperature by the Gouy method.
2.2. Preparation of ligands
The tetradentate Schiff bases have been prepared by the usual condensation techniques by the
following two steps.
2.2.1. Synthesis of BrSal-OPD. o-Phenylenediamine (OPD) and 5-bromosalicylaldehyde (BrSal)
Br
were added in ratio 3:1 for the preparation of mono-Schiff base ligand, Sal-OPD (figure 1).
Br
OPD (40 mmol) was dissolved in 25 mL of rectified spirit (RS) to which Sal (10 mmol) was
added dropwise with continuous stirring in a round bottom flask fitted with a reflux condenser.
The mixture was heated at 60-65 C to reflux for 2 h and then cooled at room temperature. The
product was filtered off, washed with RS, then dried and preserved in a desiccator over silica gel
along with calcium chloride.

2.2.2. Synthesis of unsymmetrical tetradentate Schiff bases. Ethanolic solution (30 cm3) of
mono-(5-bromosalicyledhyde)-orthophenylenediamine (BrSal-OPD, 10 mmol) was added slowly
with stirring to aldehyde derivatives in ethanol (30 cm3). Aldehyde derivatives are
2-hydroxynapthaldehyde (HNPH2), salicylaldehyde (SalH2), 5-chlorosalicyldehyde (ClSalH2),
2-hydroxyacetophenone
(HAPH2),
2-hydroxypropiophenone
(HPPH2)
and
2-hydroxybenzophenone (BzPH2 (figure 2). This mixture was further stirred for about 25-30 min
at 50-70 C and then cooled in an ice-bath. After about 10-12 h precipitate was separated out.
This product was filtered off, washed with a small amount of ice-cooled ethanol and dried over
silica gel under vacuum at room temperature.
2.3. Preparation of complexes
2.3.1. Preparation of bis(acetylacetonato)dioxomolybdenum, [MoO2(acac)2]. The starting
material [MoO2(acac)2] was prepared by following a published procedure [18]. The compound
was characterized by its metal analysis and characteristic IR and electronic spectral data.
2.3.2. Preparation of Schiff base complexes. The Schiff base complexes (figure 2) were
prepared by reactions of [MoO2(acac)2] and the diamine Schiff base in ethanol medium by the
following procedure. 5 mmol of ligand was taken in a round bottom flask containing 40 cm3 of
ethanol and 4 mmol of [MoO2(acac)2] was added and stirred. The mixture was refluxed for
45 min and the product was precipitated out slowly. After cooling, this was filtered off, washed
with ethanol and dried under vacuum CaCl2. Physical properties of prepared ligands and
complexes are given in table S1 (Supplementary Material).
2.4. Estimation of Mo(VI) content
The molybdenum content of the prepared complexes was determined by complexometric
titration method after destruction of organic part of the complexes by the treatment with conc.
H2SO4, conc. HNO3 and 70% HClO4. In acidic medium, molybdenum(VI) forms a stable
complex on boiling with excess of 1,2-diaminocyclohexanetetraacetic acid (DCTA) and
hydroxylamine hydrochloride. Molybdenum can then be determined by back-titration when
excess DCTA was estimated with zinc chloride at pH 5-5.5 using xylenol orange as indicator. In

addition to Mo-content other elemental (C, H) analytical data of the complexes are given in
table 1.
2.5. Quantum mechanical (QM) methods
The initial structure of ligands and complexes were built up and all electronic calculations were
performed using Gaussian 09 program package. The QM calculation was implemented by using
density functional theory (DFT) employing Becke’s (B) [19] exchange functional combining
Lee, Yang and Parr’s (LYP) correlation functional [20] in Gaussian 09 program package for all
molecules [21]. Pople’s 6-31G (d) basis set was used to optimize and characterize the ligands
and metal complexes which has amply been proven to give very good ground state geometries
[22]. For every molecule’s internal electronic energy, enthalpy, Gibb’s free energy and dipole
moment were calculated.
Same level of theory was used to perform the molecular orbital calculations. Hardness (η)
and softness (S) of all drugs were also calculated from the energies of frontier HOMOs and
LUMOs considering Parr and Pearson interpretation [23] of harness in DFT and Koopmans
theorem [24]. Hardness (η) and softness (S) were calculated by using the following equations:
[
]
휀퐿푈푀푂− 휀퐻푂푀푂
2
1
휂 =
; 푆 = . Partial charges of the molecules were calculated through two
휂
methods (Mulliken charge and NBO charge).
Absorption, metabolism and carcinogenic properties of all drugs were predicted by
utilizing AdmetSAR online database [25]. Structure Data File (SDF) and Simplified molecular-
input line-entry system (SMILES) strings were utilized throughout the generation process.
2.6. Antimicrobial test
The antibacterial tests were performed against some human pathogenic bacteria such as Bacillus
megaterium, Bacillus cereus, Bacillus subtilis, Salmonella typhi, Salmonella paratyphi,
Escherichia coli and four selective phytopathogenic fungi such as Macrophomina phaseolina,
Fusarium equisite, Botrydiplodiia thobrome and Curvularia lunata. All strains were collected
from the Department of Microbiology, University of Chittagong. The identity of all strains was
confirmed.

2.6.1. Antibacterial activities. For the detection of antibacterial activities the disc diffusion
method [26] was done. Nutrient Agar (NA) was used as the basal medium for culture of test
bacteria and DMSO was used as a solvent for the initial preparation of the desired compound
solution [16]. NA medium was prepared using the following composition: beef extract (3 g),
peptone (5 g), NaCl (0.5 g), agar (15 g) and distilled water (1000 mL). A total of 1000 mL of
distilled water was placed in a beaker and 15 g of agar powder, 3 g of beef extract, 5 g of
peptone and 0.5 g of NaCl were added slowly and mixed thoroughly with a glass rod. The
mixture was heated to boiling for 10 min. After 10 min of boiling, the medium was transferred to
250 mL conical flasks at a volume of 200 mL per flask. The conical flask was closed with a
cotton plug and autoclaved at 121 C and 15 psi pressure for 15 min. Culturing of different
micro-organisms was then performed.
2.6.2. Antifungal activities. Potato Dextrose Agar (PDA) slants was prepared for maintenance
and culture preservation [27]. Small portions of mycelia of the collected fungal isolates were
transferred to the freshly prepared slants with the help of sterilized needles. The slants were
incubated at 27±2 °C for 3 to 5 days. Glass Petri plates were sterilized and the molted sterilized
PDA medium was poured at the rate 10 mL per petri plate. 0.10% solutions were prepared by
dissolving 0.001 g solid samples in 1 mL DMSO. Sterilized Potato Dextrose Liquid medium
(50 mL) was dispensed into 200 mL conical flasks conical flasks. Each of the flasks was labeled
and 100 µL of our test compound (0.1% concentration) were added. The flasks were shaken well
to mix thoroughly. Then 100 µL of 12 test samples each were added in each separate conical
flask and shaken well to mix thoroughly. After that, 1 mL of fungal suspension was added
carefully at each of the 13 conical flasks. All the conical flasks were incubated at 27±2 °C for
5 days. A control conical flask was prepared with DMSO solvent to observe the result.
3. Results and discussion
Ligands and complexes are characterized with conventional methods, elemental analysis,
1
spectral studies (FTIR, electronic, H NMR and mass spectra), magnetic and conductance
studies.

3.1. Infrared spectra
For the diamine Schiff bases and their complexes, the characteristic stretching modes are for
ν(C=N), ν(C-O), ν(C-N) and ν(C=C). The IR spectra for the prepared ligands and complexes
were taken in the range 4000-400 cm-1. Some tentative infrared spectral band assignments
characteristic to the complexes are included in table 1 and that of ligands are included in
table S2. It helped to indicate regions of absorptions due to the above-mentioned vibrations. The
presence of Mo-N and Mo-O vibrations confirms structural information about the coordination
environment of the molybdenum. Vibration frequency of the M=O groups confirms the presence
of molybdenum(VI) in the form of stable dioxocation, [MoO2]2+. On the basis of the FTIR
studies, bands observed for the present complexes in the regions 1575-1625, 1520-1570, 1385-
1460, 1350-1385 and 1250-1310 cm-1 have been assigned as ν(C=N), aromatic ν(C=C), ν(C-C),
ν(C-N) and ν(C-O), respectively. Bands near 3500 cm-1 for ligands are characteristic of phenolic
OH group. The bands appearing at 1350-1385 cm-1 (specially the highest frequency ones near
1385 cm-1) have been assigned to ν(C-N) [5, 6]. Again the bands appearing near 1285 cm-1 have
been assigned to ν(C-O) [2, 4]. Two sharp infrared bands for the prepared complexes in the
region around 870 and 960 cm-1 were observed due to the presence of MoO2 group. Bands
appearing in the regions 470-515 and 375-430 cm-1 are assigned to Mo-N and Mo-O vibrations,
respectively [3, 6, 10].
3.2. Electronic spectra
Because of the insolubility of the presently prepared complexes in common organic solvents
electronic spectra of the prepared ligands and complexes were recorded in DMF. Observed bands
and molar extinction coefficient (ε) values for complexes are shown in table 2. Observed bands
for ligands are given in table S2. There was no evidence of any d→d transition over the visible
region due to the absence of any peak above 500 nm. The observed bands lower to 300 nm of the
complexes may be assignable to ligand transition. The absorption bands appearing in the energy
region lower than 500 nm are attributable to a ligand to metal charge transfer (LMCT) transition.
3.3. 1H NMR Spectra
The 1H NMR spectra of the ligand BrSal-OPD-HAP and complexes were obtained in DMSO and
CDCl3 at room temperature using TMS as an internal standard. The free ligand exhibits a peak at

10.92 ppm, which is due to hydrogen-bonded phenolic protons as shown in figure 3. The
chemical shift observed for the OH protons in the ligands was not observed in any of the
complexes. The presence of a sharp singlet at 8.85-9.17 ppm is indicative to the -CH=N
azomethine proton. The downfield shift observed in complexes is due to the de-shielding of
azomethine protons as a result of the reduction of electron density after coordination. The
multiplets of aromatic protons appeared within the range 7.22-8.60 ppm. The CH3- and CH2-
1
proton signals are recognized at 2.50 and 3.16 ppm, respectively. H NMR assignments of the
complexes are given in table 2.
3.4. Mass spectrometry
The mass specta of (BrSal-OPD-HAP) and [MoO2(BrSal-OPD-HAP)] show molecular ion peak at
m/z = 408.4 and m/z = 534.3, respectively, which correspond to the molecular weight of the
respective compounds. The series of peaks in the ranges of 108.2, 122.4, 218.3, 234.5, 322.2,
336.5 and 408.1 may correspond to various fragments of BrSal-OPD-HAP. Again the mass
spectrum of [MoO2(BrSal-OPD-HAP)] shows peaks at 117.0, 219.1, 306.0, 360.2, 453.0, 495.1
and 534.3 may correspond to various fragments. In both cases, their intensity gives an idea of
stability of these fragments. The mass spectra of [MoO2(BrSal-OPD-HAP)] is given in figure 4.
The m/z values of all complexes are tabulated in table 2.
3.5. Conductivity measurements
The molar conductance values of the presently prepared complexes in DMF solution (ca. 10-3 M)
are shown in table 2. The low conductance values (4.0-15.0 Ohm-1 cm2 mol-1) of the prepared
complexes indicate their non-electrolytic nature.
3.6. Optimization of structure
The optimized structures of ligands are labeled as L1-L6 (ligands). The molecular formula and
thermochemistry of ligands like enthalpy, free energy, and electronic energy are reported in
table 3. The HOMO and LUMO energies, HOMO-LUMO gap, hardness and softness of all
ligands are presented in table S3. The bond distances and angles of ligands and their
corresponding complexes are shown in tables S4 and S5. A comparison on experimental and
theoretical IR frequencies of all ligands is shown in table S6. Selected pharmacokinetics

parameters of all ligands are reported in table S7. Optimized structures of ligands L1-L3 and
their complexes are shown in figure 5. Those of other ligands and complexes are presented in
figure S1. Frontier molecular orbitals, HOMO–LUMO of ligands (L1-L3) are in figure 6. Those
for remaining ligands are in figure S2. Molecular electrostatic potential of all ligands and
complexes are in figure 7.
3.6.1. Thermodynamic properties. Thermochemical data of the molecules obtained from the
calculations using the same level of theories discloses the potential stability and reactivity of the
molecules. Modification of ligands influences the structural properties including free energy,
partial charge distribution and dipole moment [20]. More negative values are observed for the
energy, enthalpy and free energies [28]. Free energy is a pivotal criterion to represent the
interaction of binding partners where both the sign and magnitude are important to express the
likelihood of biomolecular events occurring. Positive free energy values indicate that energy is
required to drive the interaction and binding will not occur spontaneously. All the values in this
inquiry are negative (table 3) meaning the binding will occur spontaneously without any extra
energy expenditure. The highest free energy change is observed for L6.
3.6.2. Frontier molecular orbital. In the concept of frontier molecular orbitals, the term
“frontier” refers to the orbitals that are at the outer edges of a molecule. These tend to be the
orbitals that are the most spatially delocalized and hence, the orbitals with the highest energies
(either occupied or unoccupied). In particular, two orbitals are of importance. These are the
highest occupied molecular orbital or (HOMO) and the lowest unoccupied molecular orbital
(LUMO). The HOMO–LUMO gap is related to the chemical hardness and softness of a
molecule. “Highest” and “lowest” refer to the energies. Energy (eV) of HOMO, LUMO,
HOMO-LUMO energy gap, hardness and softness of ligands and complexes are shown in
table S3. Bond distances and angles of selected ligands and complexes are tabulated in tables S4
and S5, respectively. Large HOMO-LUMO gap is related to high kinetic stability and low
chemical reactivity [29]. HOMO-LUMO gap, hardness and softness were calculated for the
compounds and smaller the HOMO-LUMO gap increases the softness and the compound
becomes more reactive. The lower frontier orbital energy gap and high dipole moment illustrates
the higher reactivity of the drugs. Higher softness makes the compound more polarizable and

chemically reactive. In this analysis, it is found that L1 has lower HOMO-LUMO gap and higher
softness which may contribute to its higher chemical activity than other ligands. A decreased
HOMO–LUMO gap in most of the ligands promotes softness which makes them relatively more
polarizable and chemically more reactive. However, for L2, there is an increase in the energy gap
significantly, thus lowering the chemical reactivity. Frontier molecular orbitals, HOMO–LUMO
of ligands L1-L3 have been shown in figure 6 (remaining are in figure S2).
3.6.3. Vibrational frequency. The vibrational band assignments were made using the Gauss-
View molecular visualization program for the ligands. The spectra contain some characteristic
bands of the stretching vibrations of the C-H, C-N, C-N, C-O, and C-H groups. A comparison on
experimental and theoretical IR-Frequencies of all ligands is tabulated in table S6 and IR spectra
obtained by the program are presented in figure S3. The aromatic structure shows the presence of
C-H stretching vibrations in the region 2900-3150 cm-1, which is the characteristic region for the
identification of C-H stretching vibrations. In this region, the bands are not appreciably affected
by the nature of the substituent. In the infrared spectra of the free ligands, the band observed in
the region 3250-3376 cm-1 is due to the OH group [10]. The bands observed at 1610-1625 cm-1
are due to v(C=N) of the azomethine group.
3.6.4. Molecular electrostatic potential. For the prediction of the reactive sites for electrophilic
and nucleophilic attack for the investigated compounds, molecular electrostatic potential (MEP)
was calculated at B3LYP/6-31+G(d,p) optimized geometries [30]. The different values of the
electrostatic potential at the surface are represented by different colors [31]; red represents
regions of most electro negative electrostatic potential, blue represents regions of the most
positive electrostatic potential and green represents region of zero potential. Potential decreases
in the order red < orange < yellow < green < blue. The MEP surface provides necessary
information about the reactive sites. The total electron density onto which the electrostatic
potential surface has been mapped is shown in figure 7.
3.6.5. Atomic partial charge. Different methods have been proposed for assigning partial
charges to the atoms of a molecule, including both quantum chemical and empirical schemes.
Partial charge is an important factor for a molecule to disclose its reactivity or stability [32].

Several different methods have been proposed for assigning partial charges to the atoms of a
molecule, including both quantum chemical and empirical schemes. Two different methods
(Mulliken and NBO) are used here to compute the atomic partial charges of our drugs, which
show positive charge when calculated with Mulliken and NBO methods [33]. Both NBO and
Mulliken method have a significant role in the application of quantum chemical calculations
because atomic charges affect some properties including dipole moment and polarizability.
Figure S4 shows the quantum chemical calculations of atomic partial charges of all ligands and
complexes.
3.7. Discussion on synthesis and geometry
Ortho-phenylenediamine (OPD) forms bis-Schiff bases with various aldehydes or ketones
because of the two amino functions. But attempts of the preparation of mono-Schiff base OPD
met the success. In preparing the mono-product, OPD and 5-bromosalicylaldehyde were mixed
in an excess molar ratio of ortho-phenylendiamine in the ratio 1:4. The presence of excess of
diamine helped the formation of mono-products instead of bis-product. In spite of our several
attempts, mono-products of salicylaldehyde of o-hydoxynapthaldehyde could not be isolated due
to their high solubility. This mono-product when reacted with other aldehydes or ketones gave
the desired unsymmetrical bis-product. Further attempts have been made to prepare metal
complexes of these unsymmetrical bis-products. It has been observed that cooling of the reaction
mixture in an ice bath is necessary for easy isolation of compounds in all cases. Also heating of
Br
the solution in ethanol of the Sal-OPDH did not change its property suggesting that mono-
product did not rearrange to bis-product on heating. Rather, it helped the faster completion of the
Br
reaction. Sal-OPD-HNPH2 being quite soluble in dry ethanol, product was obtained only after
Br
refluxed and then on concentration and on long cooling. Sal-OPDSalH2 was obtained similarly
as crystal. On the other hand BrSal-OPD-HAPH2 and BrSal-OPD-HPPH2 were obtained after
reflux, concentration and long cooling in a refrigerator. Complexes are moderately soluble in
most of the organic solvents but they are soluble in DMF or DMSO. The elemental analytical
data confirmed [MoO2L] composition that satisfied coordination requirements of Mo(VI) for an
octahedral configuration. It is also supposed the tetradentate nature of the ligands coordinated
through two azomethine nitrogens and two phenolic oxygens. [MoO2(acac)2] used as starting
material for complexes shows an IR band at 1580 cm-1 which is assigned to ν(C=O) due to

coordinated acetylacetone. The release of acetylacetone (acac) from [MoO2(acac)2] after
complexation forming [MoO2L] retaining the cis-dioxo bond was confirmed by the isolation of
[Cu(acac)2] from filtrate with Cu(CH3COO)2·H2O.
The high oxidation state +6 of molybdenum is stabilized by formation of dioxocation,
[MoO2]2+ and the chemistry of molybdenum is dominated by this stable dioxo-species commonly
referred to as molybdenum, [MoO2]2+ entity. The most characteristic feature of the
dioxomolybdenum complexes is only one sharp and strong (O=M=O) stretching frequency
observed in their infrared spectra at 900±50 cm-1 in the case of a trans-MoO2 group and two IR
bands in the case of a cis-MoO2 groups [34] due to the νasym(O=Mo=O) and νsym(O=Mo=O). The
position of these two cis-ν(Mo=O) bands in different complexes are found to vary from ligand to
ligand, indicating that the extent of location of electron cloud on Mo orbital significantly
influences the Mo=O bond. The dimeric dioxomolybdenum(VI) complexes show two or more
vibrational bands in this region in which there is oxygen bridged ----Mo---O---Mo--- chain
interaction and the ν(Mo=O) frequency occurs at a much lower wavenumber (850 cm-1) [35]. As
two bands in the region around 870-960 cm-1 were observed, table 3 argues the presence of a cis–
MoO2 group and the absence of any dimeric oxygen bridged chain structure which indicates the
monomeric capture of these complexes. The peaks between 1580 and 1670 cm-1 have been
assigned to ν(C=N). Location of C=N band was previously described in the same region
[5, 9, 10]. The band corresponding to the C=N group changed on complexation, which indicates
that the azomethine nitrogen is involved in coordination [9]. The integration of aromatic OH
peak is generally less than 2.0 due to intramolecular hydrogen bonding. The chemical shift
observed for the OH proton in the ligands was not observed in any of the complexes. This
disappearance of the singlet for the OH proton in the 1H NMR spectra of the complexes indicates
that the pheenolic oxygen atoms are coordinated to the central metal atom via deprotonation
[4, 5]. Therefore, the absence of ν(O-H) bands characteristics to ligands in the complexes and
negative shift of ν(C=N) indicate that the coordinated ligands acted as dinegative tetradentate
ones involving coordination through two deprotonated oxygens and two azomethine nitrogens
[7, 9]. The presence of a sharp singlet for the CH=N azomethine proton at 3.72 ppm of the
complex showed a downfield shift in the frequency, confirming coordination of the azomethine
nitrogen to central atom. This downfield shift may be assigned to the de-shielding of protons as a
result of the reduction of electron density after coordination. In addition, no characteristic

acetylacetone band is present in [MoO2L] complexes, indicating that no molybdenum
acetylacetonate impurity is present in the prepared [MoO2L] complexes.
The mass spectra of (BrSal-OPD-HAP) and [MoO2(BrSal-OPD-HAP)] correspond to
[M+1], supporting the structure of the complexes and confirming the M:L (1:1) type
stoichiometry of the metal chelates. For isotopic abundance, some fragments were found in
which one or two units were less or more than the calculated value. Elemental analysis data and
Mo-content also support the molecular formula as [MoO2L]. The low conductance values of the
prepared complexes indicate their non-electrolytic nature, indicating configuration of
molybdenum in its +6 oxidation state which is satisfied by the dinegatively charged tetradentate
ligand as expected.
Electronic spectral bands show no bands beyond 500 nm, indicating no d→d transition
over the visible region which is expected in the molybdenum(VI) complexes having 4d0
configuration. The diamagnetic behavior of these complexes supports 4d0 electronic
configuration consistent with 6+ oxidation state of the central molybdenum ion. The absorption
bands lower than 500 nm are attributable to a ligand-to-metal charge-transfer [LMCT] transition.
The bands in the higher energy region are attributable to π→π* or n→π* transitions within a
ligand molecule. Thus, the electronic spectral data and magnetic susceptibility values clearly
confirmed that the prepared complexes are genuine molybdenum(VI) species rather than
molybdenum(V).
Computational chemistry study complies with the proposed structure as [MoO2L]. Bond
angles and distances given in tables S4 and S5 are measured from the optimized structure of the
ligands and complexes. DFT has been employed to search their thermodynamic, frontier
molecular orbital, vibrational frequency, atomic partial charge, equilibrium geometry and
molecular electrostatic potential. All negative values are observed for the energy, enthalpy and
free energies, indicating that binding will occur spontaneously without any extra energy
expenditure [30]. In our analysis, it is found that L1 has lower HOMO-LUMO gap and higher
softness which may contribute to its higher chemical activity than other ligands. However, there
is an increase in the energy gap significantly for L2, thus lowering the chemical reactivity. The
comparisons on IR frequencies of selected regions comply with experimental and theoretical
values of all ligands. The characteristic region of the Schiff base derivative spectrum is 1500-
1700 cm-1 (IR spectra generated by the program are given in Supplementary Material), which is

attributed to C=N stretching vibration. The azomethine C=N stretching vibration gives rise to a
band at 1638 cm-1 in the infrared of experimental spectrum.
3.8. Pharmacokinetic parameters
Pharmacokinetic properties are calculated in AdmetSAR which predicts all compounds are non-
carcinogenic [25, 36]. Pharmacokinetic parameters were calculated to search their biological
action e.g. absorption, distribution, metabolism, excretion and toxicity. Selected pharmacokinetic
parameters of all ligands and complexes are given in table S7. All ligands are P-glycoprotein
non-inhibitors. P-glycoprotein inhibition can block the absorption, permeability and retention of
the drugs. P-glycoprotein inhibition can block the absorption, permeability and retention of the
ligands. The ligands show positive response for blood brain barrier (BBB) criteria, predicting
that drugs will go through BBB. However, Schiff base ligands show non-inhibitory property for
human ether-go-go-related gene (hERG). Inhibition of hERG can lead to long QT syndrome
[37].
3.9. Antimicrobial studies
In the present investigation ligands and complexes have been evaluated against ten selective
human pathogenic bacteria such as Bacillus megaterium, Bacillus cereus, Bacillus subtilis,
S. Aureus, Salmonella typhi, Salmonella paratyphi, S. Dysenteriae, P. Mutabilies, Escherichia
coli, Inaba Et and four selective phytopathogenic fungi such as Macrophomina phaseolina,
Fusarium equisite, Botrydiplodiia thobrome and Curvularia lunata. The antibacterial activities
of the test complexes were studied and detected by the disc diffusion method. The inhibition
zones of the test organisms for different ligands and complexes are presented in table 4. It was
found that almost all ligands and complexes are effective against the mentioned organisms
except Escherichia coli. C1, C4, C5 and C6 have no inhibitory effect against it. Ligands show a
bit lower inhibition than complexes. Ligands L3 and L6 show better inhibition than their
respective complexes. From such observation it may be indicated that the present complex
systems exhibit moderate antibacterial activity.
The percentage inhibition of mycelia growth of fungi due to the effect of studied
complexes has been compared with that for a standard antibiotic, nystatine. The results are
tabulated in table 5. The overall results indicate that prepared ligands and complexes showed

considerable inhibition of redial growth of mycelium against tested microorganisms. In both
cases, complexes showed a bit higher inhibition than corresponding complexes. Instead results of
inhibition by L3, L6 ligands and their respective complexes are comparable. Inhibition results
obtained are consistent with the result of our previous experiments [4-6].
4. Conclusion
The unsymmetrical Schiff bases were derived by the condensation of o-hydroxyaldehydes
(L1-L3) or ketones (L4-L6) with ortho-phenylenediamine. The prepared complexes with such
ligands have been found to be [MoO2L] (where LH2 = dibasic tetradentate ligands). The
analytical data indicate that the complexes have 1:1 (metal:ligand) stoichiometry. Conductivity
measurements indicate their non-electrolytic nature. The magnetic measurements along with
electronic spectral data of the prepared complexes support 4d0 electronic configuration of the
central metal ion consistent with the 6+ oxidation state of molybdenum ion. The infrared data
indicate the presence of a cis-MoO2 group in the complexes. The Schiff base ligands possess a
planar configuration with respect to the position of the donor ONNO atoms. The [MoO2L]
complexes are thought to possess a distorted octahedral structure. However, exact geometry of
each compound might be predicted by crystal structural evidences. AdmetSAR analysis predicts
that all compounds are non-carcinogenic and ligands are P-glycoprotein non-inhibitor. It may be
predicted that the prepared complexes exhibit moderate antibacterial and antifungal activity.
References
[1]
[2]
R. Ziessel. Coord. Chem. Rev., 216, 195 (2001).
J. Anandakumaran, M.L. Sundararajan, T. Jeyakumar, M.N. Uddin. Amer. Chem. Sci. J.,
11, 1 (2016).
[3]
[4]
[5]
M.N. Uddin, D.A. Chowdhury, M.M. Rony, M.E. Halim. Modern Chem., 2, 6 (2014).
M.N. Uddin, D.A. Chowdhury, K. Hossain. J. Chin. Chem. Soc., 59, 1520 (2012).
M.R. Hasan, M.A. Salam, M.A. Hossain, M.N. Uddin. J. Taibah Univ. Sci., 10, 766
(2016).
[6]
[7]
M.N. Uddin, S. Khandaker, Moniruzzaman, S. Amin, W. Shumi, M.A. Rahman, S.M.
Rahman. J. Mol. Struct., 1166, 79 (2018).
D.A. Chowdhury, M.N. Uddin, M.A.H. Sarker. Chiang Mai J. Sci., 35, 483 (2008).

[8]
[9]
M.N. Uddin, M.A. Salam, M.A.B. Siddique. Amer. J. Chem. Appl., 1, 19 (2014).
V.Z. Mota, G.S.G. de Carvalho, P.P. Corbi, F.R.G. Bergamini, A.L.B. Formiga, R. Diniz,
M.C.R. Freitas, A.D. da Silva, A. Cuin. Spectrochim. Acta, Part A, 99, 110 (2012).
[10] M. Lashanizadegan, M. Jamshidbeigi. Synth. React. Inorg. Met-Org. Nano-Met. Chem.,
42, 507 (2012).
[11] M.M. Abd-Elzaher. Synth. React. Inorg. Met-Org. Nano-Met. Chem., 30, 1805 (2000).
[12] Y.J. Thakor, S.G. Patel, K.N. Patel. J. Chem. Pharm. Res., 2, 518 (2010).
[13] M.S.N.A. Prasad, G. Neeraja, B.A. Kumar, K.M. Rao, B.K. Babu, R.B. Birudu. J. Chem.
Pharm. Sci., 10, 1406 (2017).
[14] C. Bi, Y. Fan. Synth. React. Inorg. Met-Org. Chem., 34, 687 (2004).
[15] S. Duman, I. Kizilcikli, A. Kaca, M. Akkurt, B. Ulkuseven. Polyhedron, 29, 2924 (2010).
[16] D. Millic, V. Vrdoljak, D. Matkovic-Calogovic, M. Cinddric. J. Chem. Crystallogr., 39,
553 (2009).
[17] R.J. Cross, P.D. Newman, R.D. Peacock, D. Stirling. J. Mol. Catal. A, 144, 273 (1999).
[18] T.J. Korstanje, E. Folkertsma, M. Lutz, J.T.B.H. Jastrzebski, R.J.M. Klein Gebbink. Eur.
J. Inorg. Chem., 12, 2195 (2013).
[19] A.D. Becke. Phys. Rev. A, 38, 3098 (1988).
[20] C. Lee, W. Yang, R.G. Parr. Phys. Rev. B, 37, 785 (1988).
[21] E. Pauwels, Uncovering Radiation Chemistry in the Solid State Through Periodic
Density-Functional Calculations: Confrontation with Experimental Results and Beyond,
in: A. Lund, M. Shiotani (Eds.), Appl. EPR Radiat. Res., 667-702, Springer International
Publishing (2014).
[22] H. Kruse, L. Goerigk, S. Grimme. J. Org. Chem., 77, 10824 (2012).
[23] J.L. Calais. Int. J. Quantum Chem., 47, 101 (1993).
[24] R.G. Pearson. Proc. Natl. Acad. Sci., 83, 8440 (1986).
[25] F. Cheng, W. Li, Y. Zhou, J. Shen, Z. Wu, G. Liu, P.W. Lee, Y. Tang. J. Chem. Inf.
Model., 52, 3099 (2012).
[26] M.N. Uddin, D.A. Chowdhury, M.T. Islam, F. Hoque. Orbital Elec. J. Chem., 4, 273
(2012).
[27] D.A. Chowdhury, M.N. Uddin, N. Lucky. Bull. Pure Appl. Sci., 22C, 39 (2003).
[28] N.C. Garbett, J.B. Chaires. Expert Opin. Drug Discov., 7, 299 (2012).

[29] T. Stein, J. Autschbach, N. Govind, L. Kronik, R. Baer. J. Phys. Chem. Lett., 3, 3740
(2012).
[30] I. Kostova, N. Trendafilova, G. Momekov. J. Inorg. Biochem., 99, 477 (2005).
[31] D. Petrey, B. Honig. Methods Enzymol., 374, 492 (2003).
[32] A.R. Katritzky, V.S. Lobanov, M. Karelson. QSPR: Chem. Soc. Rev., 24, 279 (1995).
[33] P. Bultinck, R. Vanholme, P.L.A. Popelier, F. De Proft, P. Geerlings. J. Phys. Chem. A,
108, 10359 (2004).
[34] D.A. Chowdhury, M.N. Uddin, A.K.M.L. Rahman. Chiang Mai J. Sci., 33, 357 (2006).
[35] A. Syamal. Coord. Chem. Rev., 16, 309 (1975).
[36] A. Smelcerovic, K. Tomovic, Z. Smelcerovic, Z. Petronijevic, G. Kocic, T. Tomasic, Z.
Jakopin, M. Anderluh. Eur. J. Med. Chem., 135, 491 (2017).
[37] F. Montanari, M. Pinto, N. Khunweeraphong, K. Wlcek, M.I. Sohail, T. Noeske, S.
Boyer, P. Chiba, B. Stieger, K. Kuchler, G.F. Ecker. Mol. Pharm., 13, 163 (2016).

Figure 1. Structure of the ligand BrSal-OPD.

Ligands
Complexes
R1
R1
N C
N
HC
N C
HO
N
HC
Mo
O
O
O
O
OH
R3
R3
R2
R2
Compound
L1/C1
R1
H
H
R2
Br
Br
Br
Br
Br
Br
R3
Fused Ph
L2/C2
L3/C3
L4/C4
L5/C5
H
Cl
H
H
H
H
-CH3
-CH2CH3
Ph
L6/C6
Figure 2. General structure of the ligands and their complexes.

Ar-OH
DMSO
Ar-H
CH3
CH=N
Figure 3. 1H NMR spectra of ligand BrSal-OPD-HAPH2.

Figure 4. The mass spectra of complex [MoO2(BrSal-OPD-HAP)].

L1
C1
C2
C3
L2
L3
Figure 5. Optimized structure of representative ligands (L1-L3) and their complexes.

HOMO
LUMO
L1
L2
L3
Figure 6. Frontier molecular orbitals, HOMO–LUMO of ligands (L1-L3).

-0.2922
+0.0958
-0.3084
+ 0.0981
-0.2577
+0.0676
L1
L2
L3
-0.2996
+0.0920
-0.2640
+ 0.0975
-0.2856
+0.1083
L4
L5
L6
-1.3210
+ 0.1861 -1.3029
-0.2327
-1.3007
-0.2309
C1
C2
C3
-1.3305
-0.2186
-1.3220
-0.2254
-1.2885
-0.2323
C4
C5
C6
Figure 7. Molecular electrostatic potential of all ligands and complexes.

Table 1. FTIR and elemental analysis data of the complexes.
Infrared spectral data (cm-1)
Elemental analysis
Sl No.
Complex
ν(C=N)
MoO2(BrSal- 1624 vs 1425 ms 1375 s
OPD-HNP) 1596 vs
MoO2(BrSal- 1602 vs 1430 ms
OPD-Sal) 1575 s 1420 ms
MoO2(BrSal- 1612 vs
ν(C-C)
ν(C-N)
ν(C-O)
1270 ms
1300 s
ν(Mo=O)
958 vs
904 s
ν(Mo-N) ν(Mo-O) % C
%H
% Mo
14.20
505 w
430 ms
400 w
420 s
50.52
2.58
C1
C2
C3
C4
C5
C6
475 ms
(50.46) (2.65) (16.79)
44.98 2.65 19.03
(45.87) (2.48) (18.41)
44.00 2.30 15.80
(43.23) (2.18) (17.27)
46.73 2.91 20.01
(46.91) (2.80) (17.93)
48.51 3.30 18.90
(48.11) (3.12) (17.47)
52.55 2.91 16.20
(52.07) (2.84) (15.99)
1372
ms
935 vs
900 s
1285 ms
470 s
500 s
380 vs
400 s
945 ms
905 ms
950 vs
878 s
OPD-ClSal)
MoO2(BrSal-
OPD-HAP)
MoO2(BrSal-
OPD-HPP)
MoO2(BrSal-
OPD-BzP)
1590 w 1395 ms 1350 s
1283 vs
1290 w
540 s
375 s
515 w
560 ms
552 ms
515 s
1598 vs 1425 ms 1368 s
410 ms
400 s
951 ms
900 s
1599 vs 1420 ms 1370ms
1280 s
1273 vs
1282 s
923 vs
887 ms
1612ms
1421s
1373 s
500 s
415m
 Calculated values are given in parentheses
 vs = very strong, s = strong, ms = medium strong, w = weak, sh = shoulder, flsh = flat shoulder, br =
broad

Table 2. 1H NMR assignments, UV-vis, conductance and mass spectral (m/z) data of the complexes.
Chemical shift (δ) in ppm
Electronic spectral band
(nm)
Λm
Complex
ε (M-1cm-1)
5.5×104
7.1 ×104
6.3×104
3.8×104
9.0×104
5.7×104
m/z
(Ohm-1cm2 mol-1)
N=CH-
Ar-H
-CH3
MoO2(BrSal-OPD-
HNP)
MoO2(BrSal-OPD-
Sal)
MoO2(BrSal-OPD-
ClSal)
MoO2(BrSal-OPD-
HAP)
MoO2(BrSal-OPD-
HPP)
MoO2(BrSal-OPD-
BzP)
9.15
7.80-8.60
---
390, 350, 324(sh), 270,
248, 238
4.0
5.0
573.24
523.18
557.62
534.21
551.23
599.28
9.07
8.85
9.17
9.05
9.21
7.83-8.25
7.40-8.20
7.88-8.45
7.62-8.46
7.87-8.55
---
---
490(flsh), 371, 313, 303,
269, 246
383(sh), 358, 317,
297(sh), 270
6.0
2.65
2.61
---
435, 415, 385(sh),
333(sh), 320, 296
13.0
15.0
9.0
391, 336, 313, 308, 252,
239
515, 373, 326(sh), 321,
272
 Electronic spectra and conductance data were carried out in DMF solvent.
1
 H NMR assignments were carried out in DMSO solvent.
Table 3. The molecular formula, electronic energy, enthalpy, Gibbs free energy in Hartree and dipole moment
(Debye) of all ligands and complexes.
Name
Molecular formula
Electronic energy
Enthalpy
Gibbs free energy
Dipole moment
L1
L2
L3
L4
L5
L6
C1
C2
C3
C4
C5
C6
C24H17BrN2O2
C20H15BrN2O2
-3739.687
-3586.923
-4044.346
-3626.019
-1103.876
-6148.136
-7847.140
-7694.605
-8151.992
-7733.677
-7772.748
-10254.578
-3739.663
-3586.923
-4044.323
-3625.997
-1103.855
-6148.135
-7847.117
-7694.581
-8151.967
-7733.652
-7772.721
-10254.555
-3739.742
-3586.993
-4044.398
-3626.072
-1103.927
-6148.212
-7847.193
-7694.658
-8152.046
-7733.652
-7772.807
-10254.633
3.880
5.592
4.944
6.420
4.246
4.918
7.729
7.077
7.492
6.662
6.964
5.983
C20H14BrClN2O2
C21H17BrN2O2
C22H20BrN2O2
C20H14Br2N2O2
C24H15BrN2O4Mo
C20H13BrN2O4Mo
C20H12BrClN2O4Mo
C21H15BrN2O4Mo
C22H17BrN2O4Mo
C20H10Br2N2O4Mo

Table 4. Comparison on inhibition zones (nm) against test organisms ‘bacteria’.
Inhibition zone in diameter (mm)
Bacteria
Ligands
Complexes
L1
L2
L4
L5
C1
C2
C4
C5
L3
L6
C3
C6
B. Megaterium
B. cereus
7
8
8
9
6
10
8
7
9
8
11
8
10
12
10
14
12
12
8
8
11
6
9
12
8
7
10
11
8
8
13
9
6
11
9
8
13
7
B. subtilis
S. Aureus
9
8
10
10
6
8
11
10
9
11
6
8
14
7
12
8
10
7
6
10
7
S. Typhi
8
10
9
10
7
10
6
S. Paratyphi
S. Dysenteriae
P. Mutabilies
E. Coli
9
7
7
7
8
9
9
7
8
3
8
8
6
8
8
8
7
8
15
2
13
8
16
1
13
2
20
0
16
10
12
18
0
16
0
24
9
22
0
25
8
22
0
Inaba Et
10
11
6
10
14
10
9
14
12
11
12

Table 5. Comparison on percentage inhibition of mycelia growth of fungi.
% Inhibition zone of mycelial growth of fungi
Compounds
M. Phaseolina
F. Equisite
B. Theobrome
C. Lunata
L1
C1
27.8
36.36
34.7
23.5
35.25
24.6
26.4
31.57
46.4
18.5
20.03
10.4
L2
C2
49.8
30.02
25.8
55.26
34.5
13.74
38.6
L3
32.5
C3
31.81
40.3
26.66
15.5
31.57
29.8
36.05
15.2
L4
C4
45.46
51..3
54.09
57.7
20.82
14.6
36.84
17.2
18.52
22.9
L5
C5
23.33
31.3
21.05
20.5
32.43
22.9
L6
C6
59.09
71.78
30.01
44.0
15.79
70.05
17.92
75.0
Nystatine
Graphical abstract
MoO2(5BrSal-Opd-HNP)
Complexes
R1
N C
N
HC
Mo
O
O
O
O
R3
R2