DMSO coordinated dioxidomolybdenum(VI) complexes chelated with 3-methoxybenzhydrazone related ligands: Synthesis, structural studies and in vitro cytotoxicity

Article abstract of DOI:10.1016/j.poly.2019.04.045

Three new DMSO coordinated dioxidomolybdenum(VI) complexes [MoO₂L^3OMe(DMSO)] (1), [MoO₂L^4OMe(DMSO)] (2) and [MoO₂L^5OMe(DMSO)] (3) (where, L^3OMe = 2-oxy-3-methoxybenzaldehyde-3-me

Full text of DOI:10.1016/j.poly.2019.04.045

Accepted Manuscript
DMSO coordinated dioxidomolybdenum(VI) complexes chelated with 3-me-
thoxybenzhydrazone related ligands: Synthesis, structural studies and in vitro
cytotoxicity
T.M. Asha, M.R.P. Kurup
PII:
S0277-5387(19)30292-X
https://doi.org/10.1016/j.poly.2019.04.045
POLY 13905
DOI:
Reference:
Polyhedron
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Revised Date:
Accepted Date:
12 January 2019
15 April 2019
24 April 2019
Please cite this article as: T.M. Asha, M.R.P. Kurup, DMSO coordinated dioxidomolybdenum(VI) complexes
chelated with 3-methoxybenzhydrazone related ligands: Synthesis, structural studies and in vitro cytotoxicity,
Polyhedron (2019), doi: https://doi.org/10.1016/j.poly.2019.04.045
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DMSO coordinated dioxidomolybdenum(VI) complexes chelated with 3-
methoxybenzhydrazone related ligands: Synthesis, structural studies and in vitro
cytotoxicity
T. M. Ashaa, M. R. P. Kurupa,b,
*
aDepartment of Applied Chemistry, Cochin University of Science and Technology, Kochi 682 022,
Kerala, India
bDepartment of Chemistry, School of Physical Sciences, Central University of Kerala, Tejaswini
Hills, Periye, Kasargod 671 316, Kerala, India
Abstract:
[MoO2L3OMe(DMSO)] (1), [MoO2L4OMe(DMSO)] (2) and [MoO2L5OMe(DMSO)] (3) (where, L3OMe
2-oxy-3-methoxybenzaldehyde-3-methoxy-benzhydrazonato, 2-oxy-4-
L4OMe
Three
new
DMSO
coordinated
dioxidomolybdenum(VI)
complexes
=
=
methoxybenzaldehyde-3-methoxybenzhydrazonato and L5OMe = 2-oxy-5-methoxybenzaldehyde-3-
methoxybenzhydrazonato) (Scheme 1) were synthesized by reacting [MoO2(acac)2] with the
corresponding aroylhydrazone in presence of the solvent, DMSO and fully characterized. The
various characterization techniques included elemental analysis, spectroscopic techniques (IR,
1
electronic and H NMR), thermogravimetric analysis and cyclic voltammetry. The molecular and
crystal structures of 1, 2 and 3 were determined by single crystal X-ray diffraction method. In all
complexes the molybdenum atom displays a distorted octahedral geometry. In addition, the
discussion on coordination geometries and non-covalent interactions were also supported using
Hirshfeld surface analysis. The in vitro cytotoxicity of the aroylhydrazone ligands and their
molybdenum complexes against lymphoma ascites cell line demonstrated that the complexes are
more cytotoxic than their corresponding ligands.
Keywords: Molybdenum(VI) complex, DMSO, Elemental analysis, Hirshfeld surface analysis,
Cytotoxicity, Lymphoma
Scheme 1
*Corresponding author at: Department of Chemistry, School of Physical Sciences, Central University of Kerala,
Tejaswini Hills, Periye, Kasaragod, 671 316, India, E-mail address: mrpcusat@gmail.com , mrp@cukerala.ac.in
(M.R.P. Kurup).
1

1. Introduction
Aroylhydrazones characterized by azomethine group (RC=N–) are excellent multidendate
ligands that form a significant class of compounds in medicinal and pharmaceutical chemistry and
are known to have biological applications due to their antibacterial [1-6], antifungal [3-6] and
antitumor [7,8] activities. Moreover the incorporation of transition metals into these compounds [9]
can lead to the enhancement of their biological property [10,11]. As one of the versatile element of
the periodic table, spanning oxidation states of -2 to +6, molybdenum has drawn the attention of the
coordination chemist in general [12-16]. At the present moment, the coordination chemistry of
molybdenum has become a prospective area of research due to the significant enzymatic role played
by molybdenum in biochemical reactions [17-19] especially in the oxidation of aldehydes, purines
and sulfides [20].
In this context, the oxidomolybdenum complexes coordinated with tridendate ligands have
drawn significant attention due to their similarity to the active site of majority of molybdoenzymes
[12,21]. This enzymatic role of molybdenum in biological reactions has created a tremendous
impetus in the syntheses of a number of model complexes mimicking oxotransferase
molybdoenzymes [13,22-27]. Molybdenum(VI) Schiff base complexes with a cis-MoO2 core are
excellent enzyme model systems for this purpose. Moreover possessing an Mo=O unit has been
widely used in catalysis for numerous industrially important chemical reactions such as hydrogen
generation [28], alkene epoxidation [29,30] and sulfide oxidation [31].
In spite of the synthesis of many molybdenum Schiff base complexes, there are few reports on
the cytotoxicity of these complexes, though our group have reported the synthesis and in vitro
cytotoxicity studies of dioxidomolybdenum(VI) complexes derived from an ONO donor
aroylhydrazone with different donor auxilliary ligands [32]. In continuation of our previous study
[32], the present study focuses on the effect of position of the methoxy substituent on the aldehydic
part (keeping the hydrazide part constant) on their crystal structures and in vitro-cytotoxicity.
2. Results and discussion
2.1 Synthesis and characterization
The aroylhydrazones, H2LR (R= 3OMe, 4OMe and 5OMe) are soluble in both protic
solvents such as MeOH and EtOH, as well as in aprotic solvents such as DMF and DMSO. The
reaction of the aroylhydrazones with [MoO2(acac)2] in 1:1 molar ratio in presence of DMSO
yielded solid complexes corresponding to the general formula [MoO2LR(DMSO)] (R= 3OMe (1),
4OMe (2) and 5OMe (3)). The complexes are stable at room temperature and are insoluble in most
of the inorganic solvents, but readily soluble in DMSO and DMF. The molar conductance values of
2

the complexes were measured in DMF (10-3 M) at room temperature and showed values within the
range (5-10) Ω-1 cm2 mol-1 indicating their non-electrolytic nature in solution [33]. The
aroylhydrazone ligands and their respective complexes were characterized by IR, 1H NMR and UV-
visible spectroscopic techniques along with thermal and cyclic voltammetric measurements.
2.2 IR spectra: The IR spectra of the aroylhydrazones, H2L3OMe, H2L4OMe and H2L5OMe exhibit
medium and broad band centered at 3580, 3448 and 3468 cm-1 respectively and are assigned to
ν(O–H) vibrations. Weak and sharp bands at 3184, 3226 and 3217 cm-1 respectively corresponds to
the ν(N–H) vibrations. On the other hand sharp bands at 1645, 1624 and 1654 cm-1 respectively are
attributed to the ν(C=O) vibrations [34].
The IR spectra of the complexes are mostly similar. The complexes do not exhibit ligand
bands of ν(O–H), ν(N–H) and ν(C=O) vibrations indicating the enolization and deprotonation of the
aroyl hydrazones with concomitant coordination of the enolic and phenolic groups to the
molybdenum atom, which is in accordance with the result obtained by X-ray crystallography [34].
Moreover the appearance of new C–O bands at 1251, 1296 and 1239 cm-1 for complexes 1, 2 and 3
suggest the tautomerisation of hydrazone ligands and coordination in the enolate form. The
characteristic imine band in H2L3OMe, H2L4OMe and H2L5OMe, which exist at 1644, 1630 and 1647
cm-1 respectively were found to have shifted to lower frequency of 1619, 1615 and 1643 cm-1 for
their corresponding complexes [35] indicating the coordination of azomethine nitrogen atom to the
molybdenum ion [36]. Medium to strong band at about 1431-1499 cm-1 for the free hydrazone
ligands are assigned to phenolic ν(C–O) stretch which undergoes a shift to lower frequency in the
case of molybdenum complexes [37] suggesting that the phenolic oxygen atom also coordinate to
molybdenum ion. Only a slight change is observed in the position of the bands in the 1046-1132
cm-1 region which are assigned to ν(N–N) stretch in the case of molybdenum complexes. The
Mo=O stretching modes occurring as a pair of sharp and strong bands at 948 and 893 cm-1; 901 and
853 cm-1; 949 and 852 cm-1 for the respective complexes 1, 2 and 3 are assigned to the
antisymmetric and symmetric stretching modes respectively. This is in accordance with the
observation on similar complexes [32,37,38]. The infrared spectral assignments for the
dioxidomolybdenum complexes 1-3 are presented in the Table S1 of the supporting information.
1
1
2.3 H NMR spectra: The H NMR spectra of the hydrazone ligands, H2L3OMe-5OMe and their
1
molybdenum(VI) complexes were recorded in DMSO. The H NMR spectra of the free
aroylhydrazones exhibited a singlet in the downfield region of the spectrum at δ= 11.972-12.120
ppm due to the iminolic proton (HN–N). The phenolic OH proton (OHphenolic) resonates at δ=
10.746-11.614 ppm and Hazomethine–C=N at δ= 8.550-8.695 ppm.
3

Upon complexation, the OH and NH proton signals disappeared indicating the deprotonation of
phenolic OH and NH and subsequent coordination of oxygen atom of the phenolic group and
azomethine nitrogen atom to molybdenum atom. The participation of the azomethine nitrogen in
complexation is signaled by an appreciable downfield shift of the azomethine proton signal. All the
aromatic proton signals of the aroylhydrazones and their Mo complexes were observed in the
expected region of δ= 6.504-7.648 ppm. All the three complexes exhibit resonance peaks
corresponding to the coordinated DMSO molecule at δ= 2.546-2.565 ppm which are tabulated in
Table S2.
2.4 Electronic spectra: Electronic spectra of the aroylhydrazones and their molybdenum
complexes were recorded in DMF as well as in DMSO and the spectral characteristics of the
compounds are listed in Table S3(a) and S3(b). The electronic spectra of the complexes 1-3 exhibit
strong absorptions between 420-452 nm which is believed to originate from the charge transfer
transition of the type L→Mo(dπ) between the highest occupied ligand molecular orbital and the
lowest empty d orbital of molybdenum [38]. In addition to that, complexes 1-3 exhibit strong
absorption between 300-330 nm regions owing to the intraligand transitions [38]. Absence of bands
due to d-d transition supports the existence of Mo(VI) ion [39].
2.5 Thermogravimetric analysis: Thermal behavior of the complexes 1, 2 and 3 were studied
using thermogravimetric analysis and the experiments were carried out under nitrogen atmosphere
in the temperature range 35–900 °C at a heating rate of 10 °C min-1. The samples were purged by a
stream of dry nitrogen flowing at 20 mL min-1. The thermal curves of all the three complexes are
presented in Figure 1.
The TGA curves of the complexes reveal that all the complexes are stable upto a temperature of
150 °C and undergo decomposition at two well defined stages (Table 1). The loss of weakly
coordinated DMSO molecule occurred between the temperature range of 200-240 °C, 150-210 °C
and 170-205 °C for complexes 1, 2 and 3 respectively. With further elevation in temperature, the
second stage of decomposition took place in the temperature range of 270-290 °C, 270-310 °C and
270-310 °C for 1, 2 and 3 corresponding to the loss of (CH3O-C6H4-CONN) moiety formed by the
dissociation of the hydrazone ligand at the –C=N– bond. Decomposition continues until the final
residue MoO3 is left which was identified by qualitative analysis.
Figure 1
Table 1
2.6 PXRD analysis: Powder diffraction data revealed the isostructurality of the molybdenum
complexes 1-3. The PXRD patterns of complexes 1-3 is depicted in Figure 2.
4

Figure 2
2.7 Electrochemical studies: The redox behavior of the aroylhydrazones and their molybdenum
complexes were examined in DMF solution by cyclic voltammetry at platinum electrode with 0.1 M
tetraethylammonium perchlorate (TEAP) as the supporting electrolyte. The CV data is tabulated in
Table 2. The aroylhydrazones, H2L3OMe, H2L4OMe and H2L5OMe exhibit an irreversible one reductive
peak around -0.458 V, 1.233 V and 1.479 V respectively.
The CV trace of complex 1 portrayed two irreversible reductive responses within the potential
window of -0.894 to -0.331 V, which can be attributed to the MoVI/ MoV and MoV/ MoVI processes,
respectively [17,40]. Whereas complexes 2 and 3 exhibited only one irreversible reductive peak
around -1.190 V and -1.198 V respectively owing to the MoVI/ MoV process. The dearth of anodic
response in the CV traces of the complexes 1-3 even at a higher scan rate can be attributed to the
rapid decomposition of the reduced species [41].
Table 2
2.8 Crystallographic description of the complexes
The crystal data of complexes 1-3 are presented in Table 3. The molecular structures and atom
numbering schemes for the complexes 1-3 are shown in Figure 3 and the selected bond distances
and bond angles are presented in Table 4. Crystal structures of the three complexes revealed that in
all complexes, the aroylhydrazones act as a tridentate ligand bonding through its imine nitrogen,
N(1), phenoxy oxygen, O(1) and the hydroxyl oxygen, O(3) from the enolized carbonyl group
forming five and six membered chelate ring around cis-MoO2 centre. The chelate rings form bite
angles O(1)–Mo(1)–N(1) (82.093(8)° for 1, 80.716(6)° for 2 and 82.093(6)° for 3) and
O(3)–Mo(1)–N(1) (71.755(8)° for 1, 72.300(6)° for 2 and 71.763(7)° for 3). Molybdenum ion
features a distorted octahedral geometry with an NO5 coordination sphere, where the imine
nitrogen, phenoxy oxygen, enolic oxygen and one of the oxido oxygen atom O(5) of the
dioxidomolybdenum unit occupying the equatorial position. On the other hand, the apical positions
of the octahedron are occupied by the other oxido oxygen atom O(6) and the oxygen atom of the
coordinated DMSO molecule O(7).
Table 3
Figure 3
Table 4
The values of the Mo=O bond lengths, 1.7061(2) and 1.6943(2) Å for 1, 1.7183(2) and
1.6976(1) Å for 2 and 1.7072(2) and 1.6933(16) Å for 3 are similar for other cis-MoO2 complexes
5

[15,40-43] and the Mo–O, Mo–N and N–N bond lengths are also found to be within the Mo(L)
2+
fragment. In Mo complexes, based on the MoO2 core it is expected, due to the trans effect, the
Mo–D (D = donor atom of the coordinated ligand) bonds positioned trans to the oxygen atoms of
2+
the MoO2 core are longer than the remaining ones. Thus, the longer Mo–O(DMSO) distance is
well expected for this type of complexes. The C–O bond distances C(8)–O(3) for the complexes
(1.3251(4) Å for 1, 1.3343(7) Å for 2 and 1.3298(3) Å for 3) were found to be nearer to a C–O
single bond (1.42 Å) than to a C–O double bond distance (1.16 Å).
Another fascinating observation is that the Mo atom in the molecular structures of complexes
1-3 shows a displacement towards the apical oxido oxygen atom, O(6) by around 0.2 Å from the
O1/N1/O3/O5 basal plane.
Molecular structures of all the complexes exhibited a common non-classical intermolecular
hydrogen bonding interaction, where the aldehydic proton, H(7) is involved in intermolecular
hydrogen bonding interaction with oxido oxygen atom, O(6). Similarly complexes, 1 (Figure 4)
and 2 (Figure S1) exhibit an intermolecular hydrogen bonding interaction between aromatic proton
of the salicylaldehyde and the other oxido oxygen atom, O(5). Crystal structure of complex 3
(Figure S2) exhibited two bifurcated hydrogen bonding interactions where both the oxido oxygen
atom, O(5) and O(6) are involved in bonding with methyl proton of coordinated DMSO [H(18A)]
and aromatic proton H(2) of salicylaldehyde; and methyl proton of coordinated DMSO respectively.
Whereas in complex 2, the methyl protons of DMSO [H(18A) and H(18C)] shows intermolecular
hydrogen bonding interaction with methoxy oxygen atom, O(4) and enolic oxygen atom, O(3) of
the benzhydrazide moiety. Crystal structures of 1-3 are deficient of any classical hydrogen bonding
interactions. The interaction parameters for the hydrogen bonding interactions are tabulated in
Table S4.
Figure 4
In complexes 1 and 3, the six membered chelate ring involving molybdenum atom,
Mo1/O1/C1/C6/C7/N1 is puckered with a puckering amplitudes of Q= 0.3194 (18) Å, φ=197.8(5)°
and Q= 0.2971 (16) Å, φ=25.7(4)° respectively. Furthermore complexes 1-3 do not exhibit any π-π
interactions.
2.9 Hirshfeld surface analysis
The intermolecular interactions in the crystal structures of the complexes 1-3 were visualized
with the help of Crystal Explorer 17.5 [44]. The Hirshfeld surface of the complexes 1-3 are shown
in Figure 5 that have been mapped over a 3D dnorm, shape index and curvedness. A measure of
globularity (G) and asphericity (Ω) [45] were also made (Table S2). Globularity values for all the
6

complexes are in the range 0.680–0.691 which shows that all of them deviate from spherical surface
[46].
Figure 5
Asphericity (Ω) values (Table S5) are a measure of anisotropy of objects and it was found to be
0.198-0.216 indicating their deviation from symmetry [47]. Graphical plots of the molecular
Hirshfeld surfaces mapped with dnorm employs a red–white–blue color scheme, where the white
surface indicates contacts with distance equal to the sum of van der Waals radii, whereas the red
and blue color indicates distance shorter (in close contact) or longer (distance contact) than van der
Waals radii, respectively [48]. The medium red color spots in the Hirshfeld surface mapped with
dnorm of the complexes 1-3 display the major C–H···O interaction due to the presence of non-
classical hydrogen bonding interaction involving the complexes in the asymmetric unit (Figure 6).
Shape index patterns give a perception about the various π-π stacking interactions present in the
complex which appears as “bow-tie” patterns. Dearth of such patterns in the shape index surface of
complexes (Figure 6) indicate the absence of any π-π stacking interactions in the crystals of these
complexes substantiating the results obtained from the crystal data [49,50]. The curvedness is a
measure of the shape of the surface area of the molecule. The flat areas of the surface correspond to
low values of curvedness, while sharp curvature areas correspond to high values of curvedness and
usually tend to divide the surface into patches, indicating interactions between neighboring
molecules. The large flat region delineated by a blue outline refer to the π···π stacking interactions.
Therefore the curvedness of the complexes (Figure 6) also reveals that π···π stacking interactions
are absent in these complexes [50,51].
The combination of de and di in the form of a 2D fingerprint plot provides a summary of
intermolecular contacts in the crystal and are in complement to the Hirshfeld surfaces. 2D
fingerprint plots of Hirshfeld surface for the complexes and the relative contributions of different
interactions overlapping in the full fingerprint plots are shown in Figure 7. Complementary regions
are visible in the fingerprint plots where one molecule act as donor (de>di) and the other as an
acceptor (de< di). Decomposition enables separation of contributions from different interactions
which overlap in full fingerprint plots. The decomposition of fingerprint plot shows that the non-
directional H···H/H···H interactions have the highest contribution (40.9% in 1, 40.3% in 2 and
41.6% in 3) of the total Hirshfeld surface. Despite the high share of this interaction, its role in the
stabilization of structure is quite small in magnitude because this interaction is between the same
species [52]. The O···H/H···O intermolecular interactions appear as distinct spikes in the 2D
fingerprint plots. The proportions of this interaction are 32.7, 32.4, and 33% of the Hirshfeld
surfaces for each molecule of 1, 2 and 3, respectively. No significant C–H···π interactions are
7

observed in these complexes while the C···H close contacts are 14.4%, 16.4%, and 14.6% in 1, 2,
and 3, respectively. Relative contributions from all the major interactions to the Hirshfeld surface
are specified in Figure 8.
Figure 6
Figure 7
Figure 8
2.10 In vitro cytotoxicity
In vitro cytotoxicity of the complexes 1-3 were evaluated using Dalton’s lymphoma ascites cell
line (DLA). The results of the investigation (Table 5) demonstrate a dose-dependent (10, 25, 50,
100 and 200 μg/mL) behavior for all the studied complexes against the aforementioned cell line.
The free aroylhydrazones showed very low cytotoxicity compared to their corresponding
molybdenum complexes showing the essential role made by the metal, molybdenum in facilitating
the potency of these complexes. The potency of the compound to kill the cells followed the order
3>1>2 (Figure 9) indicating that complex 3 is the more effective complex in controlling the growth
of DLA cell lines among the three complexes. This may be attributed to the difference in the
position of the methoxy substituent of the salicylaldehyde part of these complexes.
Difference in the cell lines and treatment duration made it difficult for us to compare the
cytotoxicity effect of the present complexes with that of the other molybdenum complexes other
than those previously reported by our group [32].
Table 5
Figure 9
3. Experimental section
3.1 Materials
All chemicals used were procured commercially and used without subsequent purification.
2-Hydroxy-5-methoxybenzaldehyde, 3-methoxybenzhydrazide, [MoO2(acac)2], were obtained from
Sigma Aldrich, 2-hydroxy-3-methoxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde from
Alfa Aesar. Solvents methanol, DMF and DMSO were purchased from Spectrochem.
3.2 Instrumentation and characterization procedures
Elemental analyses were carried out using a Vario EL III CHNS analyser. Infrared spectra
were recorded as KBr pellets on a JASCO FT-IR-5300 spectrometer in the range 4000-400 cm-1.
8

Electronic spectra were recorded using a Thermo Scientific Evolution 220 model UV-vis
spectrophotometer in the 200-900 nm range. Molar conductivities of the complexes in DMF
solutions (10-3 M) at room temperature were measured using a Systronic model 303 direct reading
1
conductivity meter. The H NMR spectra were recorded using a Bruker AMX 400 FT-NMR
Spectrometer using TMS as internal standard at ambient temperature. Thermogravimetric (TG)
analysis of the complexes was carried out by heating in a nitrogen gas at a rate of 10 ºC per minute
on a Perkin Elmer Pyris TGA thermobalance. Electrochemical measurements were carried out
using a CH 6017B instrument using Pt working electrode, a Pt auxiliary electrode and Ag/AgCl
reference electrode. Cyclic voltammograms were recorded in DMF containing 0.1 M TEAP
(tetraethylammonium perchlorate) as a supporting electrolyte and a 5 x 10-4 M complex solution
deoxygenated by bubbling with nitrogen gas before use. The X-ray powder diffraction patterns of
complexes 1-3 were recorded on a Bruker AXS D8 Advance diffractometer.
3.3 Synthesis
3.3.1. Syntheses of the aroylhydrazones
2-Hydroxy-3-methoxybenzaldehyde-3-methoxybenzhydrazone (H2L3OMe): 2-Hydroxy-
3-methoxybenzaldehyde, 0.152 g (1.0 mmol) was dissolved in 20 ml methanol. The solution was
then added to a methanolic solution of 0.166 g (1.0 mmol) of 3-methoxybenzhydrazide. The
reaction mixture was refluxed for 3 h resulting in a light yellow colored solution. A precipitate was
formed when the solution was allowed to cool at room temperature overnight. The yellow
precipitate obtained was filtered, washed with methanol and dried in air.
Yield: 0.18 g, 63%. Anal.Cal. for C16H16N2O4 (300.31 g mol-1); C, 63.99; H, 5.37; N, 9.33.
Found: C, 63.92; H, 5.29; N, 9.35. IR (KBr) νmax, cm-1: ν(O–H) 3580(m), ν(N–H) 3184(m),
1
ν(C=O) 1645(s). H NMR (400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.806 (s, 3H, methoxy), 3.824 (s,
3H, methoxy), 6.851-7.520 (m, 7H, aromatic), 8.645 (s, 1H, HC=N), 10.993 (s, 1H, OH group),
12.081 (s, 1H, NH group). UV/vis (DMF) λmax, nm (ε, L mol-1 cm-1): 302 (15600).
Similar procedure was applied for the preparation of H2L4OMe and H2L5OMe
.
2-Hydroxy-4-methoxybenzaldehyde-3-methoxybenzohydrazone, (H2L4OMe): Yield: 0.20
g, 67%. Anal.Cal. for C16H16N2O4 (300.31 g mol-1); C, 63.99; H, 5.37; N, 9.33. Found: C, 63.95; H,
1
5.32; N, 9.37. IR (KBr) νmax, cm-1: ν(O–H) 3580(m), ν(N–H) 3184(m), ν(C=O) 1645(s). H NMR
(400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.834 (s, 3H, methoxy), 3.778 (s, 3H, methoxy), 6.504-7.513
(m, 7H, aromatic), 8.550 (s, 1H, HC=N), 11.614 (s, 1H, OH group), 11.972 (s, 1H, NH group).
UV/vis (DMF) λmax, nm (ε, L mol-1 cm-1): 331 (84125).
9

2-Hydroxy-5-methoxybenzaldehyde-3-methoxybenzohydrazone, (H2L5OMe).: Yield: 0.17
g, 57%. Anal.Cal. for C16H16N2O4 (300.31 g mol-1); C, 63.99; H, 5.37; N, 9.33. Found: C, 63.85; H,
1
5.41; N, 9.31. IR (KBr) νmax, cm-1: ν(O–H) 3580(m), ν(N–H) 3184(m), ν(C=O) 1645(s). H NMR
(400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.798 (s, 3H, methoxy), 3.901 (s, 3H, methoxy), 6.922-7.589
(m, 7H, aromatic), 8.695 (s, 1H, HC=N), 10.746 (s, 1H, OH group), 12.120 (s, 1H, NH group).
UV/vis (DMF) λmax, nm (ε, L mol-1 cm-1): 295 (583125), 353 (44782).
3.3.2. Synthesis of the dioxidomolybdenum(VI) complexes
(3-Methoxysalicylaldehyde-3-methoxy-
benzylhydrazonato)dimethylsulfoxidedioxidomolybdenum(VI), (1). A solution of H2L3OMe
(0.300 g, 1.00 mmol), which was dissolved in 20 mL of methanol was added to a solution of
[MoO2(acac)2] in 20 mL methanol. A dark orange precipitate formed immediately. DMSO was
added dropwise until the precipitate was completely dissolved in the solution. The reaction mixture
was then refluxed for 4 h and was allowed to stand at room temperature. Orange block shaped
crystals were formed after slow evaporation for 2 days. The products were filtered, washed with
ethanol and dried in air.
Yield: 0.17 g, 35%. Molar conductance (10-3 M DMF): 6 Ω-1 cm2 mol-1. Anal.Cal. for
C18H20MoN2O7S (504.39 g mol-1); C, 42.86; H, 4.00; N, 5.55; S, 6.36. Found: C, 42.92; H, 4.09; N,
5.45; S, 6.31. IR (KBr) νmax, cm-1: ν(C=N) 1610, ν(Caro–O) 1523, ν(N–N) 1180, ν(C–O) 1256,
1
νasym (cis-MoO2) 931, νsym (cis-MoO2) 896. H NMR (400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.818
(s, 3H, methoxy), 3.827 (s, 3H, methoxy), 7.028-8.250 (m, 7H, aromatic), 8.914 (s, 1H, HC=N).
UV/vis (DMF) λmax, nm (ε, L mol-1 cm-1): 322 (23150), 452 (8129).
Similar procedure was applied for the preparation of the complexes 2 and 3.
(4-Methoxysalicylaldehyde-3-methoxy-
benzylhydrazonato)dimethylsulfoxidedioxidomolybdenum(VI), (2). Yield: 0.16 g, 32%. Molar
conductance (10-3 M DMF): 12 Ω-1 cm2 mol-1. Anal.Cal. for C18H20MoN2O7S (504.39 g mol-1); C,
42.86; H, 4.00; N, 5.55; S, 6.36. Found: C, 42.85; H, 4.04; N, 5.59; S, 6.35. IR (KBr) νmax, cm-1:
ν(C=N) 1610, ν(Caro–O) 1523, ν(N–N) 1180, ν(C–O) 1256, νasym (cis-MoO2) 931, νsym (cis-MoO2)
896. 1H NMR (400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.824 (s, 3H, methoxy), 3.817 (s, 3H,
methoxy), 6.545-7.648 (m, 7H, aromatic), 8.846 (s, 1H, HC=N). UV/vis (DMF) λmax, nm (ε, L mol-
1 cm-1): 315 (22145), 421 (7120).
10

(5-Methoxysalicylaldehyde-3-methoxy
benzylhydrazonato)dimethylsulfoxidedioxidomolybdenum(VI), (3). Yield: 0.20 g, 40%. Molar
conductance (10-3 M DMF): 8 Ω-1 cm2 mol-1. Anal.Cal. for C18H20MoN2O7S (504.39 g mol-1); C,
42.86; H, 4.00; N, 5.55; S, 6.36. Found: C, 42.75; H, 4.03; N, 5.51; S, 6.32. IR (KBr) νmax, cm-1:
ν(C=N) 1610, ν(Caro–O) 1523, ν(N–N) 1180, ν(C–O) 1256, νasym (cis-MoO2) 931, νsym (cis-MoO2)
896. 1H NMR (400 MHz, DMSO-d6, Me4Si, ppm) δ: 3.822 (s, 3H, methoxy),3.774 (s, 3H,
methoxy), 6.886-7.597 (m, 7H, aromatic), 8.903 (s, 1H, HC=N).UV/vis (DMF) λmax, nm (ε, L mol-1
cm-1): 329 (25140), 430 (4123).
3.3.3 X-ray single crystal diffraction studies
Diffraction quality block shaped orange crystals 1, 2 and 3 were mounted on a Bruker SMART
APEXII CCD diffractometer, equipped with a graphite crystal, incident-beam monochromator and a
fine focus sealed tube with Mo Kα (λ = 0.71073 Å) radiation as the X-ray source. The unit cell
dimensions were measured and the data collection was performed. The programs SAINT and
XPREP were used for data reduction and APEX2 and SAINT were used for cell refinement [53].
Absorption corrections were carried out using SADABS based on Laue symmetry using equivalent
reflections [54]. The crystal structures were solved by direct methods using SHELXS-97 and
refined by full matrix least-squares refinement on F2 using SHELXL-2014/7 [54] on a WinGX
software package [55]. The molecular and crystal structures were plotted using ORTEP-3 [55] and
DIAMOND version 3.2 g [56].
In all the complexes, anisotropic refinements were performed for all non-hydrogen atoms and
all H atoms on C atoms were placed in calculated positions, guided by difference maps, with C–H
bond distances of 0.93–0.96 Å. H atoms were assigned as Uiso = 1.2 Ueq (1.5 for Me). The
reflections (0 1 0), (1 -1 1), (-1 0 1), (0 0 1), (0 4 0) and (-1 -1 1) in 2 and (1 -2 4), (0 0 1), (0 1 0), (0
-1 1), (-1 1 0) and (1 0 0) in 3 were omitted owing to bad agreement.
3.3.4. Hirshfeld surface calculations
Hirshfeld surface analysis represents a new radical and visually appealing approach for gaining
additional insight into the intermolecular interactions between the molecules in the crystals. The
size and shape of Hirshfeld surface allows the qualitative and quantitative investigation as well as
visualization of intermolecular close contacts in molecular crystals. Hirshfeld surface analyses
were carried out and 2D fingerprint plots were plotted using the software package Crystal Explorer
17.5 [57]. Surfaces in 3D (dnorm) have been mapped over a range of -0.5 Å to 0.5 Å, shape index
(−1.0 to 1.0 Å) and curvedness (−4.0 to 0.4 Å) where dnorm function signifies the ratio covering the
11

distance of any surface point to the nearest interior (di) and exterior (de) atom and van der Waals
radii (rvdw) of the atoms. It is given by the Equation 1. The dnorm surfaces are mapped over a fixed
color scale. The red spots over the surface indicate the intercontacts involved in hydrogen bonds
[58]. The dark red spots on the dnorm surface arise as a result of the short interatomic contacts, i.e.,
strong hydrogen bonds while the other intermolecular interactions appear as light-red spots.
퐝퐢 ‒ 퐫퐯퐝퐖
퐝퐞 ‒ 퐫퐯퐝퐖
퐢
퐞
Equation 1
퐝퐧퐨퐫퐦
=
+
퐫퐯퐝퐖
퐫퐯퐝퐖
퐢
퐞
The information generated through a Hirshfeld surface can be further quantified using two
dimensional fingerprint plots [59]. The 2D fingerprint plots were displayed by using the expanded
0.6-2.8 Å view with de and di distance scales displayed on the graph axes where the frequency of
occurrence of interactions (the number of points with a given (de, di) pair) are represented by the
different colors blue (low frequency), green (medium) and red (high). Again, the complementary
regions are visible in the FPs, where one molecule act as donor (de> di) and the other as an acceptor
(de< di) [60].
3.3.5. In vitro cytotoxicity studies
The aroylhydrazones and their complexes were studied for their short term in vitro
cytoxicity using Dalton’s lymphoma ascites cells (DLA). The tumour cells aspirated from the
peritoneal cavity of tumour bearing mice were washed thrice with PBS (Phosphate Buffered Saline)
or normal saline. Cell viability was determined by Trypan blue exclusion method. Viable cell
suspension (1 x 106 cells in 0.1 mL) was added to tubes containing various concentrations of the
test compounds (samples dissolved in DMSO) and the volume was made up to 1 mL using PBS
control tube containing only cell suspension. These assay mixtures were then incubated for 3 hours
at 37 ºC. Further cell suspension was mixed with 0.1 mL of 1% trypan blue and kept for 2-3
minutes and loaded on a haemocytometer. Dead cells take up the blue colour of trypan blue while
live cells do not take up the dye. The numbers of stained and unstained cells were counted
separately and the % cytotoxicity was calculated using Equation 2.
퐍퐨. 퐨퐟 퐝퐞퐚퐝 퐜퐞퐥퐥퐬
% Cytotoxicity = 퐍퐨. 퐨퐟 퐥퐢퐯퐞 퐜퐞퐥퐥퐬 + 퐍퐨. 퐨퐟 퐝퐞퐚퐝 퐜퐞퐥퐥퐬 100
Equation 2
×
4.
Conclusion
Three new DMSO coordinated mononuclear cis-dioxidomolybdenum(VI) complexes of the
type [MoO2LR(DMSO)] have been successfully synthesized and characterized by various
physicochemical techniques and by single crystal X-ray diffraction studies. Crystallographic
studies revealed that the binegative hydrazones satisfy the +2 charge of the MoO2 moiety leading to
12

the formation of uncharged complexes where the molybdenum atom displays a distorted octahedral
geometry. Moreover the donor solvent molecule, DMSO in the complexes is attached loosely to the
2+
MoO2 moiety thereby making the substitution at the sixth position easy. Electrochemical study
depicted the irreversible redox behaviour of these complexes. Finally all the complexes displayed a
concentration dependent cytotoxic profile where the highest activity was exhibited by complex 3
with the methoxy substituent at the fifth position suggesting that the position of the substituents can
also influence the cytotoxicity of the complexes. Similarly the effect of position of the substituents
on the hydrazide part will be studied in due course.
Appendix A. Supplementary data
CCDC 1881036, 1881037 and 1881038 contain the supplementary crystallographic data for
[MoO2L3OMe(DMSO)] (1), [MoO2L4OMe(DMSO)] (2) and [MoO2L5OMe(DMSO)] (3) respectively.
These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 IEZ, UK; fax: (+44)
1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Acknowledgement
T.M. Asha acknowledges the CSIR, New Delhi, India for the award of a Senior Research
Fellowship (09/239(0510)/2015-EMR-I). The authors are thankful to the Sophisticated Analytical
Instrumentation Facility, Cochin University of Science and Technology, Kochi, India for elemental
analysis, 1H NMR spectra and single crystal X-ray diffraction measurements.
References
[1]
[2]
[3]
[4]
A.A.A. Abu-Hussen, J. Coord. Chem. 59 (2006) 157.
P.B. Sreeja, M.R.P. Kurup, A. Kishore, C. Jasmine, Polyhedron 23 (2004) 575.
K. Singh, M.S. Barwa, P. Tyagi, Eur. J. Med. Chem. 41 (2006) 147.
P. Pannerselvam, R.R. Nair, G. Vijayalakshmi, E.H. Subramanian, S.K. Sridhar, Eur. J.
Med. Chem. 40 (2005) 225.
[5]
S.K. Sridhar, M. Saravanan, A. Ramesh, Eur. J. Med. Chem. 36 (2001) 615.
[6]
N.A. Mathews, A. Jose, M.R.P. Kurup, J. Mol. Struc. 1178 (2019) 544.
[7]
R. Mladenova, M. Ignatova, N. Manolova, T. Petrova, I. Rashkov, Eur. Polym. J. 38 (2002)
989.
[8]
O.M. Walsh, M.J. Meegan, R.M. Prendergast, T.A. Nakib, Eur. J. Med. Chem. 31 (1996)
989.
13

[9]
F.A. Afkhami, G. Mahmoudi, A.A. Khandar, A. Franconetti, E. Zangarando, N. Qureshi, J.
Lipkowski, A.V. Gurbanov, A. Frontera, European J. Inorg. Chem., 2018 (2019) 262; G.
Mahmoudi, A.A. Khandar, F.A. Afkhami, B. Mirslaw, A.V. Gurbanov, F.I. Zubkov, A. Kennedy,
A. Franconetti, A. Frontera, CrystEngComm. 2019 (21) 108; D. Sadhukhan, M. Maiti, A. Bauza, A.
Frontera, E. Garribba, C.J. Gomez-Garcia, Inorg. Chim. Acta 2019 (484) 95; S.K. Seth, A. Bauza,
G. Mahmoudi, V. Stilnovic, E. Lopez-Torres, G. Zaragoza, A.D. Keramidas, A. Frontera,
CrystEngComm. 2018 (20) 5033.
[10] Z. Travnicek, M. Malon, Z. Sindelar, K. Dolezal, J. RoIcik, V. Krystof, M. Strnad, J. Marek,
J. Inorg. Biochem. 84 (2001) 23.
[11] M. Sonmez, I. Berber, E. Akbas, Eur. J. Med. Chem. 41 (2006) 101.
[12] J.M. Berg, R.H. Holm, J. Am. Chem. Soc. 107 (1985) 925.
[13] R.H. Holm, Chem. Rev. 87 (1987) 1401.
[14] R.H. Holm, Coord. Chem. Rev. 100 (1990) 183.
[15] S. Purohit, A.P. Koley, L.S. Prasad, P.T. Manoharan, S. Ghosh, Inorg. Chem. 28 (1989)
3735.
[16] A. Rana, R. Dinda, P. Sengupta, S. Ghosh, L.R. Falvello, Polyhedron 21 (2002) 1023; M. E.
Judmaier, C. Holzer, M. Volpe, N.C. Mosch-Zanetti, Inorg. Chem. 51 (2012) 9956; c) T.M. Asha,
M.R.P. Kurup, J Chem Crystallogr., 2018, https://doi.org/10.1007/s10870-018-0756-9.
[17] O.A. Rajan, A. Chakravorty, Inorg. Chem. 20 (1981) 660.
[18] M.M. Abu-omar, A. Loaiza, N. Hontzeas, Chem. Rev. 105 (2005) 2227.
[19] J. Topich, Inorg. Chem. 20 (1981) 3704.
[20] E.I. Stiefel, Science 272 (1996) 1599.
[21] E.I. Stiefel, in: S. J. Lippard (Ed.), Progress in Inorganic Chemistry, John Wiley & Sons Inc,
New York 22 (1977) 1.
[22] A. Majumdar, S. Sarkar, Coord. Chem. Rev. 255 (2011) 1039.
[23] R.H. Holm, E.I. Solomon, A. Majumdar, A. Tenderholt, Coord. Chem. Rev. 255 (2011) 993.
[24] S. Metz, W. Thiel, Coord. Chem. Rev. 255 (2011) 1085.
[25] R. Hille, Chem. Rev. 96 (1996) 2757.
[26] D. Collison, C.D. Garner, J.A. Joule, Chem. Soc. Rev. 25 (1996) 25.
[27] J. Liimatainen, A. Lehtonen, R. Sillanpaa, Polyhedron 19 (2000) 1133.
[28] J.P. Cao, L.L. Zhou, L.Z. Fu, J.X. Zhao, H.X. Lu, S.Z. Zhan, Catal. Commun. 57 (2014) 1.
[29] J. Zhang, P. Jiang, Y. Shen, W. Zhang, X. Li, Microporous Mesoporous Mater 206 (2015)
161.
[30] S. Rayati, N. Rafiee, A. Wojtczak, Inorg. Chim. Acta 386 (2012) 27.
[31] E. Zamanifar, F. Farzaneh, J. Simpson, M. Maghami, Inorg. Chim. Acta 414 (2014) 63.
14

[32] T.M. Asha, M.R.P. Kurup, Inorg. Chim. Acta 483 (2018) 44.
[33] W.J. Geary, Coord. Chem. Rev. 7 (1971) 81.
[34] M.M. Fousiamol, M. Sithambaresan, V.A. Smolenski, J.P. Jasinski, M.R.P. Kurup,
Polyhedron 141 (2018) 60.
[35] A. Aravindakshan, B. Joseph, U.L. Kala, M.R.P. Kurup, Polyhedron 123 (2017) 206.
[36] B.S. Garg, M.R.P. Kurup, S.K. Jain, Y.K. Bhoon, Transit Met. Chem. 16 (1991) 111; M.
Kuriakose, M.R.P. Kurup, E. Suresh, Polyhedron 26 (2007) 2713.
[37] R.A. Lal, A. Kumar, J. Chakraborty, S. Bhaumik, Transit. Met. Chem. 26 (2001) 557.
[38] S. Roy, Saswati, S. Lima, S. Dhaka, M.R. Maurya, R. Acharyya, C. Eagle, R. Dinda, Inorg.
Chim. Acta 474 (2018) 134.
[39] A.P. Koley, S. Purohit, S. Ghosh, L.S. Prasad, P.T. Manoharan, J. Chem. Soc. Dalton
Trans., 0 (1988) 2607.
[40] R. Dinda, P. Sengupta, S. Ghosh, W.S. Sheldrich, Eur. J. Inorg. Chem., 2003 (2003) 363.
[41] R. Dinda, S. Ghosh, L.R. Falvello, M. Tomas, T.C.W. Mak, Polyhedron 25 (2006) 2375.
[42] E.B. Seena, M.R.P. Kurup, Polyhedron 26 (2007) 3595.
[43] P. Nag, R. Bohra, R.C. Mehrotra, R. Ratnani, Tran. Met. Chem. 27 (2002) 321; J.H.
Enemark, J.J.A. Cooney, J.J. Wang, R.H. Holm, Chem. Rev. 104 (2004) 1175.
[44] M.J. Turner, J.J. McKinnon, S.K. Wolf, D.J. Grimwood, P.R. Spackman, D. Jayatilaka,
M.A. Spakman, Crystal Explorer 17.5, 2017, University of West Australia.
[45] S.S. Sreejith, N. Mohan, M.R.P. Kurup, J. Mol. Struc. 1145 (2017) 170.
[46] A.Y. Meyer, Chem. Soc. Rev. 15 (1986) 449.
[47] P.P. Devi, D. Kalaivania, Acta Cryst. E72 (2016) 570.
[48] P. Venkatesan, S. Thamotharan, A. Illangovan, H. Liang, T. Sundius, Spectrochim. Acta
Part A 153 (2016) 625.
[49] M. Malecka, E. Budzisz, CrystEngComm. 16 (2014) 6654.
[50] G. Mahmoudi, A. Bauza, A. Rhodriguez-Dieguez, P. Garczarek, W. Kaminsky, A. Fronter,
CrystEngComm. 18 (2016) 102.
[51] Y. Li, C.G. Zhang, L.Y. Cai, Z.X. Wang, J. Coord. Chem. 66 (2013) 3100.
[52] C.F. Matta, J. Hernandez- Trujillo, T.H. Tang Dr, R.F.W. Bader, Chem. Eur. J. 9 (2003)
1940.
[53] SMART and SAINT, Area Detector Software Package and SAX Area Detector Integration
Program, Bruker Analytical X-ray, Madison, WI, USA, 1997.
[54] SADABS, Area Detector Absorption Correction Program; Bruker Analytical X-ray;
Madison, WI, USA, 1997.
[55] G.M. Sheldrick, Acta Crystallogr. C71 (2015) 3.
15

[56] L.J. Farrugia, J. Appl. Crystallogr. 45 (2012) 849.
[57] K. Brandenburg, Diamond version 3.2g, Crystal Impact, GbRBonn, Germany, 2011.
[58] A. Wang, B.M. Craven, J. Pharm. Sci. 68 (1979) 361; M. A. Spackman, P. G. Byrom,
Chem. Phys. Lett. 267 (1997) 215; M.A. Spackman, D. Jayatilaka, Cryst. Eng. Comm. 11 (2009)
19; S. K. Seth, D. Sarkar, A.D. Jana, T. Kar, Cryst. Growth Des. 11 (2011) 4837.
[59] J.J. Mckinnon, M. A. Spackman, A.S. Mitchell, Acta Cryst. B60 (2004) 627.
[60] S.S. Sreejith, A. Nair, V.A. Smolenski, J.P. Jasinski, M.R.P. Kurup, Inorg. Chim. Acta 469
(2018) 264; S. K Wolff, D.J. Grimwood, J.J. McKinnon, M.J. Turner, D. Jayatilaka, M.A.
Spakman, Crystal Explorer (Version 3.1) 2012.
16

Table 1. Results of thermogravimetric analysis of complexes 1-3
Weight loss
Temperature
End
Residue
Compound
observed
Molecules lost
range (°C)
(a) 200-240
(b) 270-290
(a) 150-210
(Calculated)%
14.70 (15.46)
33.42 (32.31)
15.61(15.46)
DMSO
Complex 1
MoO3
MoO3
Hydrazone fragment[a]
DMSO
Complex 2
(b) 270-310
(a) 170-205
(b) 270-310
31.17 (32.31)
17.90 (15.46)
32.01 (32.31)
Hydrazone fragment[a]
DMSO
MoO3
Complex 3
Hydrazone fragment[a]
[a] = CH3O-C6H4-CONN
Table 2. Cyclic voltammetry results for the studied compounds
Compound
[a]
Epc
H2L3OMe
-0.458
H2L4OMe
-1.233
H2L5OMe
-1.479
Complex 1
Complex 2
Complex 3
-0.331, -0.894
-0.190
-0.198
[a]Solvent: DMF; working electrode: platinum; auxiliary electrode: platinum; reference electrode: Ag/AgCl; supporting
electrolyte: 0.1 M TEAP; scan rate: 100 mV/ s. Epc is the cathodic peak potential.
Table 3. Crystal data and refinement details of 1–3.
17

[MoO2L5OMe(DMSO)] (3)
Parameters
[MoO2L3OMe(DMSO)] (1)
[MoO2L4OMe(DMSO) ](2)
Empirical formula
C18H20MoN2O7S
504.36
C18H20MoN2O7S
504.36
C18H20MoN2O7S
504.36
Formula weight
Crystal system
Triclinic
Triclinic
Triclinic
1
1
1
Space group
P
P
P
Cell parameters
a (Å)
8.5060(6)
10.7073(6)
12.0592(7)
69.403(2)
82.375(3)
87.739(3)
1018.98(11)
2
7.5269(6)
10.8302(10)
13.5388(13)
98.681(4)
103.478(4)
102.701(4)
1022.94(16)
2
8.4972(3)
10.6204(4)
12.5081(5)
110.271(2)
102.808(2)
96.366(2)
1010.55(7)
2
b(Å)
c (Å)
α (°)
β (°)
γ (°)
Volume(V) (Å3)
Z
Calculated density (ρ)(Mg m-3)
Absorption coefficient, μ (mm-1)
F(000)
1.644
1.637
1.658
0.789
0.789
0.795
512
512
512
Crystal size (mm3)
θ (°)
0.35 x 0.30 x 0.30
3.107 - 28.179
0.30 x 0.20 x 0.20
2.781-28.199
0.50 x 0.30 x 0.20
2.654- 28.315
≤
≤
≤
≤
≤
≤
≤
≤
≤
≤
≤
≤
-11
-12
-16
h
k
l
10
14
16
-9
h
7
-11
-13
-16
h
k
l
10
14
16
≤
≤
14
Limiting indices
-14
-17
k
≤
≤
≤
≤
l
17
Reflections collected / unique reflections (Rint
)
7643 / 5017 , (Rint= 0.0139)
95.6
8072 / 4559 , (Rint= 0.0166)
99.2
16659/4899 , (Rint= 0.0214)
99.8
Completeness to θ
Absorption correction
Semi-empirical from equivalents
0.798 and 0.761
Semi-empirical from equivalents
0.790 and 0.755
Semi-empirical from equivalents
0.791 and 0.757
Maximum and minimum transmission
Data / restraints / parameters
Goodness-of-fit(GOF) on F2
Final R indices [I>2σ(I)]
4693 / 0 / 266
4559 / 0 / 266
4899 / 0 / 266
1.108
1.092
1.046
R1 = 0.0320, wR2 = 0.0739
R1 = 0.0378, wR2 = 0.0797
0.738 and -0.679
R1 = 0.0223, wR2 = 0.0587
R1 = 0.0262, wR2 = 0.0616
0.335 and -0.435
R1 = 0.0284, wR2 = 0.0689
R1 = 0.0336, wR2 = 0.0724
1.421 and -0.499
R indices (all data)
Largest difference peak and hole (eǺ-3)
R1 = Σ||F0| - |Fc|| / Σ|F0|, wR2 = [Σw(F02-Fc2)2/Σw(F02)2]1/2
Table 4. Selected bond lengths (Å) and bond angles (°) of compounds 1–3.
18

Bond Lengths
C(1)–O(1)
1
2
3
1.350(3)
1.325(3)
1.427(4)
1.405(5)
1.285(3)
1.298(3)
1.394(3)
2.232(2)
2.020(3)
1.706(18)
1.694(19)
2.306(19)
1.347(2)
1.334(2)
1.430(3)
1.419(3)
1.294(2)
1.296(2)
1.403(2)
2.227(15)
1.998(13)
1.718(13)
1.697(15)
2.323(15)
1.359(2)
1.330(2)
1.408(4)
1.417(4)
1.282(3)
1.289(3)
1.403(2)
2.238(17)
1.998(14)
1.707(16)
1.694(17)
2.311(15)
C(8)–O(3)
C(15)–O(2)
C(16)–O(4)
C(7)–N(1)
C(8)–N(2)
N(1)–N(2)
N(1)–Mo(1)
O(3)–Mo(1)
O(5)–Mo(1)
O(6)–Mo(1)
O(7)–Mo(1)
Bond Angle
O(6)–Mo(1)–O(5)
O(6)–Mo(1)–O(1)
O(5)–Mo(1)–O(1)
O(6)–Mo(1)–O(3)
O(5)–Mo(1)–O(3)
O(1)–Mo(1)–O(3)
O(6)–Mo(1)–N(1)
O(5)–Mo(1)–N(1)
O(1)–Mo(1)–N(1)
O(3)–Mo(1)–N(1)
O(6)–Mo(1)–O(7)
O(5)–Mo(1)–O(7)
O(1)–Mo(1)–O(7)
O(3)–Mo(1)–O(7)
N(1)–Mo(1)–O(7)
106(10)
105(17)
105.09(9)
98.91(8)
103.73(7)
97.32(8)
96.39(7)
149.76(6)
92.84(8)
159.82(8)
82.09(6)
71.76(6)
168.92(7)
85.92(8)
79.22(6)
79.97(6)
76.10(6)
97.99(9)
105.24(9)
97.30(9)
94.90(8)
150.06(8)
92.17(9)
158.66(9)
82.08(8)
71.75(8)
167.74(9)
85.92(9)
79.42(7)
80.19(7)
75.62(7)
99.05(7)
103.91(6)
95.75(7)
95.56(6)
151.42(6)
95.78(7)
156.91(7)
81.97(6)
72.29(5)
169.59(6)
84.95(6)
80.71(6)
80.39(6)
73.85(5)
19

Table 5. Percentage of cell death for the aroylhydrazones and their molybdenum complexes.
Drug
Percentage cell death (DLA) %
Concentration
H2L3OMe
1
H2L4OMe
2
H2L5OMe
3
μg/ mL
200
100
50
8
6
2
0
0
25
12
8
9
6
4
0
0
24
16
8
8
7
4
1
0
32
22
16
10
4
20
2
4
10
0
0
20

O
N
N
H2L3OMe
N
H
OCH3
OCH3
OH
OCH3
O
H2L4OMe
N
H
OH
OCH3
OCH3
H2L5OMe
O
N
N
H
OH
OCH3
Scheme 1: Structures of the aroylhydrazones.
Figure 1: Thermograms of complexes 1-3.
21

Figure 2: Powder XRD diffraction pattern of complexes 1-3 (a-c).
MeOH
Reflux
H
H
N
NH2
O
+
R
N
N
H3CO
R
H3CO
OH
O
OH
O
H2L3OMe-5OMe
[MoO2(acac)2]
R
N
N
MeOH
DMSO
H3CO
O
O
R= 3-MeO (Complex 1)
R= 4-MeO (Complex 2)
R= 5-MeO (Complex 3)
Mo
O
O
O
S
Complex 1-3
Scheme 2: Synthesis of the aroylhydrazone ligands and the molybdenum complexes.
22

Figure 3: ORTEP plot of [MoO2L3OMe(DMSO)] (1) (a), [MoO2L4OMe(DMSO)] (2) (b) and [MoO2L5OMe(DMSO)] (3) (c)
along with atom numbering scheme of the non-hydrogen atoms. Displacement ellipsoids are drawn at 50% probability.
23

Figure 4: Diagram depicting major hydrogen bonding interactions in [MoO2L3OMe(DMSO)] (1).
Figure 5: (a) Hirshfeld surface mapped with dnorm (color scale from -0.1203 to 1.2821 (for 1 and 2; color scale from -
0.2153 to 1.4542 (for 3)), (b) shape index and (c) curvedness for the compounds 1-3.
24

Figure 6: 2D fingerprint plots with de and di ranging from 1 to 2.8 Å for 1-3 and their major decomposition plots.
Figure 7: (a) Non-classical hydrogen bonding interactions present in 1 involving C7–H7···O2 and C12–H12···O5, (b)
viewing the same short contacts in Hirshfeld surface with external molecules.
25

Figure 8: Percentage contributions to the Hirshfeld surface area for the various close intermolecular contacts for
molecules.
Figure 9: Cytotoxicity profiles of the aroylhydrazones and their molybdenum complexes.
26

Three new DMSO coordinated dioxidomolybdenum(VI) complexes of aroylhydrazones were
synthesized and spectral and structural studies were done The in vitro cytotoxicity of the
aroylhydrazone ligands and their molybdenum complexes against lymphoma acsites cell line
demonstrated that the complexes are more cytotoxic than their corresponding ligands.
27

DMSO coordinated dioxidomolybdenum(VI) complexes chelated with 3-
methoxybenzhydrazone related ligands: synthesis, structural studies and in-vitro
cytotoxicity
T. M. Asha and M. R. P. Kurup
Graphical Abstract
28