Ru3+, Mn2+, Co2+, Ni2+, Cu2+, and Zn2+ uni-metallic complexes of 3-(-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) methylene) hydrazono)indolin-2-one, preparation, structure elucidation and antibacterial activity

Article abstract of DOI:10.1016/j.molstruc.2021.131194

Ru³⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺ uni-metallic complexes of dihydrazone derived from the condensation of 3-hydrazonoindolin-2-one with 4-formyl antipyrine were synthesized. The resulted dihydrazone and its chelated compounds structurally characterized basing on spectroscopic tools (NMR, FT-IR, EAS, ESI-MS) thermo-gravimetric, elemental, magnetic and molar conductance measurements. This structural elucidation leads us to conclude that the dihydrazone has been performed as a neutral bidentate chelator linked the Ru³⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺ ions via the carbonyl and azomethine of isatin moiety adopting regular or distorted octahedral structures around the central metallic ions. The structural description of dihydrazone and its chelated compounds have been endorsed basing on the Density Functional Theory calculations. The optimized geometry, global reactivity descriptors, and LUMO-HOMO orbitals and of the molecules have been calculated by the DFT-B3LYP method and 6e311G(d,p) basis set. The molecular electrostatic potential picture has been painted utilizing the same level of theory to envision the molecules charge distribution and chemical reactivity. The DFT studies of the designated compounds revealed small HOMO-LUMO gap which is a strong indication to the large reactivity these compounds. The TG analysis has confirmed the complexes chemical formulae and assured that the thermo-degradation processes occur in three or four steps ended with the formation of metal oxide or carbon-contaminated metal oxide residues. The In-vitro antibacterial of dihydrazone and its chelated compounds have been evaluated against E. coli, P. aeruginosa, K. pneumonia and B. subtilis, the observed antibacterial result denoted that Cu²⁺ and Zn²⁺ complexes have a good activity in comparation with the free dihydrazone.

Full text of DOI:10.1016/j.molstruc.2021.131194

Journal of Molecular Structure 1246 (2021) 131194
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
3
+
2+
2+
2+
2+
2+
Ru , Mn , Co , Ni , Cu , and Zn uni-metallic complexes of
-(-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)
3
methylene) hydrazono)indolin-2-one, preparation, structure
elucidation and antibacterial activity
a,∗
a
b
Mohamad M.E. Shakdofa , Quad M. Selim , Adel M.E. Shakdofa
a
Department of Chemistry, college of Science and Arts at Khulais, University of Jeddah, Jeddah, Saudi Arabia
b
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
3+
2+
2+
2+
2+
2+
Ru , Mn , Co , Ni , Cu , Zn uni-metallic complexes of dihydrazone derived from the condensation
of 3-hydrazonoindolin-2-one with 4-formyl antipyrine were synthesized. The resulted dihydrazone and its
chelated compounds structurally characterized basing on spectroscopic tools (NMR, FT-IR, EAS, ESI-MS)
thermo-gravimetric, elemental, magnetic and molar conductance measurements. This structural elucida-
tion leads us to conclude that the dihydrazone has been performed as a neutral bidentate chelator linked
Received 1 April 2021
Revised 23 June 2021
Accepted 26 July 2021
Available online 31 July 2021
the Ru3 , Mn , Co , Ni , Cu , Zn ions via the carbonyl and azomethine of isatin moiety adopting
regular or distorted octahedral structures around the central metallic ions. The structural description of
dihydrazone and its chelated compounds have been endorsed basing on the Density Functional Theory
calculations. The optimized geometry, global reactivity descriptors, and LUMO-HOMO orbitals and of the
molecules have been calculated by the DFT-B3LYP method and 6e311G(d,p) basis set. The molecular elec-
trostatic potential picture has been painted utilizing the same level of theory to envision the molecules
charge distribution and chemical reactivity. The DFT studies of the designated compounds revealed small
HOMO-LUMO gap which is a strong indication to the large reactivity these compounds. The TG analy-
sis has confirmed the complexes chemical formulae and assured that the thermo-degradation processes
occur in three or four steps ended with the formation of metal oxide or carbon-contaminated metal ox-
ide residues. The In-vitro antibacterial of dihydrazone and its chelated compounds have been evaluated
against E. coli, P. aeruginosa, K. pneumonia and B. subtilis, the observed antibacterial result denoted that
+
2+
2+
2+
2+
2+
Keywords:
Antibacterial
Dihydrazone
Indolin-2-one
Isatin
Uni-metallic complexes
Cu2 and Zn complexes have a good activity in comparation with the free dihydrazone.
+
2+
©
2021 Elsevier B.V. All rights reserved.
1
. Introduction
preparing of a wide variety of heterocyclic, hydrazone and Schiff
base compounds as well as a raw material for drug synthesis.
They have varied activities comprising antibacterial, antiviral,
antimicrobial, antioxidant, antitubercular, anti-HIV, anticancer,
and anticonvulsant activities [9-14]. Ammar el al reported that
the designated (morpholino-sulfonyl) isatin derivatives showed
antitumor properties against CACO, HCT116, MCF-7, and HepG2
cancer cell lines and good inhibition activity against EGFR tyrosine
kinase [15]. While the complex of isatin-Schiff base causes cell
death in p53-positive tumors [16] while isatin-chromone deriva-
tives have in vitro α-glucosidase inhibitory effect [17]. In addition,
the isatin derivatives acted also as a non-toxic corrosion inhibitor
for mild steel [18]. Hydrazone chelators were played a crucial
part in the development of coordination chemistry while their
chelated compounds have been structurally investigated exten-
sively due to their appealing physical and chemical properties, in
Nitrogen-based heterocyclic compounds are important and
unique class of organic compounds, they possess physiologi-
cal and pharmacological properties [1,2] and are constituents
of many biologically important molecules, including many vi-
tamins, nucleic acids, pharmaceuticals, antibiotics, dyes, and
agrochemicals, amongst many others. In general, these com-
pounds have a role in treatment of Alzheimer’s disease, and
possess anticancer, antitumor, Free Radical Scavenging activ-
ity [3-8]. 1H-indol-2,3-dione (Isatin) is an industrially flexible
Nitrogen-based heterocyclic substrate which could be utilized for
∗
Corresponding author at: Department of Chemistry, college of Science and Arts
at Khulais, University of Jeddah, Jeddah, Saudi Arabia.
E-mail address: mshakdofa@uj.edu.sa (M.M.E. Shakdofa).
https://doi.org/10.1016/j.molstruc.2021.131194
0
022-2860/© 2021 Elsevier B.V. All rights reserved.

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
addition to their broad variety of usages in numerous scientific
areas comprising anticancer, [19] antitumor [20,21], antibacterial
tions [48]. Diamagnetic corrections have been gauged from Pascal’s
constant [49]. Tacussel type CD6NG conductivity bridge has been
utilized for recording the molar conductance of 10 3 M solutions
(DMSO). The resistance measured in ohms and the molar conduc-
tance has been computed by the posted equation [50].
−
[
19], antioxidant [22,23] antimicrobial [24,25], antifungal [26],
antiviral [27] anti-tyrosinase [28], and α-glucosidase inhibitors
29] agents. Verma et al reviewed that the hydrazones chelators
[
have anticonvulsant, analgesic, anti-inflammatory, cardio protec-
tive, antiplatelet, Antihypertensive and antiprotozoal activities
2
.2. Synthesis of the dihydrazone
[
30,31]. Mono- and bi-nuclear MO22 complexes of ONO appended
+
aroyl-hydrazone have in vitro cytotoxicity against lymphoma as-
cites cell line [32]. Santos el al reported that the acyl-hydrazone of
ionized derivatives acted as radical scavenging, myeloperoxidase/
The
dihydrazone,
3-(-(1,5-dimethyl-3-oxo-2-phenyl-2,3-
methylene)hydrazono)indolin-2-one
dihydro-1H-pyrazol-4-yl)
(
HL) was prepared by mixing the solution of 3-hydrazonoindolin-
-one (161 g, 10 mmol, 40 mL MeOH) with a solution of 4-formyl
acetylcholinesterase inhibitor [33]. The Cu2 complexes of 3,5-
+
2
ꢀ
dihydroxy-N -(pyridin-2-ylmethylene)benzohydrazide, 4-methoxy-
antipyrine (216, 10 mmol, 30 mL MeOH). The mixture has been
refluxed on a water bath for 4 hrs. Then reduce the solution vol-
ume to about 40 mL and let it to cool at room temperature. The
orange powder which precipitated has been separated out, washed
with MeOH, and dried in the void to afford the corresponding
dihydrazone (1) (Fig. 1) (329 mg, 0.916 mmol, 94%) as an or-
ange solid, m.p. 220°C. Elemental analysis (EA) for C20H17 N O
ꢀ
ꢀ
N -(pyridin-2-ylmethylene) benzohydrazide, and 2-hydroxy-N -(1-
(
pyridin-2-yl) ethylidene)benzo-hydrazide had a significant urease
inhibitory activities [34]. Fekri el al reported that the Cu2 , Ni
+
2+
and Co2 complexes of N -(pyridin-2-ylmethylene)benzohydrazide,
+
ꢀ
2
2
-(2-hydroxybenzylidene)hydrazine-1-carboxamide and 2-(pyridin-
-ylmethylene)hydrazine-1-carboxamide had higher antibacte-
5
2
rial and anticancer activities than the parent chelators [35].
(
359.39 g /mol): calcd.(Found) %C 66.84 (66.65), %H 4.77 (4.79),
Ni2 complexes of benzoyl-hydrazone derivatives are acted as a
+
−1
%
N 19.49 (19.13). IR (KBr, cm ), 3290, 3173 ν(NH), 3067, 2951,
catalysis for the preparation of 2-aryl-benzoxazoles [36]. Homo-
831 ν(C-H), 1761 ν( C=O13), 1645 ν(21C=O ), 1620 ν( C=N16 ),
7
23
8
2
binuclear VO2 and Ni
+
2+
dihydrazone complexes are acted as a
600 ν( C=N ), 995 ν( N-N17 ). 1H-NMR (600 MHz, DMSO-d ):
18
17
16
1
6
9
catalysis for the Suzuki-Miyaura cross-coupling and (ep.)oxidation
of unsaturated cycloalkene (1,2-cyclohexene) [37]. As a result of the
exciting bioactivity of hydrazonic chelators and their complexes
and in continuance of our earlier researches, on the designing of
bio-effective metal complexes [38-45]. Our objective was to pre-
δ(ppm) = 10.70 (s, 1H, H15), 8.62 (s, 1H, H19 ), 8.44 (d, H, H ),
.42 (m, 1H, H10); 8.16 (m, 1H, H11 ), 7.60 (d, 1H, H12), 3.39 (s,
7
H, 28CH ), 2.71 (s, 3H,
H, H40&41), 7.02 (m, 1H, H42). 13C-NMR (150 MHz, DMSO-d ):
24
CH ), 6.88 (d, 1H, H36&38), 7.35 (dd,
3
1
3
3
6
1
53.12(C1), 113.67 (C2), 132.73 (C3), 130.60 (C4), 136.00 (C5),
20.75 (C6), 168.65(C7), 147.47(C8), 162.98(C18), 103.13 (C20),
66.06 (C21), 156.66 (C22), 15.14 (C24), 37.35 (C28), 137.04 (C32),
25.54 (C33), 125.54 (C34), 131.91 (C35), 131.91 (C37), 124.66(C39).
pare the uni-metallic Ru3 , Mn , Co , Ni , Cu , and Zn com-
+
2+
2+
2+
2+
2+
1
plexes of dihydrazone chelator, 3-(-(1,5-dimethyl-3-oxo-2-phenyl-
1
2
,3-dihydro-1H-pyrazol-4-yl) methylene)hydrazono)indolin-2-one
1
(
HL). The structure of synthetic compounds was studied via
analytical, spectral tools as nuclear magnetic resonance (NMR),
infrared (IR), mass spectrum (MS), electronic absorption spectrum
2
.3. Preparation of uni-metallic complexes (2-8)
(
EAS), Density Functional Theory calculations, elemental and
The Ru3
2-8) have been synthesized by mixing the following salts
RuCl ].3H O, [Zn(CH COO) ].2H O, [Cu(CH COO) ].2H O, [CuCl ].
+
,
Zn
2+
,
Cu
2+
,
Ni
2+
,
Co
2+
,
and Mn
2+
complexes
thermogravimetric measurements as well as the measurements
of molar conductance and magnetic moment for complexes were
done. Likewise, the biocidal effect of the synthetic compounds
has been assessed against a panel of bacterial strains involving E.
coli, P. aeruginosa, K. pneumonia and B. subtilis basing on agar well
diffusion methodology.
(
[
3
2
3
2
2
3
2
2
2
2
H O [Ni(CH COO) ].6H O, [Co(CH COO) ].6H O and Mn(CH3
2 3 2 2 3 2 2
COO) ].4H O (1 mmol, in 50 mL of EtOH) to 3-(-(1,5-
2
2
dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylene)
hydrazono)indolin-2-one (HL) (359 mg, 1 mmol, in 30 mL of
EtOH). The mixtures have been refluxed for 5 hrs. with stirring.
The resultant solid-colored complexes separated out, on heating,
washed many times with hot EtOH and ultimately dried in vacuum
2
. Experimental
2
.1. Physical and analytical measurements
over P O10.
4
The metal salts, absolute ethanol, DMSO (assay = 99.0-99.8%)
+
2
.3.1. Mn2 -complex (2)
were acquired from MERCK company and utilized without any
extra purification. 3-hydrazonoindolin-2-one were prepared by a
published method [24]. The elemental analyses (C,H,N) of dihy-
drazone and its chelated compounds have been analyzed at Cairo
University, Egypt in the Laboratory of Micro-Analytical, while chlo-
ride and metal ions contents have been evaluated by The Standard
analytic techniques [46,47]. KBr discs technique was used to mea-
sure the IR spectra of the dihydrazone and its chelated compounds
on Perkin–Elmer 1430 infrared spectrophotometer in the 400-4000
Yield (66.3%), m.p. =290 °C; color: brown; μeff
=
6.03
BM; molar conductivity (ꢀm)=15.4 ohm 1cm mol
−
2
−1
.
EA for
[
Mn(HL)(OAc) (H O) ].H O,
C H MnN O , (586.46 g/mol):
24 29 5 9
2
2
2
2
calcd.(Found) %C 49.15(49.06), %H 4.98(5.23), %N 11.94(11.77),
Mn 9.37(9.07). IR (KBr, cm 1), 3422 ν(H O), 3326, 3196 ν(NH),
−
%
2
076, 2927, 2815 ν(C-H), 1708 ν( C=O13), 150 ν(21C=O23),
7
3
8
16
18
17
1
616 ν( C=N ), 2587 ν( C=N ), 1564/1354(210) νs(CH COO)/
3
16 17
ν
as(CH COO)(ꢁ), 1022 ν( N-N ), 581 ν(Co←O), 495 ν(Co←N).
3
cm 1 range. The EAS in the 200-1100 nm regions have been mea-
sured utilizing 1-cm quartz cells in DMSO on a SHMADZU 2600
spectrophotometer. The JEUL JMS-AX-500 mass spectrometer has
been utilized for recording the mass spectrum. Brucker Avance
−
2.3.2. Co2 -complex (3)
+
Yield (63.1%), m.p. >300 °C; color: reddish brown;
ohm 1cm mol
−
2
−1
.
EA for
μeff
=
5.01 BM;
ꢀ
m=11.9
H33CoN O11 , (626.49 g/mol):
6
00-DRX spectrometers has been utilized for recording the NMR
[Co(HL)(OAc) (H O) ].3H O,
C
24
2
2
2
2
5
spectra in DMSO-d . The Perkin Elmer 7 Series thermal analyzer
calcd.(Found) %C 46.01(45.85), %H 5.31(5.39), %N 11.18(10.91), %Co
6
9.41(9.43). IR (KBr, cm 1), 3425 ν(H O), 3238 ν(NH), 3047, 2929
−
has been utilized for recording the thermogravimetric analysis (TG)
from 25 to 1000 °C with heating rate 10 °C/min. Gouy Matthey Bal-
ance has been has been utilized for measuring the magnetic sus-
ceptibilities at 25°C and has been computed by the posted equa-
2
ν(C-H), 1721 ν( C=O13), 1650 ν(21C=O ), 1620 ν( C=N16 ), 1576
7
23
8
1
8
17
ν( C=N ), 1557/1340(217) νs(CH COO)/ νas(CH COO)(ꢁ), 1019
3
3
16
17
ν( N-N ), 522 ν(Co←O), 495 ν(Co←N).
2

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Fig. 1. preparation of the dihydrazone ligand (1)
+
2
.3.3. Ni2 -complex (4)
C20H23RuN5O5Cl3, (602.84 g/mol): calcd.(Found) %C 39.85(39.33),
%H 3.51(3.82), %N 11.62(11.89), %Cl 17.64(17.23), %Ru 16.77(16.55).
Yield (69.3%), m.p. =270 °C; color: light Brown; μ = 3.03 BM;
eff
−1
2
−1
−1
ꢀ
C24
m
= 13.1 ohm cm mol . EA for [Ni(HL)(OAc) (H O) ].H O,
IR (KBr, cm ), 3416 ν(H2O), 3139 ν(NH), 3076, 2952, 2840
2
2
2
2
ν(C-H), 1716 ν( C=O13), 1663 ν(21C=O ), 1618 ν( C=N16 ), 1593
7
23
8
H NiN O , (590.22 g/mol): calcd.(Found) %C 48.84(48.52), %H
29 5 9
.95(5.04), %N 11.87(11.89), %Ni 9.94(10.00). FT-IR (KBr, cm 1), 3411
−
ν( C=N ), 1011 ν( N-N17 ), 622 ν(Ru←O), 500 ν(Ru←N).
18
17
16
4
ν(H O), 3201 ν(NH), 3061, 2932 ν(C-H), 1660 ν( C=O13), 1645
7
2
1
2
23
8
16
18
17
ν( C=O ), 1619 ν( C=N ), 1573 ν( C=N ), 1549/1349(200)
2.4. Computational details
1
6
17
ν
s(CH COO)/ νas(CH COO)(ꢁ), 1027 ν( N-N ), 515 ν(Ni←O), 452
3
3
ν(Ni←N).
The Gaussian 09 Rev. A.02-MSP package program has been used
to carry out the Density Functional Theory,[51] and the found data
have been imagined by the Gauss View Rev. 5.0.9 software [52].
The dihydrazone molecular structure (HL) in the ground state has
been optimized utilizing the Density Functional Theory with Bec-
kee3eLeeeYangeParr (B3LYP) functional levels for the 6-311G(d,p)
basis set [53,54].
+
2
.3.4. Cu2 -complex (5)
Yield (60.1%), m.p. >300 °C; color: olive; μ
= 1.66 BM;
eff
−1
2
−1
ꢀ
C24
m
= 11.3 ohm cm mol . EA for [Cu(HL)(OAc) (H O) ]3H O,
2
2
2
2
H CuN O11 , (631.10 g/mol): calcd.(Found) %C 45.68(45.51), %H
33 5
.27(4.99), %N 11.10(11.16), %Cu 10.07(9.77). FT-IR (KBr, cm 1),
−
5
3
421 ν(H O), 3238 ν(NH), 3063, 2926, 2841, 2778 ν(C-H), 1719
2
ν( C=O13), 1643 ν(21C=O ), 1618 ν( C=N16 ), 1588 ν( C=N17 ),
7
23
8
18
2
.5. In vitro antibacterial study
555/1332(229) νs(CH COO)/ νas(CH COO)(ꢁ), 1032 ν( N-N17 ),
16
1
5
3
3
22 ν(Cu←O), 475 ν(Cu←N).
The evaluation of the antibacterial action of the compounds (1-
) has been evaluated against Escherichia coli, (E. coli) Pseudomonas
8
+
2
.3.5. Cu2 -complex (6)
aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumonia) and
Bacillus subtilis (B. subtilis) by agar well diffusion method [55,56].
The bacterial strains have been cultivated on Mueller-Hinton agar
at pH 7.4. The plates of agar have been incubated at 37°C for 24 h
(bacteria). A negative (DMSO; 2% v/v) and positive controls Tetra-
cycline have been also included to compare the activity. The ap-
pearing of inhibition zones has been considered as positive for the
existence of antimicrobial action in the test substance. The micro-
bicidal process was carried by agar well diffusion method [55,56].
Therefore, the average of three independent replicates was calcu-
lated while the activity index has been calculated by published for-
mula [57].
Yield (56.8%), m.p. >300 °C; color: olive; μeff
=
1.75
9.1 ohm 1cm mol
−1
.
−
2
EA for [Cu(HL) Cl ].2H O,
BM; ꢀ
C48H39CuN10O , (889.25 g/mol): calcd.(Found) %C 54.03(54.44), %H
m
=
2
2
2
6
4
.31(4.24), %N 15.75(15.32), Cl% 7.79(7.67), %Cu 7.15(6.92). FT-IR
−
(
KBr, cm 1), 3416 ν(H O), 3147 ν(NH), 3081, 3001, 2944, 2871
2
ν(C-H), 1715 ν( C=O13), 1653 ν(21C=O ), 1621 ν( C=N16 ), 1520
7
23
8
ν( C=N ), 1012 ν( N-N17 ), 580 ν(Cu←O), 480 ν(Cu←N).
18
17
16
+
2
.3.6. Zn2 -complex (7)
Yield (53.6%), m.p. =277 °C; color: orange;
ꢀ
m
=
8.8
ohm 1cm mol
−1
.
−
2
EA
for
[Zn(HL)(OAc) (H O) ].2H O,
2 2 2 2
C24H31ZnN O10, (614.92 g/mol): calcd.(Found) %C 46.88(48.07),
5
−
%
H 5.08(5.14), %N 11.39(11.43), %Zn 10.65(10.78). IR (KBr, cm 1),
3. Results and discussion
3
432 ν(H O), 3328 ν(NH), 3077, 2962, 2928, 2814 ν(C-H), 1709
2
ν( C=O13), 1655 ν(21C=O ), 1613 ν( C=N16 ), 1565 ν(18 C=N17 ),
7
23
8
The chelation of dihydrazone, 3-(-(1,5-dimethyl-3-oxo-2-
phenyl-2,3-dihydro-1H-pyrazol-4-yl)methylene)hydrazono)indolin-
1
5
554,1352(202) νs(CH COO)/ νas(CH COO)(ꢁ), 1012 ν(16 N-N17 ),
3
3
82 ν(Zn←O), 503 ν(Zn←N). 1H-NMR (600 MHz, DMSO-d ):
2+
2+
2+
2+
3+
6
9
2-one (HL) (1) with the Mn , Co , Ni , Cu , and Ru salts
δ(ppm) = 10.88 (s, 1H, H ), 8.42 (s, 1H, H19 ), 7.52 (d, H, H ),
15
leading to the formation of steady and colored uni-metallic com-
plexes (2-8). It has found that the designated chelated compounds
are non-hygroscopic and insoluble in most organic solvents like
acetonitrile, ethanol, methanol, and chloroform and fully soluble in
DMF and DMSO. The spectral, analytical, theoretical and analyses
data were recorded in Section 2.3,Table 1 & 2. It verified that the
chelated compounds (2-8) were comprised in molar ratio (1L:1M)
which agrees with the expected structures (Figs. 2 & 3).
7
.37 (m, 1H, H10); 8.37 (m, 1H, H11 ), 7.42 (d, 1H, H12), 3.35 (s,
H, 28CH ), 2.51 (s, 3H, CH ), 6.92 (d, 1H, H36&38), 7.04 (dd, 1H,
24
3 3
H40&41), 6.98 (m, 1H, H42).
3
2
.3.7. Ru3 -complex (8)
+
Yield (70.7%), m.p. >300 °C; color: brown; μeff
=
1.59;
=2 7.7 ohm 1cm mol
−
2
−1
.
EA for [Ru(HL)Cl (H O)].H O,
ꢀ
m
3
2
2
3

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Table 1
The different quantum chemical parameters of ligand and its complexes (1-8).
−
No.
HL
EHOMO (eV)
IP
ELUMO (eV)
EA
ꢁE (eV)
c (eV)
η(eV)
σ (eV 1)
Pi=-c (eV)
W (eV)
ꢁNmax
-0.2206
-0.1874
-0.1740
-0.2025
-0.1602
-0.1805
-0.1683
0.2206
0.1874
0.1740
0.2025
0.1602
0.1805
0.1683
-0.1060
-0.1077
-0.0974
-0.1094
-0.1257
-0.1257
-0.1286
0.1060
0.1077
0.0974
0.1094
0.1257
0.1257
0.1286
0.1145
0.0796
0.0766
0.0931
0.0345
0.0548
0.0397
0.1633
0.1475
0.1357
0.1560
0.1429
0.1531
0.1484
0.0573
0.0398
0.0383
0.0466
0.0173
0.0274
0.0198
17.46
25.11
26.13
21.48
57.94
36.48
50.40
-0.1633
-0.1475
-0.1357
-0.1560
-0.1429
-0.1531
-0.1484
0.2328
0.2733
0.2405
0.2613
0.5917
0.4274
0.5552
-2.85
-3.70
-3.54
-3.25
-8.28
-5.58
-7.48
(
(
(
(
(
(
2)
3)
4)
5)
6)
7)
Table 2
Some energetic properties of dihydrazone and its complexes calculated by DFT method.
No.
HL
EHOMO (eV)
ELUMO (eV)
Total energy (eV)
binding Energy (a.u.)
Dipole Moment (Debye)
-0.2206
-0.1874
-0.1740
-0.2025
-0.1602
-0.1683
-0.1805
-0.1060
-0.1077
-0.0974
-0.1094
-0.1257
-0.1386
-0.1257
-0.3266
-0.2951
-0.2714
-0.3120
-0.2858
-0.3069
-0.3061
-1197
-2957
-3189
-3314
-3447
-3585
-4954
4.61
6.71
6.67
7.24
7.57
11.23
9.72
(
(
(
(
(
(
2)
3)
4)
5)
7)
6)
Fig. 2. Structure of uni-metallic Mn2+, Co2+, Ni2+, Cu2+and Ru3+ complexes (2-5) and (7-8).
ohm 1cm mol , which are within the anticipated range for the
non-electrolytic species [58]. This finding signaled to the lack of
any anions out of the coordination sphere of all these metals
chelates. The significantly high value of complex (8) may be due
to the preferential solvolysis by DMSO [58].
−
2
−1
3
.2. Nuclear magnetic resonance
To attain advantageous info about dihydrazone structure and
recognition of hydrogen bonding as well as defining its mode of
chelation. The experimental 1H and 13C NMR chemical shifts in
DMSO–d6 of the free dihydrazone is outlined in Section 2.2 and
explained, basing on the atom labeling in Fig. 4. The 1H-NMR spec-
trum of dihydrazone (Supl. 1) demonstrated two singlets chemical
shift at 10.70 and 8.62 ppm which could be attributed to the pro-
ton of NH and azomethine groups [59]. These signals were verified
Fig. 3. Structure of uni-metallic Cu2+ complex (6).
by its disappearing in the spectrum with D O. In addition, the two
2
singlets chemical shift looked at 3.39 and 2.70 ppm assigning to
the to three protons of N–CH3 and C–CH3 of antipyrine moiety cor-
respondingly [60]. The protons of indolin-2-one moiety were ap-
peared as doublet at 8.44 ppm and 7.60 ppm assigning to (H-C6)
3
.1. Molar-conductance measurements
The molar conductance of metal chelates (2-8) has been
−
3
3
carried out in DMSO at concentration 10
M. All metal
and (H-C ) correspondingly [59]. As well as multiples at 7.50 and
2
1
chelates (2-8) showed molar conductance values between 8.8-33.9
7.42 ppm assigning to (H-C ) and (H-C ) correspondingly [59]. The
4

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Fig. 4. Fig. 5; The 3D orbital pictures of the HUMO-LUMO level for dihydrazone by the DFT/B3LYP/6e311ppG(d,p).
five protons of phenyl ring of antipyrine moiety were appeared in
3.4. FT-IR spectra
6
.88-7.35 ppm range [60] . The 1H-NMR spectrum of Zn complex
2+
showed that the chemical shift of the protons of NH and azome-
thine (H18 C=N17 ) groups are appeared at the same position indi-
cating that the NH and azomethine groups did not take part in
the chelation to the metallic ions which supported the suggested
mode of chelation. The 13C-NMR spectrum of dihydrazone (Supl. 2)
demonstrated various chemical shift assured the proposed struc-
ture of dihydrazone. the number of chemical shifts be like the
number of magnetically non-equivalent carbon atoms in the dihy-
drazone. The two azomethine carbon atoms (13C=N, C=N) were
appeared at 162.98 and 147.47 ppm while the two-chemical shift
at 168.65 and 166.06 ppm were imputed to carbonyl carbons of
the indolin-2-one and antipyrine moieties correspondingly [25,41].
Moreover, the spectrum displayed two signals at 153.12 and 156.66
The diagnostic FT-IR data of dihydrazone and its uni-metallic
chelated compounds (1-8) are depicted in Section 2. The dihy-
drazone (HL) spectrum displayed several weak and broad bands
at 3290, 3173, 3067, 2951 and 2831 cm 1 which could be as-
cribed to the stretching vibrations of ν(NH) of the isatin moiety,
aromatic and aliphatic C–H correspondingly [61,62]. Likewise the
strong bands at 1761 and 1645 could be attributed to the isatin
−
8
18
and antipyrine carbonyl groups ν( C=O)[63] ν( C=O)[60] respec-
9
−1
tively. Whereas the moderate bands at 1620 and 1600 cm could
be allocated to the azomethine groups [63]. While the bands at
995 cm 1 could be owing to ν(N-N)[61]. The bonding mode of
the dihydrazone with metallic cations have been elucidated from a
comparison between the FT-IR spectra of chelated compounds and
that of the free dihydrazone. This comparison displayed that The
IR spectral data of all complexes revealed that the bands relating
to ν(N-H) of isatin moiety as well as the carbonyl and azomethine
of antipyrine moiety appeared around the original position, signal-
ing that these groups did not contribute to the chelation. The FT-IR
spectra of all complexes demonstrated that the bands of carbonyl
and azomethine groups of isatin moiety are shifted to lower wave
numbers and appearing in the ranges 1666-1721 and 1520-1593
−
were imputed to carbon atoms attached the nitrogen of indolin-
4
2
-one and pyrazoline moieties ( C-NH, 15C-N) [25,41]. The other
carbons of indolin-2-one and phenyl moieties were observed in
the 113.67-137.04 ppm range [25,41]. In addition, the spectrum re-
vealed two singlet chemical shift at δ 37.35 and 15.14 ppm imputed
to carbon atoms of methyl groups of antipyrine moiety of N–CH3
and C–CH3 correspondingly [41].
cm 1 respectively, supportive to the chelation of these groups to
−
3
.3. Mass spectrum of dihydrazone (MS)
metallic ions. The spectra of all complexes revealed also new bands
in the 515–622 and 452-503 cm 1 ranges which could be assigned
to the ν(O→M) and ν(N→M) respectively [64]. From that data of
elemental analyses and FT-IR we can be concluded that the dihy-
drazone linked the metallic ions as a neutral bidentate chelator via
carbonyl and azomethine groups of isatin moiety. In the acetate
−
The MS for dihydrazone (1) (Supl. 3) verified the anticipated
structure with molecular ion peak m/z equal 359. Moreover, The
MS demonstrated base peak at m/z 159 which was allo-
=
cated to a 2-phenyl-1l2-pyrazol-3(2H)-one. In addition, the MS
showed eight fragments which can be explained as follow. The
first fragment (a) at m/z 345 due to the losing methyl group
from the dihydrazone molecule, the next fragment (b) at m/z
−
−
complexes (3) and (8), The νas(COO ) and νs(COO ) of acetate ions
were displayed at 1555,1339; 1563,1334 and 1523, 1326 cm 1. The
−
difference between the two values (ꢁ= νas -νs) was 216, 229 and
−1
=
331 owing to the losing of fragment (a) a methyl group, the
197 cm which is implying that acetate ions bonded to the metal-
lic cations as a uni-dentate ligand [65,66].
third fragment (c) at m/z =255 anticipated to the losing of frag-
ment (b) a phenyl moiety. The fourth fragment (d) at m/z =282
which may be due the losing of phenyl moiety from the lig-
and molecule. Moreover, the other four fragments which ap-
peared at m/z =172, 187, 145 and 216 which may be assigned
to the fragments (E)-3-((l3-methylene)hydrazono) indolin-2-one
3.5. The electronic absorption spectrum (EAS) and magnetic moment
(μeff) measurements
The EAS of the dihydrazone (HL) and its metal chelates (1-
8) have been recorded in DMF and their data have been sum-
marized in Table 3. The EAS of dihydrazone (HL) divulged two
(
(
e), 1,5-dimethyl-2-phenyl-1,2-dihydro-3H-4l3-pyrazol-3-one (f), 3-
l2-azanylidene)indolin-2-one (h) and 4-((l2-azanyl)methyl)-1,5-
∗
dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (i) correspond-
bands at 265, 295 nm which are owing to π→π transitions
ingly (Supl. 3).
within the phenyl and isatin moieties which is approximately un-
5

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Fig. 5. Fig. 4: The optimized structure of dihydrazone obtained using B3LYP/6-311G(d,p) level for HL.
Table 3
UV-Vis. spectra of the dihydrazone (HL) and its, Ru3 , Mn , Co , Ni , Cu and Zn complexes (2-8).
+
2+
2+
2+
2+
2+
No
Bands (nm) in DMSO
Electronic transition
μ
eff (BM)
Geometry
∗
−−
HL(1)
265, 280, 318, 380
π→π , n→π
–
Mn2 complex (2)
+
264, 290, 321, 357, 414, 561, 627, 709, 814
(ν1) A1g→ T1g(4G)
6
4
6.03
octahedral
6
4
(
(
(
ν
ν
ν
2) A1g→ Eg(4G)
6 4
3) A1g→ Eg(4D)
6
4
4) A1g→ T1g(4p)
Co2 complex (3)
Ni2 complex (4)
Cu2 complex (5)
Cu2 complex (6)
+
270, 290, 320, 400, 500, 685, 1088
265, 285, 313, 400, 561, 625, 708, 1080
269, 298, 325, 400, 688, 1084
(v1) T1g(F)→ T2g(F)
4
4
5.01
3.03
1.66
distorted octahedral
distorted octahedral
4
4
(
(
v2) T1g(F)→ A2g
4 4
v3) T1g(F)→ T1g(p)
+
3
(ν1) A2g(F)→3T2g(F),
3
3
(
(
v2) A2g(F)→ T1g(F)
3 3
ν
3) A2g(F)→ T1g(P)
2 2
+
(υ3) B1g→ Eg(dx2-y2→dxy)
tetragonally distorted
octahedral
2
2
(
υ
2) B1g→ A1g (dx2-y2→dz2)
+
2
2
268, 289, 323, 402, 655, 1098
263, 296, 318, 400
(υ1) B1g→ B2g (dx2-y2→dyz dxz)
1.75
Dia.
1.59
Zn2 complex (7)
+
–
–
Ru3 complex (8)
+
265, 282, 313, 405, 606
LMCT
2
octahedral
2
T2g→ A2g
ence of three bands in the EAS of Co2 complex (3) at 1088,
+
shifted on chelation. While the two bands which observed at 310,
∗
2+
3
90 nm probably assigning to n→π transition within the azome-
685 and 500 nm supporting that the Co
complex (3) has an
thine and carbonyl chromophore imputing that the azomethine
nitrogen and carbonyl oxygen participate in the chelation pro-
cess through the their electron pairs.[59,67,68] The μeff value of
Mn2 complex (2) is equal to 6.03 BM. This value anticipated to
high spin Mn2 configuration (d ) [69]. In high-spin octahedral
octahedrally structure [Fig. 2]. The low value of ν /ν (1.59) ra-
1 2
tio regarding the typical range for an octahedral Co2 com-lexes
(1.95–2.48), signaling to its distortion. The Co2 complex (3) dis-
+
+
+
played μeff equal 5.01 BM which is matched with the normal
2+
value for high spin octahedral Co complexes [73]. The EAS for
+
5
Mn2 complex, the ground state is 6A1g. Since there are no ex-
cited terms for sextet spin multiplicity, d–d transitions are doubly
forbidden. But some forbidden transitions happen and therefore,
these transitions have an exceptionally low molar extinction co-
+
2+
Ni complex displayed three peaks at 1080, 625 and 561 nm can
be attributed to the 3A2g(F)→3T g(F)(ν1), 3A2g(F)→ T1g(F)(v2) and
3
2
3A2g(F)→ T (P)(ν3) transitions correspondingly which is consis-
3
1g
tent with an octahedrally structure (Fig. 1) [71,74,75]. The ν /ν
2
1
efficient value. So the EAS of Mn2 complexes display four tran-
+
value is 1.53 which is lower than the typical value for an octa-
sitions: 6A1g→ T (4G)(ν ), 6A1g→ Eg(4G)(ν ), 6A1g→ Eg(4D)(ν ),
4
4
4
2+
1g
1
2
3
hedrally Ni
complex (1.5–1.75), underlined that, the octahedral
and 6A1g→ T (4p)(ν ) [70,71]. The EAS of Mn complex (2) dis-
4
2+
2+
1g
4
geometry of Ni
complex (4) is distorted [74]. The μeff value
+
for Ni2 complex is 3.03 BM which lies in the range for a d
8
played four peaks at 814, 709, 627, 561 nm which could be com-
pliant with Mn2 ions in an octahedrally environment (Fig. 2).[70]
+
2+
electronic configuration of Ni
complexes in an octahedral field
The 4F ground state of Co in a sphere of octahedral symmetry is
2+
2+
[76]. In six coordinated (octahedral crystal field) of Cu ion, the
split into 4A2g, 4T2g and 4T1g(P) and three spin-allowed transitions
ground state is t2g6eg3 with 2Eg term while the excited state is
t2g5eg4 with 2T2g term. So, the anticipated electronic transition is
4
4
4
4
4
4
(
v ) T g(F)→ T2g(F), (v ) T g(F)→ A
and (v ) T g(F)→ T1g(p)
1
1
2
1
2g
3
1
2
2
are expected [71,72]. In accordance with this description the pres-
E → T2g. But because of the Jahn-Teller effect the octahedrally
g
6

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Table 4
loss The thermogravimetric analysis (TG) of Ru3 , Mn Co , Ni , Cu and Zn complexes (2-8).
+
2+
2+
2+
2+
2+
No.
Temp. range o
C
Weight loss (%)
Found(calcd.)
assignment
the residue composition
(
(
(
2)
3)
4)
25-70
2.83 (3.07)
6.60 (6.14)
20.75(20.27)
56.60(56.37)
6.47 (6.83)
6.33 (5.75)
18.72(18.98)
55.32(54.69)
3.39 (3.05)
6.78 (6.10)
18.64(18.98)
53.38(53.98)
Dehydration process (H2O)
[Mn(HL)(CH3COO)2(H2O)2]
[Mn(HL)(CH3COO)2]
[Mn(HL)]
7
2
2
0-225
Loss of two coordinated water molecules
Loss of two acetate ions (2CH3COOH)
Complex decomposition forming MnO+C
Dehydration process (3H2O)
25-290
90-730
MnO+C
25-105
[Co(HL)(CH3COO)2(H2O)2]
[Co(HL)(CH3COO)2]
[Co(HL)]
1
2
3
10-180
00-290
00-660
Loss of two coordinated water molecules
Loss of two acetate ions
Complex decomposition forming CoO
Dehydration process (H2O)
CoO
25-120
[Ni(HL)(CH3COO)2(H2O)2]
[Ni(HL)(CH3COO)2]
[Ni(HL)]
1
1
3
20-170
70-350
50-580
Loss of two coordinated water molecules
Loss of two acetate ions
Complex decomposition forming NiO+2C
NiO+2C
(
5)
25-115
8.66 (8.56)
6.29 (5.71)
18.11(18.84)
51.97(52.38)
4.47(4.05)
Dehydration process (3H2O)
[Cu(HL)(CH3COO)2(H2O)2]
[Cu(HL)(CH3COO)2]
[Cu(HL)]
1
1
2
15-165
70-282
82-420
Loss of two coordinated water molecules
Loss of two acetate ions
Complex decomposition forming CuO+C
Dehydration process (2H2O)
CuO+C
(
(
6)
7)
25-70
Cu(HL)2(Cl)2]
Cu(HL-Ph)2]
1
3
80-320
20-600
25.98(25.54)
57.72(58.76)
5.66(5.86)
Loss of two Cl ions and 2C6H5 moieties
Complex decomposition forming CuO+2C
Dehydration process (2H2O)
CuO+2C
25-150
[Zn(HL)(CH3COO)2(H2O)2]
[Zn(HL)(CH3COO)2]
[Zn(HL)]
1
2
4
50-200
00-400
00-580
6.60(5.86)
Loss of two coordinated water molecules
Loss of two acetate ions
18.87(19.33)
49.06(49.86)
3.10 (2.99)
3.78 (2.99)
17.82(17.64)
54.26(53.65)
Complex decomposition forming ZnO+3C
Dehydration process (H2O)
ZnO+3C
(
8)
25-90
[Ru(HL)(Cl)3(H2O]
[Ru(HL)(Cl)3]
[Ru(HL)]
9
2
2
0-200
Loss of one coordinated water molecule
Loss of three chloride ions
30-280
80-500
Complex decomposition forming 1/2Ru2O3+C
1/2Ru2O3+C
structure is deformed either by compression or elongation the oc-
tahedron leading to tetragonal symmetry in which the 2Eg is split
into 2B1g(dx2-y2) and 2A1g(dz2) levels while the 2T2g also splits
into 2B2g(dxy) and 2Eg(dxz,dyz) levels. Thus, three bands are ex-
pounds (2-8) have been estimated and their data have been listed
in Table 1 [83]. The energy of the lowest un-occupied molecu-
lar orbital (ELUMO) acts as an electron recipient and specifying the
molecular ability to nucleophilic attacking because it can accept
electrons. The outermost highest occupied molecular orbital energy
(EHOMO) can act as an electron donor and specifying the molec-
ular ability to electrophilic attacking because it has electrons. The
HOMO and LUMO of dihydrazone (HL) and its chelated compounds
were shown by DFT/B3LYP/6-311G(d,p) calculation and have been
displayed in Fig. 4 and Supls. 4-5. The negatively and positively
zone were specified by green and red colors, consecutively. The
HOMO and LUMO regions are spread over the pyrazoline and in-
dole moieties as well as the hydrazonic linkages. The LUMO and
HOMO orbitals energies as well as their adjacent orbitals are neg-
ative, signifying that the dihydrazone (HL) is stable [84]. The di-
hydrazone chelates metallic ions via the carbonyl oxygen O(13) be-
longs indole moiety as well as the azomethine nitrogen atom N(16)
Fig. 4. These atoms are the active locations for chelation because
they are from the highly electronegatively charges atoms. More-
over, these atoms are from the atoms in which the HOMO level
is centered on them suggesting that these sites are the favored
positions for nucleophilic attack at the metallic cations (Fig. 4).
This imply that these locations with high coefficients HOMO den-
sity have been directed to the metallic cations [85]. The values of
pected for tetragonal (D4h) symmetry viz. 2B1g← A , 2B1g← B2g,
2
2
1g
2B1g← Eg which can be manifested around 1000, 650 and 500 nm
2
consecutively [71,72,77]. In accordance with the above description
the presence of two bands in EAS of Cu2 chelated compounds
+
(
5-6) at 688, 1084 and 655, 1098 nm ascribed to the transitions
2
2
2
2
(
ν ) B → A1g(dx2-y2→d ) and (ν ) B → B (dx2-y2→dxy) tran-
1
1g
z2
2
1g
2g
sitions pointed out that these chelated compounds have a tetrago-
nally distorted octahedral structure (Fig. 2) [71,78-80]. The third
2
2
band which assigned to the (υ ) B → Eg(d
→dxy) does not
2
3
1g
x2-y2
+
appear here may be due to the boarding of the bands. The Cu
complexes (5-6) displayed μeff values at 1.66 and 1.75 BM re-
spectively which is associated to spin-only value for Cu2 com-
+
plexes.[81] The magnetic moment value of Ru3 complex (8) is 1.59
+
BM which is well compatible with d5 low spin Ru complex [81].
3+
The low spin paramagnetic Ru3 complexes, a d5 system with 2T2g
as the ground term originating from the 5t2g configuration and the
first excited doublet levels in the order of increasing energy are
+
2A2g and 2T1g, which arise from 4
t
1eg configuration. Hence, two
2g→
2g
bands corresponding to 2T2g→ A and 2T2g→ T are possible.
2
2
1g
However, the EAS of Ru3 complex (8) displayed one bands at 606
+
which may be assigned to 2T2g→ A transition. While the band
2
separation energy (ꢀE = E
−EHOMO) of the compounds (1-8)
2g
LUMO
noticed at 405 nm is possibly because of the charge transfer tran-
sitions (LMCT) happening from the filled chelator (HOMO) orbital
to the singly occupied ruthenium t2 orbital (LUMO). The band lo-
cation is like to those noted for other octahedrally Ru3 complexes
displayed that the chelated compounds (2-8) are fewer stable and
more active than the dihydrazone (HL) [86]. The Ionization poten-
tial (IP = - EHOMO) is the energy essential to eliminate an electron
from a molecule [87], while the electron affinity (EA= - ELUMO)
is the energy liberalized when the system earn an extra electron
+
[
71,82].
[
87]. The absolute hardness (η = (IP−EA)/2) and absolute soft-
3
3
.6. Density Functional Theory (DFT) study
ness (σ =1/η) can be serve as a measure the resistance of atom
to a charge transfer and the ability of an atom or group of atoms
to accept electrons respectively [88]. From the values of absolute
hardness and absolute softness, it can predict the molecules stabil-
ity and reactivity. The soft molecules owned a small energy gap
.6.1. Molecular parameters
As specified by the theorem of Koopman, quantum chemi-
cal parameters of the dihydrazone (HL,1) and its chelated com-
7

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Fig. 6. Molecular electrostatic potential (MEP) and electrostatic potential (ESP) of the dihydrazone (1).
Fig. 7. The Order of antimicrobial activity of the ligand and its complexes.
whereas the hard ones owned a great energy gap. So, the hard
because an electrophile is a chemical species that can accept elec-
trons from the environment and its energy must decrease upon ac-
cepting electronic charge. Therefore, its electronic chemical poten-
tial must be negative exactly as supported by the values in Table 1.
the electrophilicity index (ω) values are small signifying to a good
nucleophile. ii) The dihydrazone chelates with the metal ions via
the carbonyl oxygen atoms O(13) and azomethine nitrogen atoms
N(16). These atoms are from the atoms of high electronegative
charge, which approves that they are the active locations for chela-
tion iii) The estimated dipole moment value of the ligand (HL) is
4.61 Debye is less than that of the complexes (2-8) (6.67-11.23 De-
bye). This may be due the chelation of metallic cations with the
dihydrazone (HL) occurred by the carbonyl oxygen and azomethine
nitrogen atoms. Other energetic properties of dihydrazone and its
complexes were calculated by DFT method and listed in Table 2.
The data of table 2 indicated that the complexes binding energy
are higher than binding energy the dihydrazone (HL) suggesting
molecules are less reactive than the soft ones because of the soft
molecules can easily give electrons to a receiver. In the coordina-
tion compounds, the metallic cations and ligands can perform as
Lewis’s acid and Lewis’s base respectively, the chelators are the
most effective for coordination. Thus, it can be concluded that the
chelator with a proper σ value has a well tendency to chelate the
metallic cations efficiently. This supposition was emphasized by
the value of chemical potential (Pi= −χ) for the chelator [84,85].
From the calculated values of the chemical potentials (Pi= −χ), ab-
solute electronegativities (χ = (IP+EA)/2), index of electrophilicity
2
(
ω= Pi /(2η)) and reactivity index (ꢀNmax= −Pi/η) [89] we can
conclude that: i)ꢁNmax is the stabilization scale for the system
energy when the system earns a further electronic charge from
the environment, the electrophilicity index (χ) is positive. Certain
amount and the direction of the charge transfer is completely de-
termined by the electronic chemical potential (Pi) of the molecule
8

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Fig. 8. The activity index of antibacterial activity of the dihydrazone and its complexes against gram-negative bacteria activity.
Fig. 9. The activity index of antibacterial activity of the dihydrazone and its complexes against gram-positive bacteria activity.
that the prepared metal complexes are more stable than the dihy-
drazone (HL) [90].
tum chemical calculations of molecular system due to the atomic
charge affect polarizability, electronic structure, dipole moment
vibrational spectra, and more properties for a molecular system
[91]. The data acquired by Mulliken analysis demonstrated that
the atoms of hydrogen have positive charges in 0.083084-0.233649
a.u. because they lose electrons to the neighboring carbon atoms,
but H15 has a maximum positive charge than the other hydro-
gen atoms, which may be due to the attachment of this hydro-
gen atom to the electronegative atom (N14). The nitrogen and oxy-
3
.6.2. Mulliken atomic charges for the dihydrazone (HL,1)
The Mulliken atomic charges of the dihydrazone atoms were es-
timated by Mulliken population analysis applying the DFT/B3LYP
levels with the 6-311G(d,p) basis set in gas phase and the re-
sult has been listed in Supl. 6 and has been shown in Supl. 7.
The atomic charge play a major role in the application of quan-
9

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
Table 5
The effect data of prepared compounds against (concentration used 1mg/mL of DMSO) against E. coli, P. aerug-
inosa, K. pneumonia and B. subtilis.
Inhibition zone (IZ, mm) and Activity Index (AI, %)
Compounds
E. coli
P. aeruginosa
B. subtilis
K. pneumonia
IZ(mm)
AI (%)
IZ(mm)
AI (%)
IZ(mm)
AI (%)
IZ(mm)
AI (%)
DMSO
Tc
–
–
–
–
33
25
20
21
25
20
26
30
22
100%
76%
61%
64%
76%
61%
79%
91%
67%
40
16
23
20
26
17
19
27
19
100%
40%
58%
50%
65%
43%
48%
68%
48%
36
18
17
19
19
22
26
22
20
100%
50%
47%
53%
53%
61%
72%
61%
56%
38
15
18
20
15
23
25
21
23
100%
39%
47%
53%
39%
61%
66%
55%
61%
HL(1)
+
Mn2 Complex (2)
Co2 Complex (3)
+
Ni2 Complex (4)
+
Cu2 Complex (5)
+
Cu2 Complex (6)
+
Zn2 Complex (7)
+
Ru3 Complex (8)
+
gen atoms have a negatively Mulliken charge indicating that these
atoms behaved as electron recipients. The carbon atoms are nega-
tively charged except C1, C3, C7, C8, C21, C22 and C32 which may
be due to the connection of these carbon atoms to nitrogen and
oxygen atoms [92].
3.7. Thermogravimetric analysis
The thermogravimetric data of complexes (2-8) in the tem-
perature ranged from room temperature to 1000°C with a rate
of heating 10°C/min (Supl. 8) were listed in Table 4. The com-
plexes showed three or four decomposition steps in the temper-
ature ranged from 25 to 730°C with total weight loss of ranged
from 78.96-88.17% (calcd. 77.29-88.35%) leaving residue of metal
oxide or metal oxide polluted by carbon atoms. The thermogram
3
.6.3. Electrostatic potential (ESP) and Molecular electrostatic
potential (MEP) analyses
of Mn2 , Co , Ni , Cu
+
2+
2+
2+
and Ru complexes (2-5) and (7-
3+
The charge distributions and visualizing variably charged re-
gions for the of dihydrazone (HL) molecule was achieved by re-
viewing the molecular electrostatic potential (MEP) and electro-
static potential (ESP) via DFT calculation (Fig. 6). MEP is commonly
utilized as a reactivity map to recognize the hydrogen bonding in-
teractions on organic molecules as well as the sites of nucleophilic
and electrophilic reactions [91,93]. MEP, V(r) at a specified point
r(x, y, z) in the vicinity of a molecule, is specified in terms of the
energy interaction between the electrical charge generated from
the molecule’s electrons and nuclei and a positive test charge (a
proton) located at r. For the system studied the V(r) value has been
calculated by the next equation [91].
8) showed four decomposition steps which explained as follow,
Firstly, the dehydration process within the temperature ranged
from 25–150°C which was related to the losing of one or three hy-
drated water molecules with weight loss of 2.83-8.66% (calcd. 2.99-
8.56%). Secondly the liberation of two or one molecules of coordi-
nated water within the temperature ranged from 70–225°C with
weight loss of 3.78-6.78% (calcd. 2.99-6.14%). Thirdly, the elimi-
nation of two acetate ions or three chloride ions within temper-
ature ranged from 170–400°C with weight loss of 17.82-20.75%
(calcd. 17.64-20.27%). The last steps within the temperature ranged
from 280–730°C were related to complete decomposition of the
molecule with mass loss of 49.06 -57.72% (calcd. 49.86-58.76%).
ꢀ
ZA
(r)
2+
The thermograms of the Cu
complex (6) showed three decom-
V (r) =
∫
d(r)
RA − r (r − r)
position steps which explained as follow: firstly, dehydration pro-
cess at 25–70°C which was related to the losing of two hydrated
water molecules with weight loss of 4.47% (calcd. 4.05%). Secondly
the elimination of two chloride ions and two phenyl rings at 180-
320°C with weight loss equal to 25.98% (calcd. 25.54%). The last
step at 320-600°C was allocated to complete decomposition of the
complex molecule with mass loss equal to 57.72% (calcd. 58.76%).
A
ꢀ
where, ZA is the nucleus A charge, situated R , ρ(r ) denotes
A
to the molecule electronic density function and r’ refers to the
dummy integration variable [94]. In the MEP, the various val-
ues of the electrostatic potential at the surface are symbolized
by various colors (from red to blue). The electron rich area, elec-
tropositive sites and zero electrostatic potentials areas are symbol-
ized by red, blue green colors, respectively. To expect the effec-
tive sites of electrophilic and nucleophilic attacks for dihydrazone
3.8. In-vitro antibacterial study
(
HL), the 3D plots of MEP and ESP of dihydrazone (HL), utilizing
The in-vitro antibacterial study of the dihydrazone (HL, 1) and
its uni-metallic complexes (2-8) has been examined against E. coli,
P. aeruginosa, K. pneumonia and B. subtilis based on agar well dif-
fusion method and has been evaluated via the diameter of inhi-
bition zone. The result of in-vitro antibacterial has been listed in
Table 5 and displayed graphically in Fig. 7. The in-vitro antibacte-
rial results demonstrated that the dihydrazone (1) has a moderate
effect against E. coli and a low effect against P. aeruginosa, K. pneu-
the DFT/B3LYP/6–311G(d,p) method are shown in Fig. 8. As illus-
trated in this Fig. the MEP of the dihydrazone (HL), shows that
the highest positive potential area (blue) concentrated on the hy-
drogen atoms and some carbons atoms with values ranged from
+
0.083084 to 0.0.465996 a.u., pointing to the probable sites for nu-
cleophilic attack while the highest negative potential sites concen-
trated on the electronegative atoms (oxygen and nitrogen) make
it to the favored sites for chelation with metallic ions. These sites
offer info about the location in which the inter-molecular inter-
actions may be formed. From these finding, it may be concluded
that the nitrogen and oxygen atoms are the sites of the strongest
repulsion while hydrogen atoms are the sites of the strongest at-
traction. It is clear from the ESP shown in Fig. 8, the negative ESP
monia and B. subtilis. The highest activity was found for Zn2 com-
plex against gram-negative strains E. coli and P. aeruginosa with IZ
equal to 30 and 27 mm with AI equal 91 and 68% respectively.
The lowest effect against gram negative strains E. coli and P. aerug-
+
inosa was noted for Cu2 complex (5) with IZ equal to 16 and 17
+
mm and AI equal 48 and 43%. In case of gram-positive strains K.
(colored in red shades) is focused on the molecule except the hy-
pneumonia and B. subtilis the highest activity was found for Cu2
+
drogen atoms and is manifested as a yellowish blob.
complex (6) with IZ equal to 25 and 26 mm with AI equal 72 and
10

M.M.E. Shakdofa, Q.M. Selim and A.M.E. Shakdofa
Journal of Molecular Structure 1246 (2021) 131194
6% respectively. While the Ni2 and Mn complexes showed the
lowest activity against the two strains respectively with IZ equal to
5 and 17 mm and AI equal 39 and 47% respectively. The enhance-
+
2+
6
and other complexes against gram-negative bacteria while the
Cu2 complex (6) is more active against gram-positive bacteria.
+
1
ment of the antibacterial activity of some complexes may also be
clarified based on the chelation theory, because of the alteration in
the metallic ions polarization which leading to the modification of
the complex’s lipophilicity. The action mechanism of antibacterial
effect of chelated compounds may be attributed to the increase-
ment in the lipophilic character of the complexes resulting from
chelation. Chelating process diminishes the polarity of the metallic
ions mainly due to the partial sharing of their positive charge with
the donor atoms as well as probable π-electron delocalization in
the whole chelating ring. The chelation also raises the lipophilic
character of the central metallic ions, which consequently favors
the penetration via the cell membrane lipid layer so inhibit the
bacterial wall synthesis or activate enzymes that destroy the cell
wall. The action mode of complexes may also involve the hydro-
gen bonds formation with the imino group by the active sites that
will lead to interfering with the synthesis of cell wall [95]. The hy-
drogen bond formation is leading to damage the cytoplasmic mem-
brane and the cell permeability may also be altered leading to cell
death.
Funding statement
This work was funded by the Deanship of Scientific Research
(DSR) University of Jeddah, Jeddah, Saudi Arabia under grant no
(UJ-02-055-DR).
Data availability statement
The data that supports the findings of this study are available
in the supplementary material of this article.
Credit author statement
All authors conceived and designed the experiments,
performed the experiments, analyzed the data, contributed
reagents/materials/analysis tools, wrote the paper, reviewed drafts
of the paper. All authors read and approved the final manuscript.
Declaration of Competing Interest
The orders of antibacterial of the dihydrazone and its
chelated compounds against E. coli was found to be Tc>Zn2
+
7)>Cu2 (6)>Ni (4)=HL(1)>Ru (8)>Co (3)>Mn (2)>Cu (5),
+
2+
3+
2+
2+
2+
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
(
2
+
2+
2+
against P. aeruginosa is found to be Tc>Zn (7)>Ni (4)>Co
3)>Mn2 (2) =Cu2+(6)=Ru (8)> Cu (5)>HL(1), against K.
+
3+
2+
(
pneumonia was found to be Tc>Cu2 (6)>Cu2+(5)=Ru3+(8)
+
Zn2+(7)>
2+
2+
2+
Supplementary materials
>
Co (3)>Mn (2)>HL(1)=Ni (4)
and
+
against
B.
subtilis
was
found
to
be
Tc>Cu2 (6)>Cu (5)=
2+
Zn2 (7)>Ru (8)>Co (3)=Ni (4)>HL(1)>Mn (2).
+
3+
2+
2+
2+
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2021.131194.
Further-
more, the activities of the prepared dihydrazone and its metallic
complexes were reinforced by determining the index of activity
in accordance to the published equation [57], and then were
displayed in (Figs. 8 & 9). The index of activity confirms the
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