Synthesis, crystal analysis and DFT calculations of Ni(II) and Pd(II) complexes of 3,3'-((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazole-3-ium)

Article abstract of DOI:10.1016/j.molstruc.2018.11.043

Ni(II) and Pd(II) Complexes of 3,3'-((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazole-3-ium) were synthesised in good yield and characterized by spectroscopic and X-ray diffraction techniques. These novel complexes, which are neutral in charge, possess square planar geometry where the coordination of the tetradentate ligand is through C2 of the imidazole moiety. These complexes are identified to be single cis-isomers as confirmed by ¹H NMR and single crystal X-ray diffraction data. DFT/B3LYP calculations were also conducted using the theoretical model of the precursor heterocyclic ligand and Ni(II) and Pd(II) metal complexes. The results of these theoretical data which are calculated to be the structural parameters of optimized structures exhibited good agreement with those obtained from X-ray crystal diffraction analysis. Both metal complexes are subjected to further theoretical studies such as determination of the HOMO-LUMO gap, molecular electrostatic potential (MEP) and calculation of reactivity descriptors and the obtained results attest the superiority of these compounds as novel heterocyclic functional materials.

Full text of DOI:10.1016/j.molstruc.2018.11.043

Accepted Manuscript
Synthesis, crystal analysis and DFT calculations of Ni(II) and Pd(II) complexes of 3,3'-
((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazol-3-ium)
Amal Al-Azmi
PII:
S0022-2860(18)31353-X
DOI:
https://doi.org/10.1016/j.molstruc.2018.11.043
MOLSTR 25872
Reference:
To appear in: Journal of Molecular Structure
Received Date: 19 July 2018
Revised Date: 11 November 2018
Accepted Date: 12 November 2018
Please cite this article as: A. Al-Azmi, Synthesis, crystal analysis and DFT calculations of Ni(II)
and Pd(II) complexes of 3,3'-((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-
allyl-1H-imidazol-3-ium), Journal of Molecular Structure (2018), doi: https://doi.org/10.1016/
j.molstruc.2018.11.043.
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ACCEPTED MANUSCRIPT
Synthesis, Crystal Analysis and DFT Calculations of Ni(II) and Pd(II) Complexes of 3,3`-((1,2-
phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazol-3-ium)
Amal Al-Azmi
Chemistry Department, Kuwait University, P. O. Box 5969, Safat 13060, Kuwait
*Correspondent e-mail: amalrchem@gmail.com, amal.alazemi@ku.edu.kw
PdCl2(CH3CN)2,
K2CO3, DMF, reflux
O
O
N+
N
NH
NH
-
2Cl
N+
N
NiCl2, K2CO3
DMF, reflux

ACCEPTED MANUSCRIPT
Synthesis, Crystal Analysis and DFT Calculations of Ni(II) and Pd(II) Complexes of 3,3`-
((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazol-3-ium)
Amal Al-Azmi
Chemistry Department, Kuwait University, P. O. Box 5969, Safat 13060, Kuwait
*Correspondent e-mail: amalrchem@gmail.com, amal.alazemi@ku.edu.kw
Abstract
Ni(II) and Pd(II) Complexes of 3,3'-((1,2-phenylenebis(azanediyl))bis(2-oxoethane-2,1-
diyl))bis(1-allyl-1H-imidazol-3-ium) were synthesized in good yield and characterized by
spectroscopic and X-ray diffraction techniques. These novel complexes, which are neutral in
charge, possess square planar geometry where the coordination of the tetradentate ligand is
through C2 of the imidazole moiety. These complexes are identified to be single cis-isomers as
confirmed by 1H NMR and single crystal X- ray diffraction data. DFT/B3LYP calculations were
also conducted using the theoretical model of the precursor heterocyclic ligand and Ni(II) and
Pd(II) metal complexes. The results of these theoretical data which are calculated to be the
structural parameters of optimized structures exhibited good agreement with those obtained from
X-ray crystal diffraction analysis. Both metal complexes are subjected to further theoretical
studies such as determination of the HOMO-LUMO gap, molecular electrostatic potential (MEP)
and calculation of reactivity descriptors and the obtained results attest the superiority of these
compounds as novel heterocyclic functional materials.
Keywords: Heterocyclic carbenes, Ni-NHC complex, Pd-NHC complex, DFT, Crystal structure.
1. Introduction
N-heterocyclic carbenes (NHCs) have garnered great interest in recent years due to their
structural characteristics and for exhibiting significant roles in cross-coupling reactions [1,2].
Among them NHC-metal complexes coupled with imidazolium salts are considered as unique
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organometallic species and efficient catalysts. Several imidazolium salts are utilized as ionic
liquids in several organic syntheses. This property has enabled them to exhibit important
advantage for a wide range of reactions which contributes significantly to green chemistry [1].
For example, imidazolium ionic liquids with an ‘ionophilic’ diphenyl anthracene were designed
as effective organic light-emitting diodes (OLEDs) [2].
NHC ligands are demonstrated to be electronically neutral in most cases and are non-participant
in plenty of homogeneous catalysis. At the same time, they yield complexes with many metals
such as palladium, nickel, platinum, ruthenium, rhodium, iridium, copper, silver and gold,
thereby creating useful catalysts. These catalysts are used in many catalytic reactions such as
transfer hydrogenation, olefin metathesis, Heck, Sonogashira and Suzuki coupling reactions [3-
17]. In addition, chiral N-herterocyclic carbenes formed from chiral imidazolium salts are
utilised as asymmetric acylation catalysts [18]. Moreover, many of these metal NHC complexes
display potent antimicrobial and anticancer activities [19,20]. They are also used as precursors
for NHCs, which react with other catalytically important metals, particularly Pd and Ni. Metal
NHC complexes offer better substitutes for phosphine ligands, which are known to be expensive
and sensitive towards moisture, air and heat [9]. In addition, the NHC ligands are well
recognized for their role in improving the π– coordination and flexibility [21].
The imidazole moiety of NHC could coordinate to the metal ions either through its C2 atom or
through C4. Several Pd complexes have been reported in the literature where the imidazole
moiety coordinates with the metal through the C2 and they are considered as ‘normal
complexes’. However, some metal complexes were detected and isolated as ‘abnormal NHCs’ in
which the attachment is via C4. Such difference in mode of attachment could cause significant
variations associated with physical/chemical properties of the resulting metal complexes and
hence their applications as well. For example, Albrecht et al. [11a]. showed that the ‘abnormal
NHC’ were efficient in the hydrogenation of olefins but the normal NHCs were not.
In most cases, Pd(II) and Ni(II) derivatives of NHC- imidazole complexes are square-planar and
neutral. As a result, the difference in mode of attachment through either C2 or C4 could cause
the formation of geometrical isomers. Barnard and his co-workers [11b] synthesized isomers of
Pd(II) complexes with two chelating bidentate ligands due to the intersection between ‘normal
and abnormal’ coordination modes of attachments via C2 and C4 of the imidazolium portion,
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which were separated and identified. However, in case of Ni(II), no geometric isomers were
reported, and the ligands were connected through the C2 mode.
Many novel Ni(II) complexes with N-donor functionalized NHCs have been reported and these
complexes possess square planar geometry and are cis-isomers with respect to Ni(II) [11b]. With
the benzimidato functionalized complexes too, the cis-isomers were identified, and the prepared
complexes were tested in Kumada cross-coupling reaction of PhMgCl with 4-chloro and 4-fluoro
anisoles; the benzimidato function showed the highest reactivity compared to reactions reported
previously, thereby giving the required product in a very high yield in 30 and 150 minutes for 4-
choloro and 4-fluoroanisoles, respectively, where only 1 mol% of catalyst was introduced [12].
A report by Jung showed preparation of Pd(II) complex with tridentate NHCs, which is air/H2O-
stable and can activate C-H bonds of different hydrocarbons such as cyclopentane, cyclohexane,
THF, dimethyl ether, toluene and acetone [21]. In addition, Lee et al. demonstrated that a
‘heteroleptic’ cis Pd(II) complex with a bidentate carbene amino ligand and 3-CF3-5-2-
pyridyllpyrazolate was used in MCR in catalysing a Heck reaction and proved to be efficient,
particularly aryl halides with effortful substituents [9]. Furthermore, interests in such NHCs
complexes with various deprotonated imides increased dramatically after Gosh referred to their
role in biomedical and catalysis applications [9,11b].
Here, we report successful synthesis of Ni(II) and Pd(II) complexes of 3,3`-((1,2-phenylenebis-
(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1H-imidazol-3-ium), which were characterized
by spectroscopic and single crystal X-ray diffraction techniques. Density functional theory
(DFT) calculations on the obtained metal carbene complexes were also investigated in detail.
2. Experimental
Melting points were determined with a Sanyo (Gallenkamp) instrument. Infrared spectra were
recorded using KBr pellets and a Jasco FT-IR 6300 instrument, and υmax was recorded in cm-1.
1H and 13C NMR spectra were determined by using a Bruker DPX instrument at 400 MHz for 1H
NMR and 100 MHz for 13C NMR and DMSO-d6 as a solvent with TMS as an internal standard.
Chemical shifts are reported in d (parts per million). Mass spectra were measured using GCeMS
DFS Thermo spectrometer, with EI (70 eV) mode. X-ray crystal structure determined by using
Single Crystal X-ray Diffractometer Rigaku Rapid II and Bruker X8 Prospector. Both N,N`-
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bis(chloroacetyl)-1,2-phenylenediamine [22], 1-allylimidazole [23] were prepared according to
procedures laid out in the literature.
2.1. Synthesis
2.1.1. Preparation of PdCl2(CH3CN)2: PdCl2 (1.77 g, 10.0 mmol) is refluxed in excess
acetonitrile for 2 hrs and the solution is filtered and cooled in an ice-bath to obtain the desired
product; thereafter, the filtrate was concentrated further, and extra solid was collected (2.10 g,
8.10 mmol, 81%)
2.1.2. Preparation of Ni Complex 7: A mixture of 1-allylimidazole (2.40 g, 22.0 mmol) and
N,N-bis(chloroacetyl)-1,2-phenylenediamine (2.61 g, 10.0 mmol) in DMF was refluxed until the
reaction reached completion, as evidenced by TLC (1:1) EtOAc:hexane. The imidazolium salt
was used in the next stage without any purification and not isolated due to its instability. Next,
K2CO3 (12.0 mmol) and NiCl2 (0.39 g, 3.01) was added to the formed suspension. The mixture
was heated at 150oC overnight. The reaction mixture was cooled, and excess distilled water was
added to it, followed by extraction with chloroform. Then, the organic layers were combined and
dried. The complex was further recrystallised from chloroform, and X-ray was performed on the
collected crystals.
Light green powder (0.98 g, 2.13 mmol, 71%), M.p. 271-274oC, MS 460, 100%, accurate mass
for (C22H22N6O2Ni) found: 460.1153, required: 460.1152, 1H NMR (d6-DMSO): 3.99 (1H, t, 1.2
Hz), 4.014 (1H, td, 1.8 Hz, 5.2 Hz), 4.35 (2H, dd, 5.4 Hz, 15.9 Hz), 4.69 (2H, d, 17.4 Hz), 5.00
(4 H, t, 1.2 Hz), 5.14 (2H, dd, 1.2 Hz, 10.2 Hz), 5.83 (2H, m), 6.64 (2H, m), 7.34 (2H, d, 1.8 Hz),
7.48 (2H, d, 1.8 Hz), 8.26 (2H, m). 13C NMR (d6-DMSO) 166.31, 162.53, 143.36, 133.29,
122.77, 121.95, 121.64, 119.95, 117.72, 54.53, 51.59, IR (KBr disc) υmax: 3409.53, 3154.01,
3116.4, 3081.69, 2987.2, 2954.41, 2917.77, 2852.2, 1599.66, 1559.19, 1477.21, 1442.49 cm-1.
2.1.3. Preparation of Pd Complex 8: A mixture of 1-allylimidazole (2.40 g, 22.0 mmol) and
N,N-bis(chloroacetyl)-1,2-phenylenediamine (2.61 g, 10.0 mmol) in DMF was refluxed until
reaction reached completion, as evidenced by TLC (1:1) EtOAc:hexane. Imidazolium salt was
used in the next stage without any purification and not isolated due to its instability. Next, K2CO3
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(12.0 mmol) and PdCl2(CH3CN)2 were added to the formed suspension. The mixture was heated
at 150oC overnight. The reaction mixture was cooled, and excess of distilled water was added to
it, followed by extraction with chloroform. The organic layers were combined and dried. The
complex was further recrystallised from chloroform. X-ray was performed on the collected
crystals.
Light brown powder (1.05 g, 2.10 mmol, 69%), M.p. 217oC decomp., MS 508, 7%, 54, 100%,
1
accurate mass for (C22H22N6O2Pd) found: 508.0833, required: 508.0834, H NMR (d6-DMSO):
4.16 (2H, d, 15.6 Hz), 4.43 (2H, d, 15.6 Hz), 4.73 (2H, d, 15.6 Hz), 4.90 (1H, s,), 4.95 (2H, d, 1.8
Hz), 4.97 (2H, d, 1.2 Hz), 5.18 (1H, d, 1.2 Hz), 5.19 (1H, d, 1.2 Hz), 5.90 (2H, m), 6.72 (2H, dd,
3.0 Hz, 6.3 Hz), 7.44 (2H, d, 1.8 Hz), 7.60 (2H, d, 1.8 Hz), 8.26 (2H, m), 8.33 (1H, s). 13C NMR
(d6-DMSO) 165.35, 162.79, 143.59, 133.39, 123.16, 122.99, 122.19, 121.52, 120.22, 118.10,
56.23, 52.28, IR (KBr disc) υmax: 3417.24, 3164.61, 3126.04, 2983.34, 2922.59, 1662.34,
1594.84, 1551.45, 1473.35, 1442.49, 1412.6, 1376.93, 1302.68 cm-1.
2.2. Single crystal analysis
Single crystals suitable for X-ray diffraction technique were grown by slow solvent evaporation.
The data collections were made on a Rigaku R-AXIS RAPID II diffractometer using filtered Mo-
Kα radiation at 150K. Crystalclear software package was employed to generate hkl and p4p
files. The structures were solved by direct methods using Rigaku's CrystalStructure
crystallographic software package except for refinement, which was performed using SHELXL-
2017/1. The non-hydrogen atoms were refined anisotropically. Hydrogen atoms are placed at
calculated positions and refined using the riding model. In case of the Pd complex, both alkene
moieties in the structure are disordered over two sites and were refined using PART command.
One of the alkene sites of Ni(II) complex 7 is also disordered and this site too was refined using
PART command. In both Ni(II) and Pd(II) complexes 7 and 8, there were some solvent
molecules in the crystal network which were highly disordered and could not be refined
successfully. Consequently, these disordered solvent peaks were eliminated using the SQUEEZE
technique. The details of the SQUEEZE Results (Version = 30715) have been embedded in the
cif file. The thermal ellipsoid representation (50% probability) of Ni(II) and Pd(II) Complexes
are given in (Figure 1a), and the crystal nature, unit cell descriptions and crystallographic
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refinement parameters are summarized in (Table S1). The packing pattern of both complexes in
their crystal form showing square-shaped continuous voids in the network are also presented in
(Figure 1b).
Fig. 1a: Thermal Ellipsoid representation of the crystal structures of Pd and Ni Complexes.
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Fig.1b: The packing pattern of Pd complex and Ni complex in crystal showing square shaped
continuous voids in the network.
3. Results and Discussion
3.1. Synthesis and NMR characterization of Ni(II) 7 and Pd(II) complexes 8
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The N-heterocyclic carbenes (NHC) ligand employed for the synthesis of Ni(II) 7 and Pd(II) 8
complexes were synthesized by a multistep reaction procedure. To begin with, N,N`-
bis(chloroacetyl)-1,2-phenylenediamine 2 and 1-allylimidazole 5 were synthesised in good yields
using adopted procedures reported previously in literature (Scheme 1) [22,23]. Both 2 and 5 were
1
characterized by H NMR spectra and peak features were consistent with those reported
previously [22,23]. The precursor tetradentate imidazolium ligand 6 was then synthesised from
compounds 2 and 5 by refluxing them together in DMF for 18 h. The synthesised ligand is
observed to be unstable and hence its characterization was not possible. However, this crude
ligand in the reaction mixture could be used in situ without any further purifications for the
synthesis of Ni(II) and Pd(II) complexes 7 and 8 (Scheme 2).
To synthesize the Ni(II) complex 7, NiCl2 was added to the crude mixture of 6 in DMF in the
presence of K2CO3 and the reaction mixture was refluxed for 16–18 hours. The Ni(II) complex 7
formed were then isolated from the reaction mixture which on recrystallisation from chloroform
furnished light green crystalline powder in good yield (71%). The formed complex is neutral,
square planar, and is in cis form, as observed from the X-ray crystal structure. Furthermore, the
attachment mode of Ni was via C2 of the imidazole moiety which was confirmed again by NMR
1
spectral analysis. The H NMR spectra showed the expected protons of the methylene and allyl
groups at
δ 3.99-5.83 ppm and the aromatic protons at δ 6.64 and 8.26 ppm along with the
disappearance of carbenic proton peaks. The most significant 13C NMR spectral features are the
carbonic carbon peak which detected downfield at 166.3 and the Ni-C (observed at 162.5).
The Pd(II) complex 8 was prepared in the same manner as that of Ni(II) complex using
PdCl2(CH3CN)2, K2CO3 and DMF under reflux condition for 18 hrs. The formed complex was
also recrystallised from chloroform to yield light brown crystals in 69% yield. Pd(II) complex 8
isolated was also cis, square planar and uncharged, and there was no evidence of formation of
1
geometric isomers in H NMR spectra. As expected, the carbene protons were absent and the
attachment of the ligand was at C2 of the imidazole site; the NH protons were also missing in the
13
1H NMR spectra, thereby demonstrating the carbene formation. In C NMR, the C=O function
was spotted at 165.3 and Pd-C at 162.8, respectively.
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O
Cl
Cl
NH2
NH2
NH
NH
1) DCM, TEA
2) Chloroacetyl chloride, ice bath
1
O
N
2
H
N
NaH, THF
Br
+
N
N
5
3
4
Scheme 1: Synthetic routes for N,N`-bis(chloroacetyl)-1,2-phenylenediamine 2 and 1-
allylimidazole 5.
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O
O
N+
O
O
Cl
Cl
N
NH
NH
NH
NH
N
N
DMF, 150oC
-
2Cl
+
N+
N
6
2
5
NiCl2, K2CO3, DMF, reflux,
16-18 hrs
PdCl2(CH3CN)2,
K2CO3, DMF, reflux,
18 hrs
O
O
N
N
N
Ni
N
N
N
O
O
N
N
N
N
Pd
7
N
N
8
Scheme
2:
Synthesis
of
Ni(II)
and
Pd(II)
Complexes
of
3,3`-((1,2-
phenylenebis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-allyl-1
H
-imidazol-3-ium) 7 & 8.
3.2. Crystal structures and packing features of Ni and Pd complexes
The structures of Ni(II) complex 7 and Pd(II) complex 8, which were obtained from single
crystal X-ray diffraction technique are depicted in (Figure.2).
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Fig. 2: Crystal structures of Ni(II) and Pd(II) complexes 7 and 8, respectively [24,25].
Both complexes exhibited similar geometry despite the difference in their central metal ions. The
crystal structures reveal that the metal sites in both Pd(II) and Ni(II) complexes are square planar
in geometry and are considerably distorted to minimize steric constraints caused by terminal
alkene fragments of the ligand. As expected, both Pd and Ni metals were coordinated with two
atoms each of nitrogen and carbon from the ligand in their respective complexes. The
coordination was in a manner that the resulting two complexes were neutral in charge and hence
no counter ions were present in the crystal network. The crystal structures also confirm cis
geometry of these complexes at the metal sites.
The crystal data also provide valuable information regarding the bond lengths associated with the
metal ions. It was observed that in Pd(II) complex 8, the Pd-N and Pd-C bond lengths were
approximately 2.05 and 1.96 Å, respectively. At the same time, in the case of Ni(II) complex 7,
the corresponding bond lengths were 1.90 (Ni-N) and 1.83 Å (Ni-C), which were shorter than
that of Pd complex. It was also noted from the crystal structure that the distortion of the square
planar geometry at the metal centre was more severe in the case of the Ni complex than that of
Pd(II) complex. The calculated torsion angle comprising atoms N4-C11-Ni1-C15 was 58o for the
7, whereas it was only 51o for 8 whose relevant torsion angle constituted the atoms N1-C1-Pd1-
C17 (the atom assignments are as depicted in Figure 2). It was evident that when the metal-
ligand bond lengths decreased, as in the case of 7, more strains resulted at the ligand periphery
and, hence, there was a higher distortion at the square planar geometry to relieve the steric
crowding around the alkene moieties.
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The packing features of both the Ni and Pd complexes in their crystal network were the same.
The packing was observed to be very efficient and the crystals were stable at room temperature
even under strong X-ray exposure. The molecular arrangements in these crystals were in such an
ordered manner that the resulting crystal networks provided square shaped continuous voids,
which extended as long channels along the c-direction (Figure 1b). The void dimensions in these
crystals are large enough to accommodate small guest molecules. Such pores have
supramolecular networks with the availability of catalytically important metal sites (like Ni and
Pd, in this case) and are very important in molecular recognition, host-guest encapsulations,
sensors, molecular sieves and enzyme-like catalysis. Thus, the nature as well as stability of their
crystal packing offer wide applicability of these novel metal complexes for many potential
applications.
3.3. DFT calculations
Quantum chemical calculations for the ligand and its metal complexes were used to optimize the
geometry and spectral calculation using the Gaussian 03W suite program [26] and employing the
Becke3–Lee–Yang–Parr (B3LYP) exchange-correlation functional [27-29] with standard 6-
311++G (d,p) basis set. The obtained geometrical optimized structures and frontier molecular
orbitals (FMO’s) were visually inspected using the GaussView program [30].
3.3.1. Molecular Geometry
The DFT-optimized structure of the ligand is presented in (Figure 3). The dihedral angles data
indicate that the phenyl ring, NH’s groups and the carbon of carbonyl groups all lie on a single
plane (Table S2), while the methylene group, imidazole ring and allyl branch are planar to each
other. In addition, the data shows that the hydrogen of NH’s groups are perpendicular to the
plane of oxygen of carbonyl and methylene groups (H-NH-CO-O = 90.0° and H-NH-CO-CH2 =
-90.0°), respectively, while both the oxygen of carbonyl and methylene exist in opposite
directions. Furthermore, the oxygen atom planes are perpendicular to the phenyl ring plane
(CHPh-NH-CO-O = -90.0°), while the carbonyl are tilted on the imidazole ring plane by 45.00°.
The bond angle data indicates that the phenyl ring, carbonyl, methylene and allyl groups almost
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have the ideal values with respect to its hybridization (for sp2 = 120° and sp3 = 109.5°) (Table
S3). The NH groups have sp3 hybridization and show strong bond angle deformation, for
example, H-NH-CHPh = H-NH-CO = CO-NH-CHPh
≈ 120.0°. The obtained imidazole ring bond
angles display a small deviation from the X-ray values, 108.5 and 125.5°, by ~ 1.0–2.0°. The
bond length data of the ligand, presented in (Table S4), exhibits very good agreement with those
obtained from the X-ray crystal structure of analogue compounds, showing difference ranging
from 0.015 to 0.133 Å [31]. The bonds N+im-CHim and Nim-CHim—for example, N10-C23, N9-
C23, N11-12 and N4-C12—are the most deviated bonds from the X-ray values, shorter by -0.133
Å, and also shorter than other (N-CH)im bonds which can be attributed to the involvement of
these atoms in resonance of the imidazole ring. For example, the other (N-CH)im bonds—such as
N10-C22, N9-C21, N11-C28 and N4-27—are longer than the X-ray bonds by only 0.015 Å [31].
Fig. 3. DFT-optimized structure of a ligand
The Ni(II) complex DFT-optimized structure, presented in (Figure 4), indicates that it has square
planar geometry. The dihedral angle data show that the phenyl ring and N-atoms of amine groups
are planar (N-CHPh-CHPh-CHPh
on the N+im and Nim planes (N-M-C-N+
≈
179.8°) (Table S2). The plane of N’s nitrogen atoms is tilted
20.00° and 98.00°; N-M-C-Nim -57.5° and -135.5°).
≈
≈
im
The X-ray data display the same trend with difference from DFT values ranging from 0.55° to
4.50°. The imidazole carbons bonded to metal lie above and/or below the phenyl and N groups
plane (C-M-N-CHPh
≈ 164.00° and 79.00°), exhibiting deviation from obtained X-ray data in the
range of 0.20°–4.5°. The Ni(II) atom lies below the plane of carbonyl oxygens, methylene
groups and imidazole carbons, which coincides with the X-ray crystal structure with average
differences of 0.82°, 5.75° and 11.50°, respectively. Moreover, the imidazole ring dihedral angle
data showed a small deviation from planarity by 2.53°–11.34 ° and the allyl group is tilted by
≈
100.00 °. The Ni(II) complex 7 bond angle data more clearly indicated the distortion of the
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square planar structure, where C-M-N = 91.81° and 90.54° (N7-Ni4-C24 and N8-Ni4-C23),
which is very close to the ideal value (90.0°) (Table S3). The other C-M-N showed deviation
from the ideal value 180.0° (N7-Ni4-C23 = 162.5° and N8-Ni4-C24 = 165.54°). The X-ray data
show the same trend with a very small difference from the DFT-calculated value ranges from
0.08° to 2.97°. Furthermore, the N-M-N (85.73°) and C-M-C (95.78°) deviated from the ideal by
~ 5° and coincide with those obtained from X-ray measurements 85.73° and 96.30°, respectively.
Finally, the bond length data of M-C was 1.881 and 1.894 Å longer than those obtained from the
X-ray by 0.039 and 0.051 Å, respectively (Table S4). The M-N DFT calculated bond length,
1.908 and 1.910 Å, almost coincided with those obtained from X-ray, 1.894 and 1.909Å. Thus,
bond length data showed another type of distortion in bonds of the square planar structure (Table
S4).
Fig. 4. DFT-optimized structures of the Ni(II) complex 7 and Pd(II) complex 8.
The dihedral angle data show that the phenyl ring and nitrogen atoms of amine groups are almost
co-planar, with average deviation from planarity by 0.45° (Table S2). Both DFT and X-ray
dihedral angles showed that the amine nitrogen atoms plane is tilted on the N+im and Nim planes
(N-M-C-N+
≈
21.90° and 78.64°; N-M-C-Nim
≈ -81.15° and -137.89°) with average difference
im
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of 5° and 3.75°, respectively. The imidazole carbons bonded to metal lie above the plane of
phenyl and amine groups (C-M-N-CHPh
from obtained X-ray data by an average difference of 4.69°. Pd(II) atom is almost planar with
phenyl group in both DFT and X-ray data, where M-N-CHPh-CHPh 178.45° and 3.12°,
respectively. The DFT dihedral angles C-N+im-C-M and C-Nim-C-M exhibit deviation from the
X-ray values by only 1.50°. Moreover, Pd(II) lies below the plane of carbonyl oxygens and
methylene groups in both DFT and X-ray structures where M-N-CO-O -169.70° and 151.50°,
respectively, and CH2all-N+im-C-M
15.47° and 15.82°, respectively. The dihedral angles
≈ 166.45° and 58.50°), thereby exhibiting deviation
≈
≈
≈
≈
imidazole ring showed a small deviation from planarity and the allyl group tilted on it in both
DFT and X-ray structures.
The DFT bond angle data of Pd(II) complex 8 displayed a distortion of the square planar
geometry, as shown in (Table S3), where C-M-N = 89.14° and 90.21° (N12-Pd7-C16 and N13-
Pd7-C29), which coincided with those of X-ray, 89.95° and 91.98°, respectively. The other C-M-
N are more deviated from the ideal value of 180.0° (N12-Pd7-C29 = 162.17° and N13-Pd7-C16
= 168.12°), which is very close to the X-ray values (difference –0.65°). Furthermore, the N-M-N
(82.78°) and C-M-C (99.95°) deviated from the ideal by ~ 10.0° and coincide with those
obtained from X-ray measurement 82.78° and 98.28°, respectively.
From the bond length data in (Table S4) that the length of the two M-C bonds is not equal—from
DFT, they are 2.001 and 2.027 Å, while from the X-ray, they are shorter by 0.029 and 0.068 Å,
respectively. On the other hand, both DFT-calculated and X-ray-measured M-N bond length
coincides, at 2.047 and 2.057 Å, respectively. As a result, the data showed that there are two
types of bond length distortion of the square planar geometry. Firstly, each bond of the same type
is not equal; secondly, the bond M-N is longer than M-C by 0.038 and 0.086 Å, for DFT and X-
ray, respectively.
3.3.2. Molecular electrostatic potential
The molecular electrostatic potential is a well-established method to predict electrophilic and
nucleophilic reactions, hydrogen-bonding interactions and biological recognition processes
[32,33]. To predict the reactive regions for electrophilic and nucleophilic attack for the
investigated molecules, the MEP at the DFT-optimized geometry was calculated. The different
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values of the electrostatic potential at the surface are represented by different colours and
potential increases in the order red < orange < yellow < green < blue. The negative regions of the
MEP (red, orange and yellow) are related to electrophilic reactivity. As shown in (Figure 5), the
ligand MEP showed negative regions localized over the carbonyl group oxygen and nitrogen
atoms of amine groups, thereby indicating the possible sites for electrophilic attack while the
most positive regions are localized over the hydrogen atoms of NH groups. In case of complexes,
the most negatively charged regions are localized on the carbonyl oxygens and the most
positively charged regions are over the nitrogen atoms of amine groups and imidazole rings
(Figure 6).
Fig. 5. MEP of the ligand
Fig. 6. MEP of the Ni(II) complex and MEP of the Pd(II) complex.
3.3.3. Frontier molecular orbitals (FMOs)
All molecules have frontier molecular orbitals (FMOs), which are simply the highest occupied
molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The energies of
these two important molecular orbitals of the ligand and its metal complexes were calculated
using B3LYP/6-311G method and are presented in (Table S5). They are used to obtain frontier
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electron density for predicting the most reactive positions. The gap between HOMO and LUMO
illustrates the chemical stability of a molecule. The energy gap ꢀE, EHOMO–ELUMO, explains the
ultimate charge transfer in the molecule [34]. The qualitative graphical representation of
molecular orbitals can provide insight into concepts such as reactivity, conjugation, aromaticity
and lone pair [35].
The 3D plots of FMOs in the optimized state, HOMO and LUMO for the ligand, presented in
(Figure 7), indicated that the HOMO is localized on the phenyl ring, nitrogen atoms of NHs and
carbonyl oxygen atoms (EHOMO = -8.23 eV), while the LUMO is on the hydrogen atoms of NH
and carbonyl groups (EHOMO = -4.82 eV). The energy gap
S5).
ꢀE was found to be 3.41 eV (Table
(A)
(B)
Fig. 7. The ligand frontier MO (A) HOMO and (B) LUMO.
The plots of FMO’s of complexes, depicted in (Figures 8 and 9), clarifies that the HOMO is
localized on metal atoms, amine groups and coordinated imidazole carbon in the Ni(II) complex
7; on the other hand, it is localized on the metal atom, imidazole ring and allyl group in the
Pd(II) complex 8. The LUMO orbital in both complexes was spread over all the molecule atoms.
The frontier MO energy data indicated that the EHOMO, –12.85 and –12.64 eV, and ELUMO, –11.64
and –11.79 eV, of Ni(II) and Pd(II) complexes, respectively, are very close to each other. Thus,
the complexes have an energy gap
ligand, 1.22 and 0.85 eV, for Ni(II) and Pd(II), respectively,. For solar cell applications and
similar purposes, molecules have small EHOMO-LUMO and can absorb more photons from the
ꢀE that is almost equal to one-third of that obtained for the
ꢀ
same light beam leading to higher circuit current density and a higher overall power conversion
efficiency [36]. The Pd(II) complex, however, has the lowest energy gap while the ligand has the
highest, and more suitable than Ni(II) and ligand, respectively, for solar cell applications and
17

ACCEPTED MANUSCRIPT
similar purposes. Moreover, the decrease in the HOMO-LUMO energy gap indicates the ease of
charge transfer interactions within the molecule, which may be responsible for the bioactivity of
the molecules [37].
(A)
(B)
Fig. 8. The Ni(II) complex 7 frontier MO (A) HOMO and (B) LUMO.
(A)
(B)
Fig. 9. The Pd(II) complex 8 frontier MO (A) HOMO and (B) LUMO.
3.3.4. Chemical Reactivity Descriptors and Dipole Moment
The EHOMO and ELUMO are related to the ionization potential (
molecules by the following relations -EHOMO and -ELUMO. In addition, other than the
traditional reactivity descriptors, such as FMOs, there are certain other chemical reactivity
descriptors such as electronegativity ( ), global hardness ( ), softness ( ) and electrophilicity (
which can be calculated from HOMO–LUMO. The electronegativity ( ) is a measure of the
I) and the electron affinity (A) of
I
=
A =
χ
η
δ
ω)
χ
molecule power to attract electrons and is calculated in the following manner [34]:
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ACCEPTED MANUSCRIPT
ꢁ ꢃ
ꢀ = − ꢂ
ꢊ
.
ꢄꢅꢆꢇꢆ + ꢄꢈꢉꢇꢆ
The large
χ
values characterize Lewis acid, while small values are to the bases. As presented in
χ
(Table S5), Ni(II) and Pd(II) complexes 7 and 8 have higher electronegativity than the ligand,
almost double, and thus complexes are considered as Lewis acids.
Global hardness (η) is a measure of the charge transfer resistance while global softness (δ)
describes the capacity of a molecule to receive electrons and is equal to the reciprocal of global
hardness [37].
ꢁ ꢃ
ꢊ
,
ꢋ = − ꢂ
ꢄꢅꢆꢇꢆ − ꢄꢈꢉꢇꢆ
ꢁ
ꢌ = ꢍ
.
Soft molecules, with a small energy gap, are more reactive than hard ones because they can
easily offer electrons to an acceptor. Thus, the data showed that the ligand is the hardest, while
Pd(II) complex is the softest. The electrophilicity (ω) is a measure of energy lowering due to the
maximal electron flow between the donor and the acceptor, HOMO and LUMO, respectively,
and can be calculated from the electronegativity and chemical hardness.
ꢐ
ꢎ = ꢏꢂꢍ
.
From (Table S5), it is evident that the ligand has the lowest electrophilicity index, 12.51 eV,
while Ni(II) complex has a high value, approximately ten times of the ligand—123.42 eV—and
Pd(II) complex has the highest value of 175.48 eV. These values clear the strong energy
transformation between HOMO and LUMO that occurs in complexes.
Finally, the dipole moment (ꢀtotal) in a molecule is another important electronic property. The
dipole moment reflects the molecular charge distribution and is given as a vector in three
dimensions, ꢀx, ꢀy and ꢀz. Therefore, it can be used as descriptor to depict the charge movement
across the molecule. The direction of the dipole moment vector in a molecule depends on the
centres of positive and negative charges. If geometries are symmetric, the components of dipole
moments are zero [38]. The total dipole moment for the ligand is 3.65 Debye, while the ꢁx and ꢁz
components are zero. Both Ni(II) and Pd(II) complexes showed lower total dipole moment than
the ligand, 2.42 and 1.64 Debye, respectively, with non-zero components (Table S5).
4. Conclusion
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Successful trials for growing single crystals of Ni(II) and Pd(II) complexes were conducted. The
single crystal XRD studies of complexes revealed that the nitrogen atom of NH groups and
imidazole carbons were involved in coordination with the metal ion and formed a square planar
geometry. The DFT-optimized geometry of the ligand clears the existence of a hydrogen bond
between nitrogen atoms of one NH group and hydrogen atoms of the other NH group. The data
indicated that the phenyl ring, NH groups and the carbon of carbonyl groups lie on one plane.
The DFT-optimized structures of both complexes showed square planar geometry in agreement
with the obtained XRD data. The bond length and angles data for the DFT-optimized structure
agreed with those observed from X-ray. The electrostatic potential colour map derived from
optimized geometry of the ligand and its metal complexes clearly describes the possible reactive
sites for electrophilic and nucleophilic attacks. The calculated values of HOMO-LUMO energies
gap showed that Pd(II) complex is the lowest one while the ligand is the highest. Furthermore,
the reactivity descriptors’ ionization potential, electron affinity, hardness, softness,
electrophilicity and electronegativity index attest to the superiority of these compounds. The
future work will explore these two complexes in coupling reactions and in addition to other
metals like Ag and Au will be prepared which are potentially biological active.
Acknowledgements
The author acknowledges the financial support received from Kuwait University through
research grant SC 05/17, and the facilities provided by Kuwait University (GS 01/01, GS 01/03,
GS 01/05 and GS 03/08,). Thanks are to Dr. Mohamed. H. Abdel-Rhman, Mansoura University
(Egypt) for conducting DFT calculations.
References
[1]
Martı´n, R., Teruel, L., Aprile, C., Cabeza, J. F., A´ lvaro, M., Garcı´a, H., Imidazolium
ionic liquids in OLEDs: synthesis and improved electroluminescence of an ‘ionophilic’
diphenylanthracene, Tetrahedron, 2008, 64, 6270–6274.
[2]
Herrmann, W. A., N-Heterocyclic Carbenes: A New Concept in Organometallic
Catalysis, Angew. Chem. Int. Ed., 2002, 41, 1290-1309.
20

ACCEPTED MANUSCRIPT
[3]
[4]
[5]
[6]
[7]
Peris, E., Crabtree, R. H., Recent homogeneous catalytic applications of chelate and
pincer N-heterocyclic carbenes, Coordination Chemistry Reviews, 2004, 248, 2239-2246.
Crudden, C. M., Allen, D. P., Stability and reactivity of
N-heterocyclic carbene
complexes, Coordination Chemistry Reviews, 2004, 248, 2247-2273.
Nolan, S. P., Ed., N-Heterocyclic Carbenes in Transition Metal Catalysis; Wiley-VCH:
Weinheim, 2006, Germany.
Glorius, F. Ed., N-Heterocyclic Carbenes in Transition Metal Catalysis; Springer: 2007,
Berlin.
Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. J., Palladium Complexes of N-Heterocyclic
Carbenes As Catalysts for Cross-Coupling Reactions-A Synthetic Chemist Perspective,
Angew. Chem. Int. Ed, 2007, 46, 2768-2813.
[8]
[9]
Unger, Y.; Strassner, T., Platinum(II) complexes with amide-functionalized NHC ligands,
J. Organometallic Chem., 2012, 713, 203-208.
Sie, M.-H; Hsieh, Y.-H; Tsai, Y.-H; Wu, J.-R; Chen, S.-J, Kumar, P. V.; Lii, J.-H; Lee, H.
M., A Heteroleptic Palladium(II) Complex Containing a Bidentate Carbene/Amido Ligand
and 3-(Trifluoromethyl)-5-(2-pyridyl)pyrazolate: Fast Catalyst Activation in the Heck
Coupling Reaction, Organometallics, 2010, 29, 6473-6481.
[10] Unger, Y.; Strassner, T., Platinum (II) complexes with amide-functionalized NHC ligands,
J. Organometallic Chem., 2012, 713, 203-208.
[11] a) Heckenroth, M., Neels, A., Garnier, M. G., Aebi, P., Ehlers, A. W., Albrecht, M., On
the Electronic Impact of Abnormal C4-Bonding in N-Heterocyclic Carbene Complexes,
Chem. Eur. J., 2009, 15 (37), 9375-9386. b) Tan, K. V.; Dutton, J. L.; Skelton, B. W.;
Wilson, D. J. D.; Barnard, P. J., Nickel (II) and Palladium (II) Complexes with Chelating
N-Heterocyclic Carbene Amidate Ligands: Interplay between Normal and Abnormal
Coordination Modes, Organometallics, 2013, 32, 1913-1923-6481.
21

ACCEPTED MANUSCRIPT
[12] Berding, J.; van Dijkman, T. F.; Lutz, M.; Spek, A. L.; Bouwman, L., N-donor
functionalized N-heterocyclic carbene nickel (II) complexes in the Kumada coupling,
Dalton Trans., 2009, 6948–6955.
[13] Dog˘an, O.; Gurbuz, N.; Ozdemir, I.; Cetinkaya, B.; Sahin, O.; Buyukgungor, O.,
Synthesis, characterization and catalytic activity of novel
N-heterocyclic carbene-
palladium complexes, Dalton Trans., 2009, 7087–7093.
[14] Lee, J. H.; Yoo, K. S.; Park, C. P.; Olsen, J. M.; Sakaguchi, S.; Prakash, G. K. S.;
Mathew, T.; Jung, K. W., An Air/Water-Stable Tridentate N-Heterocyclic Carbene-
Palladium (II) Complex: Catalytic C-H Activation of Hydrocarbons via
Hydrogen/Deuterium Exchange Process in Deuterium Oxide, Adv. Synth. Catal., 2009,
351, 563-568.
[15] Kumar, M. R.; Park, K.; Lee, S., 2010, Synthesis of Amido-N-imidazolium Salts and their
Applications as Ligands in Suzuki–Miyaura Reactions: Coupling of Heteroaromatic
Halides and the Synthesis of Milrinone and Irbesartan, Adv. Synth. Catal., 352, 3255-
3266.
[16] Hemmert, C., Poteau, R., dit Dominique, F. J.-B.; Ceroni, P.; Bergamini, G.; Gornitzka,
H., Amide-Functionalized Bis (NHC) Systems: Anion Effect on Gold–Gold Interactions,
Eur. J. Inorg. Chem., 2012, 3892-3898.
[17] Suzuki, Y.; Muramatsu, K.; Yamauch, K.; Morei, Y.; Sato, M. Chiral
N-herterocyclic
carbenes as asymmetric acylation catalysts. Tetrahedron, 2006, 62, 302-310.
[18] Hemmert, C.; Fabié, A.; Fabre, A.; Benoit-Vical, F.; Gornitzka, H.; Synthesis, structures,
and antimalarial activities of some silver(I), gold(I) and gold(III) complexes involving N-
heterocyclic carbene ligands, Euro. J. Med. Chem., 2013, 60, 64-75.
[19] Postleb, F., Stefanik, D., Seifert H., Giernoth, R., Bionic Liquids: Imidazolium-based
Ionic Liquids with Antimicrobial Activity, Z. Naturforsch. 2013, 68b, 1123ꢂ–ꢂ1128.
22

ACCEPTED MANUSCRIPT
[20] Boselli, L.; Ader, I.; Carraz, M.; Hemmert, C.; Cuvillier, C.; Gornitzka, H., Synthesis,
structures, and selective toxicity to cancer cells of gold(I) complexes involving N-
heterocyclic carbene ligands, Eur. J. Med. Chem., 2014, 85, 87-94.
[21] Lee, J. H., Yoo, K. S., Park, C. P., Olsen, J. M., Sakaguchi, S., Prakash, G. K. S.,
Mathew, T., Jung, K. W., An Air/Water‐Stable Tridentate N‐Heterocyclic Carbene‐
Palladium(II) Complex: Catalytic C-H Activation of Hydrocarbons via
Hydrogen/Deuterium Exchange Process in Deuterium Oxide, Adv. Synth. Catal., 2009,
351, 563-568.
[22] Beer, P. D., Berry, N. G., Cowley, A. R., Hayes, E. J., Oates E.C., Wong, W. W. H, Chem.
Commun., 2003, 19, 2408-2409.
[23] Gagosz, F., Zard, S. Z., Org. Lett., 2002,
4 (24), 4345–4348
[24] Crystal data for Ni(II) complex (ref. CCDC 1831058) can be obtained on request from the
Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EW, UK. CCDC.
[25] Crystal data for Pd(II) complex: (ref. CCDC 1831056) can be obtained on request from
the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EW, UK. CCDC.
[26] Pople, J., Frisch, M., Trucks, G., Schlegel, H., Scuseria, G., Gaussian, Inc., Wallingford
CT, 2004 Gaussian 03W (Revision C. 01), Gaussian, Inc., Wallingford CT, 2003.
[27] Becke, A. D., Density-functional thermochemistry. III. The role of exact exchange, The
Journal of Chemical Physics, 1993, 98, 5648-5652.
[28] Lee, C., Yang, W., Parr, R. G., Development of the Colle-Salvetti correlation-energy
formula into a functional of the electron density, Phys. review B, 1988, 37, 785.
[29] Perdew, J. P., Wang, Y., Pair-distribution function and its coupling-constant average for
the spin-polarized electron gas, Phys. Review B, 1992, 46, 12947.
[30] Dennington, R., Keith, T., Millam, J., GaussView, version 5, Semichem Inc., Shawnee
Mission, KS, 2009.
[31] Dhamodharan, P., Sathya, K., Dhandapani, M., Systematic evaluation of a new organic
material:1-methyl-1
H-imidazol-3-ium-2,4,6-trinitrobenzene-1,3-bis(olate)for optoelectro-
23

ACCEPTED MANUSCRIPT
nics through spectral, structural, electrical, optical, quantum chemical and Hirshfeld
surface studies, J. Phys. and Chem. of Solids, 2017, 104, 175-184.
[32] Menon, V. V., Fazal, E., Mary, Y. S., Panicker, C. Y., Armaković, S., Armaković, S. J.,
Nagarajan, S., Van Alsenoy, C., FT-IR, FT-Raman and NMR characterization of 2-
isopropyl-5-methylcyclohexyl quinoline-2-carboxylate and investigation of its reactive
and optoelectronic properties by molecular dynamics simulations and DFT calculations, J.
Mol. Structure, 2017, 1127, 124-137.
[33] Okulik, N., Jubert, A. H., Theoretical analysis of the reactive sites of non-steroidal anti-
inflammatory drugs, Internet Electronic Journal of Molecular Design, 2005, 4, 17-30.
[34] S. Xavier, S. Periandy, S. Ramalingam, NBO, conformational, NLO, HOMO–LUMO,
NMR and electronic spectral study on 1-phenyl-1-propanol by quantum computational
methods, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015,
137, 306-320.
[35] Arjunan, V., Balamourougane, P., Kalaivani, M., Raj, A., Mohan, S., Experimental and
theoretical quantum chemical investigations of 8-hydroxy-5-nitroquinoline,
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2012, 96, 506-
516.
[36] Tayfuroğlu, Ö., Kılıçarslan, F. A., Atmaca, G.Y., Erdoğmuş, A., Synthesis,
characterization of new phthalocyanines and investigation of photophysical,
photochemical properties and theoretical studies, Journal of Porphyrins and
Phthalocyanines, 2018, 22, 250-265.
[37] Bouchoucha, A., Zaater, S., Bouacida, S., Merazig, H., Djabbar, S., Synthesis and
characterization of new complexes of nickel (II), palladium (II) and platinum(II) with
derived sulfonamide ligand: Structure, DFT study, antibacterial and cytotoxicity activities,
J. Mol. Structure, 2018, 1161, 345-355.
[38] Datta, A., Role of metal ions (M= Li+, Na+, and K+) and pore sizes (Crown-4, Crown-5,
and Crown-6) on linear and nonlinear optical properties: New materials for optical
birefringence, J. Phys. Chem. C, 2009, 113, 3339-3344.
24