Schiff bases of hydroxyacetophenones and their copper(II) and nickel(II) complexes: Synthesis, antioxidant activity and theoretical study

Article abstract of DOI:10.14233/ajchem.2016.20055

The synthesis of a series of Schiff base ligands derived from tryptamine and 5-methoxy-2-hydoxyacetophenone, 5-methyl-2-hydroxyacetophenone and 2-hydoxyacetophenone together with their copper(II) and nickel(II) complexes is presented. The ligands and complexes were characterized by elemental analysis, IR, ¹H and ¹³C NMR, UV-visible spectroscopy as well as magnetic measurements. Semi empirical quantum mechanical calculations and DFT calculations were performed to model the structures of the compounds. The complexes were found to have the general formula [M(L)₂]. Spectral studies reveal that these Schiff bases act as bidentate ligands and coordinate to the metal center through deprotonated phenolate oxygen and azomethine nitrogen atoms. Nickel(II) complexes establish square planar geometry around the central metal, whereas distorted tetrahedral geometry is proposed for copper(II) complexes. Electronic energy, molecular orbitals energy, HOMO-LUMO gap, ionization potentials, heat of formation and dipole moments were also optimized. The compounds are screened for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH^?) and ferric-reducing antioxidant power (FRAP) assays in which butylated hydroxytoluene (BHT) is used as a reference. The investigations reveal that the ligands appear to be more effective antioxidants, but also copper(II) complexes show good activity. Methoxy-substituted ligand shows an enhanced activity over BHT in the FRAP assay.

Full text of DOI:10.14233/ajchem.2016.20055

Asian Journal of Chemistry; Vol. 28, No. 11 (2016), 2505-2511
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.20055
Schiff Bases of Hydroxyacetophenones and their Copper(II) and Nickel(II)
Complexes: Synthesis, Antioxidant Activity and Theoretical Study
1
2
ABDULAZIZ ALI ALOMARI , MOHAMED MUSTAFA IBRAHIM1,* and MUSA E. MOHAMED
1Department of Chemistry, Faculty of Science and Arts in Mukwah, University of Al-Baha, Al Baha 65931, Saudi Arabia
2Department of Chemistry, College of Applied and Industrial Sciences, Bahri University, Khartoum, Sudan
*Corresponding author: E-mail: mohd_hashm4@hotmail.com
Received: 30 April 2016;
Accepted: 10 July 2016;
Published online: 10 August 2016;
AJC-18028
The synthesis of a series of Schiff base ligands derived from tryptamine and 5-methoxy-2-hydoxyacetophenone, 5-methyl-2-
hydroxyacetophenone and 2-hydoxyacetophenone together with their copper(II) and nickel(II) complexes is presented. The ligands and
complexes were characterized by elemental analysis, IR, 1H and 13C NMR, UV-visible spectroscopy as well as magnetic measurements.
Semi empirical quantum mechanical calculations and DFT calculations were performed to model the structures of the compounds. The
complexes were found to have the general formula [M(L)2]. Spectral studies reveal that these Schiff bases act as bidentate ligands and
coordinate to the metal center through deprotonated phenolate oxygen and azomethine nitrogen atoms. Nickel(II) complexes establish
square planar geometry around the central metal, whereas distorted tetrahedral geometry is proposed for copper(II) complexes. Electronic
energy, molecular orbitals energy, HOMO-LUMO gap, ionization potentials, heat of formation and dipole moments were also optimized.
The compounds are screened for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH•) and ferric-reducing
antioxidant power (FRAP) assays in which butylated hydroxytoluene (BHT) is used as a reference. The investigations reveal that the
ligands appear to be more effective antioxidants, but also copper(II) complexes show good activity. Methoxy-substituted ligand shows an
enhanced activity over BHT in the FRAP assay.
Keywords: Tryptamine, Hyroxyacetophenones, Metal complexes, Antioxidant activity, PM6 & DFT study.
Schiff bases, as an important class of organic com-
pounds, show a wide spectrum of biological activities.
Many studies have been reported regarding the biological
activities of Schiff bases, including their anticancer [7],
antibacterial [8], antifungal and herbicidal activities [9,10].
Developing new chemotherapeutic Schiff bases and their
metal complexes is now attracting the attention of medi-
cinal chemists [6].
INTRODUCTION
There is a significant research efforts to overcome the dele-
terious effects of free radicals in human body [1]. Free radicals
are species contain unpaired electrons such as superoxide (O2–)
and hydroxyl radicals (OH•), that produced as a result of normal
or pathological metabolitic reactions [2,3]. Overproduction of
such free radicals lead to dangerous consequences affecting
biological molecules such as lipids, proteins, enzymes, DNA
and RNA, changing their structures, altering their functions,
or promote an extended oxidative cell damage [4]. Elimination
of such free radicals becomes one of the major aims of current
research by designing suitable antioxidant drugs to be adminis-
tered [5]. Of course many naturally occurring antioxidants are
present, but their uses are limited by different factors including
difficulty of separation and purification from their natural
resources and in many cases they cannot be used in their original
form owing to unknown disasters that may originate from other
associated ingredients. This justifies the search for effective
synthetic antioxidants that are capable to get over the toxic and
side effects arising from natural ones [6].
In this study, we are encouraged to synthesize new
Schiff bases containing hydroxyl groups attached to the
aromatic ring stemmed from indole derivative, tryptamine,
coupled with hyroxyacetophenones, with their copper(II)
and nickel(II) complexes for comparing their function. The
novel compounds were characterized on the bases of elemen-
1
tal analysis, IR, H and 13C NMR spectroscopy, UV-visible,
magnetic measurements as well as semi-empirical PM6 and
DFT quantum mechanical calculations with a view to gain
more insight about their electronic structure and activity.
Further investigations were carried to evaluate the radical
scavenging abilities of these novel compounds using the DPPH•
and FRAP methods.

2506 Alomari et al.
Asian J. Chem.
ethyl acetate. Anal. calcd. for C19H20N2O2: C, 74.00; H, 6.54;
N, 9.08 %. Found: C, 74.20; H, 6.19; N, 9.13 %.
General method of preparation of the complexes: To
solutions of copper(II) acetate monohydrate and nickel(II)
acetate tetrahydrate, (1 mmol) in absolute ethanol (50 mL),
were added solutions of the appropriate Schiff base (2 mmol)
in the same solvent (20 mL), followed by a few drops of triethyl-
amine. The mixtures were heated under reflux for 5 h. The
product that had formed was filtered off, washed with absolute
ethanol and dried over anhydrous silica gel.
THAP copper(II) complex: Percentage yield (28.4 %).
The compound is soluble in THF, DMSO and DMF. Anal.
calcd. for C36H34N4O2Cu: C, 69.87; H, 5.49; N, 9.05 %. Found:
C, 70.11; H, 5.77; N, 8.92 %.
THAP nickel(II) complex: Percentage yield (60.0 %).
The compound is soluble in THF, DMSO and DMF. Anal.
calcd. for C36H34N4O2Ni: C, 70.43; H, 5.54; N, 9.13 %. Found:
C, 70.56; H, 5.20; N, 8.97 %.
TMeHAP copper(II) complex: Percentage yield (34.6
%). The compound is soluble in THF, DMSO and DMF. Anal.
calcd. for C38H38N4O2Cu: C, 70.55; H, 5.87; N, 8.66 %. Found:
C, 70.75; H, 5.57; N, 8.59 %.
TOMeHAP copper(II) complex: Percentage yield (19.1
%). The compound is soluble in THF, DMSO and DMF. Anal.
calcd. for C38H38N4O4Cu: C, 67.22; H, 5.60; N, 8.25 %. Found:
C, 67.49; H, 5.90; N, 8.23 %.
TOMeHAP nickel(II) complex: Percentage yield (19.1
%). The compound is soluble in THF, DMSO and DMF. Anal.
calcd. for C38H38N4O4Ni: C, 67.71; H, 5.64; N, 8.31 %. Found:
C, 67.54; H, 5.48; N, 8.07 %.
Attempts to prepare TMeHAP nickel(II) complex by the
same procedure were unsuccessful.
EXPERIMENTAL
Chemicals were purchased from Sigma-Aldrich and used
without further purification, ethanol was redistilled before use.
Dry dimethyl sulfoxide, ethyl acetate and dimethyl formamide
were utilized for recrystallization purposes.
IR spectrawere recorded with a Perkin-Elmer FT-IR spectro-
photometer model Spectrum 2000 using KBr pellets as support
in the range 4000-370 cm-1. 1H NMR spectra were recorded at
room temperature on a JEOL ECA-400 spectrometer, operating
with a frequency of 400 MHz, using DMSO-d6 as solvent.
Electronic spectra, in DMSO solution, were obtained using
a Varian 50 Conc UV-visible spectrophotometer over the
wavelength range 200-800 nm. Magnetic susceptibility data
were obtained from powdered samples using a Sherwood
Scientific magnetic susceptibility balance. The effective mag-
netic moments were calculated from the expression (µeff
=
2.83√χMT) BM, where χM is the molar susceptibility corrected
using Pascal’s constants for diamagnetism of all atoms in the
compounds.
Theoretical calculations of copper(II) and nickel(II) comp-
lexes were carried out using PM6 semi-empirical methods in
MOPAC2007 program, implemented on an Intel Pentium (R)
1.86 GB computer. Initial estimates for the geometries of all
the structures were obtained by molecular mechanics program
(ACD11) for Widows, followed by full optimization of all
geometrical variables (bond lengths, bond angles and dihedral
angles), without any symmetry constraints. DFT calculations
were performed for the ligands on B3LYP level of theory with
the Gaussian 09 software packages [11].All the structures were
fully optimized at Density Functional Study (DFT) level,
RB3LYP for neutral ligands and UB3LYP for cation ligands
using the high level 6-31g basis set in the gas phase, for the
purpose of calculating ionization potentials.
Preparation of 2-{1-[2-(1H-Indole-3-yl)ethylimino]-
ethyl}phenol (THAP): This ligand is prepared according to
the literature method [12]. A solution of tryptamine (0.5 g,
3.12 mmol) in 50 mL of acidified ethanol (pH 4.5) was added
to a boiling solution of 2-hydroxyacetophenone (0.426 g, 3.13
mmol) in 50 mL of acidified ethanol (pH 4.5). The mixture
was refluxed for 2 h. The solid product was filtered off and
recrystallized from ethanol (Yield 79.4 %). The compound
was soluble in ethanol, methanol, acetone, THF and DMSO,
but insoluble in water. Anal. calcd. for C18H18N2O: C, 77.67;
H, 6.52; N, 10.06 %. Found: C, 77.52; H, 6.25; N, 10.05 %.
Preparation of 2-{1-[2-(1H-Indole-3-yl)-ethylimino]-
ethyl}-4-methyl phenol (TMeHAP): The above procedure
was followed using (0.5 g, 3.12 mmol) of tryptamine and (0.468
g, 3.11 mmol) of 5-methyl-2-hydroxyacetophenone in 50 mL
of acidified ethanol. The yield was 70 %. The compound was
soluble in most organic solvents, but insoluble in water. It was
recrystallized from ethanol [12]. Anal. calcd. for C19H20N2O:
C, 77.90; H, 6.84; N, 9.57 %. Found: C, 77.62; H, 6.62; N,
9.83 %.
Antioxidant assays
DPPH• method: The total free radical scavenging capacity
of the Schiff bases and complexes was estimated and was com-
pared to BHT as standard.
Freshly prepared DPPH• solution (100 µM) in DMSO was
used in the determination. 5 µL of the samples (with a concen-
tration range between 50-250 µM) and standards were added
to 195 µL of DPPH reagent to start the reaction. The final
concentration was 97.5 µM for DPPH• and varies between
50-250 µM for the test compounds. This has been done to
determine the optimum concentration that achieves maximum
inhibition of DPPH•. The plate was read at 515 nm for 3 h
with 20 min intervals to reach a steady state against DMSO
as a blank. The percentage DPPH• quenched was calculated
according to the equation:
Abs. blank − Abs. sample
DPPH quenched (%) =
×100
Abs. blank
Ferric reducing antioxidant power assay: Total anti-
oxidant activity is measured by ferric reducing antioxidant
power (FRAP) assay of Benzie and Strain [13]. FRAP assay
uses antioxidants as reductants in a redox-linked colorimetric
method, employing an easily reduced oxidant system present
in stoichiometric excess.
Preparation of 2-{1-[2-(1H-Indole-3-yl)-ethylimino]-
ethyl}-4-methoxy phenol (TOMeHAP): The same above
procedure was followed using (1 g, 6.24 mmol) of tryptamine
and (1.04 g, 6.25 mmol) of 5-methoxy-2-hydroxyaceto-
phenone. (Yield 72.2 %). The product was recrystallized from
The FRAP reagent was prepared by mixing 50 mL of
300 mmol/L sodium acetate buffer (pH 3.6), with 5 mL of 10

Vol. 28, No. 11 (2016)
Studies of Schiff Bases of Hydroxyacetophenones and their Copper(II) and Nickel(II) Complexes 2507
mmol/L tripyridyl triazine (TPTZ) in 40 mmol/L HCl and 5 mL
of 20 mmol/L FeCl3·6H2O. Samples (10 µL) and standards
(BHT) were mixed with 300 µL of the working FRAP reagent
and the absorbance at 593 nm was measured at 0 min after
mixing and 4 min. Each test was carried out in triplicates.
The FRAP value was calculated as ferrous equivalents
which obtained by comparing the absorbance change in the
test reaction mixture with those containing known concen-
trations of ferrous ions (standard).
band was absent in the spectra of complexes due to deproto-
nation upon complexation. The metal ion is coordinated through
the oxygen atom of the hydroxyl group. The azomethine
–C=N– bands have been shifted to lower frequencies in all
complexes due to the withdrawal of electron density from the
nitrogen atom owing to coordination [14]. A similar effect
was observed in the stretching vibration of the Schiff base
phenolic C-O group, with respect to the same group in the
complexes where it was shifted to higher frequency, confirming
oxygen co-ordination to the metal [17]. The shifts observed
for indolic N-H band in the complexes with respect to the
ligands suggests an intermolecular interaction between NH
group of the indole moiety and the phenolic oxygen of another
molecule [12]. New bands in the region 429-421 cm-1 and 509-
583 cm-1 were assigned to vibrations associated with ν(M-N)
and ν(M-O) bonds, respectively [18,19].
RESULTS AND DISCUSSION
The title Schiff bases were successfully prepared according
to Scheme-I. The physical properties of all prepared ligands
and complexes have been summarized in Table-1.
Infrared spectroscopy: The IR spectra of the ligands and
complexes have been summarized in Table-2. It can be clearly
shown that the absence of the characteristic aldehydic carbonyl
stretching bands and the appearance of the azomethine –C=N–
bands, at 1609, 1605 and 1602 cm-1 for THAP, TMeHAP and
TOMeHAP, respectively indicates the formation of the Schiff
base. The broad band at 3166-3142 cm-1 could be attributed to
the intramolecular hydrogen-bonded O-H group [14-16]. This
Proton NMR spectra: 1H NMR spectra of the TOMeHAP
ligand was summarized in Table-3 with chemical shifts expressed
in ppm down field tetra methylsilane as reference.
The spectral data of the Schiff bases were consistent with
the structure proposed (Fig. 1). The singlet observed at 10.82
ppm can be attributed to the indolic N-H proton (Ha). The
CH3
NH2
CH3
O C
N
C
R
R
2 h reflux
H2O
+
+
HO
N
H
HO
N
H
R = H, CH3, OCH3
Scheme-I: Synthesis of the Schiff base ligands
TABLE-1
PHYSICAL PROPERTIES OF SCHIFF BASES AND THEIR Cu(II) AND Ni(II) COMPLEXES
Name of the compound
THAP
TMeHAP
TOMeHAP
(THAP)2Cu
m.f.
C18H18N2O
C19H20N2O
Molar mass
278.35
292.38
308.38
618.24
613.38
646.29
678.29
673.43
Colour
Yellow
Yellow
Bright yellow
Brown
Yellowish green
Brown
m.p. (°C)
112
175
µeff (BM)
–
–
–
C19H20N2O2
179
C36H34N4O2Cu
C36H34N4O2Ni
C38H38N4O2Cu
C38H38N4O4Cu
C38H38N4O4Ni
212 (dec.)
249 (dec.)
282 (dec.)
206
1.78
Diamagnetic
2.10
2.20
Diamagnetic
(THAP)2Ni
(TMeHAP)2Cu
(TOMeHAP)2Cu
(TOMeHAP)2Ni
Brown
Brownish yellow
238 (dec.)
TABLE-2
IR SPECTRA OF THE LIGANDS AND COMPLEXES
Compound
THAP
(THAP)2Cu
(THAP)2Ni
TMeHAP
(TMeHAP)2Cu
TOMeHAP
(TOMeHAP)2Cu
(TOMeHAP)2Ni
C-H aliphatic
C-O
C-H aromatic
ν(N-H)
ν(O-H)
3142-2875Brd
ν(C=N)
1609
1599
1600
1605
1589
1602
1598
1599
ν(M-O)
ν(M-N)
–
429
428
–
424
–
421
426
3433
3371
3409
2926
2940
2917
2915
2918
2913
2930
2929
1265
1237
1220
1280
1315
1222
1213
1214
731
738
745
753
740
757
745
745
–
–
–
525
583
–
509
–
Superimposed 3167-2915Brd
3417
Superimposed
3413
–
3166
–
531
536
3331
–
TABLE-3
1H NMR SPECTRA OF THE LIGANDS, s = SINGLET, t = TRIPLET, m = MULTIPLET
Compound
TOMeHAP
Ha
Hb
Hc
Hd
He
HR
Haromatic
10.82(s)
3.07(t)
3.84(t)
2.26(s)
16.81(s)
3.74(s)
6.69-7.58(m)

2508 Alomari et al.
Asian J. Chem.
ethyleneic protons (Hb) and (Hc) resonate at 3.07 and 3.84
ppm as triplets, respectively. The methyl protons (Hd) resonates
at 2.26 ppm as a singlet. Integration line confirms that 3 protons
are responsible for the signal. The signals between 6.69 and
7.58 ppm are due to 8 aromatic protons as the integration
implies. The methoxy protons resonate further down field at
3.74 ppm. This is because of the effect exerted by the electro-
negative oxygen atom directly attached. 1H NMR spectra for
the other two ligands were described in the literature [12].
No clear spectra were recorded for metal complexes due to para-
magnetic effects in solution.
TABLE-4
13C NMR SPECTRA OF THE LIGANDS
Chemical shift range (ppm)
Assignment
26.0-49.2
111.4-172.1
157.0-165.0
171.0-172.0
20.2
Ethylenic carbons -CH2-CH2-
Aromatic
Azomethine -C=N-
Phenolic -C-OH
5-methyl -CH3
5-methoxy -OCH3
Acetophenone CH3 group
55.7
14.5
UV-visible spectroscopy and magnetic measurements:
The electronic spectra of all compounds in DMSO with their
assignments are given in Table-5. The spectra of THAP exhibit
bands at 395, 317, 291 and 276 nm, which are well consistent
with reported data by Zarza et al. [12] in chloroform.
d
b
CH3
C
N
R
For the rest of the compounds bands in the region 260-
346 were associated with π-π* transitions within the aromatic
rings. Those bands undergo either hypsochromaic or batho-
chromic shifts upon complex formation. n-π* transitions in
complexes were usually obscured by the near intense charge
transfer bands. For nickel(II) complexes, weak intensity bands
at 572 nm could be assigned to d-d transitions. Those bands
indicate that nickel(II) complexes undergo geometrical
changes in solution since they are diamagnetic in the solid
state as it is usual for square planar d8 complexes [20]. Copper
complex of the methyl-substituted ligand has a magnetic
moment of 2.1 BM at room temperature. This behaviour is in
agreement with analogous copper(II) complexes with pseudo
tetrahedral geometry around the copper ion [21,22].
Computational study: The chemical structures of the
compounds under investigation are presented in Fig. 2. The
optimized molecular structure of (TOMeHAP)2Cu using PM6
semi-empirical methods is shown in Fig. 3. The calculated
quantum chemical indices EHOMO, ELUMO, ∆E (EH-EL), heat of
formation, ionization potential, electronic energy, total energies
c
HO
e
N
H
a
R = H, CH3, OCH3
Fig. 1. Proposed framework structure of the ligands
13C NMR spectra:Table-4 summarizes the key 13C spectral
data together with their assignments. Further support to the
proposed structure of the ligands can be obtained from their
13C NMR spectra.All aromatic carbon atoms lie in the chemical
shift range 111.4-172.1 ppm. The most down field peaks at
about 172.42 ppm could be assigned to the phenolic carbon
atoms C-OH. The peaks at the range 157-165 ppm can be
attributed to azomethine carbon atoms. Ethylenic carbons
appear in the range 25.9-49.1 ppm. Acetophenone methyl
group in all ligands appears at 14.5 ppm, whereas the signals
at 20.2 and 55.7 ppm were ascribed to substituted methyl and
methoxy groups, respectively.
TABLE-5
UV-VISIBLE SPECTRA OF LIGANDS AND COMPLEXES
ε (mol-1 L cm-1)
1.56 × 103
3.67 × 103
6.94 × 103
7.78 × 103
9.42 × 103
λ
max (nm)
395
317
291
276
Compound
THAP
Concentration (mol/L)
Assignment
n-π*
π-π* chelate ring
–
9.88 × 10-5
π-π* indole group
π-π* indole group
d-d transition
CT, n-π*
260
–
572
388
263
5.06 × 103
2.34 × 104
(THAP)2Ni
7.33 × 10-5
π-π* indole group
7.86 × 103
2.13 × 104
3.77 × 103
8.08 × 103
9.71 × 103
2.40 × 104
3.98 × 103
7.94 × 103
358
273
338
282
358
272
346
281
CT, n-π*
(THAP)2Cu
TMeHAP
6.47 × 10-5
1.54 × 10-4
6.57 × 10-5
1.13 × 10-4
1.48 × 10-4
1.91 × 10-4
π-π* ligand
π-π* chelate ring
π-π* indole group
CT, n-π*
(TMeHAP)2Cu
TOMeHAP
π-π* ligand
π-π* chelate ring
π-π* indole group
d-d transition
CT, n-π* transition
CT, n-π*
364.86
572
412
(TOMeHAP)2Ni
(TOMeHAP)2Cu
4.03 × 103
6.45 × 103
1.80 × 104
386
268
π-π* ligand

Vol. 28, No. 11 (2016)
Studies of Schiff Bases of Hydroxyacetophenones and their Copper(II) and Nickel(II) Complexes 2509
R
than that of nickel(II) complexes. This indicates that copper(II)
complexes are more stable than nickel(II) complexes. The heats
of formation of copper(II) complexes are 124.311, 107.987
and 51.662 kcal/mol for (THAP)2Cu, (TMeHAP)2Cu and
(TOMeHAP)2Cu, respectively, whereas for nickel(II) complexes
are 164.637 and 94.247 kcal/mol for (THAP)2Ni and
H3C
C
(TOMeHAP)2Ni, respectively.
O
HN
NH
The order of stability is therefore: copper(II) complexes
> nickel(II) complexes and the methoxy-substituted ones are
the most stable.
The gas-phase ionization potentials (IP) of the ligands
were calculated to compare their antioxidant activities and gain
more understanding of the mechanisms involved. The total
electronic energies of neutral ligands and cations are illustrated
in Table-7 and the ionization potentials were calculated accor-
ding to the relation:
N
M
N
O
C
CH3
R
R = H, CH3, OCH3; M = Cu, Ni
Ionization potential (IP) = Electronic energy of cation –
Electronic energy of neutral ligand
Fig. 2. Proposed molecular structure of Cu(II) and Ni(II) complexes
It follows that the order of ease of ionization is:
TOMeHAP > TMeHAP > THAP
and dipole moments, are given in Table-6. The concept of
HOMO-LUMO energy gap is used to develop theoretical
models, which are capable of explaining the structure and
conformation barriers in many molecular systems qualitatively
[23]. According to the data in Table-6, there is a good corre-
lation in HOMO-LUMO energy gap calculated in the gas phase
for studied complexes. Copper(II) complexes have smallest
HOMO-LUMO gaps (0.064 eV), (0.044 eV) and (0.043 eV)
for (THAP)2Cu, (TMeHAP)2Cu and (TOMeHAP)2Cu, respec-
tively, compared to nickel(II) complexes, which have higher
HOMO-LUMO gaps i.e. (1.30 eV) and (1.219 eV) for (THAP)2Ni
and (TOMeHAP)2Ni, respectively. Moreover, the heat of
formation and the total energy of copper(II) complexes is less
TABLE-7
TOTAL ELECTRONIC ENERGY AND IONIZATION
POTENTIALS OF THE LIGANDS CALCULATED BY
DFT B3LYP/6-31g IN a.u. (ATOMIC UNIT)
Ionization
potential
(a.u.)
Ionization
potential
(eV)
Total electronic
energy (a.u.)
Ligands
THAP-neutral
THAP-cation
TMeHAP-neutral
TMeHAP-cation
TOMeHAP-neutral
TOMeHAP-cation
-881.25851110
-881.00529191
-920.56359766
-920.31498152
-995.72743754
-995.48174321
0.25322009
0.24861614
0.24569433
6.89062
6.76534
6.68583
Antioxidant activity
DPPH• assay: The antioxidant activity of the ligands and
its complexes were measured in terms of their hydrogen
donating or radical scavenging ability by UV-visible spectro-
photometer using the stable 2,2-diphenyl-1-picrylhydrazyl free
radical (DPPH•).
In general, the ligands show better scavenging activity
against DPPH• radical than do their corresponding complexes
especially at higher concentrations (Fig. 4). The higher
antioxidant activity of the ligands is related to the significant
contribution of the hydroxyl group that facilitates hydrogen
transfer reactions to DPPH• radical and stabilizing the system
by a combination of hydrogen bonding and electronic effects
Fig. 3. Optimized structure of (TOMeHAP)2Cu complex
TABLE-6
CALCULATED ELECTRONIC PROPERTIES OF THE STUDY COMPLEXES USING SEMI EMPIRICAL PM6 METHOD
Dipole
moment
(Debye)
Heat of
formation
(kcal/mol)
Total energy
(eV)
Electronic
energy (eV)
Ionization
potential (eV)
∆E (H-L)
(eV)
Complex
E HOMO (eV)
ELUMO (eV)
(THAP)2Cu
-8.501
-8.218
-8.363
-6.112
-6.140
-8.437
-8.174
-8.320
-4.812
-4.921
0.064
0.044
0.043
1.300
1.219
124.3110
107.9870
51.6624
164.6370
94.2470
-6799.724
-7099.681
-7681.544
-6627.504
-7509.226
-72900.095
-78789.049
-85938.716
-72066.146
-84087.213
8.3410
8.1210
8.2691
6.1110
6.1400
1.287
1.391
1.187
2.536
2.189
(TMeHAP)2Cu
(TOMeHAP)2Cu
(THAP)2Ni
(TOMeHAP)2Ni

2510 Alomari et al.
Asian J. Chem.
7000
6000
5000
4000
3000
2000
1000
0
6570
[24]. This is reflected in their lower ionization potentials
calculated theoretically. The ionization potential values for
TOMeHAP, TMeHAP and THAP are 6.686, 6.765 and 6.890
eV, respectively. It is obvious that TOMeHAP has lower ioni-
zation potential indicating stronger donating ability, which
may result in stabilization of DPPH• radical through electron
donation and hence higher antioxidant activity. Moreover, it
is reported that methoxy substituents influence the scavenging
effects of free radicals [5,25]. Nevertheless, the title compounds
do not act as efficient radical scavengers in any way comparable
to butylated hydroxytoluene (BHT).
5407
4990
4224
1678
530
333
197 203
Furthermore, it can also be drawn from Fig. 4 that free
radical scavenging activity increased with increasing concen-
tration from 50 to 250 mM. Copper(II) complexes seem to be
more efficient in quenching radicals than their corresponding
nickel(II) congeners.
Fig. 5. Coulmn graph showing FRAP values in (µM) Fe(II) equivalents
for the different compounds in comparison to BHT
became a better antioxidants in the FRAP assay. Reverse trend
has been observed in other related copper complexes in which
halo substituent group replaces alkyl and alkoxy substiuents
[27]. In those compounds the ligand show less potency
due to the presence of electronegative atom attached to the
hydroxyacetophenone moiety. Complexation may also reduce
the oxidation potential, which results in ease of oxidation by
free radicals [28].
20
18
(TMeHAP)2Cu
16
TOMeHAP
14
(THAP)2Ni
12
(TOMeHAP)2Cu
10
(TOMeHAP)2Ni
8
(THAP)2Cu
6
Conclusion
TMeHAP
4
THAP
Schiff base ligands derived from tryptamine and hydroxy-
acetophenones have been successfully synthesized and
characterized. The antioxidant studies of the compounds reveal
that the ligands are more effective antioxidants than their metal
complexes in concentration-dependant manner. They mainly
act as a hydrogen atom transferring antioxidants in an oxida-
tive process. This effect is more remarkably pronounced for
TOMeHAP as compared to butylated hydroxytoluene (BHT),
which is a commercially available antioxidant drug. However,
chelating to the metal ions suppresses this property through
coordination to the metal centre, thus hampers hydrogen atom
abstraction mechanism through deprotonation.
2
0
50
100
150
200
250
300
Concentration (mM)
Fig. 4. Dependance of DPPH• scavenging activity of ligands and their metal
complexes on concentration evaluated through the absorbance
decrease at 515 nm
The different relative scavenging capacity of individual
compounds against different radicals may be explained by the
different mechanisms involved in the radical-antioxidant
reactions. Other factors, such as stereoselectivity of the radicals
or the solubility of these compounds in different testing
systems, may also affect the capacity of individual compounds
to react and quench different radicals [26].
Theoretical calculations using both PM6 semi-empirical
and DFT method supports the experimental results obtained.
Ferric reducing antioxidant power assay: The column
graph in Fig. 5 compares the proportions of ferric reducing
abilities of prepared compounds with butylated hydroxy-
toluene (BHT) as standard. In this series of compounds, the
highest reducing ability has been found in TOMeHAP which
accounts for 6570 µM ferrous equivalents four times as effec-
tive as BHT. This had decreased gradually from nickel(II) to
copper(II) complexes, but still better than BHT. Likewise the
trend has been observed for the methyl-substituted ligand and
its copper complex. In this category the ligand shows a potency
of approximately ten-fold of the corresponding copper
complex and approaches three times the activity of BHT. The
energy of the highest occupied molecular orbital (HOMO) can
be taken as a clue for the electron donating ability of a molecule
[25]. In contrast to ionization potentials, a higher HOMO
reflects a stronger ability to donate electrons and hence act
as a reductant. Both (TOMeHAP)2Cu and (TMeHAP)2Cu
complexes reveal bigger values of HOMO (-8.363 and -8.218,
respectively) than do (THAP)2Cu complex (-8.501) and hence
ACKNOWLEDGEMENTS
The authors thankfully acknowledge the support from
University Malaya, Malaysia for their collaboration and partial
support through grant No. PS145/2007B. Thanks were also
conveyed to University of Al-Baha, Saudi Arabia for their
encouragement and support.
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