R. Gup et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 134 (2015) 484–492
485
Synthesis of H3L1
Introduction
This compound was prepared by small changing the method of
Rajput and Rajput [21] as follows: 4-hydroxyacetophenone
(1 mmol, 0.136 g) dissolved in ethanol (10 mL) was added drop
wise to a suspension of 4-hydroxybenzohydrazide (II) (1 mmol,
0.152 g) with a catalytic amount of glacial acetic acid in ethanol
(10 mL) in room temperature. The reaction mixture was refluxed
for further 4 h. On standing over night, the white crystalline prod-
uct separated, collected by filtration, washed with small amount of
diethyl ether and then dried in vacuum. Yield 81%; Mp 285–287 °C
(Lit 274–276 °C); UV (DMF, nm) 267, 304; IR (ATR, cmꢂ1) 3285
(OH), 1625 (C@O)amide, 1617 (C@N), 1369 (CAN), 1257 and 1172
(CAOAC); 1H NMR (DMSO_d6, ppm) d 2.27 (s, 3H, N@CACH3),
6.78 (d, 2H, J = 8.5, ArH), 6.82 (d, 2H, J = 8.6, ArH), 7.67, (d, 2H,
J = 8.5, ArH), 7.77, (d, 2H, J = 8.6, ArH), 9.93 (s, 2H, OH), 10.41 (s,
1H, NH); 13C NMR (DMSO_d6, ppm) 161.1 (C@O), 160.7 (C@N),
159.3 (CAO), 130.5, 129.7, 129.5, 128.6, 125.3, 115.8, 115.5
(ArAC)), 19.8 (CH3). Analysis (%Calculated/found) for C15H14N2O3
C: 66.66/66.78, H: 5.22/5.10, N: 10.36/10.69.
Schiff base-hydrazones and their metal complexes have
received much attention in the fields of chemistry and biology
due to their broad spectrum of activities. They have a variety of
applications in biological and clinical fields. They denote anti-
bacterial, anti-fungal, anti-convulsant, anti-inflammatory, anti-
malarial, analgesic, anti-platelets, anti-tuberculosis, anti-cancer
and insecticidal activities [1–8]. The significant biological activity
of the acylhydrazones and the dependence of their mode of chela-
tion with transition metal ions present in the living systems have
been of significant interest [9–12]. Transition metal complexes of
acylhydrazones are also known to provide useful models for
elucidation of the mechanisms of enzyme inhibition [13,14]. They
act as good potential oral drugs to treat the genetic disorders such
as thalassemia [15].
DNA-transition metal complex interaction has been of interest
because of its possible application in molecular biology [14,15]
and cancer therapy [16–18]. Coordination compounds show
unique chemical and physical properties as well as the abilities
of their ligands to be adjusted to DNA interaction activities. Copper
is an important trace element for life and is involved in complex
formation in a number of biological processes. Copper(II) com-
plexes have been used as for the treatment of many diseases
including cancer [19,20]. Therefore, investigations on copper
complexes are becoming more prominent in the research area of
bioinorganic chemistry [21–28]. Herein, we described the synthe-
sis and characterization of new Cu(II) complexes of hydrazone
Schiff base ligands and their DNA binding and cleavage activities.
Synthesis of HL2
A
mixture of H3L1 (1 mmol, 0.270 g), ethyl bromoacetate
(2 mmol, 0.334 g) and dry K2CO3 (10 mmol, 0.276 g) in 25 mL ace-
tone was refluxed with stirring for 40 h and poured to 200 mL of
cold water. The white precipitate formed was filtered and washed
with water and finally recrystallized from acetone-water. Yield
40%; Mp 115 °C; UV (EtOH, nm) 250, 300, IR (ATR, cmꢂ1) 3365
Experimental section
(NH), 2911–2979 (CH)aliphatic 1755 (C@O)ester, 1657 (C@O)amide
,
1605 (C@N), 1385 (CAN), 1255 and 1082 (CAOAC); 1H NMR
(DMSO_d6, ppm) d 1.18–1.23 (tt, 6H, J = 7.0, CH3), 2.30 (s, 3H,
N@CACH3), 4.13–4.20 (q, J = 7.0, 4H, OCH2CH3), 4.82 (s, 2H,
ArAOCH2) and 4.87 (s, 2H, ArAOCH2), 6.95 (d, 2H, J = 8.8, ArH),
7.01 (d, 2H, J = 8.8, ArH), 7.77 (d, 2H, J = 4.7, ArH),7.85 (d, 2H,
J = 8.2, ArH), 10.58 (s, 1H, NH); 13C NMR (DMSO_d6, ppm) 169.3
and 169.2 (C@O)ester, 161.8 (C@O)amide, 159.3 (C@N), 131.9, 130.4,
128.5, 127.6, 115.0, 114.8 (ArAC), 65.3 and 65.2 (OCH2), 61.5 and
61.4 (COOCH2), 21.1 (CH3AC@N), 14.8 and 14.7 (CH3). Analysis
(%Calculated/found) for C23H26N2O7 C: 62.43/62.16, H: 5.92/5.88,
N: 6.33/6.57.
Material and methods
All chemicals used were analytical reagent grade. Copper(II)
acetate, ethyl 4-hydroxybenzoate, 4-hydroxyacetophenonee, ethyl
bromoacetate, K2CO3, acetone and hydrazine monohydrate were
purchased from Fluka and Sigma-Aldrich and used without further
purification. Calf thymus DNA (CT-DNA) was purchased from
Sigma-Aldrich. pBR322 DNA was purchased from Fermantas. 1H
and 13C NMR spectra were recorded on a Bruker 400 MHz spec-
trometer in DMSO_d6 with TMS as the internal standard. IR spectra
were recorded on pure solid samples with a Thermo-Scientific,
Nicolet iS10-ATR. The electronic spectra of the ligands and
complexes were recorded on a PG Instruments T80+ UV/Vis
Spectrophotometer. Carbon, hydrogen and nitrogen analyses were
carried out on a LECO 932 CHNS analyzer and copper content was
determined by atomic absorption spectroscopy using the DV 2000
Perkin Elber ICP-AES. Mass spectra were recorded on a Waters
Xevo TQ-S UPLC-MS/MS spectrometer. Room temperature mag-
netic susceptibility measurements were carried out on powdered
samples using a Sherwood Scientific MK1 Model Gouy Magnetic
Susceptibility Balance. The thermogravimetric analysis was carried
out in dynamic nitrogen atmosphere (20 mL minꢂ1) with a heating
rate of 20 °C minꢂ1 using a Perkin Elmer Pyris 1 TGA thermal ana-
lyzer in the Central Laboratory at METU. Powder X-ray diffraction
Synthesis of Cu(II) complexes
A solution of 1 mmol copper(II) acetate dihydrate (0.20 g) in
EtOH (10 mL) was added to a hot solution containing 2 mmol
H3L1 (0.54 g) or HL2 (0.884 g) in absolute ethanol (15 mL) with stir-
ring. The reaction mixture was refluxed for 3 h and then the sol-
vent was evaporated under reduced pressure. The precipitated
complexes were filtered off and finally washed with small amount
of cold water.
For [Cu(H2L1)2]ꢁ2H2O: Dark green complex; yield: 85%; m.p.:
219 °C.
leff = 1.71 B.M.; UV (DMF, nm) 276, 308, 363 sh, 380, 403
(XRD) patterns were collected using Cu K
a
monochromatic radia-
sh; FT-IR (ATR, cmꢂ1) 3182 b (OAH), 1604 m (C@NAN@C), 1362
(CAN), 1253 s and 1165 m (CAOAC). MS (ES+), (m/z): 602.76
[M]+. Analysis (%Calculated/found) for C30H30CuN4O8 C: 56.47/
56.24, H: 4.74/4.57, N: 8.78/8.52, Cu: 9.96/10.22.
tion (k = 1.54056 Å) at room temperature on a Rigaku-SmartLab
diffractometer. Scanning electron microscopy (SEM) was per-
formed using a JEOL SEM 7700F. Local composition was analyzed
by energy-dispersive X-ray spectroscopy (EDS) with an analyzer
system attached to a JEOL SEM 7700F. High-resolution transmis-
sion electron microscopy (HRTEM) was performed using a JEOL
JEM 2100F electron microscope. XRD, SEM-EDS and HRTEM
investigations were performed in the Research Centre Laboratory
at Mugla Sıtkı Koçman University.
For [Cu(L2)2]: Light brown complex; yield: 79%; m.p.: 187 °C.
l
eff = 1.73 B.M.; UV (DMF, nm) 269, 306 and 354; FT-IR (ATR,
cmꢂ1) 3449 (OAH), 1752 (C@O)ester, 1604 (C@NAN@C), 1248 and
1165 (CAOAC). MS (ES+), (m/z): 947.50 [M]+. Analysis (%Calcu-
lated/found) for C46H44CuN4O14 C: 58.37/58.42, H: 5.32/5.26, N:
5.92/5.85, Cu: 6.91/6.85.