Vol.2, No.12, 1341-1348 (2010)
doi:10.4236/ns.2010.212163
Copyright © 2010 SciRes. Openly accessible at http:// www.scirp.org/journal/NS/
Natural Science
Zinc oxide nanocomposites with antitumor activity
Emma Arakelova1*, Ashot Khachatryan1, Karapet Avjyan1, Zoya Farmazyan1,
Alvard Mirzoyan1, Lilia Savchenko1, Sedrak Ghazaryan2, Flora Arsenyan2
1Scientific Research Division, State Engineering University of Armenia,Yerevan, Armenia;
*Corresponding Author: emma_arakelova@yahoo.com
2Laboratory of Syntheses Derivatives amino acids and peptides, Laboratory of toxicology and chemotherapy IFOC (Institute of Fine
Organic Chemistry), Yerevan, Armenia
Received 25 September 2010; revised 26 October 2010; accepted 30 October 2010.
ABSTRACT
Zinc oxide nanocomposites in the form of
coatings and composite films with antitumor
activity were obtained by deposition of ZnO
nanofilms on surfaces of ethyl ether Salicyli-
dene DL-tyrosine (S1) and ethyl ether Salicyli-
dene DL-tyrosine Cu (II) chelate (S2) by magne-
tron sputtering of Zn target. Ethyl ether Sali-
cylidene DL-tyrosine, Cu (II) chelate of ethyl
ether salicylidene DL-tyrosine reveal some
anticancer properties. Their zinc oxide nano-
composites were obtained in the form of coat-
ings (S1 + ZnO, S2 + ZnO) and composite films
presenting a mixture of polyvinyl alcohol (PVA)
with S1, S2 (S1 + PVA + ZnO, S2 + PVA + ZnO),
for the purpose of increasing anticancer activity.
Considerable increase in antitumor activity re-
veal ZnO nanocomposites with salicylidene
amino acid chelates (as distinct from their
ethers) in the form of S2 + ZnO (47%) and S2 +
PVA + ZnO (48%) in comparison with S2 (20%).
Structural, spectral properties of the salicylidene
amino acids and their ZnO nanocomposites
were studied.
Keywords: Zinc Oxide; Nanofilm;
Magnetron Sputtering; Nanocompo sites;
Antitumor Activity
1. INTRODUCTION
It is known that biologically active materials formed
by deposition of metal oxide nanostructures on the or-
ganic and polymeric systems surfaces reveal an ability to
depress and kill pathogenic biological flora, and their
introduction to organisms prevents “fixing” of viruses
and bacteria to cell walls, improves antibacterial and
antiviral immunity [1-3].
Here, very important is both the choice of inorganic
material for modification of the biologically active ma-
terials surface and the deposition procedure.
Thin films or nanoscale coatings of ZnO nanoparticles
on suitable substrates have excellent electrical, optical,
and medical properties with broad range of applications
for functional coatings, sensors, in optical devices,
transparent electrodes, solar cells and antibacterial, anti-
tumor activity [4-10].
Various methods like chemical, thermal, spray pyroly-
sis, pulsed laser deposition etc. have been developed to
coat ZnO nanoparticles in the form of thin films on solid
supports such as metal, metal oxides, glass or thermally
stable substrates [6,8,11-14].
Among the known methods of obtaining nanocompo-
sitions, magnetron deposition of metal oxide nanofilms
on the organic and polymeric systems surfaces at rela-
tively low temperatures holds a unique position. Stand-out
distinguishing features of the method are ample oppor-
tunities for controlling the nanocomposition formation
process, low deposition temperature (20ºС T 100ºС)
and simplified technique of layer-by-layer deposition of
coatings, allowing growth of nanocomposites with pre-
determined structural parameters.
Development of new nanotechnologies is of great
importance for anticancer chemotherapy as the modern
methods of anticancer drug administration in therapeutic
(and slightly hither) doses are accompanied, as a rule, by
development of serious side effects that frequently are
the reasons of termination of the further course of treat-
ment.
It is known that amino acid Schiff’s bases form stable
neutral lipophilic complexes with divalent ions of
d-family metals. Some of them, for example, copper
complexes reveal radioprotective, cytostatic action, in-
hibiting reversibly DNA synthesis [15-19]. It is also
known that in organisms, basic amino acids are binding
agents for metal oxides, in particular for ZnO. Adjusting
and immune effect of ZnO on DNA synthesis, produc-
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tion of interleukin (IL-2, IL-6, IL-10) and normalization
of cytokine concentration was studied at the patients
with chronic liver disease, in particular, hepatic cirrhosis
[20].
On this basis, formation of thin films ZnO on the sur-
faces of biologically active compounds (aimed at the
surface modification) by magnetron deposition of Zn
target is of special interest.
This work is devoted to deposition of zinc oxide films
on biologically active coatings and composite films of
ethyl ether salicylidene DL-tyrosine, ethyl ether Sali-
cylidene DL-tyrosine Cu (II) chelate with PVA aimed at
modification of their surfaces and obtaining coatings and
composite films with antitumor activity.
The paper discusses the following problems:
1) Obtaining of zinc oxide nanocomposites by deposi-
tion of zinc oxide nanofilms on coatings, composite
films of ethyl ether salicylidene DL-tyrosine and ethyl
ether salicylidene DL-tyrosine Cu (II) chelate by DC-
magnetron deposition of zinc targets.
2) Study of anticancer activity of ethyl ether Sali-
cylidene DL-tyrosine, ethyl ether salicylidene DL-tyrosine
Cu (II) chelate and zinc oxide nanocomposites in the
form of coatings and composite films
3) Structural, spectral properties of salicylidene amino
acid and their chelate compounds, as well as ZnO nano-
composites coatings of S1 + ZnO, S2 + ZnO and PVA
composite films (S1 + PVA + ZnO, S2 + PVA + ZnO).
2. EXPERIMENTAL DETAILS/
METHODOLOGY (SELECT THE MORE
APPROPRIATE)
The paper is aimed at obtaining of zinc oxide nano-
composite coatings and polymer composite films with
anticancer activity by deposition of ZnO nanofilms on
surfaces of ethyl ether salicylidene DL-tyrosine, S1 and
their Cu (II) chelate, S2 by magnetron sputtering of Zn
target. Ethyl ether salicylidene DL-tyrosine and ethyl
ether salicylidene DL-tyrosine Cu (II) chelate are new
compounds for the first time synthesized in the Institute
of Fine Organic Chemistry of National Academy of Sci-
ences of the Republic of Armenia. They were used as
model compounds for obtaining zinc oxide nanocompo-
sitions.
2.1. Formation of Coatings and Composite
Films with PVA from Ethyl Ether
Salicylidene DL-Tyrosine and Ethyl
Ether Salicylidene DL-Tyrosine Cu (II)
Chelate
Coatings from ethyl ether salicylidene DL-tyrosine
and ethyl ether salicylidene DL-tyrosine Cu (II) chelate
were obtained on glass substrates as a paste with di-
methyl sulfoxide.
As solvents, olive oil, ethylene glycol (EG), polyeth-
ylene glycol (PEG), dimethyl sulfoxide (DMSO) were
tested. DMSO was chosen as a low-toxic substance with
antiinflammatory, antimicrobial action, high permeabil-
ity through biological membranes. Pastes from S1, S2
were prepared taking into account their daily maximum
permissible doses for the animals.
Several samples of polyvinyl alcohol differed in mo-
lecular mass and functional composition were used to
create needed polymeric matrix and choose the condi-
tions of obtaining the films prospectively appropriate for
their combination with S1,S2 and zinc oxide. The PVA
samples were: PVA-1, MM approximately 20000, mass
fraction of acetate group 1.3%, PVA-2, MM approxi-
mately 21000, mass fraction of acetate group 10.6%,
PVA-4, MM = 50000-60000, mass fraction of acetate
group 5.3%. PVA-4 differs from PVA-1 and PVA-2 in
higher MM, and its mass fraction of acetate group is
intermediate between PVA-1 and PVA-2.
The composition films from S1 and S2 with PVA were
obtained from 0.5 ml of 5% PVA solution with a meas-
ured amount of S1 and S2 corresponding to therapeutic
doses of S1 and S2 for white nondescript mice. The film
diameter was 2.8 cm (surface area was 6.1 cm2). On the
composite films of S1 and S2 with PVA the ZnO nano-
films were deposited by magnetron sputtering of zinc
target.
2.2. DC-Magnetron Deposition of ZnO
Nanofilms on Surfaces of Salicylidene
Amino Acids and Their Chelates
To deposit nanosize ZnO films on surfaces of coatings
and composite films of ethyl ether salicylidene DL-tyrosine,
ethyl ether salicylidene DL-tyrosine Cu (II) chelate, a
modified UVN-71P3 device, DC-magnetron intended for
sputtering of metal targets was used.
UVN-71P3 device was equipped with a system of
working gas flow measurement and control consisting of
supply and indication unit PR4000F as well as two gas
flow regulators MFC 1179 for Аr and О2 gases.
The substrates from optic glass for deposition of
coatings or composite films from the investigated com-
pounds were fixed inside the device using special clamps
ensuring their movement within the vacuum chamber.
ZnO nanofilm deposition process was carried out by
magnetron sputtering of Zn target at parallel arrange-
ment of the target and substrate. The deposition device is
powered from an energy supply source. To carry out
experiments on ZnO nanofilm deposition within the in-
vestigated temperature interval, a system based on
Peltier element or resistance heater ensuring decrease
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and stabilization of the substrate temperature was used.
ZnO nanofilms were deposited on rotating substrates (to
ensure uniform thickness) at the substrate temperature
range from 20ºС to 100ºС.
When selecting technological regimes of ZnO nano-
film deposition on the substrate (the working gases О2
and Аr ratio, operating current of the magnetron source,
target-to-substrate distance, substrate temperature), the
conditions were considered to eliminate undesirable ex-
traneous transformations of salicylidene amino acids and
their chelates.
To form zinc oxide nanocompositions of the investi-
gated compounds S1, S2 in the form of coatings and
composite films, a technique of ZnO nanofilm deposi-
tion on glass substrates was preliminary developed.
ZnO nanofilms were deposited on glass substrates by
magnetron sputtering of Zn targets (55 mm in diameter)
at the operating current from 80 mA to 500 mA, pressure
of 10-2 mm Hg, and target-to-substrate distance from 7
cm to 13 cm. As working gases, Аr and О2 were used in
the ratio of 70%-30%. To keep clean the deposition
process, the vacuum chamber was exhausted to 2 × 10-6
mm Hg before the film deposition.
2.3. Technique of Identification of Antitumor
Activity of Ethyl Ether Salicylidene
DL-Tyrosine, Their Cu (II) Chelate and
Zinc Oxide Nanocomposites on Strains
of Inoculate Tumors
The study was carried out in toxicology and chemo-
therapy laboratory of Scientific Technological Centre of
Organic and Pharmaceutical Chemistry of the National
Academy of Sciences of the Republic of Armenia under
conditions close to GLP principles and European stan-
dards.
Antitumor coatings and composite films of zinc oxide
nanocomposites of ethyl ether salicylidene DL-tyrosine,
ethyl ether salicylidene DL-tyrosine Cu (II) chelate and
initial compounds were tested on the strains of sarcoma
180 tumors inoculated to white nondescript mice. Pre-
liminary, maximum permissible doses (MPD) were de-
termined by vivisections, and on their basis-therapeutic
doses of the substances, which made as a rule 20% of the
single MPD.
For subinoculation, as a transplant the peaces of tumor
tissues not subject to necrosis and crushed to homoge-
neous mass were used. Physiological salt solution was
added to the tumor in 1:3–1:4 ratio, and the obtained
suspension was introduced to the animals (with initial
weight 22-26 g) subcutaneously by a syringe at a rate of
0.3 ml.
Nanocomposites in the form of ZnO + (S1, S2) coat-
ings were introduced to the animals subcutaneously as a
suspension in DMSO 48 hours after the tumor subin-
oculation on a daily basis during 6 days.
Zinc oxide nanocomposites and initial compounds in
the form of composite films were deposited operation-
ally in sterile conditions (box) by subcutaneous applica-
tions for 6 days through a 5-7 mm in section in spinal
and scapular parts of the animals.
48 hours after the experiment the animals were killed,
the tumors were withdrawn and weighed. Antitumor
activity was determined by the percentage of the tumor
inhibition with respect to the control animals.
2.4. Сharacterization of Ethyl Ether
Salicylidene DL-Tyrosine, Their Cu (II)
Chelates and Zinc Oxide
Nanocomposites
X-ray diffraction (XRD) patterns were obtained on
CAD4, Enraf-Nonius and DRON-2.0 X-ray diffracto-
meters. NMR spectra were recorded on Varian Mercury
300VX spectrometer with all-round frequency 300 MHz.
IR spectra were recorded on NEXUS FT-IR spec-
trometer. Mass spectra were recorded on МХ-1321А.
3. RESULTS & DISCUSSION
3.1. Selection of Optimum Surface Areas for
S1, S2
The ZnO nanofilm surface coatings are S1, S2 deposi-
tions over a certain surface area of object glass. Thick-
ness and optimum ZnO nanofilm surface area was cal-
culated for the case, when its content in the film was
5-10% of that of S1, S2. It is known from publications
that at addition of 5% ZnO to plasma of rabbit with in-
culcated Staphylococcus, antibacterial activity increases
in comparison with that for control samples without ZnO
[20]. On this basis, ZnO content in the film (5-10% of
S1, S2 weight) was taken for rough estimate, with a view
to obtain reliable optimum results. To ensure techno-
logical effectiveness of the deposition process, the sur-
face area was calculated taking into account the amount
of S1 and S2 for daily dose of 6 mice. Suspension of S1 +
ZnO nanocomposite did not reveal reliable antitumor
action (10%) at subcutaneous introduction of m1 = 1.4
mg/mouse of ethyl ether salicylidene DL-tyrosine to
mice, when ZnO deposition area on S1 was s1 = 2.54
cm2. However at the same daily dose, when ZnO deposi-
tion area on S1 coatings were s1 = 9.62 cm2 and s2 = 15.9
cm2, antitumor activity was 30%-32% for d = 100 nm
thick ZnO nanofilms (Table 1).
At subcutaneous introduction of S2 + ZnO, when the
content of ethyl ether salicylidene DL-tyrosine Cu (II)
chelate was m = 1.2 mg/mouse and s = 2.54 cm2, the
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1344
antitumor effect was only 27%. Taking into account the
calculation for the S1 with optimum result, the ZnO
nanofilm deposition area was calculated for S2 at the
following daily doses: m1 = 1.2 mg/mouse, m2 = 1.4
mg/mouse; m3 = 2.8 mg/mouse. The nanocomposites
were formed on the following surface areas of ethyl
ether salicylidene DL-tyrosine Cu (II) chelate:
s1 = 9.62cm2, s2 = 15.9 cm2, s2* = 19.8 cm2, s3 = 31.8
cm2. Chemotherapeutic investigations have revealed
increase in antitumor activity from 27% to 42% at daily
dose m1 = 1.2 mg/mouse. However with further increase
of ZnO nanofilm surface area, a slight decrease of activ-
ity takes place. At the increase of daily dose to m = 2.8
mg/mouse and selection of optimum area, s = 31.8 cm2,
increase in antitumor activity to 47% was revealed (Ta-
ble 1).
Optimum ZnO nanofilm area coated by ethyl ether
salicylidene DL-tyrosine and ethyl ether salicylidene
DL-tyrosine Cu (II) chelate was determined. Significant
increase in antitumor activity of ZnO nanocomposites of
ethyl ether salicylidene DL-tyrosine Cu (II) chelate in
comparison with the initial compound is observed. It
was revealed that ZnO quantitative content in nanofilms
makes 10% of therapeutic dose of the initial compounds.
3.2. Variation of Structural Characteristics
of PVA in Composite Films with S1, S2
It was revealed at formation of composite films PVA
with S1 and S2 that the films obtained from the mixture
of PVA-1 and S-1 did not dissolve in water after drying;
the films obtained from the mixture of PVA-2 and S-1
(as well as PVA-2 and S-2) dissolve in water; PVA-1
film did not dissolve in water after deposition of ZnO
nanofilms (by magnetron sputtering of Zn target) on its
surface, whereas PVA-2 film with ZnO did dissolve.
Solubility of the films before and after deposition of
ZnO nanofilms was studied both in model conditions at
various pH and in vivo by subcutaneous introduction to
mice and measurement of solubility time.
The following results were obtained: (PVA-1 + ZnO)
film did dissolve in animal organisms, but slowly, during
4 days. However (PVA-1 + S1 + ZnO) film resolved
under the animal skin in 6-7 days (Table 2), i.e. its pro-
longed dissolution in animal organisms was ensured.
(PVA-1 + S2 + ZnO) film did dissolve under the mice
skin.
(PVA-2 + S1) and (PVA-2 + S1 + ZnO) films did dis-
solve 4-5 days, no antitumor effect was revealed.
(PVA-2 + S2) and (PVA-2 + S2 + ZnO) films did dis-
solve in one day, however (PVA-4 + S2) and (PVA-4 +
S2 + ZnO) resolved under the animal skin in 5-6 days
(Table 2).
So, it was revealed that for ethyl ether salicylidene
Table 1. Effect of ZnO nanofilm area surface on antitumor
activity of ZnO nanocomposites.
Composition Daily dose,
mg\mouse
Coated area (S1,S2) of
glass substrates, cm2
(daily dose for 6 mice)
Antitumor
action, %
S1 1.4 - 31
S1 + ZnO 1.4 2.54 10
S1 + ZnO 1.4 9.62 30
S1 + ZnO 1.4 15.90 33
S2 1.4 - 18
S2 2.8 - 20
S2 + ZnO 1.2 2.54 27
S2 + ZnO 1.2 9.62 42
S2 + ZnO 1.4 15.9 42
S2 + ZnO 1.4 19.8 40
S2 + ZnO 2.8 31.8 47
Table 2. Effect of polymer grade on in vivo solubility and an-
titumor activity of ZnO nanocomposite films.
Composition Daily dose,
mg\mouse
In vivo solubility of
films under the mice
skin
Antitumor
action, %
S1 1.4 - 31
S1 + PVA-1 + ZnO1.4 Dissolved, 6-7 days 31
S1 + PVA-2 + ZnO1.4 Dissolved, 4-5 days No effect
S1 + PVA-4 + ZnO1.4 Dissolved, 5-6 days No effect
S2 1.4 - 18
S2 2.8 - 20
S2 + PVA-1 + ZnO1.4 Not dissolved -
S2 + PVA-2 + ZnO1.4 Dissolved, 4-5 days 24
S2 + PVA-4 + ZnO1.4 Dissolved, 5-6 days 42
S2 + PVA-4 + ZnO2.8 Dissolved, 5-6 days 48
DL-tyrosine the most optimum option of the composite
film formation is the use of PVA-1 with molecular
weight 20000, mass fraction of acetate group 1.3%. To
form the composite film with ethyl ether salicylidene
DL-tyrosine Cu (II) chelate, as an intermediate option
PVA-4 was selected with molecular weight 60000,
where the amount of acetate groups (5.7%) is intermedi-
ate between PVA-1 (1.3%) and PVA-2 (10,5%) and mo-
lecular weight is higher.
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3.3. Optimum Technological Parameters of
ZnO Nanofilm Deposition on Coatings
and S1, S2 Composite Films
Optimum technological parameters of zinc oxide nan-
ofilm magnetron deposition on the surface of ethyl ether
salicylidene DL-tyrosine, ethyl ether salicylidene DL-
tyrosine Cu (II) chelate in the form of coatings (S1, S2)
and composite films (PVA + S1, PVA + S2) were deter-
mined.
The substrate material temperature was measured de-
pending on the changes of the magnetron source operat-
ing current at various target-to-substrate distances (Fig-
ure 1(а)). It follows from this dependence that within
the investigated range of operating currents from 80 mA
to 500 mA, the substrate surface temperature was below
100˚С. At such temperatures, there were no undesirable
extraneous transformations of the surface of biologically
active substances S1 and S2. X-ray investigations were
carried out and experimental results on antitumor active-
ity were obtained for ZnO compositions formed at vari-
ous technological regimes of ZnO deposition on the re-
searched biologically active compounds. It was revealed
that the structure of 100 nm thick ZnO nanofilms with
optimum size of nanoparticles (15-30 nm) is appropriate
for interaction with the researched biologically active
compounds in form of both coatings and composite films.
Such nanosize ZnO films were obtained at the following
technological regimes: operating current from 400 mA,
operating voltage 240 V and operating pressure 10-2 mm
Hg. For these regimes, the ZnO nanofilm deposition rate
was studied depending on target-to-substrate distance
(Figure 1(b)). Optimum target-to-substrate distance, 10
cm was selected taking into account the obtained de-
pendences and uniformity of the ZnO films deposited on
the S1, S2 sample surfaces. At such target-to-substrate
distance the film growth rate made approximately 6
nm/min.
Composites on the basis of ZnO nanofilms and bio-
logically active substances S1 and S2 were obtained by
deposition of approximately 100 nm thick zinc oxide
nanofilm (using Zn target) on S1 and S2 deposited in the
form of coatings or composite films, in the following
technological regime: operating current from 400 mA,
gas mixture Ar and O2 at 70:30 ratio; operating pressure
10-2 mm Hg, target-to-substrate distance 10 cm.
3.4. Antitumor Activity of S1, S2 and Zinc
Oxide Nanocomposites
It was revealed as a result of study of acute toxicity
that MPD values for S1 and S2 are 50 mg/kg and 250
mg/kg, correspondingly. In view of these data, as pre-
liminary therapeutic dose for S1 and S2 were used 15
(a)
(b)
Figure 1. (a) Dependence of the substrate material temperature
upon the magnetron source current at various target-to-substrate
distances: 1) 7 cm; 2) 10 cm; (b) Dependence of ZnO nanofilm
deposition rate upon the target-to-substrate distances at various
magnetron source currents: 1) 200 mA; 2) 400 mA.
mg/kg and 50 mg/kg, correspondingly.
In chemotherapeutic experiments S1 at 0.3 mg/mouse
(15 mg/kg) dose did not reveal antitumor effect and
general toxic action, so in subsequent experiment the
dose was increased to 1.5 mg/mouse. It was revealed
that at such dose S1 inhibited sarcoma 180 growth by
31% and did not reveal toxic action on the animal or-
ganism. S2 at therapeutic dose of 1 mg/mouse did not
cause significant inhibition of sarcoma 180 (18%), and
with the dose increase to 2.8 mg/mouse no increase in
therapeutic action was determined (20%).
S1 + ZnO nanocomposite in the form of coatings and
composite films S1 + PVA-1 + ZnO revealed the same
activity as S1: 33% and 31%. However S2 + ZnO nano-
composites where S2 content was 1 or 2.8 mg/mouse,
revealed at subcutaneous injection to animals and film
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1346
application much higher antitumor activity (in form of
both S2 + ZnO coating, 47%, and S2 + PVA-4 + ZnO
composite films, 48%) than S2(20%).
So, as distinct from nanocomposites with S1 + ZnO,
S2 + ZnO in form of both coatings and composite films
revealed relatively higher therapeutic effectiveness than
at using S2 only.
3.5. Structural, Spectral Characteristics of
S1, S2 and Zinc Oxide Nanocomposites
Complete X-ray diffraction study of ethyl ether Sali-
cylidene DL-tyrosine was carried out using CAD4, En-
raf-Nonius diffractometer. The compound was synthe-
sized for the first time in the Institute of Fine Organic
Chemistry of National Academy of Sciences of the Re-
public of Armenia.
Figure 2 present the molecular structure (Figure 2(a))
and crystal packing on plane ac for three molecules (for
cleanness) (Figure 2(b)) of ethyl ether salicylidene
DL-tyrosine. In the compound’s crystalline structure,
bond lengths (N (2)-C (3): 1.296Å, C (1)-N (2): 1.448 Å)
are typical for C = N Schiff base bond and C-N single
bond, respectively [21]. The compound structure con-
tains intramolecular hydrogen bonds between N (2) and
O (10) atoms, N (2)-H (2)…O (10), 2.565 Å in length
and intermolecular hydrogen bonds O (18)-H (18)…O
(10), 2.623 Å in length.
IR study was carried out on ethyl ether salicylidene
DL-tyrosine Cu (II) chelate and has shown that the
compound includes free hydroxyl group of a salicylidene
fragment in the valence vibration region 3309 cm-1.
In the metal complex, shift of COO- absorption band
was occurred to 1668 cm-1 as distinct from S1 with 1733
cm-1, and a shift –CH = N to 1651 cm-1 due to interact-
tion between Cu and nitrogen on account of free electron
pair.
Also, there were differences in the region of deforma-
tion vibrations: C-O, C-O-H and C-O-C, Me-O, Me-N.
Also, IR study was carried out on ethyl ether Sali-
cylidene DL-tyrosine zinc oxide nanocomposites. The
study has revealed identity of ethyl ether salicylidene
DL-tyrosine zinc oxide nanocomposite and initial S1
spectra. They did not contain expected shifts of absorp-
tion bands of C = O, C-O-H, C-O-C functional groups in
1206-1065 cm-1 region (deformation vibrations) and in
the valence vibration region of OH group (3000-3500
cm-1). ZnO presumably presents in the form of mechanical
mixture with ethyl ether salicylidene DL-tyrosine.
Comparison of the absorption spectra of metal com-
plex and ethyl ether salicylidene DL-tyrosine Cu (II)
chelate zinc oxide nanocomposite has revealed a shift of
absorption band in the valence vibration region of OH
group from 3309 cm-1 in the initial metal complex to
(a)
(b)
Figure 2. Molecular structure (a) and crystal packing on the
plane ac (b) of ethyl ether salicylidene DL-tyrosine.
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134
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3335 cm-1 in metal oxide composite. It is likely that this
shift is related to interaction between ZnO and OH group
of the salicylidene fragment.
In case of ZnO nanocomposite films (S1 + PVA-1 +
ZnO) there is interaction of PVA-1 functional groups
with ZnO and absence of ZnO-S1 interaction. In case of
(S2 + PVA-4 + ZnO) films interactions of ZnO with
functional groups of both PVA-4 and S2 were revealed.
Study of nanocomposite films has revealed the de-
pendence of the interactions with formation of bonds in
the composite film components upon the structure of
S1and S2 compounds.
X-ray investigations of ethyl ether salicylidene DL-
tyrosine have detected presence of intramolecular hy-
drogen bond N-H…O and intermolecular hydrogen
bonds of OH hydroxyl group and carbonyl group, which
form chains in compounds. IR spectral investigations of
ZnO nanocomposite coatings (S1 + ZnO) did not reveal
ZnO-S1 bonds. Spectral investigations of ZnO nano-
composite films (S1 + PVA + ZnO) have revealed inter-
action of PVA functional groups with ZnO and absence
of ZnO-S1 interaction. IR spectral investigations of ethyl
ether salicylidene DL-tyrosine Cu (II) chelate did not
reveal intramolecular or intermolecular hydrogen bonds
in the structure; however ZnO nanocomposite coatings,
S2 + ZnO, reveal obvious formation of intermolecular
hydrogen bond of ZnO...НO type. ZnO nanocomposite
films from PVA with S2 reveal interaction of ZnO with
functional groups of both PVA and S2.
Thus, the surface modification of ethyl ether Sali-
cylidene DL-tyrosine Cu (II) chelate coatings as well of
composite films from these compounds by deposition of
ZnO nanofilms using magnetron sputtering results in
increase of antitumoral activity of the obtained nano-
composites, apparently due to formation of intermolecu-
lar hydrogen bond between ZnO and hydroxyl groups of
these compounds.
4. CONCLUSIONS
1) Zinc oxide nanocomposites of ethyl ether salicyli-
dene DL-tyrosine and ethyl ether salicylidene DL-tyrosine
Cu (II) chelate were obtained by deposition of approxi-
mately 100 nm thick zinc oxide nanofilms on coatings
and composite S1, S2 films using magnetron sputtering
of Zn targets in the temperature range of 20˚С T
100˚С at operating pressure of 10-2 mm Hg.
2) Optimum ZnO nanofilm area coated by ethyl ether
salicylidene DL-tyrosine and ethyl ether salicylidene
DL-tyrosine Cu (II) chelate was determined. Significant
increase in antitumor activity of ZnO nanocomposites of
ethyl ether salicylidene DL-tyrosine Cu (II) chelate in
comparison with the initial compound is observed. It
was revealed that ZnO quantitative content in nanofilms
makes 10% of therapeutic dose of the initial compounds.
3) Zinc oxide composite films of ethyl ether salicyli-
dene DL-tyrosine and ethyl ether salicylidene DL-tyrosine
Cu (II) chelate with polyvinyl alcohol are obtained en-
suring their prolongation in animals (mice) organizm. It
is shown that for ethyl ether salicylidene DL-tyrosine the
most optimum option of the composite film formation is
the use of PVA with molecular weight 20000 and mass
fraction of acetate group 1.3% To form the composite
film with ethyl ether salicylidene DL-tyrosine Cu (II)
chelate, the optimum option is PVA with molecular
weight 60000 and amount of acetate groups of 5.7%.
4) Chemotherapeutic investigations have shown that
antitumor activity of zinc oxide nanocomposites of ethyl
ether salicylidene DL-tyrosine in the form of both S1 +
ZnO coatings (33%) and S1 + ПВС + ZnO composite
films (31%) was approximately the same as that of
S1(31%).
5) ZnO nanocomposites with Cu (II) chelate of ethyl
ether salicylidene DL-tyrosine (as distinct from their
ester) in the form of S2 + ZnO (47%) coatings and S2 +
PVA + ZnO (48%) composite films have revealed con-
siderable increase in antitumoral activity in comparison
with S2 (20%).
6) X-ray investigations of ethyl ether salicylidene
DL-tyrosine have detected presence of intramolecular
hydrogen bonds and intermolecular hydrogen bonds,
which form chains in the compounds. IR spectral invest-
tigations of ZnO nanocomposite coatings (S1 + ZnO)
did not reveal ZnO-S1 bonds. Spectral investigations of
ZnO nanocomposite films (S1 + PVA + ZnO) have re-
vealed interaction of PVA functional groups with ZnO
and absence of ZnO-S1 interaction.
7) IR spectral investigations of ethyl ether salicylidene
DL-tyrosine Cu (II) chelate did not reveal intramolecular
or intermolecular hydrogen bonds in the structure, how-
ever ZnO nanocomposite coatings, S2 + ZnO, reveal
(judging from the deviation in valence vibrations of OH
group) obvious formation of intermolecular hydrogen
bond of ZnO-H…O type. ZnO nanocomposite films
from PVA with S2 reveal interaction of ZnO with func-
tional groups of both PVA and S2.
8) Surface modification of ethyl ether salicylidene
DL-tyrosine Cu (II) chelate coatings as well as compos-
ite films based on these compounds, by deposition of
ZnO nanofilms using magnetron sputtering resilts in
increase of antitumor activity of the obtained nanocom-
posites, apparently due to formation of intermolecular
hydrogen bonds between ZnO and hydroxyl groups of
these compounds.
5. ACKNOWLEDGEMENTS
This work was supported by Grant А-1563 awarded by the Interna-
E. Arakelova et al. / Natural Science 2 (2010) 1341-1348
Copyright © 2010 SciRes. http://www.scirp.org/journal/NS/
1348
tional Science and Technology Center.
Openly accessible at
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