Available online at www.derpharmachemica.

com

ISSN 0975-413X Der Pharma Chemica, 2016, 8(19):338-344

CODEN (USA): PCHHAX (http://derpharmachemica.com/archive.html)

Conventional and Ultrasonic synthesis of β-diketone with Mn(II), Fe(III),

Co(II), Ni(II) and Cu(II) complexes and their antimicrobial screening
Narendra A. Bhisea, Shalini T. Dengleb, Suresh T. Gaikwada and Anjali S. Rajbhoja*
a
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad (Maharashtra) 431004
India
b
Department of Chemistry, Vivekanand Arts, S.D. Commerce and Science College Aurangabad-431002 (M. S.) India
_____________________________________________________________________________________________

ABSTRACT

1-(5-bromo-2-chlorophenyl)-3-hydroxy-3-(2-hydroxyphenyl)prop-2-en-1-one and its metal complexes have been

synthesized by reaction with 5-bromo-2-chlorobenzoic acid, 2-hydroxyacetophenone and POCl3. The ligand and its
metal complexes were synthesized by conventional and ultrasonic methods. Synthesized beta-diketone shows keto-
enol tautomerism by hydrogen bonding, hence acts as a chelating agent in the preparation of metal complexes.
Synthesized compounds have been characterized by 1H-NMR, 13C-NMR, FTIR, LC-MS and elemental analysis. The
structure of the metal complexes is found to be monoclinic and have been confirmed by XRD. Solution conductivity,
magnetic susceptibility and antimicrobial screenings were also studied. The synthesized ligand and its metal
complexes showed satisfactory antimicrobial activity.

Keywords: Beta-diketone, metal complexes, Ultrasonic, magnetic susceptibility, antimicrobial screenings.

_____________________________________________________________________________________________

INTRODUCTION

β-diketones exist in the intramolecular hydrogen bonded keto-enol tautomerism hence form metal complexes, as
enolic hydrogen atom can be replaced by a metal and a ketonic oxygen, thereby completing the chelate ring. β-
diketones have many industrial and medicinal application hence are widely used. It possesses unique structural
features and chemical functionalities and toughness for light and heat as electroluminescence [1-2]. β-diketones are
versatile precursor for the synthesis of various heterocycles such as pyrazol [3], isoxazole [4], triazole [5], flavones
[6], benzodiazepine [7] and pyrimidine [8]. β-diketones are important pharmacophores of HIV-1integrase (1N)
inhibitor [9]. Cobalt is one of the major constituent of vitamin B12 (Cobalamin) and plays a vital role in many
biological activities, protects against brain atrophy or shrinkage associated with Alzheimer's disease and impaired
cognitive function [10-11]. Many of cobalt containing compound possesses antineoplastic activity [12] and show
efficient catalytic activity. β-diketones with different substituents and their complexes have been synthesized and
their properties such as lewis acidity, standard molar enthalpies of formation, standard molar enthalpies of
sublimation, vapour pressure and volatility have been studied [13]. β-diketones used in extraction processes of
many metal ions [14]. Metal complexes have chelating ability and hence gained considerable interest in nucleic acid
chemistry. The coordination behavior of β-diketones also has significant influences on the relative stabilities of the
mixed ligand complexes as well as their use in biomedicine [15-18]. Cu(II) complexes have gain considerable
importance as the antitumour candidate in recent years because copper is an essential micronutrient that participates
in several biological processes like mitochondrial respiratory reactions, cellular stress response, antioxidant, etc.,
[19-20] and hence it may be less toxic than non-essential metals like platinum [21]. Nickel(II) forms an important

338
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________
component of various enzymes, viz. urease, carbon monoxide dehydrogenase and hydrogenase [22]. In view of the
increasing interest in copper(II) and nickel(II) complexes [23–28], the free ligands and their complexes were
analyzed for their DNA binding properties with calf thymus DNA and screened for both in vitro and in vivo
antitumor activity against Dalton’s lymphoma ascites cells. During the last two to three decades ultrasound
irradiation method is extensively used by the researchers as an alternative source for organic synthesis as it
accelerates the reaction. Acoustic cavitation is responsible for sonochemistry, another important application of
sonochemistry to materials chemistry has been the preparation of biomaterials, most notably protein microspheres.
Such microspheres have a wide range of biomedical applications, including their use as echo contrast agents for
sonography, magnetic resonance imaging contrast enhancement, and oxygen or drug delivery.

MATERIALS AND METHODS

2.1 Materials
The analytical grade solvents and reagents were used for the synthetic work. Pyridine (Spectrochem), 5-bromo-2-
chlorobenzoic acid (Spectrochem), Metal nitrates (Sigma aldrich) and 2-hydoxyacetophenone (Sigma aldrich) were
purchased and used without further purification. Distilled ethanol was used for recrystallization and complex
preparation.

2.2 Experimental Section

a) Conventional method
i) Synthesis of 2-acetylphenyl-5-bromo-2-chlorobenzoate (A):
To a mixture of 5-bromo-2-chlorobenzoic acid (4g, 0.0169mol) and 2-hydroxyacetophenone (2ml,0.0169mol) was
dissolved in pyridine (20ml) and POCl3 (3ml, 0.0339mol) was added dropwise with constant stirring at 0°C. The
progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was poured on
crushed ice and acidified with dil. HCl. Obtained product was filtered and recrystallized by ethanol.

ii) Synthesis of 1-(5-bromo-2-chlorophenyl)-3-hydroxy-3-(2-hydroxyphenyl)prop-2-en-1-one (L) (Base-catalyzed

Bakervenkataraman Rearrangement):
2-acetylphenyl-5-bromo-2-chlorobenzoate (4g, 0.0113mol) was dissolved in pyridine (15ml) and a powdered KOH
(1.9g, 0.0339 mol) was added, and the reaction mixture was stirred at room temperature. The progress of reaction
was monitored by TLC. After the completion of reaction, the reaction mixture was poured on acidified crushed ice.
The yellow product obtained was filtered and dried. Obtained product was recrystallized from ethanol. M.P: 114°C.

iii) Synthesis of metal complexes:

The complexes of Mn, Fe, Co, Ni and Cu were prepared as follows, 1-(5-bromo-2-chlorophenyl)-3-hydroxy-3-(2-
hydroxyphenyl)prop-2-en-1-one (0.02mol) was dissolved in 20ml of ethanol and heated under stirring, to the hot
solution of the ligand appropriate amount of transition metal nitrate (0.01mol) [Mn(II), Fe(III), Co(II), Ni(II),
Cu(II),)] in same solvent was added. The resulting mixture was refluxed for five hours whereupon the complex
precipitation occurs after the addition of alcoholic ammonia. The obtained solid was collected by filtration, washed
with alcohol and then vacuum dried to obtain the product.

b) Ultrasound Irradiation method

i) Synthesis of 2-acetylphenyl-5-bromo-2-chlorobenzoate A:
5-bromo-2-chlorobenzoic acid (4g, 0.0169mol) and 2-hydroxyacetophenone (2ml, 0.0169mol) was dissolved in
pyridine (15ml) and POCl3 (3ml, 0.0339mol) was added dropwise at the temperature 0°C. The reaction mixture was
irradiated by ultrasound for nearly 90 min and the progress of reaction was observed through TLC. After the
completion of reaction, the reaction was worked up and the obtained product was recrystallized by ethanol. This
method gives high yield and good purity of product than conventional method.

ii) Synthesis of 1-(5-bromo-2-chlorophenyl)-3-hydroxy-3-(2-hydroxyphenyl)prop-2-en-1-one (L)

2-acetylphenyl-5-bromo-2-chlorobenzoate (4g, 0.0113 mol) was dissolved in pyridine (15ml) and a powdered KOH
(1.9g, 0.0339 mol) was added, and the reaction mixture was sonicated at room temperature. The progress of reaction
was monitored by TLC. The reaction was completed within an hour with high purity and good yield.

339
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________
iii) Synthesis of metal complexes:
The metal nitrate in ethanol were mixed separately with ethanolic solution of the ligand in 1:2 stichometry (Metal:
Ligand) and the resulting mixture solutions were sonicated at 60–70°C for about one hour in sonicator. After the
addition of alcoholic ammonia complex precipitation occurs, the solid metal complexes thus separated were then
washed with ethanol and dried in vacuum desiccator.

Con/ ))) Cl O O OH
Cl O Cl O
OH O Con/ ))) Pyridine
Pyridine KOH
OH O
POCl 3 RT
00c
O
Br
Br Br
Br
OH

Con/ ))) Cl O OH OH
O O Cl Ethanol 6'' 2'
Metal nitrate 1'' 1'
5'' 3'
1
H2 O M OH2 2 3
60 -700C 2'' 6' 4'
4'' 3''
Cl O O OH 5'
Br
(L)

Br

Scheme: Synthesis of the b-diketone (L) and its metal complexes

M= Mn, Fe, Co, Ni and Cu

Table1. The comparative results of conventional and ultrasonic methods

Compound Conventional Ultrasonication Yield % M.P/decomp.

Time (min) Time(min) Conventional Ultrasonication Temp. (°C)
A 175 90 71 90 110
L 75 55 72 88 114
[Mn(L)2](H2O)2 190 110 69.7 83 >300
[Fe(L)2](H2O)2 186 95 66.5 76.6 >300
[Co(L)2](H2O)2 172 105 72.8 82.3 >300
[Ni(L)2](H2O)2 170 84 73.8 86.1 >300
[Cu(L)2](H2O)2 160 75 75.7 89.5 >300

2.3 Characterizations:
Melting points were determined in open glass capillaries and were uncorrected. The elemental analyses were carried
out using EuroVector EA 3000 Elemental Analyser, 1HNMR and 13CNMR were recorded on a Bruker’s AVANCE-
III 400MHz FT-NMR spectrometers by using tetramethylsilane as an internal standard and CDCl3 as solvent, FTIR
were recorded using (KBr) disc on Shimadzu. The magnetic susceptibility was measured at room temperature using
a Guoy balance. Molar conductivities of metal complexes were measured at room temperature by using Equiptronics
Digital conductivitymeter (EQ-660). Synthesis was carried out by conventional as well as by ultrasound irradiation
method. Ultrasound assisted synthesis were carried out in Citizen ultrasonic sonicator.

RESULTS AND DISCUSSION

The ultrasound irradiation method is very useful to carry out chemical reactions, ecofriendly, atom economy, simple
setup and easy handling. The prepared metal complexes were coloured, stable to air and soluble in polar solvent like
DMSO and DMF. The result of elemental analysis show 1:2 (metal:ligand) stoichiometry for all the prepared metal
complexes. The presence of two coordinated water molecules appears to be hexa-coordinated of metal atom and the
probable geometry is octahedral, Magnetic study reveals that the complexes of Mn, Fe, Co, Ni and Cu were
paramagnetic in nature. The molar conductance of the metal complexes of 10-3M solution in DMF was found in the
range 8 to 15cm-1 mol-1, which indicates that these complexes are nonelectrolytes.

340
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________
3.1 1H-NMR, 13C and Mass spectral data of the Ligand(L)
1
H-NMR(400MHz, CDCl3)δ: 6.76 (s, 1H, vinylic), 6.88 – 7.83(m, 7H, Ar-H), 11.90 (s, 1H Ar-OH), 15.14 (s, 1H
enolic-OH).13C-NMR(400MHz, CDCl3)δ: 196.20 (s C-1, C=O), 98.33 (C-2, -CH=), 174.13 (s, C-3), 118.72 (s, C-
1’), 162.77 (s, C-2’), 118.90 (s, C-3’), 128.86 (s, C-4’), 119.40 (s, C-5’), 126.42 (s, C-6’), 136.47 (s, C-1’’), 133.08
(s, C-2’’), 120.78 (s, C-3”), 134.60 (s, C-4”), 131.21 (s, C-5”), 132.33 (s, C-6”). LC-MS (ESI-) at m/z 352.9 .

Table2. Analytical, physical data, magnetic moment and molar conductance values of the compounds

Elemental Analysis
Ligand/Complex F. W. Magnetic moment µeff(B.M) Molar conductance
Carbon % Hydrogen% Oxygen% Metal%
L 353.6 --- --- 49.445 2.820 13.221 ----
[Mn(L)2](H2O)2 796.14 5.87 15.2 45.126 2.324 15.812 7.447
[Fe(l)2](H2O)2 797.05 5.51 8.59 45.105 2.551 15.863 7.522
[Co(L)2](H2O)2 800.14 3.3 10.20 44.221 2.275 16.118 7.157
[Ni(L)2](H2O)2 799.9 2.69 12.10 44.997 3.132 16.093 7.985
[Cu(L)2](H2O)2 804.75 1.27 14.04 44.922 3.008 16.021 7.112

3.2) FTIR spectra of the ligand and metal complexes:

The IR spectra of free ligand and its metal complexes were made for comparison. The free ligand as expected
exhibits keto-enoltautomerism [29]. The IR spectral data of ligand and its metal complexes are listed in table 3. The
spectral band for ligand (i.e for keto carbonyl) appears at 1629 cm-1 (ν C=O), the shifting of the same band to lower
frequency in all the metal(II) complexes indicates the coordination of carbonyl group to the central metal ion. The
spectral band appear in the range 1514-1577cm\-1and 1211-1240cm-1are assigned to stretching vibrations of ν(C=C)
and ν(C–O) [30–32]. The new band appeared in the 515 – 522 cm-1 region are assigned to ν(M-O) bond. The band at
around 3543-3655 cm-1 indicates the existence of coordinated water in all the complexes.

Table 3. IR spectra of free ligand and its metal complexes

Compound ν(C=O) ν(C=C) ν(C–O) ν(OH) of H2O M–O

L 1629 1577 1211 ----- -----
[Mn(L)2](H2O)2 1602 1539 1242 3616 516
[Fe(L)2](H2O)2 1605 1514 1242 3610 515
[Co(L)2](H2O)2 1602 1537 1244 3607 516
[Ni(L)2](H2O)2 1581 1535 1244 3655 516
[Cu(L)2](H2O)2 1614 1541 1240 3543 522

POWDER XRD STUDIES

The X - ray diffraction (powder pattern) of the complexes was made with the help of X-ray diffractometer with Cu
as anode material, the generator settings 30mA, 40KV in the range 5° - 80°. The indexing and calculation of unit
cell parameters were performed using powder-X software and the powder diffraction of metal complexes K, L, M,
and N shows well defined crystalline peaks (fig.1). The indexing method yields the Miller indices (hkl), the unit cell
parameters and average particle size (table 4). The XRD pattern of K, L, M & N complexes shows monoclinic
crystal system. The average crystallite size for the above mentioned complexes was calculated using Debye
Scherrer’s formula [33]:
D = 0.9λ/β.cosθ

Where, constant 0.9 is the shape factor, λ is the X-ray wavelength of Cu Kα radiation (1.5406 Å), θ is the Bragg
diffraction angle and β is the full width at half maximum (FWHM).

341
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________

130

001

-120
-110

101
-221
-301
010

L N
032

-220
-341

113
023
203
201

222

005
111

001
012

-123

112
021 -121
101

041

101
M
K
-113

121

114
-201

-221
-331

104
-202

340
221

-214

045
-303
033

-153
020

-215
-100

123

-403

-424
-253

611

2
0 10 20 30 40 50 60 70 80
2

0 10 20 30 40 50 60 70 80
θ θ

Figure (1) XRD Patterns: K = [Cu(L)2](H2O)2, L = [Ni(L)2](H2O)2, M=[Mn(L)2](H2O)2, N=[Co(L)2](H2O)2

Table 4. XRD data and refinement parameters of K, L, M and N metal complexes

Parameters K L M N
Temperature (k) 298 298 298 298
Wavelength(A°) 1.540598 1.540598 1.540598 1.540598
Radiation Cu Kα Cu Kα Cu Kα Cu Kα
Crystal system Monoclinic Monoclinic Monoclinic Monoclinic
Unit a(A°) 11.6912 11.307 7.5795 9.500
cell b(A°) 15.5434 14.5489 10.5795 11.193
dimension c(A°) 10.7214 9.7457 15.5452 12.210
α(°) 90 90 90 90
β(°) 101 94 92 96
γ(°) 90 90 90 90
Average particle size(nm) 19.1253373 20.3075965 12.01007 16.8346247

Antimicrobial activity
In this research work Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) metal complexes of the 1-(5-bromo-2-chlorophenyl)-
3-hydroxy-3-(2-hydroxyphenyl)prop-2-en-1-one have been prepared to explore their antibacterial and antifungal
properties. The antimicrobial analysis was done on petri-plates containing solidified 20ml Muller Hinton agar
medium. These plates were inoculated with 20-24 hour culture of bacterial and fungal strains. The antimicrobial
activity was assayed by measuring the diameter of the inhibition zone formed in terms of mm.

The antibacterial analysis was done by using Agar diffusion method. The wells were filled with 250 and 500 ppm
concentration of the sample and incubated at 37 °C for 24 hours. Antibacterial activity of ligand and its metal
complexes were tested in vitro against bacteria such as S. aureus, S. typhi and E. coli at 250 and 500ppm control
plates with standard Gentamicin (for bacteria) and solvent were maintained. The results of the tested compounds
against bacteria are shown in table 5. In vitro antibacterial activity of ligand and some of the metal complexes are
moderately active as compared with standard gentamycin. Among the synthesized metal complexes Cu(II)
complexes showed excellent bacterial activity.

The antifungal activity of the synthesized compound were tested by using disc diffusion method against the fungi
such as Saccharomyces cerevisiae and Candida albicans at 10ppm and Amphotericin B used as standard in solvent
DMSO. The results of the tested compounds against fungi are shown in table 6. In vitro antifungal activity of metal
complexes compared to standard Amphotericin B among the synthesized metal complexes Ni(II) complex showed
excellent antifungal activity against C. albicans and S. cerevisiae.

342
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________
The metal complexes shows more antimicrobial activity than ligands due to the enhanced lipophilicity of the
complexes, which leads to the breakdown of permeability barrier of the cell and thus retards the normal cell process
in bacteria. With respect to standard, among the tested compounds some them were found moderately active.
Table 5. Antibacterial screening of ligand and its metal complexes

S. aureus S.typhi E.coli

Compound
250ppm 500pp 250ppm 500ppm 250ppm 500ppm
L 9 10 11 12 10 13
[Mn(L)2](H2O)2 ---- ---- ---- ---- ---- ----
[Fe(L)2](H2O)2 ---- ---- ---- ---- ---- ----
[Co(L)2](H2O)2 10 11 12 14 ---- 14
[Ni(L)2](H2O)2 13 16 13 15 12 16
[Cu(L)2](H2O)2 24 35 17 26 18 20
Gentamycin 26 27 26 30 29 31

Table6.Antifungal screening of ligand and its metal complexes

Saccharomyces cerevisiae Candida albicans

Compound
10ppm 10ppm
L 9 7
[Mn(L)2](H2O)2 ---- ----
[Fe(L)2](H2O)2 ---- ----
[Co(L)2](H2O)2 9 9
[Ni(L)2](H2O)2 11 10
[Cu(L)2](H2O)2 7 6.5
Amphotericin B 5 2

CONCLUSION

In the present work we have been synthesized the ligand and its metal complexes by conventional and ultrasonic
methods to compare the reaction time and yield of the product. The synthesized compounds were characterized by
various analytical techniques. The synthesized β-diketone ligand binds with the metal ions in a bidentate manner
with oxygen as the donor sites. The IR spectra of ligand and complexes were made comparison and to study the
mode of coordination, magnetic study reveals the paramagnetic nature of complexes. Solution conductivity suggests
the nonelectrolyte nature of complexes. The XRD pattern indicates the crystalline nature of the complexes. From
antimicrobial study it is suggested that the synthesized ligand and its metal complexes may be good candidate for
antimicrobial studies.

Acknowledgement
The Department of Chemistry acknowledges the financial assistace by UGC-SAP-DRS scheme-1. One of the author
Narendra A. Bhise is thankful for the financial assistance from University Scholar Fellowship, Dr. Babasaheb
Ambedkar Marathwada University Aurangabad.

REFERENCES

[1]O. G. Khudina. Y. V. Burgart. N. V. Murashova. V. I. Saloutin. Russian J. Org. Chem., 2003, 39, 1421.
[2]G. Aromi, P. Gamez, and J. Reedijk, Coordination Chemistry Reviews., 2008, 252 (8-9) 964.
[3]S. T. Heller, S. R, Natarajan, Org.Lett., 2006, 8, 2675.
[4]D. Simoni, F. P. Invidiata, R. Rondanin, S. Grimaudo, G. Cannizzo, E. Barbusca, N. A. Porretto, F. D. lessandro
and M. Tolomeo, J. Med Chem., 1999, 42, 4961.
[5]H. Valizadeh, M. Amiri and E. Khalili, Molecular Diversity., 2012, 4, 1.
[6]L. Tang, S. Zhang, J. Yang, W. Gao, J. Cui and T. Zhuang, Molecules, 2004, 9, 842.
[7]R. Kumar and Y. C. Joshi, ARKIVOC., 2007, 9, 142.
[8]O. G. Kuzueva, Y. V. Burgart, V. I. Saloutin and O. N. Chupakhin, Chemistry of Heterocyclic Compounds.,
2001, 37, 1130.
[9] L. T. Chertanov, J. F. Mouscadet, J. Med. Chem., 2007, 50, 1133.
[10]C. Protogeraki, E. G. Andreadou, F. Perdih, I. Turel, A. A. Pantazaki, G. Psomas, Eur. J. Med. Chem., 2014, 86,
189.
[11]A. Vogiatzoglou, H. Refsum, C. Johnston, Neurology., 2008, 7 (11), 826.

343
Anjali S. Rajbhoj et al Der Pharma Chemica, 2016, 8 (19):338-344
_____________________________________________________________________________
[12]T. W. Failes, C. Cullinane, C.I. Diakos, N. Yamamoto, J.G. Lyons, T.W. Hambley, Chem. Eur. J., 2007, 13(10),
2974.
[13]Manuel, A. R. Silva and Luis M. Santos, J. Chem. Thermodynamics., 2005, 38, 817.
[14]Binnemans, K., Chem. Rev., 2007, 107, 2592.
[15]R. Karvembu, K. Natarajan, Polyhedron., 2002, 21, 219.
[16]Huaqiang Zeng, Jianming Xie, P. G. Schultz, Bioinorg. Med. Chem. Lett., 2006, 16, 5356.
[17]M. S. Ameerunisha Begum, SounikSaha, Akhtar Hussiain, A. R. Chakravarty, Indian J. chem., 2009, 48A, 9.
[18]N. Raman, L. Mitu, A. Sakthivel, M.S.S. Pandi, J. Iran. Chem. Soc., 2009, 6, 738.
[19]R. Uauy, M. Olivares, M. Gonzalez, Am. J. Clin. Nutr., 1998, 67, 952.
[20]Y. Saito, M. Kishimoto, Y. Yoshizawa, S. Kawaii, Anticancer Res., 2015, 35, 811.
[21]C. Marzano, M. Pellei, F. Tisato, C. Santini, Med. Chem., 2009, 9, 185.
[22]R. Loganathan, S. Ramakrishnan, E. Suresh, A. Riyasdeen, M.A. Akbarsha, M. Palaniandavar, Inorg. Chem.,
2012, 51, 5512.
[23]I. Ali, W.A. Wani, K. Saleem, M.F. Hseih, Polyhedron, 2013, 56, 134.
[24]K. Saleem, W.A. Wani, A. Haque, M.N. Lone, M.F. Hsieh, M.A. Jairajpuri, I. Ali, Future Med. Chem., 2013, 5,
135.
[25]Y.J. Zheng, X.W. Li, Y.T. Li, Z.Y. Wu, C.W. Yan, J. Coord. Chem., 2012, 65, 3530.
[26]Y. Xiao, C. Bi, Y. Fan, S. Liu, X. Zhang, D. Zhang, Y. Wang, R. Zhu, J. Coord. Chem. 2009, 62, 3029.
[27]V. Mathew, J. Keshavayya, V. P. Vaidya, M.H. M. Khan, J. Coord. Chem.,2008, 61, 2629.
[28]H. Zhang, J.S. Wu, F. Peng, Anti-Cancer Drug., 2008,19, 125.
[29]R. P. Dryden, A. Winston, J. Phys. Chem.,1958, 62, 635.
[30]Y. Akama, A. Tong, J. Microchem., 1996, 53, 34.
[31]L. J. Bellamy, L. Beecher, J. Chem. Soc., 1954, 4487.
[32]Q.H. Chu, L. X. Gao, D. M. Wang, Y. H. Qi, M. X. Ding, Chem. J. Chinese U., 2000, 21, 439.
[33]M. A. Estermann, W.I.F. David, K. Shankland, B. Mccusker, Ch. Baerlocher (Eds.), Oxford Science
Publications, New York, 2002.

344