Synthesis, characterization and antimicrobial activity of novel platinum(IV) and palladium(II) complexes with meso-1,2-diphenyl-ethylenediamine- N,N'-di-3-propanoic acid - Crystal structure of H2-1,2- dpheddp·2HCl·H2O

Article abstract of DOI:10.1016/j.molstruc.2012.07.007

In the reaction of meso-1,2-diphenyl-ethylenediamine (1,2-dphen) with neutralized 3-chlor-propanoic acid, the new linear tetradentate edda-like ligand (edda = ethylenediamine-N,N'-diacetic ion) meso-1,2-diphenyl-ethylenediamine-N, N'-di-3-propanoic acid d

Full text of DOI:10.1016/j.molstruc.2012.07.007

Journal of Molecular Structure 1029 (2012) 180–186
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, characterization and antimicrobial activity of novel platinum(IV) and
palladium(II) complexes with meso-1,2-diphenyl-ethylenediamine-N,N0-di-3-
propanoic acid – Crystal structure of H2-1,2-dpheddpꢀ2HClꢀH2O
a
a
a
b
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-
´
´
´
´
Gordana P. Radic , Verica V. Glodovic , Zoran R. Ratkovic , Sladana B. Novakovic ,
c
c
c
d
´
Santiago Garcia-Granda , Laura Roces , Laura Menéndez-Taboada , Ivana D. Radojevic ,
Olgica D. Stefanovic , Ljiljana R. Comic , Srecko R. Trifunovic
a Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovi´ca 12, 34000 Kragujevac, Serbia
d
d
a,
⇑
ˇ
´
´
´
´
b
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VINCA Institute of Nuclear Sciences, Laboratory of Theoretical Physics and Condensed Matter Physics, University of Belgrade, PO Box 522, 11001 Belgrade, Serbia
c Physical and Analytical Chemistry Department, University of Oviedo, 33006 Oviedo, Spain
d
´
Department of Biology and Ecology, Faculty of Science, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia
h i g h l i g h t s
"
"
"
"
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Ligand H2-1,2-dpheddpꢀ2HClꢀH2O, palladium(II) and platinum(IV) complexes were prepared.
Structure of ligand was confirmed by X-ray analysis.
Antimicrobial activity was tested against 25 species of microorganisms.
Complexes demonstrated more potent inhibitory effects on growth of bacteria than fungi.
In general, Pd(II) complex shows higher antimicrobial activity.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 April 2012
Received in revised form 6 July 2012
Accepted 6 July 2012
Available online 16 July 2012
In the reaction of meso-1,2-diphenyl-ethylenediamine (1,2-dphen) with neutralized 3-chlor-propanoic
acid, the new linear tetradentate edda-like ligand (edda = ethylenediamine-N,N0-diacetic ion) meso-1,
2-diphenyl-ethylenediamine-N,N0-di-3-propanoic acid dihydrochloride monohydrate (H2-1,2-dpheddpꢀ
2HClꢀH2O) was prepared. The corresponding platinum(IV) complex, s-cis-dichlorido-(meso-1,2-diphe-
nyl-ethylenediamine-N,N0-di-3-propanoate)-platinum(IV) ([PtCl2(1,2-dpheddp)]) was synthesized by
heating potassium-hexachloridoplatinate(IV) and H2-1,2-dpheddpꢀ2HClꢀH2O on steam bath for 12 h with
neutralization by means of lithium-hydroxide. The palladium(II) complex, cis-dichlorido-(meso-1,2-
diphenyl-ethylenediamine-N,N0-di-3-propanoate)-palladium(II) ([PdCl2(1,2-dpheddp)]) was obtained in
the similar way using potassium-tetrachloridopalladate(II), H2-1,2-dpheddpꢀ2HClꢀH2O and lithium-
hydroxide. The compounds were characterized by elemental analysis and infrared spectroscopy. The spec-
troscopically predicted structure of the synthesized tetradentate ligand was confirmed by X-ray analysis
of the H2-1,2-dpheddpꢀ2HClꢀH2O.
Keywords:
Meso-1,2-diphenyl-ethylenediamine-N,N0-
di-3-propanoic acid
Platinum(IV) complex
Palladium(II) complex
Infrared spectroscopy
Crystal structure
Antimicrobial activity
Antimicrobial activity of the ligand and corresponding palladium(II) and platinum(IV) complexes is
investigated against 25 species of microorganisms. Testing is preformed by microdilution method and
minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) have been
determined. The difference between antimicrobial activity of the ligand and corresponding platinum(IV)
and palladium(II) complex is noticed and, in general, palladium(II) complex was the most active.
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
edda (edda = ethylenediamine-N,N0-diacetato ion) or eddp (eddp =
ethylenediamine-N,N0-di-3-propanoato ion) has been an interest-
A geometrical isomerism in metal complexes of linear flexible
tetradentate ligands having the donor atom array ONNO such as
ing field studied by numerous authors [1–14]. Such ligands occupy
four octahedral sites around the central ion and the other two sites
may be occupied by other ligands. In that case three geometrical
isomers are possible, as shown in Fig. 1.
⇑
Corresponding author. Tel.: +381 34300263; fax: +381 34335040.
E-mail address: srecko@kg.ac.rs (S.R. Trifunovic´).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.07.007

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G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
(30.00 g) was refluxed with ammonium-acetate (60.00 g) for 3 h.
The reaction mixture was cooled and the product was filtered
and washed with ethanol. Recrystallization from 1-butanol gave
N-benzoyl-N0-benzylidene-meso-1,2-diphenyl-ethylendiamine.
Hydrolysis of that compound with 70% sulfuric acid under reflux
for 1 h gave meso-1,2-diphenyl-ethylenediamine as the basic prod-
uct of hydrolysis.
X
O
O
O
X
N
X
O
N
X
N
N
O
N
X
N
O
X
2.2.2. Preparation of meso-1,2-diphenyl-ethylenediamine-N,N0-di-3-
propanoic acid dihydrohloride-hydrate, H2 -1,2-dpheddpꢀ2HClꢀH2O
3-Chloro-propanoic acid (4.34 g, 0.04 mol) was dissolved in
5.0 mL of water on ice bath and carefully neutralized with cold
water solution of 5.0 mL NaOH (1.60 g, 0.04 mol). Meso-1,2-diphe-
nyl-ethylenediamine (4.24 g, 0.02 mol) was added to this solution.
The mixture was being stirred for 4 h at 90 °C, and during this per-
iod 5.0 mL NaOH water soltion (1.60 g, 0.04 mol) was introduced.
After that, 5.6 mL 6 mol/L HCl was added and resulting solution
was evaporated to the volume of 7.0 mL; 6.0 mL conc. HCl, 6.0 mL
of ethanol and 6.0 mL of ether were added to the mixture. The
white precipitate of meso-1,2-diphenyl-ethylenediamine-N,N0-
di-3-propanoic acid dihydrochloride monohydrate, H2-1,2-
dpheddpꢀ2HClꢀH2O was separated by filtration and refined with
solution water: ethanol = 1: 2. Yield: 4.00 g (44.69%). Anal. Calcd.
for H2-1,2-dpheddpꢀ2HClꢀH2O = C20H28Cl2N2O5 (Mr = 447.344): C,
53.69; H, 6.31; N, 6.26. Found: C, 53.88; H, 6.70; N, 6.08.
s-cis
uns-cis
trans
(I)
(II)
(III)
Fig. 1. Possible geometrical isomers of [PtX2(eddp)] complex (X = monodentate
ligand): s-cis (I), uns-cis (II) and trans (III).
In most synthetic routes [1–14] edda takes a symmetric coordi-
nation position (s-cis) rather than unsymmetric one (uns-cis) [3]. It
has been suggested that the observed chelate strain of chelate rings
in uns-cis-edda complexes may be a contributing factor in deter-
mining the configuration of the edda ligand [6]. 1,3-pdda ligand
(1,3-pdda = 1,3-propylenediamine-N,N0-diacetate ion) and eddp
(eddp = ethylenediemine-N,N0-di-3-propanoate ion), with a longer
diamine and carboxylate chelate rings than edda, prefer unsymmet-
ric coordination [1,15,16], suggesting that the size of the chelate
rings in linear tetradentate edda and similar ligands have a pro-
found effect on the distribution of the geometrical isomers of the
complexes.
The synthesis and evaluation of the biological activity of the
new metal-based compounds is the field of growing interest.
Numerous complexes based on palladium(II) and platinum(IV)-
ion have been synthesized and their different biological activities
have been documented [17–19]. The impact of different palladium
and platinum complexes on the growth and metabolism of various
groups of microorganisms has been studied. Garoufis et al. [20] re-
viewed numerous scientific papers on anti-viral, antibacterial and
antifungal activity of palladium(II) complexes with different types
of ligands (sulfur and nitrogen donor ligands, Schiff base ligands
and drugs as ligands). There are other papers in the literature
showing different intensity of palladium(II) and platinum(IV) com-
plexes activity on various species of bacteria and fungi [21–34].
The aim of this paper is to synthesize new palladium(II) and
platinum(IV) complexes and in vitro research their antibacterial
and antifungal activities.
2.2.3. Preparation of s-cis-dichlorido-(meso-1,2-diphenyl-
ethylenediamine-N,N0-di-3-propanoate) -platinum(IV), s-cis-[Pt(1,2-
dpheddp)Cl2]
Potassium-hexachloridoplatinate(IV) (0.2000 g, 0.411 mmol)
was dissolved in 10.0 mL water on a steam bath and meso-1,2-di-
phenyl-ethylenediamine-N,N0-di-3-propanoic acid dihydrohloride
monohydrate (0.1839 g, 0.411 mmol) was added. The reaction
mixture was heated for 12 h and during this period 10.0 mL of
LiOH water solution (0.0394 g,1.65 mmol) was added in small por-
tions and the solution was filtered and evaporated to small volume.
The orange precipitate of s-cis-[PtCl2(1,2-dpheddp)] was separated
by filtration, washed with cold water and air-dried. Yield: 0.095 g.
(37.25%). Anal. Calc. for s-cis-[PtCl2(1,2-dpheddp)] = C20H26Cl2-
N2O4Pt (Mr = 620.396): C, 38.72; H, 3.57; N, 4.52. Found: C,
38.38; H, 3.81; N, 4.60.
We wanted to extend the investigation of platinum complexes
with derivatives ethylenediamine-N,N0-di-3-propanoate. The ini-
tial idea of this work was to prepare a new linear edda-like ligand,
meso-1,2-diphenyl-ethylenediamine-N,N0-di-3-propanoic acid (H2-
1,2-dpheddp) and corresponding platinum(IV) and palladium(II)
complexes. In all our attempts we prepared only s-cis geometrical
isomer of platinum(IV) with low solubility in water and common
organic solvents.
2.2.4. Preparation of dichlorido-(meso-1,2-diphenyl-ethylenediamine-
N,N0-di-3-propanoate)palladium(II), [Pd(1,2-dpheddp)Cl2]
K2[PdCl4] (0.200 g, 0.613 mmol) was dissolved in 10.0 mL of
water on a steam bath and meso-1,2-diphenyl-ethylenediamine-
N,N0-di-3-propanoic acid dihydrohloride monohydrate, H2-1,2-
dpheddpꢀ2HClꢀH2O, (0.2742 g, 0.613 mmol) was added. The
mixture was stirred for 2 h and during this period water solution
of LiOH (0.059 g, 2.452 mmol in 10.0 mL of water) was introduced.
The complex cis-[PdCl2(1,2-dpheddp)], as yellow precipitate, was
filtered, washed with cold water and air-dried. Yield: 0.25 g
(76.43%). Anal. Calc. for cis-[PdCl2(1,2-dpheddp)] = C20H24Cl2-
N2O4Pd (Mr = 533.732) (%): C, 45.00; H, 4.53; N, 5.25. Found: C,
45.64; H, 4.87; N, 5.31.
2. Experimental
2.1. Materials and measurements
The reagents were obtained commercially and used without
further purification. Infrared spectra were recorded on Perkin-El-
mer FT-IR spectrophotometer, Spectrum One, using the KBr pellet
technique. Elemental analyses were done on a Vario III CHNOS Ele-
mental Analyzer, Elemental Analysensysteme GmbH.
2.3. Crystal structure determination
The single-crystals of H2-1,2-dpheddpꢀ2HClꢀH2O suitable for X-
ray structure analysis were obtained by recrystallization of pow-
dered substance from a small amount of water–ethanol mixture
(1:2). The diffraction data were collected at room temperature on
Oxford Diffraction Xcalibur Gemini S diffractometer equipped with
2.2. Syntheses
2.2.1. Preparation of meso-1,2-diphenyl-ethylenediamine, 1,2-dphen
The meso-1,2-diphenyl-ethylenediamine was prepared accord-
ing to the procedure described earlier [35]. Benzaldehyde
CuKa radiation (k = 1.54184 Å) (Table 1). The data were processed
with CrysAlis software [36] and corrected for absorption by analyt-
ical numeric method [37]. Crystal structure was solved by direct

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G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
Table 1
Table 2
Crystal data, data collection and structure refinement details for H2-1,2-
Geometrical parameters (Å, °) of selected hydrogen bonds.
dpheddpꢀ2HClꢀH2O.
DAHꢀ ꢀ ꢀA (Å)
DAH
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
DAHꢀ ꢀ ꢀA
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
C20H28Cl2N2O5
445.33
293(2)
1.54184
Triclinic
P1ꢂ
N2AH2bꢀ ꢀ ꢀO3i
N1AH1aꢀ ꢀ ꢀO3i
C2AH22aꢀ ꢀ ꢀO3i
N1AH1aꢀ ꢀ ꢀO4ii
C13AH13bꢀ ꢀ ꢀO1iii
C13AH13aꢀ ꢀ ꢀO5i
O2aAH2cꢀ ꢀ ꢀO5iv
O2bAH2dꢀ ꢀ ꢀCl2i
N1AH1bꢀ ꢀ ꢀCl2i
N2AH2aꢀ ꢀ ꢀCl2i
C20AH20ꢀ ꢀ ꢀCl1i
C2AH22aꢀ ꢀ ꢀCl2i
0.90
0.90
0.97
0.90
0.97
0.97
0.82
0.82
0.90
0.90
0.93
0.97
2.16
2.00
2.52
2.56
2.46
2.45
2.06
2.24
2.20
2.33
2.73
2.75
2.750(8)
2.786(8)
3.176(10)
3.111(9)
3.076(11)
3.415(16)
2.72(3)
122
145
125
120
121
174
137
168
169
148
169
118
8.6989(18)
10.086(2)
13.461(3)
104.143(17)
105.795(17)
100.754(18)
1060.7(4)
2
b (Å)
c (Å)
3.05(5)
3.089(7)
3.137(8)
3.651(10)
3.324(9)
a
(°)
b (°)
c
(°)
V (Å3)
a Symmetry codes: (i) x, y, z; (ii) ꢂx + 1, ꢂy + 2, ꢂz + 2; (iii) x, +y + 1, +z; (iv) x, +y ꢂ 1,
Z
l
(mmꢂ1
)
3.047
476
+z.
F(000)
Crystal size
0.12 ꢁ 0.07 ꢁ 0.04
Reflections collected
Unique reflections
Rint
16321
Kragujevac. The other microorganisms were provided from a col-
lection held by the Microbiology Laboratory Faculty of Science,
University of Kragujevac.
4006
0.1762
R1, wR2 [I > 2
r
(I)]
0.1071, 0.2637
2.4.3. Suspension preparation
Bacterial suspensions and yeast suspension were prepared by
the direct colony method. The colonies were taken directly from
the plate and were suspended in 5 mL of sterile 0.85% saline. The
turbidity of initial suspension was adjusted by comparing with
0.5 McFarland0s standard (0.5 mL 1.17% w/v BaCl2 ꢁ 2H2O + 99.5
mL 1% w/v H2SO4) [42]. When adjusted to the turbidity of the 0.5
McFarland0s standard, bacteria suspension contains about 108 col-
ony forming unites (CFU)/mL and suspension of yeast contains
106 CFU/mL. Tenfold dilutions of initial suspension were addition-
ally prepared into sterile 0.85% saline. The suspensions of fungal
spores were prepared by gentle stripping of spore from slopes with
growing aspergilli. The resulting suspensions were 1:1000 diluted
in sterile 0.85% saline.
methods, using Sir2002 [38] and refined using SHELXL [39]. The
carboxyl O2AH group was found to be disordered over two sites
whose occupancies were held at 50% during refinement. H atoms
were placed at geometrically calculated positions with the DAH
distances fixed to 0.93, 0.97, 0.90 and 0.82 Å from C(sp2), C(sp3),
N and O atoms respectively. The corresponding isotropic displace-
ment parameters of the hydrogen atoms were equal to 1.2 Ueq of
the parent C and N and 1.5 Ueq of the parent O atoms. The details
of the X-ray structural analysis are given in Table 1. Hydrogen
bonds are listed in Table 2. The complete list of bond lengths and
angles between non-hydrogen atoms as well as additional figures
can be found in the Supplementary material, Table S1. Geometrical
calculations were made with PARST97 [40] and molecular graphics
with ORTEP-3 [41].
2.4.4. Microdilution method
2.4. In vitro antimicrobial assay
Antimicrobial activity was tested by determining the minimum
inhibitory concentrations (MIC) and minimum microbicidal con-
centration (MMC) by using microdilution plate method with resa-
2.4.1. Test substances
The tested compounds were dissolved in DMSO and then di-
luted into nutrient liquid medium to achieve a concentration of
10%. An antibiotic, doxycycline (Galenika A.D., Belgrade), was dis-
solved in nutrient liquid medium, a Mueller-Hinton broth (Torlak,
Beograd), while an antimycotic, fluconazole (Pfizer Inc., USA) was
dissolved in Sabouraud dextrose broth (Torlak, Belgrade).
zurin [43]. The 96-well plates were prepared by dispensing 100
of nutrient broth, Mueller-Hinton broth for bacteria and Sabouraud
dextrose broth for fungi and yeasts, into each well. A 100 L from
the stock solution of tested compound (concentration of 2000 g/
mL) was added into the first row of the plate. Then, twofold, serial
dilutions were performed by using a multichannel pipette. The ob-
lL
l
l
tained concentration range was from 1000 to 7.81 lg/mL. A 10 lL
2.4.2. Test microorganisms
of diluted bacterial, yeast suspension and suspension of spores was
Antimicrobial activity of the ligand and corresponding palla-
dium(II) and platinum(IV) complexes was tested against 25 micro-
organisms. The experiment involved 15 strains of pathogenic
added to each well to give a final concentration of 5 ꢁ 105 CFU/mL
for bacteria and 5 x 103 CFU/mL for fungi and yeast. Finally, 10
lL
resazurin solution was added to each well inoculated with bacteria
and yeast. Resazurin is an oxidation–reduction indicator used for
the evaluation of microbial growth. It is a blue non-fluorescent
dye that becomes pink and fluorescent when reduced to resorufin
by oxidoreductases within viable cells. The inoculated plates were
incubated at 37 °C for 24 h for bacteria, 28 °C for 48 h for the yeast
and 28 °C for 72 h for fungi. MIC was defined as the lowest concen-
tration of tested substance that prevented resazurin color change
from blue to pink. For fungi, MIC values of the tested substance
were determined as the lowest concentration that visibly inhibited
mycelia growth.
bacteria, including
7 standard strains (Escherichia coli ATCC
25922, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa
ATCC 27853, Staphylococcus aureus ATCC 25923; Sarcina lutea ATCC
9341; Bacillus subtilis ATCC 6633; Bacillus pumilus NCTC 8241) and
8 clinical isolates (E. coli; E. faecalis; P. aeruginosa; S. aureus;S. lutea;
B. subtilis; Proteus mirabilis; Salmonella enterica). Also, four species
of pathogenic fungi (Aspergillus fumigatus PMFKG-F23; Aspergillus
flavus PMFKG-F24; Aspergillus restrictus PMFKG-F25; Aspergillus ni-
ger PMFKG-F26); two yeast species (Candida albicans (clinical iso-
late) and Rhodotorula sp. PMFKG-F27) and four species of
probiotics (Lactobacillus plantarium PMFKG-P31, Bacillus subtilis IP
5832 PMFKG-P32, Bifidobacterium animalis subsp. lactis PMFKG-
P33; Saccharomyces boulardii PMFKG-P34) were tested. All clinical
isolates were a generous gift from the Institute of Public Health,
Doxycycline and fluconazole were used as a positive control.
Solvent control test was performed to study an effect of 10% DMSO
on the growth of microorganism. It was observed that 10% DMSO
did not inhibit the growth of microorganism. Also, in the

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G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
experiment, the concentration of DMSO was additionally de-
3.1. Infrared spectra
creased because of the twofold serial dilution assay (the working
concentration was 5% and lower). Each test included growth con-
trol and sterility control. All tests were performed in duplicate
and MICs were constant. Minimum bactericidal and fungicidal con-
As it was demonstrated for metal aminocarboxylic acid com-
plexes [44,45], the asymmetric stretching frequency of the carbox-
ylate groups of the five-membered [44] rings lies at higher energy
than the corresponding frequency of the six-membered chelate
rings [45]. Later, this was supported by Neal and Rose [46] and
Douglas et al [47,48] who found that edta-type hexadentate com-
plexes with mixed and equivalent (two five- and six-membered)
carboxylate arms, such as trans(O5)-[M(S,S-edds)]ꢂ (M = Co(III) or
Cr(III); S,S-edds = S,S-ethylenediemine-N,N0-disuccinic ion) [46–
48] and trans(O5)-[M(eddadp)]ꢂ (eddadp = ethylenediamine-N,N0-
diacetato-N,N0-di-3-propionato ion) [47,48] exhibited two very
strong and well-separated bands in the asymmetric stretching car-
boxylate frequency region. The bands were assigned to the car-
bonyl stretching vibrations of the five-membered rings at higher
energy and six-membered rings at lower energy.
The isolated platinum(IV) and palladium(II) complexes do not
show any well resolved doublets in the asymmetric C@O stretching
region (at 1618 cmꢂ1 and 1610 cmꢂ1 for platinum(IV) and at
1643 cmꢂ1 and 1580 cmꢂ1 for palladium(II) complex; Table 3),
and mentioned doublets lie at lower energy than the correspond-
ing bands of five-membered chelate rings [47,49]. The lack of
absorption between 1700 and 1750 cmꢂ1 indicates that the both
carboxyl groups of the H2-1,2-dpheddp ligand are coordinated to
the central platinum(IV) ion. The prepared ligand, meso-1,2-diphe-
nyl-ethylenediamine-N,N0-di-3-propanoic acid, has absorption
bands in the same asymmetric C@O stretching region between
1700 and 1750 cmꢂ1 (1754 cmꢂ1 and 1732 cmꢂ1, Table 3) suggest-
ing some small differences in energies of COOꢂ groups.
centration was determined by plating 10 lL of samples from wells,
where no indicator color change was recorded, on nutrient agar
medium. At the end of the incubation period the lowest concentra-
tion with no growth (no colony) was defined as minimum microbi-
cidal concentration.
3. Results and discussion
The meso-1,2-diphenyl-ethylenediamin-N,N0-di-3-propanoate
ligand was obtained in reaction between meso-1,2-diphenyl-ethy-
lenediamine and 3-chloro-propanoic acid (Fig. 2). Three geometri-
cal isomers of 1,2-dpheddp-Pt(IV) complex with two identical
monodentate ligands are theoretically possible, s-cis, uns-cis and
trans (Fig. 1). In reaction between K2[PtCl6] with H2-1,2-dpheddp
ligand only one isomer of neutral octahedral 1,2-dpheddp-Pt(IV)
complex, s-cis-dichlorido-(meso-1,2-diphenyl-ethylenediamine-N,
N0-di-3-propanoate)-platinum(IV), s-cis-[PtCl2(1,2-dpheddp)], with
tetradentate coordination of the H2-1,2-dpheddp ligand was ob-
tained (Fig. 3). The complex is slightly soluble in water and, unfor-
tunately, almost insoluble in organic solvents. In reaction between
K2[PdCl4] with H2-1,2-dpheddp ligand only one isomer of neutral
square-planar 1,2-dpheddp-Pd(II) complex, cis-dichlorido-(meso-
1,2-diphenyl-ethylenediamine-N,N0-di-3-propanoate)-palladium(II),
cis-[PdCl2(1,2-dpheddp)], with bidentate coordination of the H2-1,
2-dpheddp ligand was obtained (Fig. 4).
Fig. 2. Reaction pathways in synthesis of meso-1,2-diphenyl-ethylenediamine-N,N0-di-3-propanoic acid.

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G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
O
O
O
Cl
Cl
NH
NH
K2PtCl6
HN
Pt
O
O
LiOH
OH
N
H
HO
O
Fig. 3. Reaction pathway in synthesis of new platinum(IV) complex.
OH
O
O
OH
Cl
Cl
NH
NH
K2PdCl4
LiOH
HN
Pd
O
N
H
HO
O
OH
Fig. 4. Reaction pathway in synthesis of new palladium(II) complex.
It was not possible to assume the geometry of the complex
The difference between the molecules becomes more significant
if we compare the orientation of their carboxyl groups. In molecule
A the carboxyl group is approximately coplanar to the rest of the
aliphatic chain with the C1AC2AC3AN1 torsion angle of
175.3(7)°. In molecule B the directionality of this group is signifi-
cantly changed and the corresponding C11AC12AC13AN2 torsion
angle is equal to 55.3(10)° (Fig. S1). Such a conformation of mole-
cule B allows the formation of intramolecular NAHꢀ ꢀ ꢀO hydrogen
bond, which lacks in molecule A (Fig. S2).
based on analysis of its infrared spectrum. s-cis geometry of plati-
num(IV) complex was proposed based on its model analysis (Figs. 1
and 3).
3.2. Description of the structure
X-ray diffraction analysis of 1,2-diphenyl-ethylenediamine-
N,N0-di-3-propanoic acid confirmed expected meso orientation of
the phenyl residues and dihydrochloride form of the molecule.
The crystal structure of this compound is composed of two inde-
pendent molecules with partly different conformations and mole-
cules of crystal water, Fig. 5. Since the both acid molecules are
centrosymmetrical, the asymmetric unit contains two halves, one
from each of the independent molecules labeled as A and B. In mol-
ecule A the carboxyl O2AH group was found to be equally disor-
dered over two sites. The two molecules have relatively similar
bond distances and angles, however, having in mind a weak quality
of X-ray diffraction data caused by small size of single-crystals, the
presence of the solvent water molecule as well as the mentioned
disorder in A, the direct comparison should be taken with care.
The values of C2AC3AN1AC4 torsion angle in A and the equiv-
alent C12AC13AN2AC14 torsion angle in B are equal to 180.0(6)
and 172.3(6)° respectively, indicating somewhat different, but
essentially planar forms of these parts of the aliphatic chains.
The difference in conformation of two molecules could be ex-
plained by the fact that their carboxyl groups form quite diverse
hydrogen bonding. While the acceptor O1 from the molecule A en-
gages only in one interaction (C13ꢂH13bꢀꢀꢀO1), the corresponding
O3 acceptor in molecule B, forms three interactions, where two
represent the strongest hydrogen bonds of the crystal structure,
N2AH2bꢀꢀꢀO3 and N1AH1aꢀꢀꢀO3 (Table 2). Furthermore, the
O2AH group in molecule A is disordered over two positions as
the crystal packing allows its simultaneous interaction with two
different H acceptors (O5 and Cl2) and formation of two relatively
strong hydrogen bonds (Table 2). In contrast to this, the equivalent
O4AH group in molecule B does not form any significant interac-
tion except the relatively weak N1AHꢀ ꢀ ꢀO4 hydrogen bond.
Apart from the carboxyl groups, the crystal structure contains
additional hydrogen bonding sites such as Cl anions, molecule of
crystal water and NAH groups which together build a rather com-
plex 3D hydrogen bonding network. However as a dominant struc-
tural motif in this crystal packing one can identify the chain
formed by direct interaction of molecules A and B via the strongest
hydrogen bond, N1ꢂH1aꢀꢀꢀO3. The neighboring molecules A and B
within this chain are additionally interconnected by several
OAHꢀ ꢀ ꢀCl and NAHꢀ ꢀ ꢀCl hydrogen bonds, with a short H. . .Cl dis-
tances ranging from 2.20 to 2.33 Å (Fig. S3).
Table 3
The most important IR bands (cmꢂ1) of some compounds with linear OANANAO
ligands.
Compound
tas (COOH)
tas (COOꢂ)
Ref.
trans-[Pt(H2edta)Cl2]
uns-cis-[Pt(H2edta)Cl2]
s-cis-[Pt(H2edta)Cl2]
trans-[Pt(eddp)Cl2]ꢀH2O
trans-[Pt(1,3-pdda)Cl2]ꢀH2O
trans-[Pt(pdda)Br2]ꢀH2O
s-cis-[Pt(1,2-dpheddp)Cl2]
H2-1,2-dpheddp
1775; 1764
1758; 1742
1753; 1741
–
–
–
–
1691; 1678
1692; 1685
1725; 1716
1637; 1630
1696; 1660
1684; 1648
1618; 1610
–
[50]
[50]
[50]
[13]
[51]
[52]
This work
This work
This work
3.3. Microbiology
The results of in vitro testing of antibacterial and antifungal
activities of the ligand and corresponding palladium(II) and plati-
num(IV) complex are shown in Table 4. For comparison, MIC and
1754; 1732
cis-[Pd(1,2-dpheddp)Cl2]
1643; 1580

´
185
G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
Fig. 5. Crystal structure of meso-1,2-diphenyl-ethylenediamine-N,N0-di-3-propanoic acid with atom numbering scheme. As molecules are centrosymmetric, only atoms
belonging to asymmetric unit are labeled. Selected bond lengths (Å), Molecule A (left): O1AC1 1.207(12); C1AC2 1.482(12); C2AC3 1.506(11); N1AC3 1.472(9); N1AC4
1.498(8); C4AC5 1.499(10); C5AC6 1.368(10). Molecule B (right): O3AC11 1.234(8); O4AC11 1.270(8); C11AC12 1.498(10); C12AC13 1.510(10); N2AC13 1.494(11);
N2AC14 1.507(9); C15AC16 1.380(11).
Table 4
Antibacterial and antifungal activity of the tested ligand and corresponding palladium(II) and platinum(IV) complexes.
Species
L1
Palladium(II) complex
Platinum(IV) complex
Doxycycline
MIC/MMC
Fluconazol
MIC/MMC
MIC
MMC
MIC
MMC
MIC
MMC
Escherichia coli ATCC 25922
Pseud. aeruginosa ATCC 27853
Staphylococcus aureus ATCC 25923
Sarcina lutea ATCC 9341
Bacillus subtilis ATCC 6633
Enter. faecalis ATCC 29212
Bacillus pumilus NCTC 8241
Escherichia coli
Pseud. aeruginosa
Staphylococcus aureus
Sarcina lutea
Bacillus subtilis
Enter. faecalis
>1000
250
500
500
500
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
1000
500
1000
500
500
500
500
500
500
500
1000
500
500
500
500
500
500
125
500
500
500
125
250
125
250
250
250
>1000
500
>1000
250
250
>1000
>1000
>1000
250
1000
500
500
500
500
7.81/15.625
62.5/125
0.224/3.75
<0.448/7.81
1.953/31.25
7.81/62.5
0.112/7.81
7.81/15.625
250/>250
0.448/7.81
<0.448/3.75
0.112/1.953
7.81/62.5
250/>250
15.625/31.25
31.25/62.5
0.448/7.81
1.953/15.625
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
15.63
31.25
62.5
62.5
31.25
62.5
250
500
250
62.5
31.25
250
500
250
31.25
125
250
>1000
>1000
500
31.25
500
500
500
500
>1000
>1000
500
>1000
500
>1000
1000
>1000
500
>1000
>1000
>1000
>1000
500
500
>1000
>1000
>1000
>1000
500
Proteus mirabilis
Salmonella enterica
Bifidobacterium animalis subsp. lactis
Lactobacillus plantarum
Bacillus subtilis IP 5832
Saccharomyces boulardii
Candida albicans
Rhodotorula sp.
Aspergillus niger
Aspergillus restrictus
Aspergillus fumigatus
Aspergillus flavus
250
250
500
500
/
/
500
>1000
>1000
1000
125
250
1000
>1000
>1000
>1000
1000
1000
500
1000
>1000
1000
125
1000
500
1000
>1000
1000
>1000
1000
1000
>1000
31.25/1000
62.5/1000
62.5/1000
500/1000
500/2000
500/1000
1000/1000
/
/
/
/
/
/
>1000
250
1000
1000
>1000
1000
>1000
>1000
>1000
MIC, minimum inhibitory concentration (
lg/mL).
MMC, minimum microbiocidal concentration (
l
g/mL).
/, not tested.

´
G.P. Radic et al. / Journal of Molecular Structure 1029 (2012) 180–186
186
MMC values of doxycycline and fluconazole are also listed in Table
4. The tested ligand, palladium(II) and platinum(IV) complex
showed different degrees of antimicrobial activity in relation to
the tested species. The intensity of antimicrobial action varied
depending on the species of microorganism and on the type of
tested compounds. In general, the activity of complexes, especially
of palladium(II) complex, was higher than the ligand. Also, plati-
num(IV) and palladium(II) complexes demonstrated more potent
inhibitory effects on the growth of bacteria than fungi.
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´
Appendix A. Supplementary material
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CCDC 852978 contains the supplementary crystallographic data
for crystal structure H2-1,2-dpheddpꢀ2HClꢀH2O These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html, or from the Cambridge Crystallographic Data Cen-
tre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-
033; or e-mail: deposit@ccdc.cam.ac.uk. Supplementary data asso-
ciated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.molstruc.2012.07.007.
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ˇ ´
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´
´
´
Miloševic, J. Mater. Res. 20 (2005) 102.