Preparation and characterization of palladium(II) complexes with N-arylalkyliminodiacetic acids. Catalytic activity of complexes in methoxycarbonylation of iodobenzene Dedicated to Prof. Maria José Calhorda on the occasion of her 65th birthday.

Article abstract of DOI:10.1016/j.jorganchem.2013.10.010

The reactions of N-arylalkyl derivatives of iminodiacetic acid (H ₂Bnida, H₂Peida, H₂Ppida, o-H₂Cbida; Bn = benzyl, Pe = 2-phenylethyl; Pp = 3-phenylprop-1-yl; o-Cb = o-chlorobenzyl) with sodium tetrachloropalladate(II) in aqueous solutions were investigated. Five new palladium(II) complexes [Pd(HBnida)₂]·2H₂O (1a), [Pd(HBnida)₂] (1b), [Pd(HPeida)₂] (2), [Pd(HPpida)₂] (3) and [Pd(o-HCbida)₂] (4) were prepared and characterized by infrared spectroscopy, ¹H, ¹³C and ¹⁵N NMR spectroscopy and thermal analysis (TGA/DTA). The crystal structure of 1a was determined by single-crystal X-ray structural analysis. The palladium(II) ion in the molecule of 1a adopts a square planar coordination with two N,O-bidentate N-benzyl-hydrogeniminodiacetate ions. Complex 1a is a trans-isomer. Antitumor properties of the complexes were tested on three human cell lines. The compounds did not significantly inhibit the growth of colon (HCT 116), breast (MCF-7) and lung (H 460) tumor cell lines. All prepared palladium(II) complexes exhibit the acceptable activities towards the methoxycarbonylation of iodobenzene.

Full text of DOI:10.1016/j.jorganchem.2013.10.010

Journal of Organometallic Chemistry 760 (2014) 224e230
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Preparation and characterization of palladium(II) complexes with N-
arylalkyliminodiacetic acids. Catalytic activity of complexes in
methoxycarbonylation of iodobenzene
a
a
b
,
c
,
c
**
***
ꢀ
ꢁ
ꢁ
Neven Smrecki , Boris-Marko Kukovec , Jaros1aw Jazwinski
, Ye Liu
, Jing Zhang ,
d
,
ꢁ a
*
Ana-Matea Mikecin , Zora Popovic
a Laboratory of General and Inorganic Chemistry, Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia
b Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, Warsaw 01-224, Poland
c Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Chemistry Department, East China Normal University, 3663 North Zhongshan Road,
Shanghai 200062, PR China
d
ꢀ
ꢁ
ꢀ
Laboratory of Experimental Therapy, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactions of N-arylalkyl derivatives of iminodiacetic acid (H2Bnida, H2Peida, H2Ppida, o-H2Cbida;
Bn ¼ benzyl, Pe ¼ 2-phenylethyl; Pp ¼ 3-phenylprop-1-yl; o-Cb ¼ o-chlorobenzyl) with sodium tetra-
chloropalladate(II) in aqueous solutions were investigated. Five new palladium(II) complexes
[Pd(HBnida)2]$2H2O (1a), [Pd(HBnida)2] (1b), [Pd(HPeida)2] (2), [Pd(HPpida)2] (3) and [Pd(o-HCbida)2]
(4) were prepared and characterized by infrared spectroscopy, 1H, 13C and 15N NMR spectroscopy and
thermal analysis (TGA/DTA). The crystal structure of 1a was determined by single-crystal X-ray structural
analysis. The palladium(II) ion in the molecule of 1a adopts a square planar coordination with two N,O-
bidentate N-benzyl-hydrogeniminodiacetate ions. Complex 1a is a trans-isomer. Antitumor properties of
the complexes were tested on three human cell lines. The compounds did not significantly inhibit the
growth of colon (HCT 116), breast (MCF-7) and lung (H 460) tumor cell lines. All prepared palladium(II)
complexes exhibit the acceptable activities towards the methoxycarbonylation of iodobenzene.
Ó 2013 Elsevier B.V. All rights reserved.
Received 11 July 2013
Received in revised form
2 October 2013
Accepted 3 October 2013
Dedicated to Prof. Maria José Calhorda on
the occasion of her 65th birthday.
Keywords:
Palladium(II)
Iminodiacetate
Antitumor properties
Catalytic activity
NMR spectroscopy
X-ray structure determination
1. Introduction
in which CO acts as a most useful C1 building block to introduce
carbonyl group into the parent molecules. In the last decades,
The design of multidentate ligands which have the potential to
bind metals in a variety of modes is of great interest to us as we
attempt to gain a clear understanding of how the nature of the
metal, solvent and also the pH of the reaction mixture combine to
give a variety of structures. Using experimental methods for the
preparation of various N-arylalkyliminodiacetate ligands reported
previously [1], we have prepared five palladium(II) complexes due
to their possible catalytic and pharmacological properties.
Carbonylation represents an important method for transforming
bulk and fine chemicals into a diverse set of useful products [2e5],
palladium-catalyzed carbonylation of aryl halides in the presence
of nucleophiles has attracted much attention and become a
promising tool for the synthesis of aromatic carbonyl compounds
such as esters, acids, amides, ketones, alkynones, due to the
increasing consciousness of the environmentally benign and effi-
cient methodology in organic synthesis [6e13]. Among the aro-
matic carbonyl compounds, aromatic esters are conventionally
synthesized with the involvement of carboxylic acid precursors.
Alternatively, aryl carboxylic acid derivatives can be prepared
through palladium-catalyzed carbonylation of the corresponding
aryl halides with alcohols, which is defined as alkoxycarbonylation
of aryl halides [3,14e17]. The advantages of this method include the
broad availability of substrates and the high tolerance of palladium
catalysts against a variety of functional groups. Therefore, this route
has become a useful tool for the preparation of substituted aromatic
esters.
* Corresponding author. Tel.: þ385 1 4606354; fax: þ385 1 4606341.
** Corresponding author. Tel.: þ48 22 3432013; fax: þ48 22 6326681.
*** Corresponding author. Tel.: þ86 21 62232078; fax: þ86 21 62233424.
ꢁ
ꢁ
E-mail addresses: jaroslaw.jazwinski@icho.edu.pl (J. Jazwinski), yliu@chem.
ꢁ
ecnu.edu.cn (Y. Liu), zpopovic@chem.pmf.hr (Z. Popovic).
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.10.010

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
225
Besides their catalytic aspects, palladium(II) compounds exhibit
inherent cytotoxic behavior. On the basis of the structural analogy
(d8 ions in a square-planar geometry) and the thermodynamic
difference with platinum(II) complexes, there is much interest in
the study of palladium(II) complexes as potential anticancer drugs,
especially those bearing the chelating ligands [18e22].
Here we report the preparation, spectroscopic (IR and NMR) and
thermal characterization of five new palladium(II) complexes with
N-arylalkyliminodiacetate ligands as well as their antitumor
properties and catalytic activity (Scheme 1). The crystal structure of
the complex 1a is also reported.
1.68(29.2) NCH2CH2CH2Ar; 2.57(32.6) NCH2CH2CH2Ar; (142.0) Ci,
7.19(128.2) ortho, 7.26(128.2) meta, 7.16(125.6) para, Ar;
15N: ꢀ353.1 ppm; o-H2Cbida: 1H(13C) [ppm]: 3.46(53.9) CH2CO2H;
(172.3) CO2H; 3.96(54.2) CH2Ar; (132.9) Ci, 7.63(130.5), (136.4) ortho,
7.28(127.1), 7.41(129.1) meta, 7.23(128.6) para Ar; 15N: ꢀ353.1 ppm.
The samples have been measured about one hour after dissolution. In
a few days, the samples slowly decomposed in DMSO solutions.
2.2. Synthesis of the complexes
An aqueous solution of Na2PdCl4$xH2O (x z 3), (0.18 g; 0.5 mmol
in 20 mL) was added to a hot solution containing 1 mmol of the
appropriate ligands H2Bnida, H2Peida, H2Ppida and o-H2Cbida
(Bn ¼ benzyl, Pe ¼ 2-phenylethyl; Pp ¼ 3-phenylprop-1-yl; o-
Cb ¼ o-chlorobenzyl) and 0.04 g (1 mmol) NaOH in 25 mL of water.
The resulting yellow solution was left to stand at room temperature
for 48 h in case of complex 1a (the crystallization starts few hours
after mixing of the reactants) or overnight in case of the complexes
2e4 (2 crystallizes after few minutes, while 3 and 4 precipitate
immediately). The complexes were filtered off by suction, washed
with water (5 mL for 1a, 15 mL for 2e4) and dried. Complex 1a was
dried by standing in air for a few hours, while 2e4 were dried first
by standing in air for a few days and then in a desiccator over
anhydrous CaCl2. Drying the sample of 1a in a desiccator over solid
KOH at room temperature for one week gave [Pd(HBnida)2] (1b). The
complexes are soluble in dimethyl sulfoxide and N,N-dime-
thylformamide but almost insoluble in water and pyridine.
2. Experimental
2.1. Materials and physical measurements
Sodium hydroxide and Na2PdCl4$xH2O (x z 3), containing 30% Pd
by weight, were purchased from Alfa Aesar and used as received
without further purification. The ligands were prepared as reported
earlier [1]. CHN analyses were performed on PerkineElmer 2400
Series II CHNS analyzer in the Analytical Services Laboratories of the
ꢀ
ꢁ
RuCer Boskovic Institute, Zagreb, Croatia. The IR spectra were ob-
tained from KBr pellets in the range 4000e450 cmꢀ1 with Perkine
Elmer Spectrum RXI FTIR-spectrometer. TGA/DTA measurements
were performed at heating rate of 10 ꢁC minꢀ1 in the temperatuꢀre1
range of 25 e 600 ꢁC, under nitrogen or oxygen flow of 20 mL min
on instrument Mettler-Toledo TGA/SDTA 851e. Approximately 10 mg
of sample were placed in standard aluminum crucible (40 mL). All
[Pd(HBnida)2]$2H2O (1a). From 0.23 g H2Bnida. Yellow crystals;
yield: 0.19 g (64%). After w2 weeks, yellow prismatic crystals of 1a
(0.05 g; 17%), suitable for X-ray structural analysis, were obtained
by the slow evaporation of the filtrate. Total yield 82%. Anal. Calc.
for C22H28N2O10Pd (586.89): C, 45.02; H, 4.81; N, 4.77%. Found: C,
46.02; H, 4.84; N, 5.08%. The assigned IR data (cmꢀ1): 3586(s)
NMR measurements were performed on a Bruker DRX AVANCE 500
spectrometer equipped with a 5 mm triple broadband inverse probe
(TBI) with a z-gradient coil, and a Varian-NMR-vnmrs 600 spec-
trometer equipped with a 600 MHz PFGAuto XID (1H/15Ne31P 5 mm)
indirect probe. The measurements were carried out in DMSO-d6 so-
lutions, at the room temperature (303 K), using typical parameter
values. Residual solvent signals were used as the secondary refer-
ences, assuming 2.49 ppm (1H) and 39.5 ppm (13C) with respect to the
TMS signal (0 ppm). Typically, a set of 1H NMR,13C NMR, and 13C,1H g-
HSQC and HMBC spectra were obtained. The nitrogen-15 chemical
shifts were obtained from 15N,1H g-HMBC spectra, optimized for
nJ(1H,15N) of 3, 6, or 8 Hz, depending on the sample. The nitrogen
chemical shifts were given with respect to CH3NO2 (0 ppm). The
1H(13C) and 15N NMR chemical shifts of starting ligands (ppm) are
given below: H2Bnida: 1H(13C) [ppm]: 3.41(53.6) CH2CO2H; (172.3)
CO2H; 3.83(57.1) CH2Ar; (138.7) Ci, 7.35(128.7, 128.2) ortho, meta,
7.26(127.1) para Ar; 15N: ꢀ349.1 ppm; H2Peida: 1H(13C) [ppm]:
3.49(54.6) CH2CO2H; (172.4) CO2H; 2.88(55.8) NCH2CH2Ar;
2.72(33.7) NCH2CH2Ar; (139.9) Ci, 7.21(128.2) ortho, 7.27(128.6) meta,
7.18(129.9) para Ar; 15N: ꢀ350.1 ppm; H2Ppida: 1H(13C) [ppm]:
3.43(54.8) CH2CO2H; (172.4) CO2H; 2.67(53.5) NCH2CH2CH2Ar;
(n
(OH) of H2O); w3370(m, broad), 1718(s), 1231(m), 709(w) (
n
(OH),
n
(C]O), (OH) and
d
p(OH) of COOH); 1628(vs) and 1358(m) (nas and
ns of COOꢀ). Other IR data (cmꢀ1): 2932(w), 2711(w), 2602(w),
2515(w), 2365(w), 1942(w, br), 1494(w), 1459(w), 1434(w),
1418(w), 1319(m), 1288(w), 1114(w), 1084(w), 1065(w), 994(w),
964(w), 949(w), 921(m), 898(w), 871(w), 779(w), 751(w), 669(w),
636(w), 598(w), 571(w), 573(w).
[Pd(HBnida)2] (1b). The assigned IR data (cmꢀ1): w3450 (m,
broad), 1736(vs), 1216(s), 698(m) (n(OH), n(C]O), d(OH) and p(OH)
of COOH); 1612(vs) and 1380(vs) (nas and ns of COOꢀ). Other IR data
(cmꢀ1): 2928(m), 2744(m), 2674(m), 2598(m), 2534(m), 1494(w),
1456(w), 1416(m), 1326(m), 1260(m), 1112(m), 1084(w), 1050(w),
1026(m), 964(m), 932(m), 892(m), 872(m), 748(m), 636(w),
588(w), 558(w), 524(w), 502(w). 1H(13C) NMR (
d, ppm; J, Hz): 3.15,
3.66 (56.1), 2J 17.6 Hz CH2 (het. ring); (168.9) (het. ring); 3.37, 4.36
(63.3), 2J 15.9 CH2CO2H; (176.7) CO2H; 3.80, 4.03 (64.0), 2J 12.5
NCH2Ar; (132.3) Ci, 8.21(132.4) ortho, 7.49(128.5) meta, 7.43(129.1)
para, Ar. The main to secondary product molar ratio: 1:0.16.
[Pd(HPeida)2] (2). From 0.24 g H2Peida. Yellow crystals; yield:
0.27 g (93%). Anal. Calc. for C24H28N2O8Pd (578.88): C, 49.79; H,
4.88; N, 4.84%. Found: C, 49.87; H, 5.06; N, 4.82%. The assigned IR
data (cmꢀ1): w3450(w, broad), 1731(vs), 1216(s), 701(m) (
n
(OH),
n
(C]O), d(OH) and p(OH) of COOH); 1604(vs) and 1370(s) (nas and
ns of COOꢀ). Other IR data (cmꢀ1): 3026(w), 2930(m), 2870(m),
2534(w), 2367(w), 1496(w), 1456(m), 1436(w), 1416(w), 1327(m),
1259(m), 1114(m), 1076(w), 1033(w), 996(w), 884(broad, m),
826(w), 754(m), 625(w), 584(w), 546(w), 522(w), 500(w), 481(w).
1H(13C) NMR ( , ppm; J, Hz): 3.33, 3.72 (58.2), 2J 17.3 Hz CH2 (het.
d
ring); (169.3) (het. ring); 3.31, 4.07 (62.7), 2J 16.5 CH2CO2H; (178.2)
CO2H; 2.89 (63.5) NCH2CH2Ar; 3.49, 3.92 (32.7) NCH2CH2Ar; (138.1)
Ci, 7.48(129.1) ortho, 7.33 (128.6) meta, 7.28 (126.5) para, Ar.
Scheme 1. Methoxycarbonylation of iodobenzene with methanol catalyzed by the
palladium(II) complexes 1e4.

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
226
[Pd(HPpida)2] (3). From 0.25 g H2Ppida. Pale yellow powder;
PLATON [25]. The molecular graphics were done with ORTEP-3 [26]
yield: 0.28 g (92%). Anal. Calc. for C26H32N2O8Pd (606.93): C, 51.44;
H, 5.31; N, 4.62%. Found: C, 51.25; H, 5.63; N, 4.54%. The assigned IR
and MERCURY (Version 3.1) [27].
The crystal parameters, data collection and refinement results
for 1a are summarized in Table 1.
data (cmꢀ1): w3440(w, broad), 1732(s), 1210(w), 699(w) (
n
(OH),
n
(C]O), d(OH) and p(OH) of COOH); 1590(vs) and 1383(s) (nas and
ns of COOꢀ). Other IR data (cmꢀ1): 3026(w), 2940(w), 2864(w),
2761(w), 2464(w), 2364(w), 1893(w), 1495(w), 1454(w), 1424(w),
1334(m), 1281(m), 1115(w), 1072(w), 1050(w), 1020(w), 1005(w),
976(w), 956(w), 933(w), 896(m), 847(w), 806(w), 750(m), 626(w),
3. Results and discussion
3.1. Synthesis and general properties of the complexes
594(w), 562(w), 506(w), 457(w). 1H(13C) NMR (
d, ppm; J, Hz;
All complexes 1e4 were prepared from sodium tetra-
chloropalladate(II), sodium hydroxide and the appropriate N-ary-
lalkyliminodiacetic acid in slightly acidic aqueous solution. The
molar ratio which was described in the Experimental section was
found to be optimal for these preparations. The formation of
these complexes was most probably assisted by their very low
solubility, which allowed these reactions to proceed in a high yield
(Scheme 2).
All these complexes are air-stable substances which are practi-
cally insoluble in common laboratory solvents other than dimethyl
sulfoxide and N,N-dimethylformamide. Their solubility in water is
increased by the addition of sodium hydroxide or sodium hydro-
gencarbonate, but the dissolution is not complete when only two
moles of the base per mole of the complex are used.
DMSO-d6): major component: 3.22, 3.62 (58.6), 2J 17.3 CH2 (het.
ring); (169.0) (het. ring); 3.11, 4.05 (63.0), 2J 16.3 CH2CO2H; (178.0)
CO2H; 2.70 (61.5) NCH2CH2CH2Ar; 2.45, 2.77 (27.7) NCH2CH2CH2Ar;
2.72, 2.76 (32.6) NCH2CH2CH2Ar; (140.9) Ci, 7.16e7.38 (126.0, 128.3,
128.4) Ar; minor component: 3.35, 3.85 (58.6), 2J 17.3 CH2 (het. ring);
(168.3) (het. ring); 3.32, 3.99 (63.2), 2J 16.5 CH2CO2H; (178.1) CO2H;
2.77, 2.84 (60.4) NCH2CH2CH2Ar; 2.38, 2.72 (28.9) NCH2CH2CH2Ar;
n.a. NCH2CH2CH2Ar; (140.8) Ci, 7.16e7.38 (126.1, 128.2, 128.4) Ar.
Major to minor components molar ratio: 1:0.35. n.a. e not assigned
due to superposition with the signals of the major component.
[Pd(o-HCbida)2] (4). From 0.26 g o-H2Cbida. Pale yellow pow-
der; yield: 0.28 g (90%). Anal. Calc. for C22H22N2O8Cl2Pd (619.74): C,
42.63; H, 3.58; N, 4.52%. Found: C, 42.71; H, 3.65; N, 4.46%. The
assigned IR data (cmꢀ1): w3450(w, broad), 1738(s), 1217(s), 683(w)
It is worthwhile to mention that we were unable to obtain
analogous complexes of platinum(II) by this method. Metallic
platinum was formed when tetrachloroplatinate(II) was used
instead of tetrachloropalladate(II).
(
(
n
(OH),
n(C]O), d(OH) and p(OH) of COOH); 1612(vs) and 1377(m)
nas and ns of COOꢀ). Other IR data (cmꢀ1): 2914(br, w), 2508(w),
2364(w), 1479(w), 1434(m), 1410(m), 1327(m), 1281(w), 1259(w),
1139(w), 1111(w), 1053(w), 1027(w), 965(w), 922(w), 899(w),
879(w), 866(w), 840(w) 757(m), 637(w), 602(w), 562(w), 530(w),
3.2. Crystal structure
511(w), 477(w). 1H(13C) NMR (
d, ppm; J, Hz; DMSO-d6): major
component: 3.35, 3.80 (57.2), 2J 17.4 CH2 (het. ring); (168.6) (het.
ring); 3.61, 4.29 (63.4), 2J 16.1 CH2CO2H; (176.6) CO2H; 4.06, 4.15
(60.0) 2J 13.5 NCH2Ar “linear” component: 3.68, 4.47 (65.5), 2J 15.7
CH2CO2H; 4.09 (62.1) NCH2Ar. Major to linear components molar
ratio: 1:0.79.
The palladium(II) ion is placed at the inversion center and co-
ordinated by two N,O-bidentate HBnidaꢀ ligands in 1a, resulting
with the square-planar coordination and the formation of trans
isomer. HBnidaꢀ ligands are coordinated to palladium(II) ion via
ꢂ
imino N1 and carboxylate O1 atoms (d(Pd1eN1), 2.057(1) A;
ꢂ
d(Pd1eO1), 1.989(1) A), forming two five-membered chelate rings
2.3. Single crystal X-ray diffraction analysis and structure
determination
(Fig. 1). There are two co-crystallized water molecules in the
structure of 1a.
The suitable single crystal of 1a was selected and mounted in air
ontothe thin glass fiber. The data collectionfor 1awas carried out byan
Oxford Diffraction Xcalibur four-circle kappa geometry diffractometer
Table 1
Crystal data and details of the structure determination for 1a.
Formula
Mr
C22H28PdN2O10
586.86
with Xcalibur Sapphire 3 CCD detector, using a graphite mono-
ꢂ
chromated MoK
a
(l
¼ 0.71073 A) radiation, and by applying the Cry-
Color and habit
Crystal system, space group
Crystal dimensions (mm3)
Yellow, prism
Orthorhombic, Pbca
0.70 ꢂ 0.33 ꢂ 0.14
13.8847(2)
10.0232(2)
16.9479(2)
2358.62(6)
4
sAlis Software system, Version 1.171.32.29 [23] at room temperature
(296(2) K). The data reduction was done by the same program [23].
The X-ray diffraction data were corrected for Lorentz-
polarization factor and scaled for absorption effects by multi-
scan. The structure was solved by direct methods, implemented
in SHELXS-97 [24]. A refinement procedure by full-matrix least
squares methods, based on F2 values against all reflections, was
performed by SHELXL-97 [24], including anisotropic displacement
parameters for all non-H atoms.
ꢂ
a (A)
ꢂ
b (A)
ꢂ
c (A)
ꢂ
V (A)
Z
Dcalc (g cmꢀ3
)
1.653
0.847
1200
m
(mmꢀ1
F(000)
Range for data collection (ꢁ)
)
q
4.31e30.00
ꢀ19:19, ꢀ13:14, ꢀ23:23
h,k,l range
Scan type
No. measured reflections
No. independent reflections (Rint
The position of hydrogen atoms belonging to the carbon
atoms was geometrically optimized applying the riding model
u, 4
32768
ꢂ
ꢂ
(0.97 A, Uiso(H) ¼ 1.2Ueq(C) for methylen H atoms and 0.93 A,
Uiso(H) ¼ 1.2Ueq(C) for aromatic H atoms). The hydrogen atoms
belonging to the water molecules were found in the difference
Fourier maps. The distance between the water molecule O atoms
and the corresponding hydrogen atoms was restrained to the
)
3404 (0.0345)
1680
169
0.0241, 0.0511
0.0765, 0.0579
0.841
No. observed reflections, I ꢃ 2
s(I)
No. refined parameters
R,a wRb [I ꢃ 2
s
(I)]
R, wR [all data]
Goodness of fit on F2, Sc
Max., min. electron density (e A
ꢂ
average value of 0.82 A using SHELXL-97 DFIX instruction. The
ꢂꢀ3
)
0.35, ꢀ0.25
isotropic Uiso(H) values for these hydrogen atoms were fixed at the
same time (Uiso(H) ¼ 1.2Ueq(O)).
Maximum D/s
<0.001
P
P
a
R ¼ jjFoj ꢀ jFcjj= jFoj.
b
c
wR ¼ [S(Fo2 ꢀ F2c)2/Sw(F2o)2]1/2
.
The affirmation of chosen space groups and the analysis of the
molecular geometry and hydrogen bonds were performed by
S ¼ S[w(F2o ꢀ F2c)2/(Nobs ꢀ Nparam)]1/2
.

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
227
Scheme 2. Preparation of the complexes 1e4 and numbering scheme for 1H and 13C nuclei of the ligands and complexes. X ¼ H, n ¼ 1 for H2Bnida and [Pd(HBnida)2]$2H2O (1a);
X ¼ H, n ¼ 2 for H2Peida and [Pd(HPeida)2] (2); X ¼ H, n ¼ 3 for H2Ppida and [Pd(Ppida)2] (3); X ¼ Cl, n ¼ 1 for o-H2Cbida and [Pd(o-HCbida)2] (4). Ar ¼ aromatic ring; i ¼ ipso (1),
o ¼ ortho (2, 6), m ¼ meta (3,5), p ¼ para (4).
[33], 2-hydroxypropane-1,3-diaminetetraacetate [34] and cyclo-
hexanediaminetetraacetate [35].
There are three intermolecular OeH/O hydrogen bonds and one
weak intermolecular CeH/O hydrogen bond in the crystal structure
of 1a (Table 2). The molecules of [Pd(HBnida)2] and co-crystallized
water molecules in the crystal structure of 1a are assembled
together into an infinite 3D framework (Fig. 2). Each [Pd(HBnida)2]
molecule is hydrogen-bonded to six neighboring water molecules,
while each water molecule is hydrogen-bonded to three neighboring
[Pd(HBnida)2] molecules in this 3D framework.
3.3. Infrared spectroscopy
Complexes 1e4 exhibit similar solid-state infrared spectra. The
infrared spectrum of 1a shows na(COO) at 1628 cmꢀ1 and ns(COO) at
1358 cmꢀ1. Similar peaks of na(COO) and ns(COO) are also observed
in this region for complexes 1b (1612 cmꢀ1, 1380 cmꢀ1), 2
(1604 cmꢀ1, 1370 cmꢀ1), 3 (1590 cmꢀ1, 1383 cmꢀ1), 4 (1612 cmꢀ1
,
1377 cmꢀ1). The difference between na(COO) and ns(COO),
D value,
is greater than 200 cmꢀ1 for each of these complexes, indicating the
monodentate coordination of the carboxylate group [36,37]. The
stretching of the carbonyl group, n(C]O), which appears in the
spectra of the free ligands H2Bnida (1729 and 1714 cmꢀ1), H2Peida
(1709 cmꢀ1), H2Ppida (1738 cmꢀ1) and o-H2Cbida (1685 cmꢀ1), is
also present in the spectra of 1a (1718 cmꢀ1), 1b (1736 cmꢀ1), 2
(1731 cmꢀ1), 3 (1732 cmꢀ1) and 4 (1738 cmꢀ1). The broad bands
observed in the range of 2300e3500 cmꢀ1 indicate the extensive
hydrogen bonding in 1a, in accordance with its crystal structure.
Fig. 1. ORTEP-3 drawing of [Pd(HBnida)2]$2H2O (1a) with the atomic numbering
scheme of the asymmetric unit. The thermal ellipsoids are drawn at theꢁ50% proba-
ꢂ
bility level at 296(2) K. The selected bond distances (A) and angles ( ): Pd1eO1
1.989(1), Pd1eN1 2.057(1), O1ePd1eO1i 180, N1ePd1eN1i 180, O1ePd1eN1 84.68(5),
O1ePd1eN1i 95.32(5) (symmetry code (i): 1 ꢀ x, 1 ꢀ y, 1 ꢀ z).
The index
s
4, proposed for the geometry of four-coordinated
3.4. NMR spectroscopy
complexes [28,29], is 0 which indicates perfect square-planar ge-
ometry. Moreover, the square is only slightly distorted, as it is
evident from the values of the cis pairs of donor atoms, including
the bite angles (:O1ePd1eN1, 84.68(5)ꢁ), while the values of the
trans pairs of donor atoms amount exactly 180ꢁ due to the sym-
metry. The dihedral angle between the rings, defined by Pd1/O1/
C1/C2/N1 and Pd1/O1i/C1i/C2i/N1i atoms (symmetry code (i): 1 ꢀ x,
1 ꢀ y, 1 ꢀ z) amounts 0.02(7)ꢁ. The Pd1/O1/C1/C2/N1 chelate ring is
not planar, but twisted on C2eN1 line.
The assignments of 1H and 13C signals of the ligands were
straightforward. The CH2COOH signal appeared as a singlet (4H), as
well as ArCH2 signals in H2Bnida and o-H2Cbida (2H). Signal order
in N(CH2)nAr (n ¼ 2, 3) chains was confirmed by means of DFT GIAO
NMR calculations, which were performed at the 6-311Gþþ(2d,p)/
B3PW91//6-311Gþþ(2d,p)/B3PW91 theory level, assuming a single
arbitrarily selected rotamer for each compound and neglecting
solvent effect. Such an approach appeared to be sufficient for signal
assignments. The calculations were performed with the Gaussian
03 package [38].
The PdeN and PdeO bond distances (N and O atoms from
HBnidaꢀ) in 1a are similar to those of palladium(II) complexes with
iminodiacetate
[30],
hydrogeniminodiacetate
[31],
2-
The 1H and 13C NMR techniques were applied for the samples
[Pd(HBnida)2] (1), [Pd(HPeida)2] (2), [Pd(HPpida)2] (3), and [Pd(o-
hydroxyethyliminodiacetate [32], ethylenediaminetetraacetate
Table 2
Hydrogen bond geometry for 1a.
:(DeH/A)/ꢁ
Symmetry code on A
ꢂ
ꢂ
ꢂ
DeH/A
d(DeH)/A
d(H/A)/A
d(D/A)/A
O3eH31/O5
O5eH51/O2
O5eH52/O4
C10eH10/O3
0.82(2)
0.80(2)
0.78(2)
0.93
1.75(2)
2.01(2)
2.18(2)
2.45
2.552(2)
2.814(2)
2.784(2)
3.351(3)
166(2)
174(3)
135(3)
164
x ꢀ 1/2, y, 3/2 ꢀ z
1 ꢀ x, 1 ꢀ y, 1 ꢀ z
1 ꢀ x, y þ 1/2, 3/2 ꢀ z
x, y ꢀ 1, z

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
228
The 1H NMR spectrum of 1 contains the signals of main complex
and unidentified minor signals of the secondary compound. The
spectrum of 3 evidently contains the signal of two species exhib-
iting similar structural features. The presence of two sets of signals
may be explained assuming that two diastereomers exist in the
mixture, one with two nitrogenous stereogenic centers with the
same configuration, NR/NR (NS/NS) and the second with different
configurations, NS/NR.
The spectra of 4 were the most complicated. The inspection of all
spectra revealed the presence of at least three sets of signals. One
set of signals was identified as the signals of the free ligand; the
second one as the signals of the complex, [Pd(o-HCbida)2]. The
assignment of remaining signals was not straightforward. A pair of
doublets suggested a molecule bearing stereogenic centers or
having ring structure; on the other side chemical shift of CO2H
carbon atom (177.4 ppm) was close to the value observed for the
free ligands. Broad signals indicate an exchange process, medium
fast at the NMR timescale. Tentatively, we suggest a non-cyclic
structure for this compound (Fig. 4).
Fig. 2. The packing diagram of [Pd(HBnida)2]$2H2O (1a) (a view in the (010) plane).
The [Pd(HBnida)2] and co-crystallized water molecules are assembled into an infinite
3D framework by intermolecular OeH/O hydrogen bonds (shown by the dotted
lines).
Our NMR investigations can be summarized as follows: (i) the
signals assigned to main components of each sample agreed with
the structures of complexes: [Pd(HBnida)2], [Pd(HPeida)2],
[Pd(HPpida)2], and [Pd(o-HCbida)2]; (ii) most of the samples con-
tained additive of the secondary product, probably diastereomers
of main component of the mixture. Three species were detected in
one sample: the starting ligand and two complexes; (iii) The
presence of diastereomers and various adducts in mixtures sug-
gests the equilibrium between species in DMSO-d6 solutions.
HCbida)2] (4). Each complex contains two five-membered rings and
two nitrogen atoms bearing four substituents. Consequently, two
nitrogenous stereogenic centers were expected for each compound,
and all CH2 groups in the complex were expected to contain two
chemically non-equivalent hydrogen atoms, showing two signals in
a 1H spectrum and correlating with the signal of one carbon atom in
a 2D 1H, 13C HSQC spectrum. Furthermore, the 2D 1H, 13C HMBC
spectra allow the identification of C]O, COOH and Ci(Ar) 13C sig-
nals. Careful inspection of 1H, 13C and 2D 1H, 13C spectra allows the
identification of all signals. The most diagnostic region in 1H NMR
spectra was that from 3 to 5 ppm. As an example, a part of the
spectrum of [Pd(HBnida)2] was shown in Fig. 3.
3.5. Thermal analysis (TGA/DTA)
With the exception of complex 1a, which decomposes in two
clear consecutive steps, all other complexes 1be4 decompose in
Fig. 3. A part of the 1H NMR spectrum of [Pd(HBnida)2]. For clarity reasons, only one ligand molecule was shown. Two protons of each CH2 group are chemically non-equivalent and
produce two signals (doublets) in the 1H NMR spectrum. However, it is not the case of all complexes; some of CH2 group produced only one signal in 1H NMR.

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
229
Fig. 4. The structure of [Pd(o-HCbida)2] and suggested structure of the second complex in the mixture. For clarity reasons, only one ligand molecule was shown. Numbers in the
figure denote 1H (13C) chemical shifts (ppm) and geminal 2J(H,H) coupling constants (Hz).
Table 3
Table 5
Thermal analysis data for complexes 1e4 under nitrogen atmosphere.
Methoxycarbonylation of iodobenzene with methanol catalyzed by the different
palladium(II) complexes.a
Complex Temperature Mass loss (%);
Assignment
Observed
residue
at 600 ꢁC (%)
range (ꢁC)
observed/calculated
Entry
Pd-complex
Yield (%)b
1
2
3
4
5
1
2
3
4
75
85
73
68
95
1a
Step 1:
6.1/6.1
Two
19.6
50e155
Step 2:
water molecules
74.3/75.6
Two HBnidaꢀ ions
155e600
240e600
240e600
200e600
220e600
PdCl2(PPh3)2
1b
2
3
75.5/80.6
73.3/81.5
80.7/82.4
74.1/82.7
Two HBnidaꢀ ions 24.6
Two HPeidaꢀ ions 26.7
Two HPpidaꢀ ions 19.5
a
Palladium(II) complex concentration 2 mol%, PhI 1 mmol, Et3N 1.5 mmol, MeOH
2 mmol, CO 1.5 MPa, Time 2 h, Temp. 100 ꢁC, solvent [BMIM]PF6 (1-butyl-3-
methylimidazolium hexafluorophosphate) 2 mL.
4
Two
26.0
b
GC yields (with 100% selectivity to methyl benzoate).
o-(HCbida)ꢀ ions
(intermediate III) and insertion of CO into the PdePh bond to give
organometallic acyl palladium(II) complex PhCOPdL2I (intermedi-
ate IV); reaction of IV with triethylamine and methanol to release
methyl benzoate (PhCOOMe) and to regenerate the palladium(0)
catalyst (I) (Scheme 3). Therefore, although our complexes 1e4 are
not organometallic compounds themselves, the reaction catalyzed
by these complexes contains organometallic intermediates ac-
cording to the described mechanism.
only one step or two overlapped consecutive steps. The first step in
case of 1a corresponds to the release of two water molecules.
Thermal analysis data for these complexes are shown in Tables 3
and 4.
3.6. Catalytical performance
Compared with the phosphine-ligated palladium complexes
which are environmentally unfriendly and toxic, the phosphine-
free palladium complexes have attracted much attention in alkox-
ycarbonylation of aryl iodides with alcohols, from the point of view
of potential application in green catalysis. As shown in Table 5, the
developed phosphine-free palladium(II) complexes (1e4) exhibit
the acceptable activities towards the methoxycarbonylation of
iodobenzene with the yields up to 68% for methyl benzoate. In the
case of 2, a high activity was observed in comparison with the
typical phosphine-ligated palladium(II) complex PdCl2(PPh3)2.
Based on the mechanistic studies reported so far [39], it is
suggested that methoxycarbonylation of iodobenzene with CO,
catalyzed by the complexes 1e4 (L ¼ Bnida, Peida, Ppida and o-
Cbida), proceeds through the following steps: oxidative addition of
iodobenzene (PhI) to Pd(0)L2 complex (intermediate I) (formed in
situ by the reduction of the starting palladium(II) complex (1e4)) to
form organometallic intermediate (II) PhPdL2I; coordination of CO
to the palladium(II) ion to form the carbonyl complex PhPd(CO)LI
3.7. Evaluation of antiproliferative effect of palladium(II) complexes
in vitro
The tested palladium(II) compounds did not show anti-
proliferative activity towards tested cell lines. Slight activity was
observed on HCT 116 cells, after the treatment with compound
[Pd(HPeida)2] (2), and on all cell lines after the treatment with
[Pd(HPpida)2] (3), but it did not inhibit the growth of cells for 50% at
the maximal tested concentration (100 mM). The GI50 values for the
complexes 1, 2 and 3 are equal or greater than 100 mM in case of all
three tested cell lines.
4. Conclusions
Several palladium(II) complexes were prepared by the reactions
sodium tetrachloropalladate(II) with various N-
of
Table 4
Thermal analysis data for complexes 1e4 under oxygen atmosphere.
Complex
Temperature
range (ꢁC)
Mass loss (%);
observed/calculated
Assignment
Residue at 600 ꢁC (%)
Observed
Calculated for PdO
20.8
1a
Step 1: 50e150
Step 2: 150e320
240e400
240e500
240e500
6.1/6.1
Two water molecules
Two HBnidaꢀ ions
Two HBnidaꢀ ions
Two HPeidaꢀ ions
Two HPpidaꢀ ions
Two o-(HCbida)ꢀ ions
19.1
75.2/75.6
80.6/80.6
79.8/81.5
80.3/82.4
80.9/82.7
1b
2
3
19.6
20.2
20.1
19.5
22.2
20.4
20.1
19.5
4
220e550

ꢀ
N. Smrecki et al. / Journal of Organometallic Chemistry 760 (2014) 224e230
230
Appendix B. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2013.10.010.
References
ꢀ
ꢁ
ꢁ
[1] N. Smrecki, B.-M. Kukovec, M. Ðakovic, Z. Popovic, Inorg. Chim. Acta 400
(2013) 122.
[2] J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, UK, 2004, p. 265.
[3] R. Skoda-Foldes, L. Kollar, Curr. Org. Chem. 6 (2002) 1097.
[4] M. Mori, in: E. Negishi (Ed.), Handbook of Organopalladium Chemistry for
Organic Synthesis, vol. 2, Wiley-Interscience, New York, 2002, p. 2663.
[5] T.Y. Luh, M. Leung, K.T. Wong, Chem. Rev. 100 (2000) 3187.
[6] X. Wu, H. Neumann, M. Beller, Chem. Soc. Rev. 40 (2011) 4986.
[7] D.M. D’Souza, T.J.J. Müller, Nat. Protoc. 3 (2008) 1660.
[8] B. Willy, T.J.J. Müller, Arkivoc 1 (2008) 195.
[9] J. Marco-Contelles, E. de Opazo, J. Org. Chem. 67 (2002) 3705.
[10] C.J. Forsyth, J. Xu, S.T. Nguyen, I.A. Samdal, L.R. Briggs, T. Rundberget,
M. Sandvik, C.O. Miles, J. Am. Chem. Soc. 128 (2006) 15114.
[11] L.F. Tietze, R.R. Singidi, K.M. Gericke, H. Bockemeier, H. Laatsch, Eur. J. Org.
Chem. (2007) 5875.
[12] A. Arcadi, M. Aschi, F. Marinelli, M. Verdecchia, Tetrahedron 64 (2008) 5354.
[13] P. Bannwarth, A. Valleix, D. Grée, R. Grée, J. Org. Chem. 74 (2009) 4646.
[14] Y.V. Gulevich, N.A. Bumagin, I.P. Beletskaya, Russ. Chem. Rev. 37 (1988) 299.
[15] M. Beller, B. Cornils, C.D. Frohning, C.W. Kohlpaintner, J. Mol. Catal. A 104
(1995) 17.
Scheme 3. The proposed mechanism for methoxycarbonylation of iodobenzene (PhI)
in the presence of triethylamine (Et3N), catalyzed by the complexes 1e4 (L ¼ Bnida,
Peida, Ppida and o-Cbida), with the reaction intermediates IeIV.
[16] T.A. Stromnova, I.I. Moiseev, Russ. Chem. Rev. 67 (1998) 485.
[17] A.S. Prasada, B. Satyanarayanaa, J. Mol. Catal. A: Chem. 370 (2013) 205.
[18] H. Daghriri, F. Huq, P. Beale, Chem. Rev. 248 (2004) 119.
[19] A.S. Abu-Surrah, M. Kettunen, Curr. Med. Chem. 13 (2006) 1337.
[20] A.S. Abu-Surrah, H.H. Al-Sa’doni, M.Y. Abdalla, Cancer Ther. 6 (2008) 1.
[21] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev. 253 (2009) 1384.
[22] E. Gao, L. Lin, L. Liu, M. Zhu, B. Wang, X. Gao, Dalton Trans. 41 (2012) 11187.
[23] Oxford Diffraction CrysAlis CCD and CrysAlis RED, Version 1.171.32.29, Oxford
Diffraction Ltd., Abingdon, Oxfordshire, England, 2008.
arylalkyliminodiacetatic acids in aqueous solutions. Complex 1a is a
trans-isomer. According to the great similarity of their infrared
spectra, all other complexes 1be4 presumably have molecular
structures analogous to 1a, but without co-crystallized water
molecules. The coexistence of several species in dimethyl sulfoxide
solutions of these complexes was observed by NMR spectroscopy.
The complexes did not significantly inhibit the growth of colon,
breast and lung tumor cell lines. However, all prepared complexes
exhibit the acceptable activities towards the methoxycarbonylation
of iodobenzene. The choice of the ligand non-coordinating moiety
in the prepared complexes affects the efficiency of these complexes
as catalysts. The yield of the product was the lowest for the complex
containing o-chlorobenzyl derivative of the ligand, possibly
because of the steric or electronic influence of the chlorine atom
attached to the aromatic ring in the ortho position. At this stage it is
not yet clear why the efficiency of the complex containing 2-
phenylethyl group is significantly greater when compared with
the analogous complexes containing shorter (benzyl) or longer (3-
phenylprop-1-yl) carbon chains.
[24] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112.
[25] A.L. Spek, J. Appl. Crystallogr. 36 (2003) 7.
[26] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[27] C.F. Macrae, I.J. Bruno, J.A. Chisholm, P.R. Edgington, P. McCabe, E. Pidcock,
L. Rodriguez-Monge, R. Taylor, J. van de Streek, P.A. Wood, J. Appl. Crystallogr.
41 (2008) 466.
[28] L. Yang, D.R. Powell, R.H. Houser, Dalton Trans. (2007) 955.
[29] S. Balboa, R. Carballo, A. Castiñeiras, J.M. González-Pérez, J. Niclós-Gutiérrez,
Polyhedron 50 (2013) 512.
[30] J. Chakraborty, M.K. Saha, P. Banerjee, Inorg. Chem. Commun. 10 (2007) 671.
[31] J. Chakraborty, H. Mayer-Figge, W.S. Sheldrick, P. Banerjee, Polyhedron 24
(2005) 771.
[32] I.N. Polyakova, T.N. Polynova, M.A. Porai-Koshits, A.M. Grevtsev, J. Struct.
Chem. 20 (1979) 555.
[33] A.L. Poznyak, A.B. Ilyukhin, V.S. Sergienko, Russ. J. Inorg. Chem. 42 (1997)
1660.
[34] R.-F. Song, C.-Z. Zhang, F. Li, S.-C. Jin, Z.-S. Jin, Chem. Res. Chin. Univ. 8 (1992)
399.
[35] I.N. Polyakova, A.L. Poznyak, V.S. Sergienko, Crystallogr. Rep. 48 (2003) 278.
[36] G.B. Deacon, R.J. Phillips, Coord. Chem. Rev. 33 (1980) 227.
[37] K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination
Compounds, Part B, sixth ed., Wiley, Hoboken, 2009.
Acknowledgments
[38] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb,
J.R. Cheeseman, J.A. Montgomery, T. Vreven Jr., K.N. Kudin, J.C. Burant,
J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi,
G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo,
J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi,
C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador,
J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain,
O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz,
Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko,
P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng,
A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen,
M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision B.5, Gaussian, Inc.,
Pittsburgh PA, 2003.
This research was supported by the Ministry of Science, Edu-
cation and Sports of the Republic of Croatia (Grant No. 119-
1193079-1332 and 098-0982464-2514).
Appendix A. Supplementary material
CCDC 949216 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[39] J. Liu, B. Liang, D. Shu, Y. Hu, Z. Yang, A. Lei, Tetrahedron 64 (2008) 9581.