A QM/MM MD simulation study of hydrated Pd

2+
S. Adnan Ali Shah, Thomas S. Hofer, M. Qaiser Fatmi,
Bernhard R. Randolf, Bernd M. Rode
*
Theoretical Chemistry Division, Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
Received 27 April 2006; in nal form 17 May 2006
Available online 13 June 2006
Abstract
Structural and dynamical properties of Pd
2+
in aqueous solution have been investigated by a combined quantum mechanical/molec-
ular mechanical (QM/MM) molecular dynamics (MD) simulation at HartreeFock level. For the structural elucidation of the Pd
2+
com-
plex in aqueous solution several data sets such as radial and angular distribution functions (RDF/ADF) were employed. Dynamics have
been characterized by the ligands mean residence time (MRT) and ion-ligand stretching frequencies. For a nal decision, whether
besides the tightly bound four in-plane ligands additional axial ligands are present, an extension of the methodical accuracy beyond that
of a one-shell QMM/MM MD simulation appears necessary.
2006 Elsevier B.V. All rights reserved.
1. Introduction
Palladium(II) complexes have a variety of physiochemi-
cal properties and potentially useful biological activities.
Pd
2+
complexes of acetone schi bases exhibit strong cyto-
toxicity against cancer cells [1], being more ecient than
the standard anticancer drug tamoxifer [1]. Various Pd
2+
complexes with aromatic N-containing ligands have shown
very promising antitumor properties both in vitro and
in vivo for cis-platin resistant model systems or against
cis-platin-insensitive cell lines [2]. Palladiums remarkable
catalytic properties are responsible for the widespread use
of this metal in the chemical industry [3,4]. It has been
observed experimentally that numerous analogous com-
pounds of Pd
2+
and Pt
2+
have very similar structural
parameters, but substantially dierent kinetics (approxi-
mately six orders of magnitude faster in the case of Pd
2+
compounds) [5]. The dierence in the kinetics of chemical
reactions is important for understanding the dierent cata-
lytic and biochemical roles of Pd- and Pt- compounds
[68], respectively. Due to the important role of Pd
2+
com-
plexes in several biological and industrial aspects structural
and dynamical properties of Pd(II) ions in aqueous solu-
tion have become a major subject of both experimental
and theoretical investigations.
Elding has studied Pd
2+
and Pt
2+
complexes in aqueous
solution showing the existence of [Pd(H
2
O)
4
]
2+
and
[Pt(H
2
O)
4
]
2+
as complexes in square planar arrangements
[911]. NMR and theoretical studies of aqueous solutions
of Pd
2+
and Pt
2+
showed that these cations coordinate to
four H
2
O ligands, with ligand exchange rates of
k = 5.6 10
2
s
1
for Pd(II) and k = 3.9 10
4
s
1
for
Pt(II) [1215,5]. Sanchez-Marcos et al. reported a molecu-
lar dynamics study of the square-planar [Pd(H
2
O)
4
]
2+
com-
plex, which showed two further water molecules in the
axial regions at larger distances, classifying these water
molecules as meso-shell [16]. Some transition metals such
as Cu(II) and Ti(III) show distorted structures with two
dierent ion-O distances within the rst shell [17,18]. This
well-known JahnTeller eect has been shown to be
strongly dynamical and leads to enhanced exchange rates
of rst shell ligands [17,18]. The present work attempted
to clarify the structural and dynamical properties of the
[Pd(H
2
O)
n
]
2+
complex by the hybrid QM/MM MD
approach and to investigate whether a JahnTeller like
behavior could be deduced for Pd(II) as well.
0009-2614/$ - see front matter 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.cplett.2006.05.132
*
Corresponding author. Fax: +43 512 507 2714.
E-mail address: Bernd.M.Rode@uibk.ac.at (B.M. Rode).
www.elsevier.com/locate/cplett
Chemical Physics Letters 426 (2006) 301305
2. Methodology
2.1. Potential functions
The QM/MM MD methodology partions the system
into two regions, one comprising the ion and its rst
hydration shell, which is treated quantum mechanically,
while the remaining region is treated by molecular
mechanics. This methodology has produced very satisfac-
tory results in numerous studies on ion solvation [1921].
In each simulation step ab initio energy and gradient cal-
culations were performed at HartreeFock level. The
BJHCF2 water model was used to describe the water
water interaction, while the ion-water pair potential func-
tions were newly constructed from ab initio quantum
mechanical energy surface calculations at the restricted
HartreeFock (RHF) level employing the Dunning dou-
ble-f plus polarisation function (DZP) basis sets for oxy-
gen and hydrogen [22] and the LANL2DZ ECP basis set
for Pd
2+
. The minimum energy for the Pd
2+
water inter-
action was found to be 98.3 kcal/mol at a distance of
1.94 A

. To construct the Pd
2+
-water pair potential func-
tion, more than 11000 ab initio energies were tted with
the Levenberg-Marquardt algorithm to the following ana-
lytical formula:
DE
2bd
Fit

q
Pd
2q
O
r

A
O
r
5

B
O
r
6

C
O
r
10

D
O
r
12

X
2
i1
q
Pd
2q
H
r
i

A
H
r
5
i

B
H
r
7
i

C
H
r
11
i

D
H
r
12
i

1
A, B, C and D are the tting parameters (Table 1), q
Pd
2, q
O
and q
H
are the charges of palladium, oxygen and hydrogen,
respectively, and r and r
i
are the PdO and PdH distances,
respectively. Table 1 summarizes the optimised parameters.
The net charges of oxygen and hydrogen were set to
0.6598 and 0.3299, respectively, according to the BJH
CF2 water model [2325] employed in this simulation.
Throughout the whole calculation, the geometry of water
was kept constant at its experimental gas phase values
[26] (OH = 0.9601 A

, HOH = 104.47).
A total of 11500 ab initio energy points were generated
to describe the waterPd
2+
water energy surface and to
construct a three-body correction function. The three-body
correction energy is dened as
DE
3bd
corr
E
ab
WMW
E
ab
M

X
2
W1
E
ab
W
!

X
2
W1
E
2bd
MW
E
2bd
WW
2
where E
ab
WMW
, E
ab
M
and E
ab
W
are the SCF energies of
[Pd(H
2
O)
2
]
2+
, Pd(II) and water, respectively. E
2bd
MW
is the en-
ergy of PdH
2
O obtained from the pair potential (Eq. 1)
and E
2bd
WW
denotes the waterwater interaction according
to the BJHCF2 [23,24] water model. The three-body cor-
rection energies were tted to the equation:
DE
3bd
Fit
0:97e
0:76r
1
r
2

e
0:26r
3
CL r
1

2
CL r
2

2
3
where r
1
and r
2
are the distances PdO
1
and PdO
2
, respec-
tively, and r
3
is the distance between O
1
and O
2
. CL is a
cut-o limit set to 6.0 A

, where three-body terms become

negligible.
2.2. QM/MM MD Simulation
The system consisted of a cubic box with a side length
24.71 A

containing one Pd(II) and 499 water molecules,

corresponding to a density of the system as of the pure
solvent at 298 K (0.99702 g/cm
3
) [20]. A canonical NVT-
ensemble was used employing periodic boundary condi-
tion, and the temperature was kept constant at 298.16 K
by the Berendsen algorithm [27,28] with a relaxation time
of 0.1 ps. The cuto distances were set to 5.0 A

for OH
and 3.0 A

for HH non-Coulombic interactions. For all

other pair interactions the cut-o was set to 12.35 A

. In
order to account for the long-range electrostatic interac-
tions, the reaction eld method was employed [29]. The
exible BJHCF2 water model [23,24] was used, which
includes an intramolecular potential enabling thus explicit
hydrogen movements. Therefore, the time step for the
simulation was set to 0.2 fs. The one-shell QM/MM
MD simulation was started from an equilibrated congu-
ration of the classical three-body corrected simulation.
The diameter of the QM region was set to 6.2 A

in accor-
dance with the PdO radial distribution function (RDF)
obtained from the classical simulation. After 3 ps of re-
equilibration the QM/MM MD simulation was performed
for 30 ps.
3. Results and discussion
3.1. Structural properties
Pd
2+
O and Pd
2+
H radial distribution functions
(RDFs), and their corresponding integration numbers
obtained from the QM/MM MD simulation are plotted
in Fig. 1. The maximum of the rst peak in the Pd
2+
O
radial distribution functions corresponding to the rst
hydration shell is located at 2.07 A

. The experimentally
determined Pd
2+
O distances ranges from 2.00 to 2.03 A

[911]. Next to the rst shell a second peak is visible corre-

sponding to an additional ligand centered at 2.66 A

. The
rst shell is sharp and narrow, indicating a well-structured
and rigid rst hydration shell. The running integration
numbers as derived from Pd
2+
O RDF predict a rst shell
coordination number of 4, while a single water molecule is
found in the extended rst shell. The Pd
2+
O RDF reaches
Table 1
Optimised parameters for the PdO and PdH two-body interactions in
kcal/mol A

n
Parameters in kcal/mol A

n
A B C D
PdO 4876.81 42552.17 173738.28 142052.52
PdH 665.90 7307.31 9049.10 4941.17
302 S. Adnan Ali Shah et al. / Chemical Physics Letters 426 (2006) 301305
zero between rst shell and the next peak, indicating that
no exchange process occurred during the simulation time.
QM/MM MD simulations of Cu(II) and Ti(III) had shown
two dierent distances for the rst shell ligands due to
JahnTeller distortions [17,18], but in those cases, the dis-
tances of all six ligands vary within the subpicosecond
range, which is completely dierent from the structure
observed here. A classical molecular dynamics study of
aqueous Pd(II) performed by Sanchez-Marcos et al. [16]
reported six ligands at two PdO distances, namely
2.0(4.0) and 2.67(2.0)A

, which supports a hydration model

with a strongly distorted octahedron. A broad peak
observed between 3.8 and 5.0 A

with a maximum at
4.50 A

in our simulation corresponds to a second shell con-

taining in average of 11.2 water molecules.
The coordination number distribution of hydrated Pd
2+
obtained from the QM/MM MD simulations is displayed
in Fig. 2. A four-fold coordination in the rst hydration
shell with an occurrence of 100% is observed, which is in
agreement with experimental data reported by Elding
et al. [911] and theoretical studies performed by Marcos
et al. [16]. For the inter-shell region a single ligand coordi-
nation is observed with a probability of 100%, which is in
contrast to the result reported by Sanchez-Marcos et al.
with two axial water molecules [16], while experimental
investigations did not detect the presence of more distant
rst shell ligands so far. The second hydration shell dis-
plays a broad distribution of coordination numbers rang-
ing from 9 to 16 with a maximum at 12.
Fig. 3a displays the OPd
2+
O angle distribution
obtained from the QM/MM MD simulation. Two broad
peaks are obtained at 90 and 175, reecting the
square-planar geometry of the rst hydration shell (Fig. 4).
Figs. 3b,c display the relative orientation of the water
ligands which gives further insight into the hydrates struc-
ture. Two dierent angles were dened: h as the angle
between the OPd vector and the vector resulting from
the sum of the OH vectors, and the tilt angle is the angle
between the PdO vector and the plane dened by the OH
vectors. The distribution of the h angle shows a broad peak
indicating high exibility in the ligands orientation. The
maximum of the h angle distribution of the rst shell is
observed at 170.0. The tilt angle varies from 50 to
+50 with a half width of 42, further indicating the ex-
ibility of the rst shell structure.
2 3 4 5 6
Distance in
0
2
4
6
8
10
12
14
16
18
20
g
(
r
)
0
4
8
12
18
20
22
28
32
36
40 40
I
n
t
e
g
r
a
t
i
o
n

n
u
m
b
e
r
s
Fig. 1. PdO (solid line) and PdH (dashed line) RDFs and their running
integration numbers obtained from the QM/MM MD.
0 2 4 6 8 10 12 14 16 18 20
Coordination number
0
10
20
30
40
50
60
70
80
90
100
P
r
o
b
a
b
i
l
i
t
y

i
n

%
extended -1st shell
1st shell
2nd shell
Fig. 2. Coordination number distributions (CNDs) of the palladium(II)
ion in aqueous solution obtained from the QM/MM MD simulation
60 90 120 150 180
0
2
4
6
8
120 140 160 180
0
2
4
6
P
r
o
b
a
b
i
l
i
t
y

i
n

%

-60 -30 0 30 60
Angle in degree
0
1
2
3
(a)
(b)
(c)
Fig. 3. The OPd
2+
O (a), theta (b) and tilt (c) angle distributions of the
Pd(II)water geometry.
S. Adnan Ali Shah et al. / Chemical Physics Letters 426 (2006) 301305 303
The power spectrum of the Pd
2+
O vibrational mode
in the rst shell obtained from the QM/MM MD
simulation is displayed in Fig. 5. The frequencies were
scaled by the standard factor of 0.89 [30,31]. The peak
maximum for the PdO stretching vibration is observed
at 398 cm
1
corresponding to a force constant of
130 N m
1
. A shoulder is visible at lower frequencies rep-
resenting the PdO stretching vibration of the single axial
ligand at 2.66 A

.
As detailed information on water exchange reactions
between hydration shells of ions are important to quantify
the reactivities of ions, the rate of water exchange processes
was evaluated by mean residence times (MRT) analysis of
the water molecules in the second shell, using the direct
method [32]. During the simulation time of 30 ps no
exchange between the rst shell ligands in the plane and
second shell was observed. Also the single axial ligand
remained in its position. The mean residence time in the
second shell was determined as 4.6 ps, which is similar to
other divalent transition metal ions such as Cd(II) or
Hg(II) [33,34]. Besides the mean residence time, simula-
tions can also provide dynamic properties in terms of the
lability of hydration shells and the sustainability of
exchange processes (see Table 2). The sustainability mea-
sures the rates of success of exchange events in leading to
longer-lasting changes in the hydration structure. A sus-
tainability coecient S
ex
can be dened as
S
ex

N
0:5
ex
N
0
ex
4
where S
ex
is the sustainability coecient, N
0
ex
is the number
of all transitions through a shell boundary (t
*
= 0), and
N
0:5
ex
denotes the number of exchanges persisting longer
than 0.5 ps. Its inverse (1/S
ex
) accounts how many attempts
are needed to produce one lasting exchange between the
hydration shells and/or bulk. In the second shell a sustain-
ability coecient of 0.06 was found, thus in average 17 at-
tempts to leave or enter the second shell lead to an
successful exchange event. This number is close to the
values for Cu(II), Ti(III), V(II) and Cd(II), which also
show 1/S
ex
values of 17 [17,18,35,33].
4. Conclusion
The results obtained in our one-shell QM/MM MD
simulation and other theoretical investigations show that
the hydration structure of Pd(II) is apparently highly
asymmetric. The four-fold coordination forming a plane
as deduced from experiments is also conrmed, but the
theoretical investigations predict a further coordination
with one (this work) or two (Ref. [16]) ligands at an elon-
gated distance. As previous investigations of the Jahn
Teller distorted ions Cu(II) [17] and Ti(III) [18] have indi-
cated that the inclusion of only the rst hydration shell
could be insucient to describe hydrated systems with
high asymmetry, it seems mandatory to revisit hydrated
Pd(II) employing an enlarged quantum mechanical sub-
system, comprising two shell, although this will boost
the computational eort from 6 to about 1215 months
of CPU time.
200 400 600 800
Frequency in cm
-1
0
10
20
30
40
50
P
r
o
b
a
b
i
l
i
t
y

i
n

%

Fig. 5. Power spectrum of the PdO stretching frequency in cm
1
.
Table 2
Second shell mean ligand residence times (s) for t
*
values of 0 and 0.5 ps,
number of accounted ligand exchange events N, sustainability of migra-
tion processes to/from the second hydration shell S
ex
obtained from QM/
MM MD simulation
2nd Shell
System Method t
*
= 0.0 ps t
*
= 0.5 ps S
ex
1/S
ex
N
ex
/10 ps s N
ex
/10 ps s
Pd-water QM/MM 330 0.30 22.7 4.64 0.06 16.7
Fig. 4. Square-planar structure of the Pdwater complex in the rst
hydration shell, plus an additional axial ligand as predicted by the QM/
MM MD simulation. First shell oxygens are depicted in red (plane) and
violet (axial position), second shell oxygens in orange (snapshot taken by
MOLVISION).
304 S. Adnan Ali Shah et al. / Chemical Physics Letters 426 (2006) 301305
Acknowledgements
Financial support for this work by Austrian Science
Foundation (FWF) (Project P16221-N08) and a Technol-
ogy Grant (BMBWK)/(RFTE) for SAAS are gratefully
acknowledged.
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