The Role of an Alkyl–Phenyl Spacer on the Reactivity of Novel Platinum(II) Complexes with Thiourea Nucleophiles

Article abstract of DOI:10.1002/kin.21085

The presented work, submitted as a paper, deals with the substitution reactions of mononuclear and dinuclear platinum(II) complexes of di-2-pyridylaminodiaquaplatinum(II), (Pt1); di-2-pyridylaminomethylbenzenediaquaplatinum(II), (Pt2); 1,2-bis(di-2-pyridy

Full text of DOI:10.1002/kin.21085

The Role of an Alkyl–Phenyl
Spacer on the Reactivity of
Novel Platinum(II)
Complexes with Thiourea
Nucleophiles
WANGOLI PANYAKO ASMAN
School of Chemistry and Physics, University of KwaZulu-Natal, 3209, Scottsville, Pietermaritzburg, South Africa
Received 24 December 2016; revised 21 January 2017; accepted 23 January 2017
DOI 10.1002/kin.21085
Published online in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: The presented work, submitted as a paper, deals with the substitution reactions of
mononuclear and dinuclear platinum(II) complexes of di-2-pyridylaminodiaquaplatinum(II),
(
Pt1);
pyridylaminomethyl)benzenetetraquaplatinum(II),
methyl)benzenetetraquaplatinum(II), (Pt4);
benzenetetraquaplatinum(II), (Pt5). These reactions were carried out on aqua complexes by
di-2-pyridylaminomethylbenzenediaquaplatinum(II),
(Pt3);
1,4-bis(di-2-pyridylaminomethyl)-
(Pt2);
1,2-bis(di-2-
1,3-bis(di-2-pyridylamino-
and
ꢀ
ꢀ
ꢀ
three nucleophiles, viz., thiourea, N,N -dimethylthiourea, and N,N,N N -tetramethylthiourea
under pseudo–first-order conditions as a function of nucleophile concentration and temper-
ature by stopped-flow and UV–visible spectrophotometric techniques. In addition, some DFT
calculation was performed. The activation parameters support an associative substitution
mechanism. ꢁC 2017 Wiley Periodicals, Inc. Int J Chem Kinet 1–17, 2017
INTRODUCTION
responsible for their anticancer activity [4–6]. This has
led to the need of understanding their chemical and the
biomedical transformations under physiological condi-
tions. To achieve this, many aspects of substitution re-
actions on monofunctional Pt(II) complexes have been
carried out [7,8]. The results reported on substitution
reactions of these monofunctional Pt(II) complexes
mostly suggest an associative mechanism [9,10], al-
though in some cases dissociative mechanisms have
also been reported [11]. Despite the side effects of
this class of complexes, they have been widely used
as anticancer therapeutics. However, their limitations
have led to considerable interest in the development
Ligand substitutions on square-planar platinum(II)
complexes have attracted continued attention owing
to their intrinsic chemical and biomedical applica-
tions in antitumor treatment [1–3]. The interaction
of these platinum-based drugs with deoxyribonucleic
acid (DNA) is widely accepted as the mechanism
Correspondence to: W. P. Asman; e-mail: pwangoli@yahoo.com.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
ꢁC
2017 Wiley Periodicals, Inc.

2
ASMAN
of multinuclear platinum(II) complexes as a promising
class of new anticancer drugs [12,14]. These mult-
inuclear complexes have shown potential antitumor
activity and are reported to circumvent cisplatin re-
sistance cell lines [1,2,5,6,13]. Recent reports in this
area demonstrate a bright prospect in the utilization
of multinuclear metal complexes in cancer chemother-
apy [4,5].
ring in ortho, meta, and para positions. The investiga-
tion reveals for the first time information on substitu-
tion mechanisms of transition metal complexes with
multidentate ligands (4H2O) as leaving groups in cis
coordination. This study was motivated by the fact that
dinuclear platinum(II) complexes have been reported
to be promising anticancer agents owing to their forma-
tion of long-range intrastrand and interstrand cross-link
DNA adducts [16,18]. The adducts are not common
in mononuclear platinum(II) complexes, thus making
their mechanism the center of focus.
Despite the advantages of these multinuclear plat-
inum complexes, extensive study has been with regard
to cisplatin which is reported to be among the most ac-
tive antitumor agents in clinical use [15,16]. Cisplatin
being amongthemainstays in cancer chemotherapyhas
contributed to more detailed studies of monofunctional
platinum(II) complexes. However, its narrow spectrum
of activity and side effects [17,18] has led to many
different and creative approaches toward the design
of new classes of platinum-based complexes that ad-
dress the side effects associated with cisplatin. One way
of exploring this has been a paradigm shift from the
mononuclear to multinuclear platinum complexes that
may form different intrastrand and interstrand cross-
link DNA-adducts with an expanded spectrum of activ-
ity [19–21]. The multinuclear complexes have shown
pharmaceutical significance, for instance the advance-
ment BBR3464 to clinical trials, and exhibiting anti-
tumor activity in both cisplatin-sensitive and resistant
cell lines [22,23].
Collectively, this class of complexes has been re-
ported to display novel mechanisms of action over
classical mononuclear complexes such as cisplatin and
its analogues. Results from recent studies by Jaganyi
et al. [24], Hofmann and van Eldik [25], and Farrell et
al. [26] have reported the reactivity of dinuclear plat-
inum(II) complexes to vary with the bridging linker
that connects the two platinum centers. However, the
actual thermodynamic or kinetic contribution of the
bridge to the mechanism of substitution remains to be
elucidated. Moreover, the molecular geometry, sym-
metry, and steric or electronic connotations adopted by
the complexes remain unexplored. Variation in substi-
tution rates by changing the bridging spacer and intro-
duction of more bifunctional platinum centers remain
a promising strategy in tuning platinum anticancer
agents with improved efficacy [4–6].
In the current study, the 2,2-dipyridylamine ligand
was used due to its unique coordination that forms
six-membered chelates upon binding to the metal cen-
ter and the ability of nitrogen donor ligands to sta-
bilize both low and high oxidation states of com-
plexes [29,30]. The current study explores how sym-
metry, geometry, electronic, steric as well as nucle-
ophilic strength influences the rates of such substitu-
tion reactions. Thiourea nucleophiles were employed
due to their differences in nucleophilicity, steric hin-
drance, and their biological relevance. For instance,
thiourea (TU) is a strong σ-donor with high solubility
and can act as a good model compound for thiolate
and thioether present in the cells [31] and as a pro-
tecting agent to minimize nephrotoxicity in cisplatin
treatment [4]. It is also known to act as a chemopro-
tective agent that alleviates the side effects in the nor-
ꢀ
mal tissue [4]. While N,N -dimethylthiourea (DMTU)
a highly permeate molecule, decreases injury in a wide
variety of biological systems and inactivates reactive
oxygen species [32,33]. It is envisaged that the kinetic
tuning of the dinuclear complexes in Scheme 1 will
shed light on their mechanistic interaction with bio-
logical molecules and provide a better understanding
of their metabolism.
EXPERIMENTAL
Materials and Reagents
The nucleophiles TU (99%), DMTU (99%),
ꢀ
ꢀ
N,N,N N -tetramethylthiourea
2,2-dipyridylamine (99%),
(99%),
1,3-bis(bromomethyl)benzene
(TMTU;
benzyl
1,2-bis(bromomethyl)benzene
(99%),
98%),
bromide
(99%),
1,4-
The current study has been undertaken to inves-
tigate the role of alkyl–phenyl spacer on the multi-
ple substitutions of the complexes with bidentate NˆN
bis(bromomethyl)benzene (99%), and AgClO4
(99.99%) were all obtained from Sigma Aldrich.
Potassium tetrachloroplatinate (K2PtCl4) was ob-
tained from Strem chemicals. Ultrapure deionized
water was used in all experiments. All other reagents
were of analytical grade and used without further
purification.
donors of the form [Pt(NˆN)X2]2 with biological
nucleophiles. The reaction of these complexes with
cis-PtCl2 configuration mimics the mechanism of cis-
platin. In this paper, dinuclear complexes with configu-
+
ration [Pt(NˆN)X2Pt(NˆN)X2]4 were formed by vary-
+
ing the connectivity of the alkyl spacer on the phenyl
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
3
2
+
4
+
H
N
2+
H
2
O
N
N
N
N
OH2
N
Pt
N
N
Pt
N
O
N
H O
2
OH2
Pt
N
N
H
2
OH
2
Pt
H O
OH2
2
Pt1
Pt2
Pt3
4
+
4+
N
N
N
N
OH2
N
H O
2
Pt
N
H O
2
N
OH2
H O
N
2
N
Pt
Pt
N
OH2
Pt
N
N
OH
2
H O
2
Pt4
Scheme 1 Schematic structures and abbreviations for the Pt(II) complexes.
Synthesis of Ligands
(400 MHz, CDCl3, 303 K) δ 8.40 (2H, d, py), 7.60 (2H,
t, py), 7.37 (2H, d, py), 7.27 (2H, d, ph), 7.20 (1H, t,
ph), 7.16 (2H, d, ph), 6.94 (2H, t, py), 5.55 (2H, s,
Syntheses of ligands were carried out using the stan-
dard Schlenkline procedures under dry nitrogen. The
ligands, namely di-2-pyridylaminomethylbenzene,
13
CH2); C NMR (400 MHz, CDCl3, 303 K) δ 157.5,
1
48.6, 139.8, 137.4, 128.0, 117.4, 114.4, 51.3, TOF
1
2
2
,2-bis(di-2-pyridylaminomethyl)benzene, 1,3-bis(di-
-pyridylaminomethyl)benzene,
-pyridylaminomethyl)benzene,
+
+
MS ES , m/z: 262.134 [M + H] .
,2-Bis(di-2-pyridylaminomethyl)benzene. Yield,
.369 g, (37%). Anal. Calcd. for C28H24N6, C, 75.65;
and
were
1,4-bis(di-
prepared
1
0
according to the literature procedure [34], starting
H, 5.44; N, 18.91; Found C, 75.39; H, 5.27; N, 19.28.
ꢀ
with 2,2 -dipyridylamine and their respective bromo
1
H NMR (400 MHz, CDCl3, 303 K) δ 8.32 (4H, d, py),
alkyl halide linkers. For each ligand, the respec-
tive bromoalkyl halide (0.855 g, 5.00 mmol) was
7
.53 (4H, t, py), 7.27 (2H, d, ph), 7.22 (4H, d, py), 7.04
13
(2H, t, ph), 6.86 (4H, dd, py), 5.64 (4H, s, CH2);
C
dissolved in 3 mL DMF at room temperature and
NMR (400 MHz, CDCl3, 303 K) δ 157.1, 148.2, 137.3,
ꢀ
2
,2 -dipyridylamine (0.856 g, 5.00 mmol) and KOH
+
1
36.4, 127.6, 126.4, 117.3, 114.6, 48.3, TOF MS ES ,
(1.137 g, 20.26 mmol) in 5.00 mL DMF was added
+
m/z: 445.2141 [M + H] .
dropwise. The resulting solution was stirred under
nitrogen at room temperature for 24 h and then
dried under in vacuo. The residue was washed with
water and extracted with CHCl3 (3 × 50 mL), and
the extracts dried over anhydrous sodium sulfate
and filtered. The filtrate was taken to dryness under
reduced pressure. The residue was chromatographed
on silica gel by elution with CHCl3:CH3OH (5:1).
The resulting yellow product was recrystallized
from an acetone–water mixture (1:2 v/v). However,
synthesis of 1,2-bis(di-2-bromomethyl)benzene was
carried out in DMSO and recrystallized in ethyl
acetate–petroleum ether.
1
,3-Bis(di-2-pyridylaminomethyl)benzene. Yield,
0.463 g, (46%). Anal. Calcd. for C28H24N6, C, 75.65;
H, 5.44; N, 18.91; Found C, 75.75; H, 5.36; N, 19.19.
1
H NMR (400 MHz, CDCl3, 303 K) δ 8.25 (4H, d,
py), 7.53 (4H, t, py), 7.27 (2H, d, ph), 7.22 (4H, d, py),
7
.04 (2H, t, py), 6.86 (4H, t, py), 5.64 (4H, s, CH2);
13
C NMR (400 MHz, CDCl3, 303 K) δ 157.1, 148.1,
+
139.6, 136.9, 128.4, 125.0, 114.3, 51.1, TOF MS ES ,
+
m/z: 445.2136 [M + H] .
1,4-Bis(di-2-pyridylaminomethyl)benzene. Yield,
0.599 g, (59%). Anal. Calcd. for C28H24N6, C, 75.65;
H, 5.44; N, 18.91; Found C, 75.57; H, 5.32; N, 19.27.
1
H NMR (400 MHz, CDCl3, 303 K) δ 8.28 (4H, d,
Di-2-pyridylaminomethylbenzene. Yield, 0.277 g,
py), 7.47 (4H, t, Py), 7.22 (4H, s, ph), 7.13 (4H, d,
(21%). Anal. Calcd. for C17H15N3, C, 78.13; H, 5.79;
13
py), 6.82 (4H, dd, py), 5.43 (4H, s, CH2); C NMR
1
N, 16.08; Found: C, 77.78; H, 5.55; N, 16.48. H NMR
(400 MHz, CDCl3, 303 K) δ 157.1, 148.1, 137.6, 137.1,
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

4
ASMAN
+
1
26.9, 117.1, 114.5, 51.0, TOF MS ES , m/z: 467.1957
Pt5. Yield, 106 mg (0.11 mmol) (51%). Anal. Calcd.
+
[
M + Na] .
for C28H24N6Pt2Cl4, C, 34.45, H, 2.48, N, 8.61; Found
1
C, 34.23, H, 2.34, N, 8.26. H NMR (400 MHz,
DMSO-d6, 303 K), 8.28 (4H, d, py), 7.63 (4H, t, py),
7
.19 (8H, s, py), 6.94 (4H, d, ph), 5.35 (4H, s, CH2),
Syntheses of Complexes
13
C NMR (400 MHz, DMSO-d6, 303 K): 157.6, 147.9,
+
The complexes were synthesized from their respective
ligands according to the literature method by Krebs
et al. [35] A 50-mL solution of K2PtCl4 was stirred,
and the corresponding molar equivalent of respective
ligands dissolved in a small amount of water was added
dropwise. The reaction mixture was refluxed overnight
at 50°C. The resulting platinum(II) complexes were ob-
tained as precipitates, washed with ultrapure water and
diethyl ether, and finally dried in vacuo. The synthe-
sized ligands and complexes were characterized using
137.6, 127.3, 117.6, 115.0, 50.4, TOF MS ES , m/z:
941.05 [M – Cl] . Pt NMR –2194.8 ppm.
+
195
Aquation of Chloro Complexes
Owing to the low solubility of the chloro complexes,
the complexes were converted to their aqua ana-
logues according to Bugar cˇ i c´ et al. [36] procedure.
The aqua solutions were prepared from their corre-
sponding chloro complexes by removing the chloride
ion using AgClO4. An almost stoichiometric amount
of AgClO4 was added to the solution and refluxed for
24 h at 50°C in the dark. The white AgCl precipitate
that formed was removed by filtration through a 0.45-
µm pore membrane filter. This was to ensure complete
conversion to aqua and removal of silver ions. The
aqua solutions were made to the required concentra-
tion using a solution of 0.1 M HClO4 acid. The use of
acidic solutions of pH 1.0 ensured that complex solu-
tions are in the aqua form and maintained a constant
ionic strength of 0.1 M. This ensured that pKa values
were determined at similar ionic strength. The aqua so-
lutions were titrated with NaOH solution to determine
the pKa of the complexes. While for all kinetic stud-
ies, a pH of 2.0 and an ionic strength at 0.1 M using
NaClO4 was maintained to minimize effects of ionic
strength.
1
13
195
H− C and Pt NMR, mass spectrometry and ele-
mental analysis.
Pt1. Yield, 66 mg, (63%), yellow powder. Anal.
Calcd. for C10H9N3PtCl2, C, 27.54; H, 2.08; N, 9.64;
Found C, 27.36; H, 2.29; N, 9.16. H NMR (400
1
MHz, DMSO-d6, 303 K), 8.80 (2H, d, py), 7.98 (2H,
t, py), 7.27 (2H, d, py), 7.14 (2H, t, py), 4.04 (1H,
13
s, N─H), C NMR (400 MHz, DMSO-d6, 303 K),
+
1
70.8., 150.4, 141.0, 119.4, 114.3, 60.1, TOF MS ES ,
195
m/z: 437.9808, Pt NMR –2103.4 ppm.
Pt2. Yield, 69 mg, (44%). Anal. Calcd. for
C17H15N3PtCl2, C, 38.72; H, 2.87; N, 7.97; Found C,
1
3
8.46; H, 3.07; N, 8.10. H NMR (400 MHz, DMSO-
d6, 303 K), 9.05 (2H, d, py), 8.04 (2H, t, py), 7.68 (2H,
d, py), 7.53 (2H, d, py), 7.36 (2H, t, py), 7.26 (5H, d,
ph), 5.43 (2H, s, CH2); 13C NMR (400 MHz, DMSO-
d6, 303 K): 153.8, 151.8, 142.1, 136.3, 129.8, 122.1,
+
+
1
17.4, 54.3, TOF MS ES , m/z: 550.0247 [M + Na] ,
1
95
Pt NMR –2189.2 ppm.
Physical Measurements
Pt3. Yield, 75 mg (0.08 mmol) (36%). Anal. Calcd.
for C28H24N6Pt2Cl4, C, 34.45, H, 2.48, N, 8.61; Found
C, 34.32, H, 2.52, N, 8.56. 1H NMR (400 MHz,
DMSO-d6, 303 K), 8.83 (2H, d, py), 8.20 (2H, t, py),
Characterization of both the ligands and complexes
1
13
ꢀ
195
using H, C , and
Pt NMR spectroscopy was
recorded on a Bruker Avance III 500 or Bruker Avance
400 spectrometers at frequencies of 500 or 400 MHz
and 125 MHz/100 MHz using either a 5-mm BBOZ
probe or a 5-mm TBIZ probe. All proton and carbon
shifts were recorded with reference to the relevant sol-
vent signal used. Chemical shift values are given in δ
7.96 (2H, d, py), 7.56 (4H, d, py), 7.44 (2H, t, py), 7.26
(
(
4H, d, py), 7.02 (2H, t, ph), 6.92 (2H, d, ph), 5.38
4H, s, CH2), 13C NMR (400 MHz, DMSO-d6, 303
K): 157.2, 153.4, 148.6, 138.2, 125.4, 117.6, 113.7,
+
+
195
5
–
1.0, TOF MS ES , m/z: 941.05 [M –Cl] , Pt NMR
2187.3 ppm.
1
(ppm) of H relative to tetramethylsilane (Si(CH3)4),
195
Pt4. Yield, 92 mg (0.10 mmol) (44%). Anal. Calcd.
whereas Pt was externally referenced to K2[PtCl6]
in D2O. For mass determination, a Waters Micro-mass
LCT Premier spectrometer was employed. Elemental
analysis was obtained on a Thermo Scientific Flash
2000. Kinetic studies for fast reactions were moni-
tored using an Applied Photophysics SX20 stopped-
flow spectrophotometer coupled to an online data ac-
quisition system, whereas a Varian Cary 100 Bio UV–
visible spectrophotometer thermostated by a Varian
for C28H24N6Pt2Cl4, C, 34.45, H, 2.48, N, 8.61; Found
C, 34.32, H, 2.52, N, 8.56. 1H NMR (400 MHz,
DMSO-d6, 303 K), 8.83 (2H, t, py), 8.22 (2H, d, py),
8
.02 (3H, d, py), 7.58 (4H, d, py), 7.44 (3H, d, py),
.28 (4H, d, ph), 7.02 (2H, d, py), 5.39 (4H, s, CH2);
C NMR (400 MHz, DMSO-d6, 303 K): 157.1, 148.8,
7
13
+
138.6, 114.2, 111.3, 54.5, TOF MS ES , m/z: 941.04
+
195
[
M – Cl].
Pt NMR –2190.6 ppm.
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
5
Peltier temperature controller to within ± 0.05°C was
used for the slow kinetic measurements. The kinetic
Computational Calculations
ꢁR
Density functional theory (DFT) calculations were
performed with the Gaussian 09 program suite
traces were analyzed using the Origin 7.5 software
package [37]. The pH of the solutions was recorded
on a Jenway 4330 conductivity/pH meter. Standard pH
calibration buffer solutions (pH 4.0, 7.0, and 10.0) were
used for calibration.
[39]. Geometrical optimizations were carried at
B3LYP/LanL2DZ level of theory. B3LYP refers to a
three-parameter functional hybrid exchange of Becke
[
[
40] with functional correlation gradient of Lee et al.
40], whereas LanL2DZ refers to Los Alamos National
Laboratory 2 Double ζ basis set [40]. The singlet states
were used due to low electronic spin of Pt(II) com-
plexes. The aqua complexes were modeled as cations
of overall charge +2 for mononuclear and +4 for din-
uclear. The DFT provided the ground state properties
of the systems and the electron density. Molecular or-
bital calculations were performed to give HOMO and
LUMO energies using LanL2DZ/B3LYP basis set.
pK Determination of the Aqua Complexes
a
To obtain the intrinsic information on the acidity of
the complexes and their effect on reactivity, their pKa
values were determined. UV–vis spectra for the deter-
mination of pKa values were recorded on a Varian Cary
100 Biospectrophotometer. NaOH was used as the base
for spectrophotometric titration in the pH range 1–10.
To avoid absorbance corrections due to dilution, a large
volume of the platinum aqua complex (250 mL) was
used. Solid NaOH pellets were used initially in the
pH range of 1–3 after which the Pasteur pipettes were
used for dropwise addition of 0.5, 0.1, 0.05, and 0.001
M of NaOH solution and similar concentrations for
perchloric acid for adjusting the pH.
RESULTS AND DISCUSSION
pK Determinations for the Aqua Pt(II)
a
Complexes
To ascertain the pKa values of the complexes, a titration
study was undertaken. Figure 1 show a typical UV–vis
spectrum recorded during spectrophotometric titration
of the aqua complex solution with NaOH. To determine
pKa values, absorbance was measured as a function
of pH. This resulted in a characteristic sigmoid curve
from which the pKa was determined by locating the
inflection point (Figs. S39 and S40 in the Supporting
Information).
The study shows the nature and conformation of the
spacer in the dinuclear complexes to have little influ-
ence on the pKa values as they are of similar magni-
tude. The ortho/para orientation effect of the alkyl sub-
stituent has a natural consequence of the preferential
stabilizing influence as exhibited in this investigation.
The effect depends on the position of the alkyl group,
which exhibits stronger electron-donating effect in the
para position than ortho and meta positions [41a–c].
The only difference among these three complexes is
the position of the alkyl group on the phenyl group.
The study notes that the slight change in the anchor-
age position results in a significant difference in their
chemical structure, pKa values, and reactivity. This in-
vestigation shows that alkyl group’s electron-donating
effect in ortho/para is stronger than in the meta posi-
tion. This is supported by computational calculations
Kinetic Measurements
Substitution reactions were performed at pH 2.0, where
the complexes exist in their aqua form (as predeter-
mined when determining pKa) and protonation of TU
nucleophiles ruled out [38]. The rate of substitution
of the aqua complexes was determined under pseudo–
first-order conditions as a function of nucleophile con-
centration and temperature using stopped flow for fast
and UV–vis spectroscopy for slow reactions by follow-
ing the change in absorbance at suitable wavelengths
(Table S1 in the Supporting Information). All the ki-
netic runs were fitted by a single exponential to deter-
mine the kobs. The activation parameters of enthalpy
#
#
(
ꢀH ) and entropy(ꢀS )were obtained by varying the
temperature between 288 and 313 K at an interval of
K. These parameters were calculated from Eyring
plots using Eq. (1):
5
ꢀ
ꢁ
ꢂ
ꢀ
ꢁꢃ
#
#
k2
ꢀH
= − RT + In
kB
h
ꢀS
R
In
+
ꢁ
T
ꢀ
#
#
ꢀ
H
ꢀS
=
+ 23.8 +
(1)
RT
R
(Table III) showing varying bond angles of C1N3C2
where kB and h are Boltzmann’s and Planck’s con-
stants, respectively, whereas R is a gas constant and T
is absolute temperature.
Pt5 (123.07°) > Pt3 (122.72°) > Pt4 (118.55°), repre-
senting para > ortho > meta, respectively. Thus, the
meta complex is more acidic since it only has inductive
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

6
ASMAN
1
.2
.1
.0
.9
0.8
.7
.6
1
3
2
2
1
1
0
.0
.5
.0
.5
.0
.5
1
λ
= 2 7 5 nm
0
0
0
1
2
3
4
5
6
7
8
pH
2
00
220
240
260
280
300
320
340
Wavelength (nm)
Figure 1 UV–vis spectra of Pt1 complex recorded as a function of pH in the range of 2–8 at 25°C; inset is a plot of absorbance
versus pH at λ = 275 nm. [Color figure can be viewed at wileyonlinelibrary.com]
2
+
+
N
N
OH2
N
N
OH
+
H O/H O
N
Pt
+
N
Pt
2
3
H O/H O
N
N
2
3
OH
OH
OH2
OH2
Ka2
N
Pt
Ka
1
Scheme 2 Proposed mechanism for stepwise deprotonation of the diaqua Pt(II) mononuclear complex.
effects, whereas the ortho/para complexes experience
both inductive and resonance effects. This investigation
shows the ortho/para orientation effect of the alkyl sub-
stituent has a natural preferential stabilizing effect. The
study shows that substituents’ position has an influence
on the stability of a complex through both electronic
and steric effects. Thus, by having alkyl substituents
at ortho and para positions behave identically but dif-
ferent from that of meta position. As such, one would
expect the meta complex to have a significantly differ-
ent pKa value as observed in this investigation.
The acidity of complexes shows that the dinuclear
complexes are slightly more acidic using first deproto-
nation for comparison. This difference can be ascribed
to the difference in the overall charge of the complexes
which is +2 for the mononuclear and +4 for the dinu-
clear complexes. Coordination of a second Pt(II) atom
results in addition of charges that make the dinuclear
platinum complexes more electrophilic thus favouring
aqua deprotonation. The results also show that the de-
protonation of the subsequent water molecules occurs
at higher pH values. This is due to the sequential re-
duction of the overall charge after each deprotonation,
which results in the Pt(II) center of the aqua/hydroxo
species being less electrophilic [8,25] leading to higher
pKa values. Complex Pt1 showed three pKa values,
which are attributed to the two aqua ligands and the
pendant acidic proton on N. The proposed deproto-
nation process can therefore be represented by the
equilibrium reaction given in Scheme 2 whereas the
pKa values are summarized in Table I. The results sup-
port a stepwise deprotonation. This investigation shows
similar behavior in deprotonation process to previous
study by van Eldik [36d] and group on dinuclear Pt(II)
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
7
Table I A Summary of pKa Values Obtained for Stepwise Deprotonation of Aqua Pt(II) Complexes Investigated
Complex
Pt1
Pt2
Pt3
Pt4
Pt5
pKa1
pKa2
pKa3
pKa4
2.72 ± 0.06
3.80 ± 0.02
5.68 ± 0.02
2.87 ± 0.02
6.97 ± 0.11
2.55 ± 0.03
3.24 ± 0.03
5.46 ± 0.02
7.37 ± 0.04
2.39 ± 0.01
3.65 ± 0.03
4.41 ± 0.02
6.90 ± 0.08
2.61 ± 0.01
3.62 ± 0.01
4.16 ± 0.03
7.43 ± 0.01
ꢁR
Boltzmann equation, y = A
2
+(A
1
−A
2
)/(1 + exp((x−x
0
)/dx), was used in determining the pKa values using the Origin 7.5 program (Figs.
S39–S41 in the Supporting Information).
Table II The Optimized Structures of the Molecular Frontier Orbitals of the Studied Complexes at B3LYP/LanL2DZ
Level of Theory (Iso Value = 0.02)
complexes coordinated to four aqua ligands that
showed four acid dissociation steps. The two aqua lig-
ands coordinated to each platinum center exhibited dif-
ferent pKa values supporting recent study by Jaganyi
and Kinunda using the same head group [41d]. This
study shows dinuclear complexes to be more acidic
than mononuclear analogues due to increased charge
as reported in the literature [36].
determine the structural and electronic properties of
the molecules. The complexes were fully optimized in
gas phase, and their frontier molecular orbitals and se-
lected geometrical parameters are summarized in Ta-
bles II and III respectively. To understand the extent
of deviation from planarity, dihedral and basal angles
were determined as shown in Fig. 2. The optimized
structures show that the six-membered chelate rings
containing the platinum adopt a twisted-boat confor-
mation. The bond angles of the amine nitrogen are
Computational Studies
2
close to 120° an indication of sp hybridized nitro-
gen atom [42a]. The introduction of the alkyl–phenyl
spacer results in a conformation that is dependent on
the position of the alkyl group on the phenyl, that form
bowl like cavity. In the case of both ortho and meta
To gain further insight into the influence of the an-
chorage position of the alkyl–phenyl spacer on the
conformation and possible kinetic properties of the
complexes, computational studies were undertaken to
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

8
ASMAN
Table III A summary of selected DFT data for the investigated complexes
R
N
3
1
2
N
N
5
1
Pt
2
3
4
H
2
O
OH
2
2
1
Pt1
Pt2
Pt3
Pt4
Pt5
HOMO–LUMO energy
LUMO (eV)
HOMO (eV)
−9.18
−13.20
4.02
−8.77
−11.88
3.11
−11.64
−15.82
4.18
−11.46
−15.65
4.19
−11.33
−15.53
4.20
࢞
E (eV)
Electrophilicity index (ω)
31.15
34.20
45.10
43.78
43.41
NBO Charges
Pt1
Pt2
N1
N2
0.766
−
0.760
−
0.770
0.770
−0.520
−0.520
−0.501
9.04
0.766
0.766
−0.516
−0.517
−0.509
5.78
0.771
0.771
−0.520
−0.521
−0.505
1.78
−0.528
−0.528
−0.634
2.30
−0.518
−0.520
−0.508
6.44
N3
Dipole moment (Debye)
˚
Bond length (A)
C1─N3
C2─N3
C1─N1
C2─N2
Pt−N1
1.3979
1.3979
1.3688
1.3688
2.0099
2.0099
1.4112
1.4091
1.3737
1.3737
2.0042
2.0041
1.4189
1.4189
1.3751
1.3751
2.0039
2.0039
11.758
1.4277
1.4182
1.3758
1.3728
2.0018
2.0018
12.088
1.4140
1.4134
1.3751
1.3753
2.0045
2.0046
13.871
Pt−N2
Pt1 . . . Pt2
Bond angles ( )
o
C1N3C2
Dihedral angles
Basal angle
127.25
39.88
140.12
120.30
50.37
129.63
122.72
43.52
136.48
118.55
50.13
129.87
123.07
44.26
135.74
Where R = H, benzyl.
−
the boat conformation is not part of the cavity created
between the two metal centers whereas in the para it
is part of the cavity. In meta and para, the phenyl ring
is positioned in the center of the cavity whereas in the
ortho it is away from the cavity. These configurations
introduce steric hindrance to the incoming nucleophile
to different degrees. DFT calculations show that there
is very little if any electronic effect when the pendant
alkyl–phenyl is attached to Pt2 or used as a spacer in Pt3
to Pt5. Both the NBO charges and the electrophilicity
index are similar in magnitude because of Pt(II) centers
being in similar environment due to identical atomic
and conjugative connectivity to at least five atoms in
all directions. This is also supported by the HOMO–
LUMO gap. The difference between the reactivity of
monomers and the dinuclear complexes is attributed
to the complex [42b]. One would therefore expect that
the reactivity of these complexes to be controlled by
the steric effect.
orbitals. The strong σ donation from H in Pt1 shows
HOMO orbitals to be localized on the pyridine rings
and on the d orbitals of the metal. The negative charge
built on the metal by strongly σ-donating –NH- moi-
ety in Pt1 destabilizes the metal dπ orbitals thus
lowering the dπ → π*. This results from increased
electron density on either a pyridine ring by conju-
gation with π electrons of the pyridine rings. The
2
complex, Pt1, involves 5dz orbitals which is the
highest occupied molecular orbital and as a con-
sequence strongly repels the incoming nucleophile
compared to Pt2. As such there is a greater repul-
2
sive effect of dz than d , d , and d orbitals be-
xz
yz
xy
cause of its orientation to the entering ligand. On the
contrary, the d , d , and d orbitals are oriented
away from the incoming ligands and are lower in
energy. The greater electron transfer from H donor
to the 5dz orbitals of the platinum center destabi-
lizes these orbitals than the dxz and dyz orbitals. This
xz
yz
xy
−
2
The study shows Pt(II) to be sensitive to the num-
ber of d electrons and their arrangement in the d
strong electron transfer to the acceptor pyridyl rings
that fills 5dz orbitals of metal center leads to higher
2
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
9
Figure 2 DFT-optimized structures of Pt1 and Pt2 showing dihedral and basal angles of the boat conformed pyridine rings.
Color figure can be viewed at wileyonlinelibrary.com]
[
stabilization energy of the Pt(II) center hence slow
reactivity.
different concentrations of nucleophile [Nu]. The kobs
values were obtained from nonlinear least squares fit
of the experimental data by fitting to Eq. (2) [9].
The study utilized the reactivity index (elec-
trophilicity index, ω) to measure the stabilization in
energy when the system acquires an additional elec-
tronic charge from the environment [43–49]. This value
supports Pt2 (34.20 eV) to be more reactive than Pt1
(−kobst)
At = A∞ + (A0 − A∞) exp
(2)
where A0, At, and Aꢀ represent the absorbance of the
reaction mixture initially, at time t, and at the end of the
reaction, respectively. The second-order rate constant,
k2, for the reaction of each metal complex was ob-
tained from the linear regression of the plots of kobs ver-
(31.15 eV), which is in line with the experimental data.
This difference in the electrophilicity values between
the two complexes indicates a measure of energy low-
ering between the ligand systems due to maximal elec-
tron flow between the donor and acceptor. For changes
in the ligand system, the dipole moments decrease in
the order Pt2 (6.44 D) > Pt1 (2.30 D) which further cor-
roborates with the reactivity of the two moieties show-
ing Pt2 with higher dipole moment to have greater re-
activity. However, the dinuclear isomers show no clear
dipole moment trend in relation to reactivity as a con-
sequence of different arrangement of substituents in
ortho, meta, and para positions. As expected, the dipole
moments followed the following order Pt3 (ortho) >
Pt4 (meta) > Pt5 (para). The trend exhibits the elec-
tron density distribution in the complexes. However,
this study shows dipole forces to have no significant
influence on the reactivity of dinuclear complexes.
ꢁR
sus nucleophile concentration using origin 7.5 [37].
Straight lines with zero or with negligible intercepts
were obtained as presented in Figs. 6 and S1–S6 in
the Supporting Information. A summary of k2 values
calculated at 25°C for the two steps are given in Table
III and the corresponding rate law described by Eq. (3)
kobs(1/2) = k−2 + k2(1st/2nd) [Nu] ≈ k2(1st/2nd) [Nu] (3)
where k−2 is a solvent path and is either zero or in-
finitesimal and k2 is the second-order rate constant
for a direct path. The two observed substitution steps
are due to the simultaneous substitution of the water
molecules followed by the dechelation of the linker as
supported by the NMR study.
Kinetic Measurements
Activation Parameters
The kinetics of substitution of coordinated aqua lig-
ands were investigated spectrophotometrically using
conventional UV–vis and stopped flow techniques. A
typical stopped-flow kinetic trace obtained is shown
in Fig. 3, whereas Figs. 4 and 5 represent the typical
UV–visible spectrophotometer kinetic traces. For each
reaction, the values of kobs were determined at five
The activation parameters for the reactions were de-
termined from the Eyring plots shown in Fig. 7 and
in (Fig.s S7–S10 in the Supporting Information). The
corresponding values for the activation parameters of
#
#
Enthalpy, ꢀH , and entropy, ꢀS , are summarized in
Table V. These results are temperature depentent and
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

1
0
ASMAN
0
0
0
0
0
0
0
.170
.168
.166
.164
.162
.160
.158
0
3
6
9
12
Time (seconds)
Figure 3 A typical kinetic trace showing a substitution step between Pt2 and TU at 290 nm, T = 298.15 K, pH 2.0, I = 0.1 M
NaClO4) on the stopped-flow spectrophotometer.
15
18
21
24
27
30
(
0
0
.6 5
.6 0
0
0
0
0
0
0
0
.90
.75
.60
.45
.30
.15
.00
3
2 0 nm
0.5 5
0
0
0
0
.5 0
.4 5
.4 0
.3 5
0
2 00
400
600
8 00
1000
120 0
14 00
T im e (m in )
3
00
320
340
360
380
400
420
W avelength (nm )
Figure 4 Absorbance spectra of Pt2 with TU; inset is a typical kinetic trace on the UV–visible spectrophotometer at 320 nm,
T = 298 K, pH 2.0, and I = 0.1 M NaClO4. [Color figure can be viewed at wileyonlinelibrary.com]
1
are in agreement with an associative substitution mech-
anism for square planar Pt(II) complexes based on the
negative activation entropy values as reported in the
literature [9,10,55].
spectroscopy. Figures 8 and 9 show arrays of H and
195
Pt NMR spectra, respectively. The pyridyl protons
(H ) were monitored due to their proximity to N-donor
atoms coordinated to the metal center. The proton res-
a
onances of this unreacted chloro complex (Pt2) labeled
Ha appear at δ = 9.05 ppm and δ = −2189.2 ppm on
Substitution Process
1
195
H and Pt NMR spectra, respectively. During the
From the kinetic studies, the substitution proceeds via a
two-step associative mechanism. The first step was at-
tributed to simultaneous substitution of the labile aqua
ligands at each platinum center. To confirm the sec-
ond step as the displacement of the ligand, substitu-
tion reaction of complex Pt2 as a chloride with TU
course of reaction, these resonances shift upfield to
1
195
δ = 8.40 ppm and δ = −3889.2 ppm on H and Pt
NMR, respectively. These shifts are attributed to the
complexation between the metal and the ligand. This
is because on coordination, the metal center pulls elec-
tron density from the pyridyl rings causing deshield-
ing of protons to lower field as indicated by Ha in
1
195
(6 equiv.) was monitored by H NMR and Pt NMR
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
11
0
0
0
0
0
0
0
0
.7
.6
.5
.4
.3
.2
.1
.0
0.35
0
0
0
0
0
.30
.25
.20
.15
.10
3
20 nm
0
500
1000
1500
2000
2500
Time (min)
3
00
310
320
330
340
350
360
370
Wavelength (nm)
Figure 5 The time-resolved UV–vis absorption spectra of Pt5 with TU; inset is a kinetic trace for time dependence of
absorbance at 320 nm showing a two-step reaction at T = 298.15 K, pH 2.0 and I = 0.1 M NaClO4. [Color figure can be viewed
at wileyonlinelibrary.com]
-
-
-
6.0
6.3
6.6
0
0
0
0
0
0
0
.6
.5
.4
.3
.2
.1
-6.9
-
-
-
7.2
7.5
7.8
TU
DMTU
TMTU
TU
DMTU
TMTU
-8.1
8.4
-
.0
0
.000
0.003
0.006
0.009
0.012
0.015
0.018
0
.00325
0.00330
0.00335
0.00340
0.00345
0.00350
[
Nu] M
-
1
1
/T (K )
Figure 6 Concentration dependence of k2 for the substitu-
tion of the simultaneous aqua ligands in Pt2 by nucleophiles
at pH 2.0, T = 298.15 K, I = 0.1 M NaClO4.
Figure 7 Eyring plots for the determination of the activa-
tion parameters for the aqua substitution of Pt2 with respec-
tive nucleophiles I = 0.1 M NaClO4, pH 2.0.
Fig. 8. The H and 195Pt NMR confirms changes in
electron distribution within the ligand–metal coordi-
nation sphere.
1
placement of the dipyridylamine ligand due to strong
trans-effect of sulfur on coordination of TU to the
Pt(II) center. These results are in accordance to the
previous work reported on Pt(II) complexes of the
type [L2PtX2] where X = anionic leaving group; L
= ammonia, amine, pyridine [51–53] Also studies
on mononuclear dipyridylamine bidentate Pt(II) com-
plexes appended to the alkyl flexible backbone re-
cently reported by our group [41d] show similar be-
havior of this ligand head group to undergo dechelation
process.
The peak at −2189.2 ppm on the 195Pt NMR
spectrum is indicative that the platinum is coordi-
nated to two nitrogen atoms [50], whereas the peak at
−
3889.2 ppm in Fig. 9 shows the formation of the
2+
Pt(TU)4 complex [20] due to the excess TU dis-
2+
placing the ligand. The formation of the Pt(TU)4
complex supports the reaction mechanism proposed
in Scheme 3. From these observations, it can be
concluded that the second step is due to the dis-
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

1
2
ASMAN
1
Figure 8 Time-dependent changes in the H NMR spectra array of Pt2 upon addition of 6 equiv. of TU in DMF. The complex
undergoes dechelation to form free ligand (starting material) after 24 h. [Color figure can be viewed at wileyonlinelibrary.com]
DISCUSSION
electronic effect although there may be minor extent
of steric factors. The slow reactivity of Pt1 is due to
the stronger σ-donor property of H which increases
−
In this paper, the role of alkyl–phenyl moiety as a
pendant and a spacer group on the reactivity Pt(II)
complexes with multisubstitution of four aqua ligands
with TU nucleophiles of different electronic and steric
demands was investigated. The general reactivity in
terms of k2 values increased in the following order:
electron density around the ligand system in compar-
ison to the ─CH2─ group. The study shows a strong
influence of the bridging moiety on the molecular and
electronic properties of the complexes [55]. This is
supported by DFT data in Table III, which shows a
higher negative charge density (−0.634) on the amine
nitrogen (N3) in Pt1 compared to Pt2 with (−0.508).
This is further supported by the electrophilicity
index values and the short C1─N3 and C2─N3
bond lengths in Pt1 compared to Pt2. The stronger
−
1
−1
−1 −1
) > Pt1 (28.85 M s
Pt2 (33.34 M
s
) > Pt4
s ) > Pt5 (0.04
−
1
−1
−1 −1
(
0.16 M
s
) > Pt3 (0.08 M
−
1
−1
M
s ) with TU as the entering nucleophile (Table
IV). This observed reactivity trend is in line with the
overall electrophilicity and the steric demands of the
complexes.
−
electron donation of H compared to ─CH2─ is also
The study shows that mononuclear Pt(II) complexes
react faster than dinuclear analogues. This is in agree-
ment with earlier findings by Adnan and Mika [54]
who attributed the retardation to increased amount of
steric demand in dinuclear Pt(II) complexes compared
to mononuclear complexes. The steric effect is due to
the “cage in-effect” as a result of the linker coordina-
tion position. The difference in reactivity between the
two mononuclear complexes is attributed mostly to the
evident in the HOMO–LUMO energy gap (ꢀE) dif-
ference between the two complexes. It is important to
note that energy gap is an important stability index. The
large gap of Pt1 (4.02 eV) compared to Pt2 (3.11 eV)
implies high stability for this complex. The net result
is a system that is more electronegative in Pt1 than
in Pt2. In addition to the electronic effect is the en-
trapment of the nucleophile in the cavity created the
two pyridine rings. The basal angle for Pt1 (140.12°)
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
13
Figure 9 (a) Time-dependent 195Pt NMR chemical shift of Pt2 in DMF-d7 showing a peak at −2189.2 ppm. (b) Addition of 6
equiv. of TU leads to the disappearance of the peak at −2189.2 ppm. (c) The peak at −3889.2 ppm is attributed to the formation
of the [Pt(TU)42 ] complex. [Color figure can be viewed at wileyonlinelibrary.com]
+
is larger than that of Pt2 (129.63°) that results in a
more effective collisions between the metal and the
nucleophile.
compared to Pt3 and Pt5 which are comparable. One
would therefore expect the cavity in Pt4 to entrap the
incoming nucleophile much better than Pt3 and Pt5 re-
sulting in higher reactivity, which is in agreement with
the observed results. Looking at the bowl-like cav-
ity between the two Pt-metal centers, it can be noted
that the ─CH2─ and the phenyl that form the pendant
attachment introduce steric hindrance at a different de-
gree to each complex on both side of the platinum atom.
For instance, the twisting of pyridyl rings in Pt5 causes
the coordinated metal ions to be maximally shielded
and thus prevented from nucleophilic attack. This is
very different to the mononuclear complexes that do
not experience this type of steric hindrance and there-
fore accounting for the difference in reactivity between
the two types of systems.
The shape and size of these cavities also influence
the effectiveness of the entrapment of the incoming nu-
cleophile exhibiting the difference in reactivity [56,57].
The DFT data show that the electronic effect of all
the three dinuclear complexes is very similar, suggest-
ing that the difference in reactivity is mostly due to
the structural conformation [58]. This is in agreement
with previous studies [58] showing the bridging linker
to confer special structural properties on the metal
complexes that controls their reactivity and stability.
Introduction of a second platinum center in Pt2 to
form a dinuclear Pt(II) complex leads to structural
and conformational differences that influence their
chemical reactivity. This difference in the three din-
uclear complexes is aided by the incorporation of an
aminomethyl spacer that provides greater flexibility to
the complexes. This results in the twisting of com-
plexes to form cavities of different shapes and sizes.
The inorganic hybrid architectures show novel chemi-
cal and physical properties of the investigated dinuclear
Pt(II) complexes.
The reactivity of the dinuclear complexes is ap-
proximately 100 times slower than the mononuclear
complexes. The reactivity trend can be summed up as
Pt4 (meta) > Pt3 (ortho) > Pt5 (para) even though the
reactivities are small. In these complexes, there are two
types of cavities which influence the reactivity. These
are the cavity due to the twisting of the two pyridine
rings attached to the Pt-atoms and the cavity created
due to the formation of the dinuclear complex. The first
cavity is measured by determining the basal angle as
shown in Fig. 2 and values presented in Table III. The
basal angle shows that Pt4 to have the smallest angle
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

1
4
ASMAN
2
+
2
+
2+
N
OH2
OH2
Nu
+ 2Nu
Nu
Nu
N
Nu
Nu
+
2Nu -2H O
2
N
Pt
Pt
+
Pt
k2(1st)
k2(2nd)
N
Nu
N
N
2
+
[
Pt(Nu)4]
Linker
Scheme 3 Proposed substitution mechanism showing simultaneous substitution of diaqua ligands with nucleophiles (Nu) on
Pt2 followed by ring opening of the ligand.
Table IV A Summary of the Second Order Rate
Constants, k2, for the Simultaneous Substitution of
Aqua Ligands (k2(1st) and the Dechelation Step k2(2nd) at
pH = 2.0, T = 298.15 K, I = 0.1 M NaClO4
of dinuclear complexes, this paper reports reactivity to
be mainly dependent on conformational makeup and
to smaller extent electronic contribution in the ortho,
meta, and para complexes to varying levels. Thus, the
stability of the complexes was maximized when steric
and electronic parameters reinforced each other.
Second-Order Rate Constant
−
1 −1)
(
M
s
The substitution of the aqua ligands by nucleophiles
TU, DMTU, and TMTU showed a clear dependence
on the steric hindrance of the nucleophile. However,
in Pt1 and Pt4 DMTU was found to be slightly faster
than TU; this enhanced reactivity is attributed to the
inductive effect introduced by the two methyl groups
on DMTU which over compensates the steric effect
3
Complex
Pt1
Nu
k2(1st)
k2(2nd) × 10−
TU
28.85 ± 0.18
33.42 ± 0.15
10.38 ± 0.05
33.34 ± 0.27
25.09 ± 0.19
11.45 ± 0.04
0.08 ± 0.001
0.02 ± 0.001
0.01 ± 0.001
0.16 ± 0.004
0.21 ± 0.003
0.04 ± 0.002
0.04 ± 0.001
0.01 ± 0.001
20 ± 3
DMTU
TMTU
TU
DMTU
TMTU
TU
DMTU
TMTU
TU
DMTU
TMTU
TU
10 ± 1
10 ± 1
Pt2
Pt3
Pt4
Pt5
30 ± 4
10 ± 0.1
10 ± 0.2
1 ± 0.03
1 ± 0.01
1 ± 0.01
40 ± 2
[59]. The small but positive enthalpy and large negative
entropy confirm the associative mode of mechanism for
all the investigated complexes. This is an indication
that the mechanistic reactions of these complexes are
characterized by bond formation in the transition state
20 ± 1
[60,61]. The activation parameters also imply a good
10 ± 1
degree of ligand participation in the transition state and
a more compact transition state than that of the starting
reactants [62].
3 ± 0.06
1 ± 0.01
DMTU
Note: Reaction of TMTU with Pt5 was too slow.
CONCLUSION
Investigation of structural differences in dinuclear
Pt(II) complexes shows steric effect of the spacer
through cavities realized through changing the anchor-
age position, which supports previous study by Mam-
banda and Jaganyi [58]. This study shows the dinu-
clear complexes to have a cage effect through adopting
bowl-shaped molecular structures that controls reactiv-
ity. The decrease in the rate of substitution of dinuclear
complexes is attributed to steric contributions imposed
by the cavities of the complexes to varying degrees as
shown by the different size and shape of cavities as
shown by Figs. S34 and S35 (in the Supporting Infor-
mation). The data obtained in this study support the
previous studies by Jaganyi and group [58] that subtle
differences in the structural makeup of the linker can
have a greater influence on the reactivity of dinuclear
Pt(II) complexes. In contrast to previous studies where
metal–metal distance has an influence on the reactivity
The substitution kinetics of mono- and dinuclear Pt(II)
complexes with 2,2 -dipyridylamine units connected
by the alkyl–phenyl spacer was investigated. The re-
sults show that upon coordination of the metal atoms
to the pyridyl rings of 2,2 -dipyridylamine the com-
plex adopts inclined planes with varying dihedral and
basal angles. When the two metals are joined together
through a bridging ligand, the dinuclear complexes
form bowl-like cavities whose shape and size are very
dependent on the position to which the phenyl moiety
is joined to the complex. The study has shown that
the reactivities of these complexes are controlled by
steric effect, which is due to the architectural frame-
work of the complexes. The mononuclear complexes
being less sterically hindered compared to the dinu-
clear complexes, as such are 100 times more reac-
tive. The cavities formed due to the presence of the
ꢀ
ꢀ
International Journal of Chemical Kinetics DOI 10.1002/kin.21085

ROLE OF AN ALKYL–PHENYL SPACER ON THE REACTIVITY OF PLATINUM(II) COMPLEXES
15
Table V A Summary of the Activation Parameters for the Simultaneous Substitution of Aqua Ligands and the
Dechelation Step of the Studied Pt(II) Complexes
Activation Enthalpy (kJ mol 1)
−
Activation Entropy (J K mol )
−1
−1
#
#
1
#
#
Complex
Pt1
Nu
ꢀH
ꢀS
ꢀH
ꢀS
2
1
2
TU
33.78 ± 0.6
33.19 ± 1.8
44.39 ± 1.0
39.81 ± 0.3
43.47 ± 1.7
40.86 ± 0.8
29.17 ± 0.5
26.37 ± 0.5
39.03 ± 0.3
19.07 ± 0.3
26.83 ± 0.6
33.52 ± 0.2
32.25 ± 1.4
37.00 ± 0.7
−143 ± 2
−144 ± 6
−115 ± 3
−121 ± 1
−111 ± 5
−126 ± 3
−192 ± 2
−229 ± 2
−183 ± 1
−226 ± 1
−201 ± 2
−191 ± 1
−193 ± 4
−196 ± 2
22.27 ± 0.6
22.60 ± 0.9
60.76 ± 3.5
20.54 ± 0.8
26.74 ± 0.9
41.02 ± 1.5
16.78 ± 0.1
12.48 ± 0.3
20.14 ± 0.1
35.31 ± 0.9
27.49 ± 0.6
31.05 ± 1.1
20.63 ± 0.6
32.52 ± 0.6
−246 ± 2
−254 ± 3
−112 ± 12
−249 ± 2
−241 ± 3
−179 ± 5
−266 ± 1
−291 ± 1
−255 ± 1
−181 ± 3
−221 ± 2
−209 ± 4
−260 ± 2
−225 ± 2
DMTU
TMTU
TU
DMTU
TMTU
TU
DMTU
TMTU
TU
DMTU
TMTU
TU
Pt2
Pt3
Pt4
Pt5
DMTU
pyridine rings, and the ─CH2─ and phenyl group as
the linker plays a big role in influencing the entrapment
of the incoming nucleophile which in turn controls the
reactivity of these complexes.
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