Kinetics and mechanism of the substitution reactions of some monofunctional Pt(II) complexes with heterocyclic nitrogen donor molecules. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O

Article abstract of DOI:10.1080/00958972.2016.1224336

Substitution reactions of [Pt(terpy)Cl]⁺ (terpy?=?2,2′;6′,2′′-terpyridine), [Pt(bpma)Cl]⁺ (bpma?=?bis(2-pyridylmethyl)amine), [Pt(dien)Cl]⁺ (dien?=?diethylenetriamine or 1,5-diamino-3-azapentane) and [Pt(tpdm)Cl]⁺

Full text of DOI:10.1080/00958972.2016.1224336

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Kinetics and mechanism of the substitution
reactions of some monofunctional Pt(II) complexes
with heterocyclic nitrogen-donor molecules.
Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O
Milica Kosović, Snežana Jovanović, Goran A. Bogdanović, Gerald Giester,
Željko Jaćimović, Živadin D Bugarčić & Biljana Petrović
To cite this article: Milica Kosović, Snežana Jovanović, Goran A. Bogdanović, Gerald Giester,
Željko Jaćimović, Živadin D Bugarčić & Biljana Petrović (2016): Kinetics and mechanism of the
substitution reactions of some monofunctional Pt(II) complexes with heterocyclic nitrogen-
donor molecules. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O, Journal of Coordination
Chemistry, DOI: 10.1080/00958972.2016.1224336
To link to this article: http://dx.doi.org/10.1080/00958972.2016.1224336
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Date: 19 August 2016, At: 01:53

Publisher: Taylor & Francis
Journal: Journal of Coordination Chemistry
DOI: http://dx.doi.org/10.1080/00958972.2016.1224336
Kinetics and mechanism of the substitution reactions of some monofunctional
Pt(II) complexes with heterocyclic nitrogen-donor molecules. Crystal
structure of [Pt(bpma)(pzBr)]Cl2·2H2O
MILICA KOSOVIĆa, SNEŽANA JOVANOVIĆb, GORAN A. BOGDANOVIĆc, GERALD GIESTERd,
ŽELJKO JAĆIMOVIĆa, ŽIVADIN D BUGARČIĆb and BILJANA PETROVIĆ1b
aFaculty of Metallurgy and Technology, University of Montenegro, Cetinski put, 81000 Podgorica, Montenegro
bFaculty of Science, University of Kragujevac, R. Domanovića 12, P.O. Box 60, 34000 Kragujevac, Serbia
cVinča Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia
dFaculty of Geosciences, Geography and Astronomy, University of Vienna, Althanstraße 14, A-1090 Wien, Austria
Substitution reactions of [Pt(terpy)Cl]+ (terpy = 2,2';6',2"-terpyridine), [Pt(bpma)Cl]+ (bpma =
bis(2-pyridylmethyl)amine), [Pt(dien)Cl]+ (dien = diethylenetriamine or 1,5-diamino-3-
azapentane) and [Pt(tpdm)Cl]+ (tpdm = tripyridinedimethane) with nitrogen-donor heterocyclic
molecules, such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr)
and imidazole (Im), were studied in aqueous 0.10 M NaClO4 in the presence of 10 mM NaCl
using variable-temperature UV-Vis spectrophotometry. The second-order rate constants k2
indicate decrease in reactivity in the order [Pt(terpy)Cl]+ > [Pt(bpma)Cl]+ > [Pt(tpdm)Cl]+ >
[Pt(dien)Cl]+. The most reactive nucleophile among the heterocyclic compounds is imidazole,
while pzI shows slightly higher reactivity than pzBr. Activation parameters were also determined
and the negative values for entropies of activation, ΔS≠, support an associative mode of
substitution for all substitution processes. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O was
determined by single-crystal X-ray analysis. The coordination geometry of the complex is
distorted square-planar while the bond distance Pt-N2(pzBr) is longer than the other three Pt-N
distances.
1Corresponding author. Email: biljanap@kg.ac.rs

Keywords: Pt(II) Complexes; Kinetics; Mechanism; Diazines; Reactivity; Deformed
coordination geometry; Crystal structure
1. Introduction
Since the antitumor activity of cis-diamminedichloroplatinum(II) (cis-[Pt(NH3)2Cl2], cisplatin)
was discovered by Rosenberg et al. [1-3], it has become one of the most widely utilized
antitumor drugs, exhibiting high efficacy against testicular and ovarian cancer, bladder tumors
and tumors of the head and neck [3]. Success of cisplatin has led to incredible growth of
investigation in this field. Much attention has been focused on developing new platinum
complexes structurally similar to cisplatin. Two platinum complexes (carboplatin and
oxaliplatin) have been introduced in clinics worldwide as second generation drugs and another
three (nedaplatin, lobaplatin and heptaplatin) have been approved in individual nations [1, 4-9].
To achieve anticancer activity in a broader range of tumors with lower side effects, alternative
platinum complexes, such as trans platinum complexes, sterically hindered cis platinum
complexes and polynuclear platinum complexes, have been investigated [2, 8, 10]. Significant
research was directed towards examining the antitumor activity of other transition metal ion
complexes, such as complexes of ruthenium(II), ruthenium(III), palladium(II), iridium(III), etc.
[10-14].
Pt(II) complexes, especially with chelating ligands containing pyridine, were frequently
studied [15-20]. Although they do not possess antitumor activity, the main goal of these
investigations was to precisely define and understand the mechanism of antitumor action of
platinum drugs because those inert ligands combine different steric and electronic effects,
causing different solubility and reactivity in their application as antitumor drugs. According to
published results, the relatively small structural modifications in the structure of inert tridentate
ligands can produce significant changes in the reactivity of such complexes [20]. For example,
the involvement of methylene group between pyridine units in terpy strongly influence kinetic
behavior of complexes. Also, the presence of substituents with different electronic effects on
terpy, primarily in 4’-position, can force or prevent substitution. Substituents with π-electron-
withdrawing effect or σ-inductive donation stabilize the transition state and enhance the rate of
reaction [21, 22].

A number of platinum complexes with terpyridine were investigated to establish the
connection between the structure, kinetics and thermodynamic parameters, stacking in the solid
state and in solution. Also, the investigations were focused on displacement of terpy or oxidative
addition on Pt(II) [23]. Furthermore, recent reports have shown that platinum terpyridine
derivatives show remarkable anticancer activity, about 100 fold higher than cisplatin in the dark
[24-26].
Beside complexes with tridentate NNN donors, much attention has been focused on
monofunctional platinum complexes with tridentate NCN ligands [27]. Pt-C bond trans to the
leaving group in such complexes causes strong trans-effect. In the case of phenyl group as
carbon donor, the reaction is 102 times faster than in the case of aliphatic carbon donor. The
presence of phenyl groups in the cis position (CNC ligands) enhances the rate of substitution and
can induce mechanistic change of substitution process. However, steric hindrance of ancillary
groups of chelate ligand could influence the lability of complexes as well [28]. The presence of
five-membered instead of six-membered heterocyclic terminal rings on tridentate ligand
increases the substitution rate while the presence of bulky groups on inert ligand backbone
prevents attack of the nucleophile and decreases the rate of substitution.
The main target for antitumor active platinum complexes is DNA, so the behavior of
Pt(II) complexes toward different purine and pyrimidine derivatives have been studied
[16-18, 20]. Also, other biomolecules which are derivatives of pyrazole, imidazole or pyrazine
could be also potential targets for platinum complexes. Further, heterocyclic derivatives of
diazines are the constituents of different drugs (analgesics, anti-bacterial, anti-viral, anti-
inflammatory, anti-glycemia, anti-parasitic) which can be injected together with anti-tumor
agents [6, 29]. All these facts imply that detailed knowledge of the interactions between Pt(II)
complexes and heterocyclic nitrogen donor compounds is important.
With the aim of gaining insight into the structure-reactivity relationship, here we report
results of kinetic and mechanistic study of the substitution reactions of monofunctional Pt(II)
complexes, [Pt(terpy)Cl]+ (terpy = 2,2':6',2"-terpyridine), [Pt(bpma)Cl]+ (bpma = bis(2-
pyridylmethyl)amine), [Pt(dien)Cl]+ (dien = diethylenetriamine or 1,5-diamino-3-azapentane)
and [Pt(tpdm)Cl]+ (tpdm = tripyridinedimethane) with 3-amino-4-iodo-pyrazole (pzI), 5-amino-
4-bromo-3-methyl-pyrazole (pzBr) and imidazole (Im). All reactions were studied in aqueous
0.10 M NaClO4 in the presence of 10 mM NaCl to mimic real conditions [15]. One of the

products of the substitution, [Pt(bpma)(pzBr)]Cl2·2H2O, was isolated and its structure was
determined by X-ray diffraction. The structures of studied complexes and ligands are shown in
figure 1.
2. Experimental
2.1. Chemicals and solutions
[Pt(terpy)Cl]Cl·2H2O, [Pt(bpma)Cl]Cl·H2O (Mr = 482.9), [Pt(dien)Cl]Cl and
[Pt(tpdm)Cl]Cl·1.25H2O are synthesized according to previously published procedures
[20, 30-32]. The kinetics of substitution reactions were studied in medium with constant ionic
strength (0.1 M) adjusted with NaClO4 (Merck, p.a.). Also, 10 mM NaCl (Merck, p.a.) was
added to the medium to prevent hydrolysis of complexes.
Ligands imidazole (Acros), 3-amino-4-iodo-pyrazole, pzI, Mr = 208.99 (Sigma Aldrich)
and 5-amino-4-bromo-3-methyl-pyrazole, pzBr, Mr = 176.01 (Sigma Aldrich) were used without
purification. Stock ligand solutions were prepared by dissolving the chemicals in perchlorate
medium shortly before use. Ultra-pure water was used in all experiments.
Synthesis of [Pt(bpma)(pzBr)]Cl2 2H2O: [Pt(bpma)(pzBr)]Cl2·2H2O was synthesized
with reaction of the methanolic solution of pzBr (0.0022 g, 12.4 µM, 4 cm3) and aqueous
solution of [Pt(bpma)Cl]Cl (0.006 g, 12.4 µM, 5 cm3) mixed in molar ratio 1:1. pH of the
colorless solution was controlled at 7 because [Pt(bpma)Cl]Cl could be converted into the
unreactive hydroxo species at higher pH. The mixture was stirred for 24 h and after two days the
colorless crystal product was filtered off and washed with methanol. The crystals of the complex
are mechanically separated for X-ray analysis. Anal. Calc. for C16H23Cl2BrN6O2Pt (%) FW =
677.28: C, 28.37; H, 3.42; N, 12.41. Found: C, 28.29; H, 3.48; N, 12.10; UV-Vis: λmax (nm) =
245; 271, 1H NMR, 200 MHz, D2O: δ (ppm): 1.89 (s, 3H, CH3-pzBr); 3.76 (s, 4H, CH2-bpma);
7.42 (t, 2H, J = 6.8 Hz, H4-bpma); 7.68 (d, 2H, J = 8 Hz, H3-bpma); 7.74 (d, 2H, J = 6.8 Hz,
H6-bpma), 8.18 (t, 2H, J = 8 Hz, H5-bpma). IR (KBr, 4000-300 cm-1): 3500-3200 (N-H stretch,
O-H stretch); 3150-2850 (-CH stretch, =CH stretch); 1630 (C=N stretch); 787 (N-H wagging)
(figures 1S-3S, Supplementary Material).

2.2. Instrumentation and measurements
UV-Vis spectra and kinetics of the reactions were monitored by a Perkin Elmer Lamda 25
spectrophotometer with automatic cell changer and Peltier temperature-controller as well as a
Perkin Elmer Lamda 35 double-beam spectrophotometer equipped with water thermostated cells.
The temperature was controlled throughout all kinetic experiments to 0.1 °C. Chemical
analyses were performed on a Carlo Erba Elemental Analyser 1106. IR spectra were recorded on
a Perkin Elmer FTIR 31725 spectrometer using KBr pellets. pH was controlled by Hanna
Instruments HI 9017 micro processor pH meter equipped with a Radiometer combined electrode.
X-ray analysis was performed on a Nonius Kappa CCD diffractometer equipped with a
monocapillary optics collimator, MoKα radiation (λ = 71073 Å). NMR spectra were scanned by
a Varian Gemini 200 MHz spectrometer at 298 K. Chemical shifts are reported in ppm relative to
TSP (sodium trimethylsilylpropane-3-sulphonate).
2.3. Kinetics measurements
The kinetics of reactions were followed by measuring the change in absorbance at suitable
wavelengths as a function of time. Working wavelengths were determined for each reaction
system, recording the spectra of reaction mixture over wavelength range between 220 to 600 nm.
Substitution reactions were studied under pseudo-first-order conditions whereas the
concentration of entering ligand was always in large excess (at least 10-fold). Reactions were
initiated by mixing equal volumes (1.5 cm3) of complex (2×10-4 M) and ligand (2×10-3 M;
4×10-3 M; 6×10-3 M; 8×10-3 M; 1×10-2 M) solutions in a quartz cuvette. The changes of
absorbance vs. time were fitted as a single-exponential function using Origin Pro 8. Values for
the pseudo-first-order rate constants, kobsd, were calculated as the average value from three to five
independent kinetic runs. Experimental data are reported in tables S2-S13 (Supplementary
Material). The values of pseudo-first-order rate constants, kobsd, at 298 K were recalculated by
Guggenheim and Kezdy-Swinbourne methods (table 14S) [33, 34]. All reactions were studied at
four different temperatures (288, 298, 308 and 313 K). The activation parameters, ΔH≠ and ΔS≠,
were calculated using the Eyring equation. Eyring plots for all studied systems are given in
Supplementary Material, figures 4S-15S.

2.4. X-ray crystallography
Crystal data and experimental details for [Pt(bpma)(pzBr)]Cl2·2H2O are summarized in table 1.
Single-crystal diffraction data were collected at low temperature (-73 °C) and corrected for
absorption by evaluation of multi-scans.
The crystal structure was solved by direct methods using SIR2002 [35] and refined using
SHELXL97 [36] both incorporated in WinGX [37] program package. Since Cl1 is located on the
crystallographic inversion center and it participates in the formula of complex compound by one
half, it was necessary to identify occupancy of the remaining Cl atoms in the asymmetric unit.
Having in mind electro-neutrality of the complex compound and analyzing the electron density
difference maps it was concluded that Cl3 is present in the crystal structure by partial occupancy
and it was treated by occupation number equal to 0.5.
All non-H atoms were refined anisotropically to convergence. All hydrogens attached to
C were placed at geometrically calculated positions with C−H distances fixed to 0.95 from Csp2
and 0.98 and 0.99 Å from methyl and methylene Csp3, respectively. The corresponding isotropic
displacement parameters of the hydrogens were equal to 1.2Ueq and 1.5Ueq of the parent Csp2
and Csp3, respectively. Water hydrogen positions were determined using the CALC-OH program
[38]. These hydrogens were placed at positions with O-H distances of 0.85 Å and refined using a
riding model. The hydrogens attached to N were located in the electron density map and refined
isotropically. Figures were produced using ORTEP-3 [39] and MERCURY [40]. Software used
for the preparation of the materials for publication: WinGX, PLATON [41], PARST [42].
3. Results and discussion
Substitution reactions of monofunctional Pt(II) complexes with selected nitrogen-donor ligands
are presented in scheme 1.
k2
[Pt(NNN)Cl]+
+
L
[Pt(NNN)L]2+ + Cl-
k-2
NNN = terpy, bpma, dien, tpdm
L = pzBr, pzI, Im
Scheme 1.

Square-planar complexes undergo substitution according to two parallel reaction paths
[43]. One involves direct nucleophilic attack by entering ligand while the other includes the
formation of aqua complex followed by rapid substitution of coordinated solvent. Considering
the fact that all reactions were studied in the presence of 10 mM NaCl, the solvolysis pathway
was suppressed and substitution proceed as direct nucleophilic attack in a reversible manner
(scheme 1) with rate constant k2 for direct reaction and k-2 for the reverse reaction.
All reactions were studied under pseudo-first-order conditions with large excess of
entering ligand concentration. Equation 1 describes the linear dependence of pseudo-first-order
rate constant kobsd vs. total entering ligand concentration.
k
obsd = k-2 [Cl–] + k2 [L]
(1)
Experimentally obtained linear dependences for all studied systems are shown in
figures 2-5. Second order rate constant k2 was determined from the slope of the observed line
whereas the intercept represents k-2[Cl-].
All reactions were also studied at four different temperatures to enable determination of
activation parameters, ΔH≠ and ΔS≠. All kinetic data are summarized in tables S2-S13,
Supplementary Material, while calculated values for the rate constants and activation parameters
are given in table 2 and table 1S (Supplementary Material).
On the base of the obtained results reactivity of studied monofunctional Pt(II) complexes
decrease in order [Pt(terpy)Cl]+ > [Pt(bpma)Cl]+ > [Pt(dien)Cl]+ > [Pt(tpdm)Cl]+. It is well
known that reactivity of Pt(II) complexes depends strongly on the structure of inert tridentate
nitrogen donor ligands, especially with pyridine moieties; the number and position of pyridine
units have a large influence on the rate of substitution [15, 20, 31]. The reactivity of
[Pt(terpy)Cl]+ has been explained by the increase of electrophilicity of metal ion due to the
presence of π back-bonding effect of aromatic in-plane coordinated three pyridine units. If the
three pyridine units are out-of-plane, caused by tetrahedral arrangement around the bridged
methylene groups in the structure of [Pt(tpdm)Cl]+, π back-bonding interactions are very weak
and complex substitution is very slow. [Pt(bpma)Cl]+ reacts slower because trans-effect of the
inert ligand is weaker due to the presence of just two pyridine units in cis position that can accept
electron density from metal ion. The reactivity of [Pt(dien)Cl]+ is slightly lower than the

reactivity of [Pt(tpdm)Cl]+. The absence of additional electronic interactions between dien
system and metal ion results in slow substitution. However, selected nitrogen-donor heterocyclic
molecules are very good entering ligands for substitution reactions of Pt(II) complexes.
Reactivity of entering ligands decrease in the order imidazole > pzI > pzBr. Imidazole shows a
very high reactivity due to the enhanced delocalization of electrons relative to other ligands [44].
Order of reactivity of pyrazole derivatives can be explained by the presence of substituents with
different polarizability. More polarizable iodo substituent increases the nucleophilicity of
nitrogen more than less polarizable bromo substituent.
In table 1 are also given the values of second order rate constants for the substitution
reactions of same Pt(II) complexes with 1,2,4-traizole and pyrazole published earlier [45-47].
Comparing these values indicates that 1,2,4-triazole shows significant reactivity due to the
presence of three nitrogens. Higher reactivity of imidazole, then pyrazole, could be connected
with their acidity constants, as previously reported [48]. Namely, imidazole has an acidity
constant pKa = 6.95, which is much higher than the acidity constant of pyrazole (pKa = 2.24).
The coordination of non-symmetrical five-membered heterocyclic nitrogen-donor
molecules to Pt(II) and Pd(II) ions was previously explained [46]. The bond with 1,2,4-triazole
could be established through N1(or N2) and through N4. Just small amounts of N4 bonded
product were detected in the reaction systems. Coordination of pyrazole derivatives toward
Pd(II) via unprotonated nitrogen was also confirmed by NMR as well as the fact that in the
reaction system only one product of the substitution is present [48]. Here, we suggest the same
manner of coordination, confirmed by the X-ray crystal structure determination of
[Pt(bpma)(pzBr)]Cl2·2H2O.
These reactions were studied at three different temperatures to determine the values of
activation parameters, ΔH≠ and ΔS≠, summarized in table 1. All activation parameters support an
associative mode of substitution.
3.1. Structure of [Pt(bpma)(pzBr)]Cl2 2H2O
Single crystal X-ray analysis of [Pt(bpma)(pzBr)]Cl2·2H2O showed that this compound consists
of [Pt(bpma)(pzBr)]2+, three chlorides and two molecules of crystal water (figure 6). In the
complex cation both ligands are coordinated to Pt(II) in the neutral form. The Cl1 is located on
the crystallographic inversion center and consequently it participates in the formula of complex

compound by one half. To preserve electro-neutrality of the complex, it is necessary that one of
the remaining two chlorides (Cl2 and Cl3) also participates by one half. As explained in the
experimental section, Cl3 is treated by occupation number of 0.5 and therefore the crystal
structure can be described by the formula [Pt(bpma)(pzBr)]Cl2·2H2O.
Ligand bpma is coordinated tridentate to platinum forming two chelate rings. Both five-
membered chelate rings adopt an envelope conformation with N5 significantly displaced from
the Pt−N−C−C basal planes (the N5 is displaced by 0.529(6) and 0.504(6) Å from corresponding
mean planes of the Pt1−N4−C5−C6 and Pt1−N6−C8−C7 fragments). Although two chelate rings
are equal in composition, conformation and spatial orientation to platinum, they are significantly
different in some torsion angles. The largest difference is found for N4−C5−C6−N5 which is
considerably larger than the corresponding N6−C8−C7−N5 torsion angle (−29.6(5) and 18.9(5)°,
respectively). All non-hydrogen atoms except N5 in the ligand bpma are approximately coplanar
(root-mean square deviation of fitted atoms is 0.049 Å) and Pt1 practically lies in their mean
plane (displacement of 0.020(2) Å) while N5 is displaced from this plane by 0.472(4) Å.
Ligand pzBr is coordinated to platinum through N2 thus completing together with bpma
the N4 square-planar coordination sphere of Pt1. As expected, all non-hydrogen atoms in pzBr
are almost ideally coplanar. Dihedral angle between mean plane of pzBr and coordination plane
(defined by Pt1, N2, N4, N5 and N6) is 67.04(9)°. Bond lengths within pzBr (table 3) are
comparable to values for the metal complexes with 4-acetyl-3-amino-5-methylpyrazole. Selected
geometrical parameters in table 3 also reveal that the coordination angles significantly deviate
from 90°.
In the crystal packing of [Pt(bpma)(pzBr)]Cl2·2H2O, Cl2- plays the most important role
in the intermolecular association of complex cations [Pt(bpma)(pzBr)]2+. Using Cl2 as link the
complex cations form a centrosymmetric dimer, which represents the main building unit in the
crystal packing (figure 7). Two intermolecular H-bonds within the dimer, N1−H…Cl2 and
N5−H…Cl2 (table 3, figure 2), are the strongest hydrogen bonds formed by complex cation.
These dimers are further interconnected into a chain via the N3−H…Cl1 hydrogen bonds.
Neighboring chains are connected by net of H-bonds formed via the Cl3- and water molecules
(table 4).

4. Conclusion
The results indicate that substitution of Pt(II) complexes by pyrazole derivatives proceed via an
associative mechanism. Reactivity of Pt(II) complexes is strongly controlled by electronic and
steric effects and decrease in the order [Pt(terpy)Cl]+ > [Pt(bpma)Cl]+ > [Pt(tpdm)Cl]+ >
[Pt(dien)Cl]+. The π-acceptor orbitals of in-plane pyridine units in terpy, especially pyridine
trans to the labile ligand, accept electrons from platinum, including electrons of incoming ligand,
and stabilize the transition state. Transition state could be stabilized by functionalization of
terpyridine with electron-withdrawing effect, primarily in 4’-position, as recently reported [21].
Bridging methylene group between pyridine units significantly slows the rate of substitution due
to steric effect of out-of-plane tpdm ligand. The absence of pyridine unit in trans position, in the
case of bpma, causes reduced reactivity, as well. The reactivity of such complexes could be
forced by involving the substituents in their backbone with σ-inductive donation, such as
cyclohexyl group, while aromatic group has an opposite effect [22]. Complexes with inert
aliphatic nitrogen donor ligand show similar reactivity as some alkildiamine-bridged dinuclear
Pt(II) complexes which reactivity depends on the chain length [49].
The reactivity of nitrogen donor heterocycles depends on the presence of substituents
with different polarizability and decrease in the order imidazole > pzI > pzBr. The manner of
coordination of pyrazole derivatives to Pt(II) is confirmed by X-ray crystal structure
determination of [Pt(bpma)(pzBr)]Cl2·2H2O. Pyrazole derivative is coordinated via N2 forming
the distorted square-planar complex. These results help understand the correlation between
electronic and steric effect on the behavior of Pt(II) complexes toward azole, constituents of
many biomolecules.
Supplementary data
Crystallographic data are deposited at the Cambridge Crystallographic Data Centre as
supplementary material number CCDC 1463008.
Acknowledgements
The authors gratefully acknowledge financial support from the Ministry of Education, Science
and Technological Development of the Republic of Serbia, Projects No. 172011 and 172014.

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Table 1. Crystallographic data and refinement parameters for
[Pt(bpma)(pzBr)]Cl2·2H2O.
Empirical formula
Formula weight
Color
C16H23BrCl2N6O2Pt
677.30
Colorless
200(2)
Temperature (K)
Wavelength (Å)
Crystal system
Space group
Unit cell dimensions
a (Å)
0.71073
Triclinic
P1−
7.6975(15)
11.568(2)
13.962(3)
110.35(3)
101.77(3)
95.19(3)
b (Å)
c (Å)
α (°)
β (°)
γ (°)
V (Å3)
1123.3(4)
Z
2
D
calc (Mg/m3)
2.002
μ (mm−1)
8.286
θ range for data collection (°)
Reflections collected
2.75 to 30.48
12725
Independent reflections, Rint
Data / restraints / parameters
6716, 0.0222
6716 / 0 / 278
1.083
2
Goodness-of-fit on F
Final R1/wR2 indices (I >2σI)
Final R1/wR2 indices (all data)
0.0302, 0.0753
0.0387, 0.0784

Table 2. Rate constants and activation parameters for substitution of Pt(II) complexes with
diazines in 0.10 M NaClO4, 10 mM NaCl.
[Pt(dien)Cl]+
ΔH≠/ kJ
ΔS≠/ J K-1
L
T/K
k2/M-1 s-1
k-2[Cl]/ M-1s-1
mol-1
mol-1
(7.2 0.2) × 10- (1.8 0.1) × 10-
5-amino-4-bromo-3-methyl-
pyrazole
298.1
298.1
298.1
298.1
298.0
52
58
62
30
22
2
3
1
4
2
-124
-101
-80
5
8
3
4
(9.1 0.7) × 10- (1.9 0.3) × 10-
3-amino-4-iodo-pyrazole
imidazole
3
4
(2.8 0.3) × 10- (2.1 0.1) × 10-
4
2
4
(7.12 0.03) ×
10-2
(5.39 0.04) ×
10-4
1,2,4-triazole 1
-165 11
(6.7 0.4) × 10- (2.15 0.05) ×
pyrazole 1
-215
6
3
10-4
[Pt(bpma)Cl]+
(8.4 0.3) × 10- (2.3 0.2) × 10-
5-amino-4-bromo-3-methyl-
pyrazole
298.0
298.2
297.9
298.0
298.0
22
15
26
22
15
3
4
3
4
2
-207
8
2
4
(1.09 0.05) ×
10-1
(2.6 0.2) × 10-
3-amino-4-iodo-pyrazole
imidazole
-230 10
-182
-79 14
4
(3.03 0.02) ×
10-1
(2.6 0.1) × 10-
9
4
(4.20 0.01) ×
(5.2 0.1) × 10-
1,2,4-triazole 2
3
10-1
(7.0 0.3) × 10- (5.0 0.4) × 10-
pyrazole 2
-217
7
2
4
[Pt(terpy)Cl]+
(1.13 0.06) ×
10-1
(3.0 0.2) × 10-
5-amino-4-bromo-3-methyl-
pyrazole
298.2
298.2
298.0
22
25
46
3
4
2
-206
9
4
(1.45 0.04) ×
10-1
(2.8 0.1) × 10-
3-amino-4-iodo-pyrazole
-190 10
4
(5.04 0.01) V
10-1
(3.4 0.4) × 10-
imidazole
-113
6
4
1,2,4-triazole 3
Pyrazole3
298.1
298.1
-
-
0.85 0.02
1.26
40
44
1
1
-114 10
-96
4
[Pt(tpdm)Cl]+
5-amino-4-bromo-3-methyl-
pyrazole
(1.87 0.02) ×
10-2
(2.0 0.6) × 10-
298.0
298.1
298.2
53
41
49
2
2
2
-114
-155
-119
6
5
6
4
(2.5 0.2) × 10- (2.2 0.5) × 10-
3-amino-4-iodo-pyrazole
2
4
(6.7 0.3) × 10- (2.4 0.2) × 10-
imidazole
2
4
1Ref. [45], 2 Ref. [46], 3 Ref. [47]
14

Table 3. Selected bond distances (Å) and angles (°) in the
crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O.
Bond distances (Å)
Pt1−N2
2.015(3)
Pt1−N4
2.003(4)
Pt1−N5
2.003(3)
Pt1−N6
2.002(4)
Br1−C14
N1−C15
N1−N2
1.862(4)
1.336(6)
1.389(5)
N2−C13
N3−C13
C13−C14
C14−C15
C15−C16
1.336(5)
1.333(6)
1.402(6)
1.365(7)
1.491(7)
Coordination angles (°)
166.46(14)
83.20(15)
83.51(14)
97.93(15)
95.39(14)
178.70(14)
N6−Pt1−N4
N6−Pt1−N5
N4−Pt1−N5
N6−Pt1−N2
N4−Pt1−N2
N5−Pt1−N2
15

Table 4. Geometrical parameters for hydrogen bonds in the crystal structure of
[Pt(bpma)(pzBr)]Cl2·2H2O.
D−H…A
D−H (Å)
H…A (Å)
D…A (Å)
D−H…A (°)
Symmetry codes
N1−H1n1…Cl2
N3−H1n3…Cl1
N3−H2n3…Cl3
N5−H1n5…Cl2
O1−H2o1…Cl2
O1−H1o1…Cl3
O1−H1o2…Cl3
O1−H2o2…Cl2
0.78(5)
0.73(8)
0.80(7)
0.98(5)
0.85
0.85
0.85
0.85
2.36(5)
2.58(7)
2.44(6)
2.15(5)
2.38
2.04
2.13
2.50
3.131(4)
3.211(5)
3.191(5)
3.132(4)
3.184
2.875
2.901
3.269
172(6)
146(7)
156(6)
174(5)
157
168
152
151
x,y+1,z
x,y,z
−x+1,−y+1,−z
−x+1,−y+1,−z+1
x,y,z
x−1,y,z
x,y,z
x,y,z
16

+
+
NH
Pt
NH
Pt
H2N
NH2
N
N
Cl
Cl
[Pt(dien)Cl]+
[Pt(bpma)Cl]+
+
+
N
N
N
Pt
Cl
N
N
Pt
Cl
N
[Pt(terpy)Cl]+
[Pt(tpdm)Cl]+
NH2
I
CH3
Br
N
H2N
N
N
N
H
N
N
H
H
5-Amino-4-bromo-3-methyl-pyrazole 4-Iodo-3-amino-pyrazole
Imidazole
(pzBr)
(pzI)
Figure 1. The structural formula of complexes and ligands.
17

12
10
8
104kobsd/s-1
pzBr
[Pt(terpy)Cl]+
[Pt(bpma)Cl]+
[Pt(tpdm)Cl]+
[Pt(dien)Cl]+
6
4
2
103[pzBr]/M
0
0
1
2
3
4
5
6
14
12
10
8
104kobsd/s-1
pzI
[Pt(terpy)Cl]+
[Pt(bpma)Cl]+
[Pt(tpdm)Cl]+
[Pt(dien)Cl]+
6
4
2
103[pzI]/M
5 6
0
0
1
2
3
4
40
35
30
25
20
15
10
5
104kobsd/s-1
Imidazole
[Pt(terpy)Cl]+
[Pt(bpma)Cl]+
[Pt(tpdm)Cl]+
[Pt(dien)Cl]+
103[Im]/M
5 6
0
0
1
2
3
4
Figure 2. Observed pseudo-first order rate constants, kobsd, as a function of entering
ligand concentration at 298 K.
18

15
12
9
5
4
3
2
1
0
104 kobsd/s-1
104 kobsd/s-1
[Pt(bpma)Cl]+
[Pt(dien)Cl]+
313.0 K
307.9 K
313.1 K
307.9 K
298.0 K
288.1 K
298.1 K
288.1 K
6
3
103[pzBr]/M
5 6
103[pzBr]/M
5 6
0
0
1
2
3
4
0
1
2
3
4
18
15
12
9
8
6
4
2
0
104 kobsd/s-1
104 kobsd/s-1
[Pt(tpdm)Cl]+
[Pt(terpy)Cl]+
313.1 K
308.2 K
308.2 K
308.0 K
298.2 K
288.0 K
298.0 K
288.1 K
6
3
103[pzBr]/M
5 6
103[pzBr]/M
5 6
0
0
1
2
3
4
0
1
2
3
4
Figure 3. Observed pseudo-first order rate constants, kobsd, as a function of entering
ligand concentration and temperature for substitution of Pt(II) complexes with
5-amino-4-bromo-3-methyl-pyrazole (pzBr) in 0.1 M NaClO4, 10 mM NaCl.
19

6
4
2
0
15
12
9
104 kobsd/s-1
104 kobsd/s-1
[Pt(dien)Cl]+
313.1 K
[Pt(bpma)Cl]+
312.9 K
307.9 K
307.9 K
298.2 K
288.0 K
297.8 K
288.1 K
6
3
103[pzI]/M
5 6
103[pzI]/M
5
0
0
1
2
3
4
6
0
1
2
3
4
24
20
16
12
8
8
6
4
2
0
104 kobsd/s-1
104 kobsd/s-1
[Pt(terpy)Cl]+
[Pt(tpdm)Cl]+
313.0 K
307.9 K
313.0 K
308.1 K
298.2 K
288.1 K
298.1 K
288.0 K
4
103[pzI]/M
103[pzI]/M
0
0
1
2
3
4
5
6
0
1
2
3
4
5
6
Figure 4. Observed pseudo-first order rate constants, kobsd, as a function of entering
ligand concentration and temperature for substitution of Pt(II) complexes with
4-iodo-3-amino-pyrazole (pzI) in 0.1 M NaClO4, 10 mM NaCl.
20

12
10
8
45
40
35
30
25
20
15
10
5
104 kobsd/s-1
104 kobsd/s-1
313.1 K
308.1 K
[Pt(bpma)Cl]+
[Pt(dien)Cl]+
313.0 K
307.8 K
6
297.9 K
288.2 K
298.1 K
288.0 K
4
2
103[Im]/M
5 6
103[Im]/M
0
0
0
1
2
3
4
0
1
2
3
4
5
6
100
90
80
70
60
50
40
30
20
10
0
18
15
12
9
104 kobsd/s-1
104 kobsd/s-1
[Pt(tpdm)Cl]+
[Pt(terpy)Cl]+
312.9 K
308.0 K
313.0 K
308.0 K
298.2 K
288.1 K
298.0 K
288.1 K
6
3
103[Im]/M
5
103[Im]/M
5 6
0
0
1
2
3
4
6
0
1
2
3
4
Figure 5. Observed pseudo-first order rate constants, kobsd, as a function of entering
ligand concentration and temperature for substitution of Pt(II) complexes with
imidazole (Im) in 0.1 M NaClO4, 10 mM NaCl.
21

Figure 6. Crystal structure and atom-numbering scheme of
[Pt(bpma)(pzBr)]Cl2·2H2O. Displacement ellipsoids are drawn at the 50%
probability level.
22

Figure 7. The dimer formed by two complex cations of [Pt(bpma)(pzBr)]Cl2·2H2O
interconnected via the N1−H…Cl2 and N5−H…Cl2 hydrogen bonds. All
hydrogens which do not participate in hydrogen bonding are omitted for clarity.
23

Graphical Abstract
k2
[Pt(NNN)Cl]+ + L
[Pt(NNN)L]2+ + Cl-
k-2
NNN = terpy, bpma, dien, tpdm L = pzBr, pzI, imidazole
15
104 kobsd/s-1
[Pt(bpma)Cl]+
313.0 K
12
307.9 K
9
298.0 K
288.1 K
6
3
0
103[pzBr]/M
5 6
0
1
2
3
4
24