Reactivity of trans-[PtCl2(NCMe)2] with cycloaliphatic amines: An ESI and NMR study. X-ray structure of

Article abstract of DOI:10.1016/j.ica.2009.09.012

The reactivity of the cyclic primary aliphatic amines cyclopropyl-, cyclopentyl- and cyclohexylamine with cis- and trans-[PtCl₂(NCMe)₂], under the same experimental conditions, is compared. Whereas cis-[PtCl₂(NCMe)₂] yields the neutral diamidine compounds, the reactions with trans-[PtCl₂(NCMe)₂] take place either with addition or substitution processes yielding the neutral diamidine complexes trans-[PtCl₂(Amidine)₂], the monocationic trans-[PtCl(Amine)(Amidine)₂]Cl and the dicationic trans-[Pt(Amine)₂(Amidine)₂]Cl₂ salts. An NMR and ESI study indicate that the main species formed is the monocationic trans-[PtCl(Amine)(Amidine)₂]Cl complex. The X-ray structure of {A figure is presented} is reported and its supramolecular arrangement is described.

Full text of DOI:10.1016/j.ica.2009.09.012

Inorganica Chimica Acta 363 (2010) 487–494
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Reactivity of trans-[PtCl2(NCMe)2] with cycloaliphatic amines: An ESI and NMR
trans-[PtCl {Z-N(H)=C(CH )NHCHCH CH } ]
study. X-ray structure of
2
3
2
2 2
Silvia Mazzega Sbovata a, Rino A. Michelin a, Mirto Mozzon a, Alfonso Venzo b, Roberta Bertani a,
,
*
Franco Benetollo c
a Dipartimento di Processi Chimici dell’Ingegneria, Università di Padova, Via F. Marzolo 9, I-35131 Padua, Italy
b C.N.R. Istituto di Scienze e Tecnologie Molecolari, Via F. Marzolo 1, I-35131 Padua, Italy
c ICIS – C.N.R., Corso Stati Uniti 4, 35127 I- Padua, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactivity of the cyclic primary aliphatic amines cyclopropyl-, cyclopentyl- and cyclohexylamine with
cis- and trans-[PtCl2(NCMe)2], under the same experimental conditions, is compared. Whereas cis-
[PtCl2(NCMe)2] yields the neutral diamidine compounds, the reactions with trans-[PtCl2(NCMe)2] take
place either with addition or substitution processes yielding the neutral diamidine complexes trans-
[PtCl2(Amidine)2], the monocationic trans-[PtCl(Amine)(Amidine)2]Cl and the dicationic trans-
[Pt(Amine)2(Amidine)2]Cl2 salts. An NMR and ESI study indicate that the main species formed is the mon-
ocationic trans-[PtCl(Amine)(Amidine)2]Cl complex.
Received 4 August 2009
Accepted 3 September 2009
Available online 10 September 2009
Dedicated to Prof. Paul S. Pregosin.
Keywords:
Platinum(II)
trans-[PtCl {N(H)=C(CH )NHCHCH CH } ]
The X-ray structure of
is reported and its supramolecular
2 2
2
3
2
Cycloaliphatic amine
Amidine complexes
arrangement is described.
Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
It is noteworthy that the nature of the products of all these reac-
tions appears to depend strongly on the geometry of the platinum
complex (cis or trans), on the nitrile ligand, on the reacting nucle-
ophile and on the experimental conditions (stoichiometry, temper-
ature, time), affording neutral, monocationic or dicationic
derivatives, where the entering nucleophile can substitute (even
partially) or not the coordinated nitrile ligands. In particular, pri-
mary and secondary aliphatic amines have been reported to react
with cis- and trans-[PtCl2(NCR)2] giving rise to neutral and cationic
diamidine derivatives depending on the nitrile, the amine and the
reaction conditions as summarized in Scheme 1 [6].
The reactivity of coordinated nitrile ligands activated towards
nucleophilic attack by protic H–OR and H–NRR0 nucleophiles, such
as alcohols and amines, to afford iminoethers and amidine deriva-
tives, respectively, has been extensively reviewed [1].
Recently, the addition to cis- and trans-[PtCl2(NCR)2] (R = Me, Et,
Ph) of dialkyl- and dibenzylhydroxylamines R2NOH (R = Me, Et,
CH2Ph, CH2-C6H4-p-Cl) [2] and of the guanidine derivatives
HN@C(NMe2)2 [3] has been reported to give the corresponding
new diimino species of the type [PtCl2{NH@C(R)ONR2}2] and
[PtCl2{NH@C(R)N@C(NMe2)2}2], respectively, the latter containing
two N-bound monodentate 1,3-diaza-1,3-diene ligands. On the
other hand, a completely different reactivity has been observed
when HN@C(NHPh)2 is the reacting guanidine [4], giving rise to
platinum(II) 1,3,5-triazapentadiene complexes. The addition of
amidine derivatives of the type PhC(@NH)NHPh to trans-
[PtCl2(NCR)2] (R = CH2Ph, Ph, C6H4-p-Cl) has been also shown to
achieve the imidoylamidinate platinum(II) complexes [Pt{NH@
C(R)NC(Ph@NPh}2], representing a new family of Pt(II)-based lumi-
nescent compounds emissive at room temperature both in solution
and in the solid state [5].
A similar behavior, summarized in Scheme 2, has been observed
for the reaction of cis- and trans-[PtCl2(NCR)2] with ammonia
[7].
The interest for amidine complexes arises from the possibility
to prepare new cytotoxic platinum compounds [8] whose antitu-
mor activity can be examined. In these derivatives the lipophilicity
can be tuned by changing R substituents. The presence of the
NH@C(sp2) moiety bonded to the platinum center together with
additional NH groups allows further interactions with the DNA to
potentially form new types of lesions with respect to the quite ac-
tive iminoether derivatives cis-[PtCl2{N(H)@C(OMe)CH2Ph}2] [9]
and trans-[PtCl2{N(H)@C(OR)Me}2] (R = Me, Et) [10].
In this frame, the introduction of cyclic aliphatic amines may be
of interest by taking into account that platinum derivatives bearing
the cyclohexylamine moiety are known to exhibit antitumor activ-
* Corresponding author. Tel.: +39 049 8275731; fax: +39 049 8275525.
E-mail address: roberta.bertani@unipd.it (R. Bertani).
0020-1693/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2009.09.012

488
S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
R1NH2
cis-{PtCl2[NH=C(R)NHR1]2}
A
R = Me, R1 = Me, Et, But, Pri : amidine in Z configuration
R = CH2Ph; R1 = Me : amidine in Z configuration
R = Ph, R1 = Me, Et, Pri : amidine in Z (>) and E configuration
cis-[PtCl2(NCR)2]
CH2Cl2,
°C, 5h
I
-10
R1R2NH
cis-{PtCl2[NH=C(R)NR1R2]2}
B
R = Me, R1 = R2 = Me, Et; R1 = Me, R2 = But : amidine in E configuration
R = CH2Ph; R1 = R2 = Me : amidine in E configuration
R = Ph, R1 = R2 = Me, Et; R1 = Me, R2 = But : amidine in E (>) and Z
configuration
R1R2NH
trans-[PtCl2(NCR)2]
trans-{PtCl2(NCR)[NH=C(R)NR1R2]} +
CH2Cl2,
-10°C, 5h
C
II
trans-{PtCl2[NH=C(R)NR1R2]2} +
D
trans-{Pt(R1R2NH)2[NH=C(R)NR1R2]2}Cl2
E
R = Me, R1 = H, R2 = Me, Et, But, Pri , D amidine in Z configuration
R = Me, R1 =R2 = Me, Et ,: D+ E : amidine in Z configuration
R = CH2Ph; R1 = Me, D amidine in Z configuration
R = CH2Ph; R1 = R2 = Me, D : amidine in E configuration
R = Ph,
R = Ph,
R
R
1 =H, R2 = Me, Et, (D), R2 =Pri, (D + E), R2 = But, (C): amidine in Z (>) and E configuration
1 = R2 = Me (D + C), Et (C) ; R1 = Me, R2 = But (C) : amidine in E (>) and Z configuration
Scheme 1.
cis-{PtCl2(NH3)[NH=C(R)NH2]} +
cis-[PtCl2(NCR)2]
NH3
25
F
I
°C,
solvent
cis-{PtCl2[NH=C(R)NH2]2} +
G
cis-{Pt(NH3)2[NH=C(R)NH2]2}Cl2
R = Me, solvent = THF : F (I/NH3 1:3) or G (I/NH3 1:5)
R = Ph , solvent = CH2Cl2, H
H
trans-[PtCl2(NCR)2]
trans-{PtCl(NH3)[NH=C(R)NH2]}Cl +
NH3
J
II
°C,
25
trans-{PtCl2[NH=C(R)NH2]2} +
solvent
K
trans-{Pt(NH3)2[NH=C(R)NH2]2}Cl2
R = Me, solvent = THF : J + K
R = Me, solvent = CH2Cl2 : J
R = CH2Ph; Ph, solvent CH2Cl2 : L
L
Scheme 2.
ity in vitro, in vivo and cis, trans, cis-[PtCl2(NH3)(C6H11NH2)(O-
COCH3)2] (JM216), is the first orally active platinum compound to
enter clinical trials. [11].
2. Results and discussion
2.1. The reactions of trans-[PtCl2(NCMe)2] with cycloaliphatic primary
amines
Recently, we reported that the reaction of cis-[PtCl2(NCMe)2]
with cyclopropyl-, cyclopentyl- and cyclohexylamine afforded the
diamidine derivatives 1a–3a, according to Scheme 3. Compound
3a, bearing the cyclohexyl ring, showed to be significantly more
cytotoxic in vitro than the cyclopropyl and the cyclopentyl analogs
with a marked activity against cis-platin resistant cell lines [12].
Herein we describe the reactions of trans-[PtCl2(NCMe)2] with
cyclopropyl-, cyclopentyl- and cyclohexylamine which yield mix-
tures of neutral and cationic amidine derivatives, whose formation
has been detected through ESI and NMR determinations.
The reactions of cyclopropyl-, cyclopentyl- and cyclohexyl-
amine under the same experimental conditions afford different
products when performed with cis-[PtCl2(NCMe)2] and trans-
[PtCl2(NCMe)2]. The addition of a 5-fold excess of RNH2 (R = cyclo-
propyl, cyclopentyl, cyclohexyl) to cis-[PtCl2(NCMe)2] at ꢀ20 °C in
CH2Cl2 leads after 5 h to the formation of the corresponding bis
amidine complexes cis-[PtCl2{Z-NH@(NHR)Me}2] (R = cyclopropyl,
1a; cyclopentyl, 2a, cyclohexyl, 3a) in high yield [12]. In the

S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
489
R
CH3
N
H
C
N
lowtemperature
5h
Cl
H
-[PtCl (NCMe) ]
cis
Pt
2
2
Cl
H
N
H
C
N
R
CH3
R=
, 1a;
, 2a;
, 3a
Scheme 3.
complexes 1a, 2a and 3a both amidine ligands are in the Z config-
uration with the formation of strong intramolecular hydrogen
bonds between each chlorine and the imino-proton of the NHR
moiety giving rise to six-membered rings, according to Scheme 3,
in agreement with what observed for the products of the addition
of other primary aliphatic amines to coordinated acetonitrile [6a,c].
The reactivity of the cyclic aliphatic amines with trans-
[PtCl2(NCMe)2], under the same experimental conditions above re-
ported for the cis complexes, takes place either with addition or
substitution processes. Spectroscopic data indicate that mixtures
of products are formed which contain the neutral diamidine com-
plexes
trans-[PtCl2(Amidine)2],
and
the
the
monocationic
dicationic
trans-
trans-
[PtCl(Amine)(Amidine)2]Cl
[Pt(Amine)2(Amidine)2]Cl2 salts (Scheme 4), as the major products.
As for the reaction with cyclopropylamine, the formation of the
neutral diamidine complex was confirmed by the X-ray structure
of complex 1b (Fig. 1).
When the reactions proceed for longer times or are carried out
at room temperature the dicationic complexes 1c, 2c and 3c are
formed as the only isolated products [13]. The chloride substitu-
tion by an entering amine was previously described for the reac-
tion of trans-[PtCl2(NCMe)2] with ammonia [7] and was reported
by us in the case of the reaction of trans-[PtCl2(NCMe)2] with iso-
Fig. 1. Perspective ORTEP drawing of
(1b) with the atom-labeling scheme.
trans-[PtCl2{N(H)=C(CH3)NHCHCH2CH2}2]
R
R
R
+
2+
CH3
CH3
CH3
N
N
N
H
Cl
N
C
C
H
C
N
H
C
N
Cl
RNH2
N
Cl
H
H
H
H
-20°C, 5h
H
-
2Cl-
(NCMe)2]
trans-[PtCl2
Cl
Pt
Pt
Pt
+
+
H
N
H
N
H2NR
H
2NR
C
H
C
H
N
R
N
R
N
R
CH3
CH3
CH3
R =
, 1b
, 2b
15%
10%
1c
2c
40%
40%
1d
40%
45%
2d
3d
, 3b 5%
3c
45%
45%
Scheme 4.

490
S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
Table 1
Selected 1H and 13C (in parentheses) NMR data (ppm).
Compound
Amidine
Amine
PtNH
CH3
NHCH (doublet)
C@N
NH2
1a
1b
1c
1d
2a
2b
2c
2d
3a
3b
3c
3d
6.61
7.50
7.07
7.29
6.60
7.50
7.06
7.69
6.52
7.60
6.91
7.01
2.24 (20.5)
2.32 (20.6)
2.30 (20.7)
2.31 (20.9)
2.17 (20.9)
2.27 (20.8)
2.26 (20.6)
2.25 (21.5)
2.11 (19.8)
2.22 (20.2)
2.23 (20.6)
2.20 (20.3)
7.15(3JHH = 7.2 Hz)
7.42 (3JHH = 8.0 Hz)
8.98 (3JHH = 7.5 Hz)
7.51 (3JHH = 8.0 Hz)
7.01 (3JHH = 7.5 Hz)
7.33 (3JHH = 8.5 Hz)
8.80 (3JHH = 9.0 Hz)
7.13 (3JHHv = 8.5 Hz)
6.88 (3JHH = 9.0 Hz)
7.37 (3JHH = 9.0 Hz)
8.71 (3JHH = 9.6 Hz)
7.14 (3JHH = 8.8 Hz)
168.1
169.9
168.8
169.7
5.11 br (2JPtH = 48 Hz)
6.00 br (2JPtH = 70 Hz)
165.8
a
166.3
166.8
5.16 br (2JPtH = 50 Hz)
5.88 d (2JPtH = 70 Hz)
164.2
a
165.4
165.4
4.86 (2JPtH = 54 Hz)
5.84 (2JPtH = 65 Hz)
a
Too low to be observed.
propylamine [6c]. It also was used to achieve symmetric and asym-
metric trans-platinum(II) complexes, trans-[PtCl2(Amine1)2] and
trans-[PtCl2(Amine1)(Amine2)] [14] starting from K2PtCl4.
their similar solubilities, attempts to separate compounds 1c–3c
from 1d–3d failed.
In Table 1 selected NMR data of compounds 1a–3a, 1b–3b, 1c–
3c and 1d–3d are reported. The 1H NMR spectra show the presence
of a unique set of signals due to both amidine ligands in each com-
pound having a Z configuration. This feature is also confirmed by
the signals of the CH3 protons which fall in the range 2.1–
2.4 ppm, whereas in the case of E configuration, the CH3 resonance
is observed at values shifted about 0.5 ppm downfield [6].
The reaction of trans-[PtCl2(NCMe)2] with cyclopropyl-
2.2. The reactions of trans-[PtCl2(NCMe)2] with cycloaliphatic primary
amines under ESI conditions
The reactions of cyclopropyl-, cyclopentyl- and cyclohexyl-
amine have been carried out also in CH3CN at room temperature
and the yellow solutions obtained by addition of 2.2-fold excess
of the amines have been immediately analyzed by ESI MS. In all
cases it was observed the formation of only the cationic species
[PtCl(Amine)(Amidine)2]+, which represents the base peak and its
isotopic distribution is in very good agreement with that calcu-
lated. The ESI data are summarized in Scheme 5.
amine at ꢀ10 °C was followed by 1H NMR in CDCl3: in
a
few minutes from the addition of 2.2 equiv. of amine to
trans-[PtCl2(NCMe)2] the formation of the monocationic species
(1d), was ob-
trans-
[PtCl(H2NCHCH2CH2){N(H)=C(CH3)NHCHCH2CH2}]Cl
The formation of the ionic species has been confirmed by MS/
MS experiments and isotope pattern analysis. The parent peaks
show the loss of the corresponding amine and subsequently the
loss of 37 Da, corresponding to HCl. Very low abundance peaks
(about 1%) corresponding to the pentacoordinate species
[PtCl(Amidine)2(Amine)2]Cl are present in all cases, which do not
increase with the time. It is noteworthy that peaks corresponding
to [Pt(Amidine)2(Amine)2]2+, which are characteristic of the ESI
MS spectra of species 1c–3c [13], are completely absent. Further
reactions occur in the ESI source involving dinuclear species, dou-
bling in abundance during the time of analysis (about 15 min),
which can be summarized as follows: [Pt2(Amidine)4(CH3CN)3]+,
m/z 905 (2); [Pt2(Amidine)4(CH3CN)4]+, m/z 946 (5); [Pt2(Ami-
dine)4(CH3CN)4(Amine)]+, m/z 1003 (10) and [Pt2(Ami-
dine)4(CH3CN)4(Amine)2]+, m/z 1060 (6) in the case of reaction
with cyclopropylamine; [Pt2Cl2(Amidine)4(CH3CN)2]+, m/z 1047
(3); [Pt2Cl2(Amidine)4(CH3CN)3]+, m/z 1088 (7); [Pt2Cl2(Ami-
dine)4(CH3CN)3(Amine)]+, m/z 1173 (12) and [Pt2Cl2(Ami-
dine)4(CH3CN)3(Amine)2]+, m/z 1258 (4) for cyclopentylamine;
[Pt2(Amidine)4(CH3CN)4]+, m/z 1114 (3); [Pt2(Amidine)4(CH3-
CN)5]+, m/z 1155 (5); [Pt2(Amidine)4(CH3CN)5(Amine)]+, m/z
1254 (12) and [Pt2(Amidine)4(CH3CN)5(Amine)2]+, m/z 1353 (2) in
the case of cyclohexylamine.
served. The 1H NMR spectrum of 1d is characterized by the signals
at 6.0 ppm (2JPtH 70 Hz) indicating the presence of a coordinated
amine and together with a signal at 7.29 ppm (PtNH) and a doublet
at 7.55 ppm of the NH moiety. The cyclopropyl ring gives rise to
multiplets in the range 0.6–0.9 ppm and also at 2.6 ppm due to
the CH proton. The methyl group of the amidine ligand gives rise
to a singlet at 2.31 ppm (CH3, 20.90 ppm in the 13C{1H} spectrum).
The signals of 1d increase within the first hour as well as those of
1b and 1c (the latter in a significant higher extent). After 24 h, only
the signals of 1c are present. Similar results are obtained in the
case of the reaction of trans-[PtCl2(NCMe)2] with cyclopentylamine
and cyclohexylamine.
As for the reaction with cyclopropylamine, 1b can be obtained
in a higher yield (ca. 50%) by performing the reaction with trans-
[PtCl2(NCMe)2] at 0 °C in THF for 1 h, where 1b is less soluble
and its precipitation prevents the displacement of the chlorides
by the amine. The role of solubility has been underlined by Natile
and coworkers [7a] for the reaction of cis-PtCl2(NCMe)2] with NH3,
which yields the corresponding neutral amidine complexes cis-
[PtCl2L{NH@C(Me)NH2}] (L = NH3 or NH@C(Me)NH2), which are
also insoluble in THF. Conversely, the analogous reactions of
trans-[PtCl2(NCMe)2] with NH3 leads to products soluble in THF
which can react further to form the cationic complex
[PtCl(NH3){Z-NH@C(Me)NH2}]Cl by chloride displacement with
NH3.
These results confirm that ESI MS technique can be useful to fol-
low reaction processes and detect intermediate species [15], even
if further reactions induced by ESI conditions can occur, in partic-
ular involving the formation of oligonuclear species [16].
In our case the ESI MS analysis of the reaction mixture indicates
that the first product formed by reacting trans-[PtCl2(NCMe)2]
with cycloaliphatic amines is the monocationic species
[PtCl(Amine)(Amidine)2]+, in agreement with the NMR results. It
is also to note that the system trans-Pt(Amidine)2 appears to be
Also the reactions of cyclopentylamine and cyclohexylamine
with trans-[PtCl2(NCMe)2] performed in THF at 0 °C for 1 h afford
mixtures of neutral and cationic diamidine complexes. If the reac-
tion time is reduced or Pt/amine molar ratio is increased, unreacted
trans-[PtCl2(NCMe)2] can be recovered. The reactions have been
carried out also in CH3CN, obtaining quite similar results. Due to

S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
491
[PtCl(Amidine)2(Amine)2]+
trans-[PtCl2(NCMe)2] + 2.2 Amine
CH3CN
ESI
prop : m/z 540 (1)
pent : m/z 652 (1)
hex : m/z 708 (1)
[PtCl(Amidine)2(Amine)]+
[PtCl(Amidine)2]+
- amine
prop : m/z 483 (100)
pent : m/z 567 (100)
hex : m/z 610 (100)
prop : m/z 426 (30)
pent : m/z 482 (10)
hex : m/z 511 (5)
-HCl
[Pt(Amidine)2-H]+
prop : m/z 389 (5)
pent : m/z 445 (12)
hex : m/z 476 (7)
Scheme 5.
Table 3
particularly stable, with exchange processes occurring on the ancil-
lary ligands without amidine loss [17] and in agreement with NMR
indications [18].
Selected bond lengths (Å) and angles (°) for trans-[PtCl2{Z-NH@C(N(H)C3H5)CH3}2]
(1b).
Pt–N(1)
Pt–Cl
2.014(5)
2.309(2)
1.298(8)
1.333(9)
1.461(9)
1.492(8)
1.476(9)
1.439(9)
1.488(9)
N(1)–Pt–Cl
94.5(2)
85.5(2)
N(1)–Pt–Cla
-
[PtCl {N(H)=C(CH )NHCHCH CH } ]
2.3. X-ray crystal structure of trans
2 3 2 2 2
N(1)–C(1)
N(2)–C(1)
N(2)–C(3)
C(1)–C(2)
C(3)–C(4)
C(3)–C(5)
C(4)–C(5)
C(1)–N(1)–Pt
C(1)–N(2)–C(3)
N(1)–C(1)–N(2)
N(1)–C(1)–C(2)
N(2)–C(1)–C(2)
N(2)–C(3)–C(5)
N(2)–C(3)–C(4)
133.4(5)
127.6(7)
120.4(6)
121.4(6)
118.2(6)
119.5(9)
116.4(9)
(1b)
Summaries of the refinement results and other crystallographic
information are provided in Table 2.
The molecular structure of 1b shows a perfect trans orientation
of the ligands, lying the metal ion in an inversion center. A view of
the molecule with the atom-labeling scheme is shown in Fig. 1 and
significant bond lengths and angles are reported in Table 3.
The square planar coordination geometry around Pt is charac-
terized by the values of the Pt–N and Pt–Cl bond distances of
2.014(5) and 2.309(2) Å, respectively, as well as by the N(1)–
Pt(1)–Cl angles (85.5(2)–94.5(2)°), in agreement with literature
data [6a,19,20] for similar Pt(II) derivatives with coordinated ami-
a
At –x, ꢀy, ꢀz.
dine ligands. Both amidine ligands are shown to be in the Z config-
uration. The molecular structure presents two intramolecular
hydrogen bonds N(2)–Hꢁ ꢁ ꢁCl of 2.364(2) Å with N(2)–Hꢁ ꢁ ꢁCl angle
of 151.4(5)°, and its centrosymmetrically related part of the mole-
cule, that stabilize the Z configuration of the ligands as already ob-
served in other amidine Pt(II) complexes [6a,19,20]. The
intramolecular interactions, together with the steric hindrance of
the ciclopyrolamine, determine the opening of the Pt–N(1)–C(1)
angle (133.4(5)°) as already observed in the complexes trans-
[PtCl2{Z-N(H)=C(NHMe)CH2Ph}2 [6a] (136.1(5)°) and trans-
[PtCl2{Z-N(H)=C(NHBut)Ph}2] [19] (138.7(3)°) showing intramolec-
ular H-bond of 2.55(9) and 2.61 Å, respectively. The N(1)–C(1) and
C(1)–N(2) bond distances of 1.298(8) and 1.333(9) Å, respectively,
and the angles N(1)–C(1)–N(2) and C(1)–N(2)–C(3) of 120.4(6)°
and 127.6(6)° suggest an electronic delocalization along the N–
C–N moiety with an sp2 hybridization of both the nitrogen atoms.
These features were found in similar amidine Pt(II) complexes such
as trans-[PtCl2{Z-N(H)@C(NHBut)Me}2] [6a] (with N(1)–C(1) and
the N(2)–C(1) bond distances of 1.304(4) and 1.321(5) Å, respec-
tively) and trans-[PtCl2{Z-N(H)@C(NHMe)CH2Ph}2] (with N(1)–
C(1) and N(2)–C(1) bond distances of 1.278(8) and 1.324(9) Å,
respectively) [6a]. The results reported here seem to suggest that
the electronic delocalization is peculiar of this type of ligands,
where the N–C(R)–N system is almost planar in analogy with the
same evidence reported for uncoordinated imino ether moieties
[21]. It is observed also that the C(1)–C(2) (1.492(8) Å) and N(2)–
C(3) (1.461(9) Å) bond distances are well comparable with those
already found in the trans-[PtCl2{Z-N(H@C(NHMe)Me}2] derivative
[6a]. The N@C–N planes of the amidine ligands form each other a
Table 2
Crystal
data
and
structure
refinement
parameters
for
trans-[PtCl {N(H)=C(CH )NHCHCH CH } ]
(1b).
2
3
2
2 2
Empirical formula
C10H20N4Cl2Pt
fw
T (K)
k (Å)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
462.29
293(2)
0.71073
monoclinic
C2/c
14.524(3)
8.583(2)
12.458(3)
105.36(3)
1497.5(6)
4
b (°)
V (Å3)
Z
qcalc (g cmꢀ3
F (0 0 0)
)
2.050
880
h range (°)
3–28
7.192
l
(Mo K
a
) (mmꢀ1
)
No. of reflections collected
1874
No. of observed [I P 2
r(I)]
1585
0.031
0.076
1.232
R (F2)a
Rw (F2)b
GOF
P
P
a
R = (|Fo| ꢀ |Fc|)/ |Fo|.
P
P
b
Rw = [ {w(|Fo|2 ꢀ |Fc|2)2}/ {w(|Fo|2)2}]1/2
.

492
S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
trans-
[PtCl {N(H)=C(CH )NHCHCH CH } ]
Fig. 2. Packing diagram for
(1b) viewed down the b-axis. Dotted line shown the interaction between the chlorine atom and the
2 2
2
3
2
hydrogen of the amino group of the adjacent molecules (00 at x, ꢀy, z + 0.5) and with hydrogen atoms of the CH3 amidine moiety (000 at 0.5 ꢀ x, 0.5 ꢀ y, ꢀz) giving rise a
supramolecular arrangement based only on hydrogen short contacts.
dihedral angle of 7.5(4)° and with the platinum square planar a
dihedral angle of 44°. Similarly to that previously observed in the
case of trans-[PtCl2{Z-N(H)@C(NHBut)Me}2] [6a] intermolecular
hydrogen bonding interactions between the chlorine atom and
3. Experimental
3.1. General procedures and materials
the hydrogen of the amino group of the adjacent molecule
The infrared spectra were taken on a Perkin–Elmer Spectrum
100 FT IR Spectrophotometer (CsI films); the wavenumbers (m)
0
00
(Clꢁ ꢁ ꢁH(1)–N(1)00 2.858(2) ÅA with angle of 153.8(4)°,
at x, ꢀy,
are given in cmꢀ1. 1H and 13C NMR solution spectra were obtained
at 25 °C using a Bruker Avance-400 spectrometer (9.4-T field) oper-
ating at 400.13 and 100.61 MHz, respectively, and using a Bruker
200 AC spectrometer operating at 200.12 and 50.32 MHz, respec-
tively; d values (parts per million, ppm) are relative to Me4Si. Suit-
able integral values for the proton spectra were obtained with a
prescan delay of 10 s. The assignments of the proton resonances
were performed by standard chemical shift correlation spectros-
copy (COSY), total COSY (TOCSY) and Nuclear Overhauser Enhance-
ment Spectroscopy (NOESY) experiments. In the phase-sensitive
NOESY measurements the presence of intense cross-peaks, in
phase with the diagonal, indicates a chemical exchange between
the correlated nuclei (exchange spectroscopy spectra) [23]. The
13C resonances were attributed through 2D-heterocorrelated COSY
experiments: heteronuclear multiple quantum correlation (HMQC)
with bilinear rotation decoupling [24] and quadrature along F1
achieved using the time proportional phase increment method
[25] for the hydrogen-bonded carbon atoms, heteronuclear multi-
ple bond correlation (HMBC) [26] for the quaternary ones. ESI MS
z + 1/2), determine the molecular packing with the formation of
polymeric chains developing along the c axis (Fig. 2).
Each chlorine atom is also involved into two short contacts with
hydrogen atoms of the CH3 groups thus giving rise to a supramo-
lecular arrangement. The shortest contact is found with the CH3
of the same amidine moiety with which the intermolecular hydro-
gen bond is formed (Clꢁ ꢁ ꢁH–C(2)00 2.788(3) Å with angle of
160.0(5)°) in a fashion of the type depicted in Fig. 2. The last short
contact is with a CH3 group of an adjacent molecule with Clꢁ ꢁ ꢁH–
C(2)000 bond distance of 2.938(2) Å and angle of 167.6(6)° (000 at
0.5 ꢀ x, 0.5 ꢀ y, ꢀz). In the crystal packing the shortest distance be-
tween chlorine atoms is 3.973(3) Å and between platinum atoms
of 6.229(2) Å.
It is noteworthy that this supramolecular packing is achieved
through the occurrence of hydrogen bonds an other short hydro-
gen contacts, without unsaturated moieties involvement (coopera-
tive hydrogen bonds, electrostatic and
p–p interaction are the
most relevant synthons in supramolecurar metal–organic arrange-
ments [22]).

S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
493
analyses were performed using a Finningan LCQ-Duo ion-trap
instrument, operating in positive ion mode (sheathgas flow N2
30 au, source voltage 4.0 kV, capillary voltage 21 V, capillary tem-
perature 200 °C). The He pressure inside the trap was kept con-
stant. The pressure directly read by an ion gauge (in the absence
of the N2 stream) was 1.33 ꢂ 10ꢀ5 Torr. The collision-induced dis-
sociation experiments were performed by applying a supplemen-
tary RF voltage (tickle voltage) to the end caps of the ion-trap in
the range 0–80% of its maximum value (5 V peak to peak). Sample
solutions were prepared by reacting trans-[PtCl2(NCCH3)2] (3 mg)
in CH3CN (5 ml) with 2.2 equiv. of the amine and immediately
analyzed.
All work was carried out under a N2 atmosphere using standard
Schlenck techniques. All solvents were reagent grade and were dis-
tilled prior to use. Deuterated solvents were purchased from Cam-
bridge Isotope Laboratories (CIL) and stored under molecular
sieves. Trans-[PtCl2(NCMe)2] was synthesized as described in the
literature [27].
perature and washed with Et2O (3 ꢂ 15 ml). By 1H NMR spectros-
copy, the reaction product revealed to be a mixture of products
where
trans-[PtCl(NHCHCH2CH2CH2CH2){N(H)=C(CH3)NHCHCH2CH2CH2CH2}2]Cl
(2d)and
the
most
abundant
were
the
complexes
trans-[Pt(NHCHCH2CH2CH2CH2)2{N(H)=C(CH3)NHCHCH2CH2CH2CH2}2]Cl2
(2c). Complex 2c was obtained as a pure product by performing the
reaction at room temperature for 24 h [13]. Complex 2d: IR: mC@N
1640 cmꢀ1 (s). 1H NMR (CDCl3): d = 1.57 and 1.94 (m,
N(H)CHCH2CH2, 4H), 1.69 and 1.80 (m, N(H)CHCH2, 4H), 3.75 (m,
N(H)CH, 1H), 2.25 (s, NCCH3), 7.69 (br, PtNH), 7.13 (s, 3JHH = 8.5 Hz,
NH); 5.88 (d, NH2(amine) 3JHH = 8.2 Hz, 2H). 13C {1H} NMR (CDCl3):
d = 21.5 (s, NCCH3), 23.5 (s, N(H)CHCH2CH2), 33.9 (s, N(H)CHCH2),
54.7 (s, N(H)CH), 165.2 (s, C@N).
3.2.3. Reaction of trans-[PtCl2(NCMe)2] with cyclohexylamine
A suspension of trans-[PtCl2(NCMe)2] (300 mg, 0.86 mmol) in
CH2Cl2 (30 ml) at ꢀ20 °C was treated with a 5-fold excess of cyclo-
3.2. Reactions of trans-[PtCl2(NCMe)2] with cycloaliphatic primary
amines
pentylamine 492 ll (4.3 mmol; q = 0.867 g/ml). The reaction mix-
ture was stirred at the low temperature for 5 h and then the
volume was concentrated to ca. 10 ml under reduced pressure. n-
Hexane (40 ml) was added and the suspension was stirred at
ꢀ10 °C for 1 h. The precipitate was then filtered off at room tem-
perature and washed with Et2O (3 ꢂ 15 ml). By 1H NMR spectros-
copy, the reaction product revealed to be a mixture of products
3.2.1. Reaction of trans-[PtCl2(NCMe)2] with cyclopropylamine
A suspension of trans-[PtCl2(NCMe)2] (300 mg, 0.86 mmol) in
CH2Cl2 (30 ml) at ꢀ20 °C was treated with a 5-fold excess of
cyclopropylamine 300 ll (4.3 mmol; q = 0.824 g/ml). The reac-
where
the
most
abundant
were
the
complexes
tion mixture was stirred at the low temperature for 5 h and
then the volume was concentrated to ca. 10 ml under reduced
pressure. n-Hexane (40 ml) was added and the suspension was
stirred at ꢀ10 °C for 1 h. The precipitate was then filtered
off at room temperature and washed with Et2O (3 ꢂ 15 ml). By
1H NMR spectroscopy, the reaction product revealed to be a
mixture of products where the most abundant were the
-
trans[PtCl(NHCHCH2CH2CH2 CH2CH2){N(H)=C(CH3)NHCHCH2CH2CH2CH2CH2}2]Cl
(3d) and
-
trans[Pt(NHCHCH2CH2CH2 CH2CH2)2{N(H)=C(CH3)NHCHCH2CH2CH2CH2CH2}2]Cl2
(3c). Complex 3c was obtained as a pure product by performing
the reaction at room temperature for 24 h [13]. Complex 3d: IR:
mN–H 3439, 3227, 3219 cmꢀ1 (m), mC@N 1635 cmꢀ1 (s). 1H NMR
(CDCl3): d = 1.17 and 1.99 (m, N(H)CHCH2, 4H), 1.22 and 1.82 (m,
N(H)CHCH2CH2, 4H), 1.64 and 1.20 (m, N(H)CHCH2CH2CH2, 2H),
3.10 (m, N(H)CH, 1H), 2.20 (m, NCCH3, 3H), 7.01 (br, PtNH, 1H),
7.14 (d, JHH = 8.8 Hz, NH, 1H), 5.84 (d, NH2(amine) JHH = 8.3 Hz,
2H). 13C {1H} NMR (CDCl3): d = 20.3 (s, NCCH3), 24.7 (s,
N(H)CHCH2CH2CH2), 34.3 (s, N(H)CHCH2), 25.3 (s, N(H)CHCH2CH2),
54.1 (s, N(H)CH), 165.4 (s, C@N).
trans-[PtCl2{N(H)=C(CH3)NHCHCH2CH2}2]
neutral diamidine complex
(1b), the dicationic
trans-[Pt(NHCHCH2CH2)2{N(H)=C(CH3)NHCHCH2CH2}2]Cl2
the monocationic amine- diamidine
diamine–diamidine
complex
3
3
(1c) and
complex
trans-[PtCl(NHCHCH2CH2){N(H)=C(CH3)NHCHCH2CH2}2]Cl (1d). Com-
plex 1c was obtained as a pure product by performing the reaction
at room temperature for 24 h [13]. Complex 1b has been obtained
in higher yield (50%) by reacting trans-[PtCl2(NCMe)2] (100 mg,
0.29 mmol) in THF (10 ml) at 0 °C with a 2.2-fold excess of cyclo-
3.3. X-ray measurements and structure determination
propylamine 44 ll (0.63 mmol; q = 0.824 g/ml) and crystallized
from CH2Cl2/Et2O. Anal. Calc. for C10H20N4Cl2Pt (MW 462.28): C,
Crystal was lodged in Lindemann glass capillary and centered
on a four circle Philips PW1100 diffractometer using graphite
monochromated Mo Ka radiation (0.71073 Å), following the stan-
25.98; H, 4.36; N, 12.12. Found: C, 26.11; H, 4.40; N, 12.24%. IR:
mN–H 3439, 3227, 3219 cmꢀ1 (m), mC@N 1628 cmꢀ1 (s),
m
PtCl2
dard procedures, at room temperature. All intensities were cor-
rected for Lorentz polarization and absorption [28]. The structure
was solved by standard direct methods [29]. Refinement was car-
ried out by full-matrix least-squares procedures (based on F2o)
using anisotropic temperature factors for all non-hydrogen atoms.
Hydrogen atoms were placed in calculated position with fixed iso-
tropic thermal parameters (1.2 Uequiv) of the parent carbon atom.
Structure refinement and final geometrical calculations were car-
ried out with SHELXL-97 [30] program, implemented in the WINGX
package [31].
322 cmꢀ1 (w). 1HNMR (CDCl3) : d = 0.67 and 0.81 (m, CH2, 4H),
2.32 (s, NCCH3, 3H), 2.60 (m, N(H)CH, 1H), 7.50 (s, PtNH, 1H),
3
7.42 (d, NH, JHH = 8.0 Hz,1H). 13C {1H} NMR (CDCl3): d = 21.2 (s,
CH3), 7.3 (s, CH2), 24.8 (s, CH), 169.9 (s, C@N). Complex 1d: IR: mC@N
1630 cmꢀ1 (s). 1HNMR (CDCl3) : d = 0.65 and 0.80 (m, CH2, 4H), 2.31
(s, NCCH3, 3H), 2.60 (m, N(H)CH, 1H), 7.29 (s, PtNH, 1H), 7.51 (d,
3
3
NH, JHH = 8.0 Hz,1H); 6.00 (d, NH2(amine) JHH = 8.2 Hz, 2H). 13C
{1H} NMR (CDCl3): d = 20.9 (s, CH3), 7.2 (s, CH2), 24.1 (s, CH),
169.7 (s, C@N).
3.2.2. Reaction of trans-[PtCl2(NCMe)2] with cyclopentylamine
A suspension of trans-[PtCl2(NCMe)2] (300 mg, 0.86 mmol) in
CH2Cl2 (30 ml) at ꢀ20 °C was treated with a 5-fold excess of cyclo-
4. Supplementary material
pentylamine 424 ll (4.3 mmol; q = 0.863 g/ml). The reaction mix-
ture was stirred at the low temperature for 5 h and then the
volume was concentrated to ca. 10 ml under reduced pressure. n-
Hexane (40 ml) was added and the suspension was stirred at
ꢀ10 °C for 1 h. The precipitate was then filtered off at room tem-
CCDC 742479 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.

494
S.M. Sbovata et al. / Inorganica Chimica Acta 363 (2010) 487–494
(b) P. O’Dwyer, J.P. Stevenson, S.W. Johnson, in: L.R. Kelland, N.P. Farrell (Eds.),
Acknowledgement
Platinum Based Drugs in Cancer Therapy, Humana Press, Totowa, NJ, 2000, p.
231 (Chapter 10);
This work was financially supported by the University of
Padova.
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