A new [(1R,2R)-1,2-diaminocyclohexane]platinum(II) complex: formation by nitrate-acetonitrile ligand exchange.
ABSTRACT The title compound, cis-diacetonitrile[(1R,2R)-1,2-diaminocyclohexane-κ(2)N,N']platinum(II) dinitrate monohydrate, [Pt(C(2)H(3)N)(2)(C(6)H(14)N(2))](NO(3))(2)·H(2)O, is a molecular salt of the diaminocyclohexane-Pt complex cation. There are two formula units in the asymmetric unit. Apart from the two charge-balancing nitrate anions, one neutral molecule of water is present. The components interact via N-H...O and O-H...O hydrogen bonds, resulting in supramolecular chains. The title compound crystallizes only from acetonitrile with residual water, with the acetonitrile coordinating to the molecule of cis-[Pt(NO(3))(2)(DACH)] (DACH is 1,2-diaminocyclohexane) and the water forming a monohydrate.
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ABSTRACT: The impact of cisplatin on cancer chemotherapy cannot be denied. Over the past 20 years, much effort has been dedicated to discover new platinum-based anticancer agents that are superior to cisplatin or its analogue, carboplatin. Most structural modifications are based on changing one or both of the ligand types coordinated to platinum. Altering the leaving group can influence tissue and intracellular distribution of the drug, whereas the carrier ligand usually determines the structure of adducts formed with DNA. DNA-Pt adducts produced by cisplatin and many of its classical analogues are almost identical, and would explain their similar patterns of tumor sensitivity and susceptibility to resistance. Recently some highly innovative design strategies have emerged, aimed at overcoming platinum resistance and/or to introduce novel mechanisms of antitumor action. Platinum compounds bearing the 1,2-diaminocyclohexane carrier ligand; and those of multinuclear Pt complexes giving rise to radically different DNA-Pt adducts, have resulted in novel anticancer agents capable of circumventing cisplatin resistance. Other strategies have focused on integrating biologically active ligands with platinum moieties intended to selectively localizing the anticancer properties. With the rapid advance in molecular biology, combined with innovation, it is possible new Pt-based anticancer agents will materialize in the near future.Medicinal Research Reviews 10/2003; 23(5):633-55. · 9.58 Impact Factor
- Journal of Pharmaceutical Sciences 04/1976; 65(3):315-28. · 3.13 Impact Factor
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ABSTRACT: 25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.Current Pharmaceutical Design 02/2003; 9(25):2078-89. · 3.31 Impact Factor
Acta Crystallographica Section C
A new [(1R,2R)-1,2-diaminocyclohexane]platinum(II)
complex: formation by nitrate–acetonitrile ligand exchange
Richard Paˇ zout, Jitka Houskov´ a, Michal Duˇ sek, Jaroslav Maixner, Jana
Cibulkov´ a and Petr Kaˇ cer
Acta Cryst. (2010). C66, m273–m275
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Acta Cryst. (2010). C66, m273–m275Paˇ zout et al. · [Pt(C2H3N)2(C6H14N2)](NO3)2·H2O
A new [(1R,2R)-1,2-diaminocyclo-
formation by nitrate–acetonitrile
Richard Paz ˇout,a* Jitka Houskova ´,aMichal Dus ˇek,b
Jaroslav Maixner,aJana Cibulkova ´aand Petr Kac ˇera
aInstitute of Chemical Technology, Technicka ´ 5, Prague 166 28, Czech Republic,
andbInstitute of Physics, Czech Academy of Sciences, Na Slovance 2, 18221
Prague 8, Czech Republic
Correspondence e-mail: email@example.com
Received 17 May 2010
Accepted 17 August 2010
Online 4 September 2010
The title compound, cis-diacetonitrile[(1R,2R)-1,2-diamino-
cyclohexane-?2N,N0]platinum(II) dinitrate monohydrate, [Pt-
(C2H3N)2(C6H14N2)](NO3)2?H2O, is a molecular salt of the
diaminocyclohexane–Pt complex cation. There are two
formula units in the asymmetric unit. Apart from the two
charge-balancing nitrate anions, one neutral molecule of water
is present. The components interact via N—H???O and O—
H???O hydrogen bonds, resulting in supramolecular chains.
The title compound crystallizes only from acetonitrile with
residual water, with the acetonitrile coordinating to the
molecule of cis-[Pt(NO3)2(DACH)] (DACH is 1,2-diamino-
cyclohexane) and the water forming a monohydrate.
The search for novel platinum-based anticancer complexes
remains an expanding area of the contemporary pharmaceu-
tical industry. The driving force for investigations of this group
of active anticancer therapeutics is the discovery of more
active and less toxic analogues of the chemotherapy
complexes used in today’s clinical practice (cisplatin, carbo-
platin, oxaliplatin, etc.) (Ho et al., 2003; Galanski et al., 2003;
Abu-Surrah & Kettunen, 2006). Some of the novel structures
are based on the platinum (1R,2R)-1,2-diaminocyclohexane
(DACH) carrier ligand and various leaving groups bound to
the central Pt metal atom. There are several synthetic routes
used for the preparation of DACH–platinum-based complexes
(Fuertes et al., 2004; Leh & Wolf, 1976). One of the interesting
routes for the preparation of oxaliplatin, AP5346 and other
DACH–Pt complexes is the synthetic method starting from
precursor of the DACH–Pt-based cytostatics (Pasini et al.,
1993). This is prepared by a simple method where cis-
[PtCl2(DACH)], prepared by the quantitative transformation
of DACH with K2[PtCl4], reacts with silver nitrate. The title
compound, (I), crystallizes only from acetonitrile with residual
water in such a way that the molecule forms a monohydrate.
The single-crystal structure of (I) is built up from discrete
moieties in the monoclinic space group P21, with two formula
units in the asymmetric unit. The [Pt(C2H3N)2(C6H14N2)]2+
complex cation is formed by one cyclohexane ring with a chair
conformation, a five-membered diamine ring, a central Pt
atom and two leaving groups of acetonitrile (N
This dication is balanced by two nitrate groups and one
neutral water solvent molecule.
The [Pt(C2H3N)2(C6H14N2)]2+cation is nearly planar, with
the dihedral angle between the N1A/N2A/N3A/N4A plane
and the cyclohexane plane (C3A/C6A/N1A/N2A) being
approximately 5?. The Pt1A—N1A bond is shorter than the
same bond in cis-[PtBr2(DACH)] and similar to that in cis-
[PtCl2(DACH)] (Lock & Pilon, 1981). As for the two
symmetry-independent cations of (I), they show few signifi-
cant differences in bond distances and angles, apart from the
Acta Cryst. (2010). C66, m273–m275 doi:10.1107/S0108270110033135
# 2010 International Union of Crystallography
Acta Crystallographica Section C
The molecular structure of (I), showing the atom-numbering scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
analogous Pt1—N3—C7 angles, which are 178.6 (3) (cation A)
and 174.1 (3)?(cation B). Comparable torsion angles about
the Pt atoms, e.g. N4—Pt1—N2—C2, differ by up to 8?in
cations A and B. The N—O bonds in the NO3anions lie within
expected ranges and these nitrate anions are positioned in
such a manner that their O atoms are oriented towards the H
atoms of adjacent water molecules and diamine groups,
forming hydrogen bonds.
There are three systems of supramolecular chains inter-
acting by hydrogen bonds: one formed by bifurcated N—
H???(O,O) interactions linking an N atom of the diamine
group with O atoms of a nitrate anion, and two O—H???O
chains linking an O atom of a nitrate anion to the water O
atom. The first is parallel to  and takes the form
metry codes as in Table 1; additionally, (vii) ?x, y ?1
(viii) ?x + 1, y ?1
parallel to  (Fig. 3) between a water molecule and nitrate
anions, of the form O5A???N6A???O4A???O7A???O5Aiii; the
second chain running parallel to the b axis is O5Bix???
O7Bx???O4Bx???N6Bx???O5Bx[symmetry codes: (ix) ?x + 1,
given in Table 1 and the C—H???O interactions are considered
2, ?z + 1;
2, ?z + 2] (Fig. 2). Also present are chains
2, ?z + 1; (x) x, y, z ? 1]. Details of hydrogen bonds are
For the preparation of the title compound, an aqueous suspension
(312 ml) of cis-[PtCl2(DACH)] (0.041 mol, 15.6 g) was mixed with
1.935 equivalents of AgNO3 (0.079 mol, 13.5 g) and the reaction
mixture was stirred in the absence of light at 318 K for 4 h. The by-
product, AgCl, was removed by filtration through an ultra-filter (Ø =
0.22 mm; Sigma–Aldrich) and a layer of active carbon. The colourless
filtrate was evaporated and dried (Buchi Rotavapor RII rotary
evaporator, 318 K, 2 kPa). The resulting white powder, crude cis-
[Pt(NO3)2(DACH)], was recrystallized from acetonitrile. Single
crystals of cis-[Pt(CH3CN)2(DACH)](NO3)2?H2O, (I), suitable for
X-ray diffraction analysis, were obtained from a solution of cis-
[Pt(NO3)2(DACH)] (3.1 mg, 0.0072 mmol) in acetonitrile (0.24 ml)
by spontaneous precipitation under slow programmed cooling.
a = 12.6799 (3) A˚
b = 12.0326 (3) A˚
c = 11.6791 (2) A˚
? = 94.5495 (17)?
V = 1776.29 (7) A˚3
Z = 4
Mo K? radiation
? = 7.94 mm?1
T = 120 K
0.49 ? 0.20 ? 0.10 mm
Oxford Xcalibur Atlas Gemini
Absorption correction: analytical
[CrysAlis Pro (Oxford
Diffraction, 2008), based on
expressions derived by Clark &
Tmin= 0.110, Tmax= 0.544
16828 measured reflections
7866 independent reflections
7374 reflections with I > 3?(I)
R[F2> 2?(F2)] = 0.012
wR(F2) = 0.030
S = 1.02
H atoms treated by a mixture of
independent and constrained
??max= 0.34 e A˚?3
??min= ?0.18 e A˚?3
Absolute structure: Flack (1983),
with 3554 Friedel pairs
Flack parameter: 0.027 (5)
The title structure exhibits strong pseudosymmetry in the space
group P21/c. Using this symmetry, the cyclohexane ring showed
disorder. After refinement in this space group, the R factors
Paz ˇout et al.
Acta Cryst. (2010). C66, m273–m275
Bifurcated hydrogen-bonded chains formed by N—H???(O,O) inter-
actions along the c axis. H atoms not involved in the hydrogen bonding
have been omitted for clarity. [Symmetry codes as in Table 1; additionally,
(vii) ?x, y ?1
2, ?z + 1; (viii) ?x + 1, y ?1
2, ?z + 2.]
The formation of two types of hydrogen-bonded chains parallel to the b
axis. [Symmetry codes as in Table 1; additionally, (ix) ?x + 1, y +1
(x) x, y, z ? 1.]
2, ?z + 1;
converged to 0.042, but large anisotropic displacement parameters
(ADPs) were shown by the nitrate atoms and three of the six C atoms
of the cyclohexane ring. These C atoms were split and the ADPs
changed to isotropic, and two chairs appeared with the refinement
converging to 0.039 and a goodness-of-fit of 0.023. However, the H
atoms of the water molecule and diamine groups were not visible in
the difference Fourier map. Therefore, the sample was remeasured at
a lower temperature, which showed that the reflections violating the
c-glide plane condition were real violations, not admixtures present in
low-quality data. Therefore, the model was transformed to subgroup
P21. For expansion of the structure model, the inversion was used as a
merohedral twinning operation. In this case, the volume fraction of
the inversion twin is the Flack parameter (Flack, 1983). This para-
meter refined to a final value of 0.027 (5), which confirms both that
the above configuration is the correct absolute structure and that
there is no twinning in the crystal structure. The noncentrosymmetric
refinement converged to R factors close to 0.01, gave reasonable
ADPs for the C atoms in the cyclohexane ring and all H atoms were
visible in the difference Fourier maps. There are no significant
differences between the individual cations in the space groups P21
and P21/c, apart from the disorder of the C atoms in the cyclohexane
ring shown in P21/c which is non-existent in P21. As to the two cations
in the asymmetric unit in P21, they show few significant differences in
bond distances and angles, but several are noted for the torsion
O- and N-bound H atoms were refined with N—H distances
restrained to 0.87 (2) A˚and O—H distances restrained to 0.80 (3) A˚.
All other H atoms were positioned geometrically and refined using a
riding model, with C—H = 0.96 A˚and Uiso(H) = 1.2Ueq(C).
Data collection: CrysAlis Pro (Oxford Diffraction, 2008); cell
refinement: CrysAlis Pro (Oxford Diffraction, 2008); data reduction:
CrysAlis Pro; program(s) used to solve structure: SUPERFLIP
(Palatinus & Chapuis, 2007); program(s) used to refine structure:
JANA2006 (Petr ˇı ´c ˇek et al., 2006); molecular graphics: ORTEP-3
(Farrugia, 1999) and Mercury (Version 2.3; Macrae et al., 2006);
software used to prepare material for publication: JANA2006.
This work was supported by grant No. MSM 6046137301
and research programme 2B08021 of the Ministry of Educa-
tion, Youth and Sports of the Czech Republic, and by grant
No. MPO 2A-2TP1/049 from the Ministry of Industry and
Trade of the Czech Republic. We also acknowledge institu-
tional research plan No. AVOZ10100521 of the Institute of
Physics of the Czech Academy of Sciences.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG3238). Services for accessing these data are
described at the back of the journal.
Abu-Surrah, A. S. & Kettunen, M. (2006). Curr. Med. Chem. 13, 1337–1357.
Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897.
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.
Flack, H. D. (1983). Acta Cryst. A39, 876–881.
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Pharm. Des. 9, 2078–2089.
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Leh, F. K. V. & Wolf, W. (1976). J. Pharm. Sci. 65, 315–328.
Lock, C. J. L. & Pilon, P. (1981). Acta Cryst. B37, 45–49.
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor,
R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.
Oxford Diffraction (2008). CrysAlis Pro. Oxford Diffraction Ltd, Yarnton,
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Czech Academy of Sciences, Prague, Czech Republic.
Acta Cryst. (2010). C66, m273–m275 Paz ˇout et al.
Hydrogen-bond geometry (A˚,?).
Symmetry codes: (i) ?x;y þ1
x þ 1;y;z; (v) ?x þ 2;y ?1
2;?z þ 1; (ii) x ? 1;y;z; (iii) ?x þ 1;y ?1
2;?z þ 2; (vi) ?x þ 1;y þ1
2;?z þ 1; (iv)
2;?z þ 2.