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Reaction between the diaqua form of cisplatin and 2-methylsulfanylphenylphosphonic acid yields a dinuclear phosphonato-bridged complex via NH3 elimination
Inorganic Chemistry Communications 3 (2000) 704±707
www.elsevier.nl/locate/inoche
Reaction between the diaqua form of cisplatin and 2-methylsulfanylphenylphosphonic acid yields a dinuclear phosphonato-bridged complex via NH3 elimination Christelle Mauger a, Michel Vazeux a, Alberto Albinati b, Jirõ Kozelka
c,*
a
Laboratoire de Chimie Mol eculaire et Thio-organique, UMR CNRS 6507, Universit e de Caen, ISMRa, 6 Bld Mar echal Juin, 14000 Caen, France b Institute of Pharmaceutical Chemistry, University of Milano, 42, Viale Abruzzi I-20131 Milano, Italy c Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Universit e Ren e Descartes, UMR CNRS 8601, 45 rue des Saints-P eres, 75270 Paris 06, France Received 12 September 2000; accepted 5 October 2000
Abstract Reaction between cis-[Pt NH3 2 H2 O2 2 and (2-methylsulfanyl)phenyl phosphonic acid (H2 mspp) did not yield the expected cis-diammine [(2-methylsulfanylphenyl)phosphonato]platinum(II) but the dimeric compound [{Pt(mspp) NH3 g2 6H2 O in which the dianionic mspp2ÿ ligand acts both as chelator and bridging ligand. Thus, the high trans-eect of the sulfanyl group apparently leads to elimination of one NH3 ligand. An X-ray crystal structure analysis of the dimeric complex is reported. Ó 2000 Elsevier Science S.A. All rights reserved. Keywords: Platinum complexes; 2-Methylsulfanylphenyl phosphonic acid; X-ray diractometry
1. Introduction Since the discovery of the anticancer activity of cisplatin (cis-[PtCl2 NH3 2 ]), several thousands of platinum compounds have been screened for antitumor properties [1]. Most of the active compounds have the formula cis-PtX2 L2 , where L2 are two amines or a diamine, and X2 are two anionic leaving groups or a dianion, but a number of deviations from this rule also emerged. For instance, platinum diamine complexes with methylsul®nyl acetate (Soaÿ ) and methylsul®nyl benzoate (Sobÿ ) ligands, such as [Pt(Soa)(en)]NO3 and [Pt(Sob)(en)]NO3 (1), showed cytotoxicity against L1210 leukemia cells [2], and platinum diamine complexes with nitrilotris(methylenephosphonate) (ntmp2ÿ ), such as cis-[Pt(ntmp)(NH3 2 ] (2), were found active against osteosarcoma tumors [3]. We ®gured by analogy that the ligand 2-methylsulfanylphenyl phosphonate (mspp2ÿ ) should form, upon reaction with cis-diammine platinum(II) complexes, the electrically neutral species * Corresponding author. Tel.: +33-1-42-86-21-75; fax: +33-1-42-8683-87. E-mail address: [email protected] (J. Kozelka).
cis-[Pt(mspp) NH3 2 (3), which would be a good candidate for a novel antitumor compound. We therefore prepared the ligand mspp2ÿ and reacted it with the diaqua form of cisplatin, cis-[Pt NH3 2 H2 O2 ] NO3 2 . Contrary to our expectation, the reaction yielded the dinuclear compound [fPt mspp NH3 g2 6H2 O (4). This compound is interesting, since mspp2ÿ acts both as chelator and bridging ligand, and we wish therefore to report here the synthesis and X-ray structure determination of this novel complex (Scheme 1). 2. Experimental 2.1. Synthesis of (2-methylsulfanyl)phenyl phosphonic acid C A solution of O; O-diisopropyl S-phenyl phosphorothioate A (1 g, 3.65 mmol) in dry THF was added slowly under nitrogen to a stirred THF solution of LDA (2.2 equivs.) at ÿ78°C prepared from i Pr2 NH (8 mmol) and n-BuLi (8 mmol, 1.6 M in hexane). The mixture was allowed to warm to ÿ20°C for an hour and an excess of methyl iodide (5 equivs.) was slowly added. Stirring was
1387-7003/00/$ - see front matter Ó 2000 Elsevier Science S.A. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 ( 0 0 ) 0 0 1 7 0 - 2
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
705
Scheme 1.
maintained for a further 3 h at ÿ20°C. The mixture was progressively warmed to room temperature. The reaction was quenched with an aqueous solution of ammonium chloride, extracted with ether, dried (MgSO4 ) and concentrated in vacuo to give the crude S-Me derivative B. Chromatography on silica gel (eluent: petroleum ether/ethyl acetate 80:20) gave B (94%) as a colourless oil. A procedure similar to that described by Mc Kenna using trimethylsilylbromide as a desilylating agent, followed by recrystallisation in methylene chloride, aorded C as colourless crystals. Yield 96% C7 H9 O3 PS: calcd C 41.18, H 4.44, P 15.17, found C 41.19, H 4.46, P 15.07. 2.2. Synthesis of complex 4 Complex 4 was obtained from a reaction between 360 mg (1.2 mmol) of cis-[PtCl2 NH3 2 ] (Johnson±Matthey), converted to the diaqua form by 24 h stirring with 1.99 equivs. of AgNO3 in 20 ml of water and removal of AgCl, and 1 equiv. of 2 methylsulfanylphenyl phosphonic acid C. After 10 min stirring at room temperature, 1 equiv. of NaOH (1 M) was added. The mixture was heated at 65°C during 5 h, turning blue. Upon slow cooling back to room temperature, colourless crystals, suitable for X-ray analysis, appeared (125 mg, 22%). C14 H20 N2 O6 P2 Pt2 S2 6H2 O: calcd C 17.95, H 3.44, N 2.99, S 6.85; found C 17.42, H 3.30, N 3.25, S 6.83. A second crop of the complex was obtained upon standing at 5°C but was contaminated by a bluish compound. 2.3. Crystallography Crystal data for [{Pt(mspp)(NH3 g2 6H2 O (4): M 936:67, monoclinic, space group C2=c, a 25:3415 2, b 124:09 1°, b 11:2542 2, c 22:1113 1 A,
3 , Dc 2:321 g cmÿ3 , for Z 8k V 5222:4 1 A A total of 26213 re¯ections, of (Mo±Ka) 0.71073 A. which 5952 independent (Rint 0:061) were collected on a Bruker CCD diractometer up to hmax 27:48° at 200(2) K. The intensities were corrected for Lorentz and polarization factors [4] and empirically for absorption.The structure was solved by direct and Fourier methods. From the dierence Fourier maps six water molecules were located, of which two are highly disordered. The data were re®ned by full matrix least squares, 2 minimising the function Rw Fo2 ÿ 1=kFc2 and using anisotropic displacement parameters for all atoms. Upon convergence the ®nal dierence Fourier map showed no signi®cant peaks. Full details of the data collection and re®nement are given in the Supplementary Tables. Final discrepancy factors were R 0:0324, R2w 0:0679 (for the 4438 observed re¯ections with I P 2:0r I). All calculations were carried out by using the PC version of the SHELX-97 programs [5]. 3. Results and discussion 3.1. Synthesis of 2-methylsulfanylphenyl phosphonic acid C Scheme 2 The LDA mediated rearrangement of phenylthiophosphate A to mercaptophenylphosphonate B was ®rst reported by Masson in 1993 [6]. This method which implies a phosphonyl group S ! C migration ([1,3] anionic sigmatropic process) constitutes a very valuable route for the synthesis of phosphorus-based members of thiosalicylic acid derivatives [7]. In a slightly modi®ed procedure, the starting hindered phenylphosphonate B
706
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
Scheme 2.
was synthesized in a high yield from the readily prepared O; O-diisopropyl S-phenyl thiophosphate A by using 2,2 equivs. of LDA in THF at low temperature followed by quenching with an excess of methyl iodide. Ecient bisdealkylation of the diester B can then be achieved by the elegant trans-desilylation procedure using Me3 SiBr and subsequent hydrolysis with methyl alcohol [8].
Table 1 and angles (°) for fPt mspp NH3 g (4)a Selected bond distances (A) 2 Molecule 1 0
Pt1±Pt1 Pt1±O11 Pt1±O12 Pt1±N11 Pt1±S11 P11±O11 P11±O120 P11±O13
3.2. Reaction between 2-methylsulfanylphenyl phosphonate and cis-[Pt NH 3 2 H 2 O2 NO3 2 The formation of 4 from cis-[Pt NH3 2 H2 O2 ] NO3 2 and 2-methylsulfanylphenyl phosphonate C indicates that the ligation of the sulfanyl group facilitates substitution of the ammine in trans position. This is not exceedingly surprising, since ligands binding to platinum through a sulfur atom are known to exhibit a high kinetic trans-eect [9]. The fact that the analogous reaction between Pt en H2 O2 NO3 2 and 2-methylsul®nyl benzoate yielded, according to Pasini et al. [2], the expected mononuclear cationic diamine compound 1, may be due to the chelate eect of ethylenediamine which prevented dissociation of the NH2 group trans to S. 3.3. X-ray structure analysis of 4 6H 2 O The structure consists of dimeric fPt mspp NH3 g2 units held together by van der Waals and hydrogen bond interactions. There are two independent half-dimers in the unit cell, each complete fPt mspp NH3 g2 molecule being generated by the symmetry elements listed in Table 1. One of the two independent molecules is shown in Fig. 1, and a list of relevant bond distances and angles is given in Table 1. The co-ordination around each platinum atom is slightly distorted square planar. The immediate coordination sphere consists of the ammine nitrogen, the sulphur and oxygen atoms of one mssp ligand and a second oxygen of a symmetry-related mssp moiety. 4 is the ®rst crystallographically characterized complex with the coordination sphere PtNO2 S. The bond lengths and angles, in both molecules, fall within the expected range [10]. The geometry of the two independent molecules is similar, with most bond lengths and angles being equal within the standard deviations (see Table 1). However, a very signi®cant dierence is found between the two values for the angle Pt1±O12±P110 at the junction of the two half-dimers
O11±Pt1±N11 O11±Pt1±O12 O11±Pt1±S11 O12±Pt1±N11 N11±Pt1±S11 S11±Pt1±O12 Pt1±O11±P11 Pt1±O12±P110 Pt1±S11±C111 O120 ±P11±C116 O120 ±P11±O11 S11±C111±C116 P11±C116±C111
4.097(1) 2.021(5) 2.061(4) 2.051(6) 2.220(2) 1.534(5) 1.553(5) 1.502(5) 176.9(2) 88.0(2) 92.3(1) 89.6(2) 90.2(1) 178.4(1) 116.4(3) 116.8(2) 111.8(2) 103.8(3) 112.3(3) 126.1(5) 126.2(5)
Molecule 2 4.251 (1) 2.025(4) 2.045(5) 2.029(6) 2.226(2) 1.525(5) 1.548(5) 1.484(6) 176.7(2) 88.5(2) 90.0(1) 89.0(2) 92.6(2) 178.4(2) 117.7(3) 122.9(3) 107.7(3) 100.6(3) 113.2(3) 125.1(5) 127.5(5)
a
Primed atoms are obtained by those unprimed by the symmetry operators: ÿx; 0:5 ÿ y; ÿz for molecule 1 and 0:5 ÿ x; 0:5 ÿ y; ÿz for molecule 2
Fig. 1. Ortep view (ellipsoids drawn at 50% probability) and stereoview of Molecule 1 of compound 4.
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
(116.8(2)° and 122.9(3)°, respectively). Thus the two Pt±O±P±O2 rings have slightly dierent conformations. As a consequence the Pt1±Pt10 separations are respectively. dierent, 4.097(1) and 4.251(1) A, There are a number of short intermolecular hydrogen bonds between the dimers and between dimers and water molecules, the N O and O O distances ranging between 2.90 and 3.10 A. 3.4. Behaviour of 4 towards solvents; reaction with HCl Complex 4 is practically insoluble in water, DMF and DMSO. Upon stirring with 0.1 M aqueous HCl for 20 min at 60°C, the solid turned yellow, and, after lyophilisation, a microanalysis of the dry yellow powder obtained showed the composition Pt(mspp)(NH3 1:25 HCl. Thus, protonation of the phosphonato groups and concomitant chloride coordination apparently occurred. Attempts to obtain stoichiometric mono- and di-chloro complexes, which would be interesting candidates for cytotoxic compounds, are in progress. 4. Supplementary material Additional material available from the Crystallographic Data Centre comprises details of crystal data, experimental conditions and data treatment, fractional
707
atomic coordinates, thermal parameters and full listings of bond lengths, bond angles and torsion angles.
Acknowledgements We wish to thank Dr. S. Masson and Prof. J.-C. Chottard for helpful discussions. A generous loan of cisplatin from Johnson±Matthey is gratefully acknowledged.
References [1] R.B. Weiss, M.C. Christian, Drugs 46 (1993) 360. [2] A. Pasini, G. D'Alfonso, C. Manzotti, M. Moret, S. Spinelli, M. Valsecchi, Inorg. Chem. 33 (1994) 4140. [3] M.J. Bloemink, J.P. Dorenbos, R.J. Heetebrij, B.K. Keppler, J. Reedijk, H. Zahn, Inorg. Chem. 33 (1994) 1127. [4] SAINT: SAX Area Detector Integration: Siemens Analytical Instrumentation, 1996. [5] G.M. Sheldrick, SHELX-97. Structure Solution and Re®nement Package. Universit at G ottingen, 1997. [6] S. Masson, J.-F. Saint-Clair, M. Saquet, Synthesis (1993) 485. [7] S. Masson, J.-F. Saint-Clair, A. Dore, M. Saquet, Bull. Soc. Chim. Fr. 133 (1996) 951. [8] C.E. McKenna, J. Schmidhauser, J. Chem. Soc. Com. (1979) 739. [9] J.V. Quagliano, L. Schubert, Chem. Rev. 50 (1952) 201. [10] A.G Orpen, L. Brammer, F.H. Allen, O. Kennard, D.G. Watson, R. Taylor, J. Chem. Soc. Dalton Trans. (1989) S1±S83.
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Reaction between the diaqua form of cisplatin and 2-methylsulfanylphenylphosphonic acid yields a dinuclear phosphonato-bridged complex via NH3 elimination Christelle Mauger a, Michel Vazeux a, Alberto Albinati b, Jirõ Kozelka
c,*
a
Laboratoire de Chimie Mol eculaire et Thio-organique, UMR CNRS 6507, Universit e de Caen, ISMRa, 6 Bld Mar echal Juin, 14000 Caen, France b Institute of Pharmaceutical Chemistry, University of Milano, 42, Viale Abruzzi I-20131 Milano, Italy c Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Universit e Ren e Descartes, UMR CNRS 8601, 45 rue des Saints-P eres, 75270 Paris 06, France Received 12 September 2000; accepted 5 October 2000
Abstract Reaction between cis-[Pt NH3 2 H2 O2 2 and (2-methylsulfanyl)phenyl phosphonic acid (H2 mspp) did not yield the expected cis-diammine [(2-methylsulfanylphenyl)phosphonato]platinum(II) but the dimeric compound [{Pt(mspp) NH3 g2 6H2 O in which the dianionic mspp2ÿ ligand acts both as chelator and bridging ligand. Thus, the high trans-eect of the sulfanyl group apparently leads to elimination of one NH3 ligand. An X-ray crystal structure analysis of the dimeric complex is reported. Ó 2000 Elsevier Science S.A. All rights reserved. Keywords: Platinum complexes; 2-Methylsulfanylphenyl phosphonic acid; X-ray diractometry
1. Introduction Since the discovery of the anticancer activity of cisplatin (cis-[PtCl2 NH3 2 ]), several thousands of platinum compounds have been screened for antitumor properties [1]. Most of the active compounds have the formula cis-PtX2 L2 , where L2 are two amines or a diamine, and X2 are two anionic leaving groups or a dianion, but a number of deviations from this rule also emerged. For instance, platinum diamine complexes with methylsul®nyl acetate (Soaÿ ) and methylsul®nyl benzoate (Sobÿ ) ligands, such as [Pt(Soa)(en)]NO3 and [Pt(Sob)(en)]NO3 (1), showed cytotoxicity against L1210 leukemia cells [2], and platinum diamine complexes with nitrilotris(methylenephosphonate) (ntmp2ÿ ), such as cis-[Pt(ntmp)(NH3 2 ] (2), were found active against osteosarcoma tumors [3]. We ®gured by analogy that the ligand 2-methylsulfanylphenyl phosphonate (mspp2ÿ ) should form, upon reaction with cis-diammine platinum(II) complexes, the electrically neutral species * Corresponding author. Tel.: +33-1-42-86-21-75; fax: +33-1-42-8683-87. E-mail address: [email protected] (J. Kozelka).
cis-[Pt(mspp) NH3 2 (3), which would be a good candidate for a novel antitumor compound. We therefore prepared the ligand mspp2ÿ and reacted it with the diaqua form of cisplatin, cis-[Pt NH3 2 H2 O2 ] NO3 2 . Contrary to our expectation, the reaction yielded the dinuclear compound [fPt mspp NH3 g2 6H2 O (4). This compound is interesting, since mspp2ÿ acts both as chelator and bridging ligand, and we wish therefore to report here the synthesis and X-ray structure determination of this novel complex (Scheme 1). 2. Experimental 2.1. Synthesis of (2-methylsulfanyl)phenyl phosphonic acid C A solution of O; O-diisopropyl S-phenyl phosphorothioate A (1 g, 3.65 mmol) in dry THF was added slowly under nitrogen to a stirred THF solution of LDA (2.2 equivs.) at ÿ78°C prepared from i Pr2 NH (8 mmol) and n-BuLi (8 mmol, 1.6 M in hexane). The mixture was allowed to warm to ÿ20°C for an hour and an excess of methyl iodide (5 equivs.) was slowly added. Stirring was
1387-7003/00/$ - see front matter Ó 2000 Elsevier Science S.A. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 ( 0 0 ) 0 0 1 7 0 - 2
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
705
Scheme 1.
maintained for a further 3 h at ÿ20°C. The mixture was progressively warmed to room temperature. The reaction was quenched with an aqueous solution of ammonium chloride, extracted with ether, dried (MgSO4 ) and concentrated in vacuo to give the crude S-Me derivative B. Chromatography on silica gel (eluent: petroleum ether/ethyl acetate 80:20) gave B (94%) as a colourless oil. A procedure similar to that described by Mc Kenna using trimethylsilylbromide as a desilylating agent, followed by recrystallisation in methylene chloride, aorded C as colourless crystals. Yield 96% C7 H9 O3 PS: calcd C 41.18, H 4.44, P 15.17, found C 41.19, H 4.46, P 15.07. 2.2. Synthesis of complex 4 Complex 4 was obtained from a reaction between 360 mg (1.2 mmol) of cis-[PtCl2 NH3 2 ] (Johnson±Matthey), converted to the diaqua form by 24 h stirring with 1.99 equivs. of AgNO3 in 20 ml of water and removal of AgCl, and 1 equiv. of 2 methylsulfanylphenyl phosphonic acid C. After 10 min stirring at room temperature, 1 equiv. of NaOH (1 M) was added. The mixture was heated at 65°C during 5 h, turning blue. Upon slow cooling back to room temperature, colourless crystals, suitable for X-ray analysis, appeared (125 mg, 22%). C14 H20 N2 O6 P2 Pt2 S2 6H2 O: calcd C 17.95, H 3.44, N 2.99, S 6.85; found C 17.42, H 3.30, N 3.25, S 6.83. A second crop of the complex was obtained upon standing at 5°C but was contaminated by a bluish compound. 2.3. Crystallography Crystal data for [{Pt(mspp)(NH3 g2 6H2 O (4): M 936:67, monoclinic, space group C2=c, a 25:3415 2, b 124:09 1°, b 11:2542 2, c 22:1113 1 A,
3 , Dc 2:321 g cmÿ3 , for Z 8k V 5222:4 1 A A total of 26213 re¯ections, of (Mo±Ka) 0.71073 A. which 5952 independent (Rint 0:061) were collected on a Bruker CCD diractometer up to hmax 27:48° at 200(2) K. The intensities were corrected for Lorentz and polarization factors [4] and empirically for absorption.The structure was solved by direct and Fourier methods. From the dierence Fourier maps six water molecules were located, of which two are highly disordered. The data were re®ned by full matrix least squares, 2 minimising the function Rw Fo2 ÿ 1=kFc2 and using anisotropic displacement parameters for all atoms. Upon convergence the ®nal dierence Fourier map showed no signi®cant peaks. Full details of the data collection and re®nement are given in the Supplementary Tables. Final discrepancy factors were R 0:0324, R2w 0:0679 (for the 4438 observed re¯ections with I P 2:0r I). All calculations were carried out by using the PC version of the SHELX-97 programs [5]. 3. Results and discussion 3.1. Synthesis of 2-methylsulfanylphenyl phosphonic acid C Scheme 2 The LDA mediated rearrangement of phenylthiophosphate A to mercaptophenylphosphonate B was ®rst reported by Masson in 1993 [6]. This method which implies a phosphonyl group S ! C migration ([1,3] anionic sigmatropic process) constitutes a very valuable route for the synthesis of phosphorus-based members of thiosalicylic acid derivatives [7]. In a slightly modi®ed procedure, the starting hindered phenylphosphonate B
706
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
Scheme 2.
was synthesized in a high yield from the readily prepared O; O-diisopropyl S-phenyl thiophosphate A by using 2,2 equivs. of LDA in THF at low temperature followed by quenching with an excess of methyl iodide. Ecient bisdealkylation of the diester B can then be achieved by the elegant trans-desilylation procedure using Me3 SiBr and subsequent hydrolysis with methyl alcohol [8].
Table 1 and angles (°) for fPt mspp NH3 g (4)a Selected bond distances (A) 2 Molecule 1 0
Pt1±Pt1 Pt1±O11 Pt1±O12 Pt1±N11 Pt1±S11 P11±O11 P11±O120 P11±O13
3.2. Reaction between 2-methylsulfanylphenyl phosphonate and cis-[Pt NH 3 2 H 2 O2 NO3 2 The formation of 4 from cis-[Pt NH3 2 H2 O2 ] NO3 2 and 2-methylsulfanylphenyl phosphonate C indicates that the ligation of the sulfanyl group facilitates substitution of the ammine in trans position. This is not exceedingly surprising, since ligands binding to platinum through a sulfur atom are known to exhibit a high kinetic trans-eect [9]. The fact that the analogous reaction between Pt en H2 O2 NO3 2 and 2-methylsul®nyl benzoate yielded, according to Pasini et al. [2], the expected mononuclear cationic diamine compound 1, may be due to the chelate eect of ethylenediamine which prevented dissociation of the NH2 group trans to S. 3.3. X-ray structure analysis of 4 6H 2 O The structure consists of dimeric fPt mspp NH3 g2 units held together by van der Waals and hydrogen bond interactions. There are two independent half-dimers in the unit cell, each complete fPt mspp NH3 g2 molecule being generated by the symmetry elements listed in Table 1. One of the two independent molecules is shown in Fig. 1, and a list of relevant bond distances and angles is given in Table 1. The co-ordination around each platinum atom is slightly distorted square planar. The immediate coordination sphere consists of the ammine nitrogen, the sulphur and oxygen atoms of one mssp ligand and a second oxygen of a symmetry-related mssp moiety. 4 is the ®rst crystallographically characterized complex with the coordination sphere PtNO2 S. The bond lengths and angles, in both molecules, fall within the expected range [10]. The geometry of the two independent molecules is similar, with most bond lengths and angles being equal within the standard deviations (see Table 1). However, a very signi®cant dierence is found between the two values for the angle Pt1±O12±P110 at the junction of the two half-dimers
O11±Pt1±N11 O11±Pt1±O12 O11±Pt1±S11 O12±Pt1±N11 N11±Pt1±S11 S11±Pt1±O12 Pt1±O11±P11 Pt1±O12±P110 Pt1±S11±C111 O120 ±P11±C116 O120 ±P11±O11 S11±C111±C116 P11±C116±C111
4.097(1) 2.021(5) 2.061(4) 2.051(6) 2.220(2) 1.534(5) 1.553(5) 1.502(5) 176.9(2) 88.0(2) 92.3(1) 89.6(2) 90.2(1) 178.4(1) 116.4(3) 116.8(2) 111.8(2) 103.8(3) 112.3(3) 126.1(5) 126.2(5)
Molecule 2 4.251 (1) 2.025(4) 2.045(5) 2.029(6) 2.226(2) 1.525(5) 1.548(5) 1.484(6) 176.7(2) 88.5(2) 90.0(1) 89.0(2) 92.6(2) 178.4(2) 117.7(3) 122.9(3) 107.7(3) 100.6(3) 113.2(3) 125.1(5) 127.5(5)
a
Primed atoms are obtained by those unprimed by the symmetry operators: ÿx; 0:5 ÿ y; ÿz for molecule 1 and 0:5 ÿ x; 0:5 ÿ y; ÿz for molecule 2
Fig. 1. Ortep view (ellipsoids drawn at 50% probability) and stereoview of Molecule 1 of compound 4.
C. Mauger et al. / Inorganic Chemistry Communications 3 (2000) 704±707
(116.8(2)° and 122.9(3)°, respectively). Thus the two Pt±O±P±O2 rings have slightly dierent conformations. As a consequence the Pt1±Pt10 separations are respectively. dierent, 4.097(1) and 4.251(1) A, There are a number of short intermolecular hydrogen bonds between the dimers and between dimers and water molecules, the N O and O O distances ranging between 2.90 and 3.10 A. 3.4. Behaviour of 4 towards solvents; reaction with HCl Complex 4 is practically insoluble in water, DMF and DMSO. Upon stirring with 0.1 M aqueous HCl for 20 min at 60°C, the solid turned yellow, and, after lyophilisation, a microanalysis of the dry yellow powder obtained showed the composition Pt(mspp)(NH3 1:25 HCl. Thus, protonation of the phosphonato groups and concomitant chloride coordination apparently occurred. Attempts to obtain stoichiometric mono- and di-chloro complexes, which would be interesting candidates for cytotoxic compounds, are in progress. 4. Supplementary material Additional material available from the Crystallographic Data Centre comprises details of crystal data, experimental conditions and data treatment, fractional
707
atomic coordinates, thermal parameters and full listings of bond lengths, bond angles and torsion angles.
Acknowledgements We wish to thank Dr. S. Masson and Prof. J.-C. Chottard for helpful discussions. A generous loan of cisplatin from Johnson±Matthey is gratefully acknowledged.
References [1] R.B. Weiss, M.C. Christian, Drugs 46 (1993) 360. [2] A. Pasini, G. D'Alfonso, C. Manzotti, M. Moret, S. Spinelli, M. Valsecchi, Inorg. Chem. 33 (1994) 4140. [3] M.J. Bloemink, J.P. Dorenbos, R.J. Heetebrij, B.K. Keppler, J. Reedijk, H. Zahn, Inorg. Chem. 33 (1994) 1127. [4] SAINT: SAX Area Detector Integration: Siemens Analytical Instrumentation, 1996. [5] G.M. Sheldrick, SHELX-97. Structure Solution and Re®nement Package. Universit at G ottingen, 1997. [6] S. Masson, J.-F. Saint-Clair, M. Saquet, Synthesis (1993) 485. [7] S. Masson, J.-F. Saint-Clair, A. Dore, M. Saquet, Bull. Soc. Chim. Fr. 133 (1996) 951. [8] C.E. McKenna, J. Schmidhauser, J. Chem. Soc. Com. (1979) 739. [9] J.V. Quagliano, L. Schubert, Chem. Rev. 50 (1952) 201. [10] A.G Orpen, L. Brammer, F.H. Allen, O. Kennard, D.G. Watson, R. Taylor, J. Chem. Soc. Dalton Trans. (1989) S1±S83.