DALTON FULL PAPER J. Chem. Soc., Dalton Trans., 1999, 1957–1965 1957 Cycloplatinated ferrocenylamine-carboxylate and dithiocarbamate complexes: synthesis and aqueous properties Kim McGrouther, Debbrah K. Weston, Delwyn Fenby, Brian H. Robinson * and Jim Simpson Department of Chemistry, University of Otago, P.O. Box 56, Dunedin, New Zealand. E-mail: brobinson@alkali.otago.ac.nz Received 16th February 1999, Accepted 16th April 1999 Metathetical reaction of the cyclometallated ferrocenylamine complexes [Pt{FeCp(s,h5-C5H3CHRNMe2)}(dmso)Cl] (R = H 1 or Me 3) and [Pt2{Fe(s,h5-C5H3CH2NMe2)2}(dmso)2Cl2] 2 with TlX (X = OAc or malonate), or the direct reaction with P(C6H4SO3-m)3 32 (tppms) and Et2NCS2 2(dedtc), gave [Pt{FeCp(s,h5-C5H3CHRNMe2)}(dmso)(OAc)], [{Pt[FeCp(s,h5-C5H3CHRNMe2)](dmso)}2(mal)] (mal = malonate), Na5[Pt{FeCp(s,h5-C5H3CHRNMe2)}(tppms)2], [Pt{FeCp(s,h5-C5H3CHRNMe2)}(dedtc)] and bis-Pt analogues.These complexes were characterised by analysis, ES-MS and 1H, 13C and 195Pt NMR.Metathetical reaction of 1–3 with silver(I) salts generally gave ferrocenium derivatives. Substitution trans to the Pt–N or Pt–C bond is determined by the acceptor character of the co-ordinating group and this together with steric constraints limit the range of carboxylato complexes. The acetato complex [Pt{FeCp(s,h5-C5H3CH2NMe2)}(dmso)(OAc)] crystallises with one molecule of H2O and a single crystal structure indicates a hydrogen bond between a solvent H2O and acetate ligand. Aqueous solutions of the water-soluble OAc, malonate and tppms complexes were studied by electrochemical and spectroscopic techniques.Their chemistry is regulated by pH-dependent equilibria involving aqua and hydroxo complexes and competing oxidation to the ferrocenium compound by molecular oxygen. Introduction Ferrocene is a useful building block for the synthesis of derivatives which feature as enzyme inhibitors,1 therapeutic agents,2 metabolic competitors,3 antimicrobial compounds,4 radiopharmaceutical 5 and histological agents.6 Their potential as anti-tumour agents is well documented.7 While their lipophilic character is ideal for crossing cellular membranes, their toxicity is dependent on the metabolism to water soluble derivatives via hydroxylation.Detoxification primarily occurs inside the liver microsomes.8 Conjugates of ferrocenylamines and platinum(II) are of particular interest because they may be selective molecular carriers possessing the antineoplastic properties of ferrocene and the well known cisplatin [PtCl2(NH3)2].9 Ferrocenylamine analogues of cisplatin 10,11 have been made but the facile cycloplatination of ferrocenylamines has provided 12–14 a versatile series of complexes which incorporate the two cytostatic moieties (1–3 are used in the work described herein).Toxicity, histological, platinum distribution and antitumour studies in mice have shown that these cyclometallated ferrocenylamines exhibit kidney rather than liver dysfunction, that they have reasonable toxicity and are mildly cytotoxic against standard tumours.15 However, 1–3 were active against cisplatin resistant cell lines. One of the diYculties with biological studies on the cyclometallated compounds has been their low solubility in water or saline solution; for example, peanut oil was used as a vehicle for drug injection in the toxicity work and irritation of the kidney may have been a contributing factor in the hepa- Pt dmso NMe2 C CH2 NMe2 Pt dmso CH2 NMe2 Pt dmso Fe H R Fe R = H, 1; R = Me, 2 3 Cl Cl Cl toxicity.15 It was also not clear whether, in vivo, the complexes remained intact. We therefore set out to increase the aqueous solubility, at the same time extending the range of leaving and biologically active groups in the platinum(II) co-ordination sphere.There are two potential co-ordination sites, trans to either the Pt–C (s site) or the Pt–NMe2 bond (p site), but each have specific electronic requirements.Hard neutral or anionic monodentate species or a softer donor of a chelate occupy the s site whereas soft p acceptors can replace dmso.14 Farrell 16 has shown that PtII–dmso complexes bind to DNA forming interstrand crosslinks by the displacement of dmso but a ferrocenyl cyclometallated configuration appears to strengthen the Pt–S bond as indicated by the shorter Pt–S bond length 12 and slow reactions with p acceptors.Target ligands for the work described in this paper were those with potential O–O (oxalate, ox; malonate, mal; cyclobutane- 1,1-dicarboxylate, cbdc), O–S (O-alkyl dithiocarbonate), N–S (cysteine) or S–S (diethyldithiocarbamate, dedtc) functionality as well as OAc and anionic P-donors. Within the O–O group malonate may either bridge, chelate or bind as mal-O whereas ox or cbdc must chelate; this sequence would also give an insight on the influence of the bite angle on the leaving group.Malonate is biologically active and platinum(II) complexes in which ferrocene is tethered to mal-O were found17 to be active against P338 murine leukemia cells, with congruent liver and spleen deposition. Diethyldithiocarbamate has also shown clinically therapeutic cytotoxic eVects in conjunction with platinum drugs 17,18 and it is capable of S–N, S or S–S binding. Complexes with sulfonated phosphines are a standard method to increase water solublity 19 and ferrocenylphosphines have inherent biological activity.20 Steric and electronic factors dictated that not all binding modes were achievable and the characterised complexes, solution and redox properties are described herein.Results and discussion Synthesis and structure Carboxylates. Metathetical reactions with thallium(I) salts1958 J. Chem. Soc., Dalton Trans., 1999, 1957–1965 gave a convenient route to the acetato complexes 4 and 5 (eqn. 1). Although 4 was accessible in good yield from AgOAc, metathetical reactions of 2 and 3 with AgOAc, and 1 with all other silver(I) salts, resulted in oxidation of the ferrocenyl moiety, eqn.(2). The hygroscopic ferrocenium salts 7 from AgNO3 oxidation were characterised and provided a set of water-soluble salts for sensitisation studies.21 Compounds 4–6 were characterised by microanalysis, ES-MS, FAB-MS, 1H, 13C (DEPT and heteronuclear correlation, HETCOR) and 195Pt NMR spectroscopy. Owing to the lability of the acetate group the primary ions of 4–6 in ES-MS are [(M 2 OAc) 1 CH3CN]1; at high cone voltages (40 or 80 V) both the CH3CN and dmso are lost in the primary ion.Chemical shifts for 4–6 in organic solvents are similar to those for 1–3 with ‘up and down’ Me of the SMe2 and NMe2 groups appearing as four discrete resonances with 195Pt– 1H satellites due to the planar chirality. 195Pt NMR is a useful diagnostic tool in this work and the expected 22 upfield shift from dPt[1] to dPt[4] is observed.The preparation of racemic 5 is described but both DL and meso 5 were also prepared from the appropriate stereoisomer of 2. Reaction with thallium malonate gave compound 8, eqn. (3). Surprisingly, no reaction was observed between 2 or 3 and malonate, or with TlX, where X is a potential bidentate anion, oxalate, cyclobutanedicarboxylate or acetylacetonate. FABMS and ES-MS showed that the malonate 8 was dimeric in the solid. A parent ion was not observed.The primary ion is [M 2 2(dmso)]1 followed by the cleavage ion [1 -Cl]1, an ion which may be expected if the malonato group is trans to the (Fc) C–Pt bond. Vapour pressure osmometry also confirmed the dimeric formulation in solution, as did the NMR data. In particular, J(195Pt-1H), the CH2 (mal) :Cp (Fc) ratio in the Pt dmso NMe2 CH R OC CH3 CH2NMe2 Pt dmso OC CH3 Pt NMe2 dmso CH2 OC CH3 R = H 4; R = Me 5 1-3 + TlX + + Fe Fe (1) 6 O O O 1 + AgX 4 X = OAc [7]+X– (2) Pt Me2N CH2 CO CH2 Pt OC C NMe2 dmso O dmso O H 1 + Tl(Hmal) (3) Fe Fe 8 1H NMR and one carboxylato 13C resonance were only compatible with a dimeric, O,O9 structure.Methyl and methylene carbon assignments, established via DEPT and HETCOR NMR, were compatible with the proposed structure and the non-equivalence of the prochiral NMe2 and SMe2 protons con- firmed that the cyclometallated framework was maintained. Finally, the complementarity of dPt[4] and dPt[8] shows that only one O-donor is bound per cyclometallated unit.To our knowledge this is the first bridged malonato complex in platinum(II) chemistry. trans-EVects normally favour ring closure of an malonato-O over the formation of bridged complexes and sequential chelation with the active cisplatin species cis-[PtCl- (NH3)2(OH2)]1, and cis-[Pt(NH3)2(OH2)2]21, has been demonstrated. 23 We could find no spectroscopic evidence for either O or O,O9 binding modes during the formation of 8 in buVered or unbuVered solutions, or for bidentate malonato complexes of 2 and 3.This is diYcult to rationalise as, while steric reasons may inhibit the formation of a bis-platinum analogue of 8, there are no constraints for a staggered structure derived from 2; for example, complexes of 2 with bulky phosphines are known.14 An alternative approach starting with the cis-Pt(dmso)2- (carboxylate) did not give cyclometallated products but, instead, resulted in protonation of the amine, a result not unexpected given the strong basicity of the ferrocenylamines.12 Similarly, metathetical replacement of Cl in the precursors to 1–3, trans-[PtCl2(dmso)(ferrocenylamine)], under the conditions which gave cyclometallated complexes, led to cleavage of the ferrocenylamine L, eqn.(4). The inability to isolate trans-[PtCl2(dmso)L] 1 TlX æÆ trans-[PtX2(dmso)L] æÆ decomp. (4) complexes of chelating carboxylates of 1–3 can easily be understood by reference to the structure of 8.Clearly, these carboxylates cannot bridge two cyclometallated units. Furthermore, the co-ordination of hard bases is restricted to a trans C–Pt site and chelation which requires the trans Pt–N site is not possible. Compounds 4–6 and 8 were moderately soluble in water (5 was the most soluble) but very soluble in 0.1 M NaOH as well as alcohols and CH2Cl2. A common feature of 4–6 was the crystallisation with loosely bound water molecules; these could be removed in vacuo.Values of dPt for 4–6 and 8, but not for those with other anionic groups trans to the Pt–C bond, show a strong solvent dependence (selected data are given in Table 1). For 4 hydrogen-bonding solvents cause a large upfield shift whereas the converse holds for 8; the explanation for this is not obvious as the intermolecular interactions for individual cyclometallated units should be similar for 4 and 8. This encouraged us to investigate the inter- and intra-molecular interactions in the crystal structure of 4.Crystal structure of compound 4. A perspective view of the molecule is shown in Fig. 1 with selected bond length and angle data in Table 2. Co-ordination about the Pt atom in compound 4 is similar to that observed in the closely related [Pt{CpFe- (s,h5-C5H4CH2NMe2)}(dmso)Cl] 24 but with the chloro ligand replaced by an acetato group, bound through O(2), trans to the metallated C(3) atom of the dimethylaminomethylferrocene moiety. The co-ordination sphere is completed by a dmso ligand bound through S(1) and trans to the amine nitrogen N(1).The Pt–C bond distance in the acetato complex, 1.976(8) Å, is not significantly diVerent from that observed in the chloro analogue or from those in other complexes with an equivalent set of donor atoms.25 The Pt–S and Pt–N distances are also unremarkable. In contrast, the Pt(1)–O(2) distance, 2.115(5) Å, is significantly longer than those reported for platinum(II) acetato complexes.26 This observation clearly reflects the considerable trans influence of the s-bound C(3) atom noted previously.12 The cyclopentadiene rings of the ferrocene moiety are planar, and inclined at an angle of 3.8(6)8; they adopt an approximately eclipsed conformation.The platinum boundJ. Chem. Soc., Dalton Trans., 1999, 1957–1965 1959 Table 1 195Pt NMR and E1/2 data Compound Group trans to PtC dPt a E1/2 b/V Compound Group X trans to PtC, L trans to PtN dPt a 8441 36 mal OAc OAc Cl Br I Cl OAc — 22091 22078 22122 22143 22195 22279 22136, 22156 22075 — 0.06 0.24 0.23 0.25 0.27 0.30 0.03 0.03 — 9 11 13 14 12 L = tppms, X = Cl L = X = tppms L = X = dedtc L = PPh3, X = Cl L = CO, X = Cl L = X = dedtc L = PPh3, X = Cl L = X = tppms 2(2600) 2(3259) 21974 22553 22303 21981, 22227 22557 2(3258) a dPt in CDCl3 except for those in italics which are in D2O.b Recorded in CH2Cl2 except for those in italics which are in D2O; referenced against SCE at 200 mV s21, platinum electrode at 20 8C.C(2)–C(6) ring is almost coplanar with the adjacent fivemembered platinocyclic ring [interplanar angle 0.1(6)8]. The oxygen atom O(4) of the solvent water molecule makes close contact, d [O(3) ? ? ? O(4)] 2.837(7) Å, with the carbonyl oxygen atom O(3) of the co-ordinated acetate ligand, suggesting a reasonably strong hydrogen bonding interaction in the crystal lattice. Interestingly, similar interactions are observed in two other platinum complexes with monodentate acetate ligands.26 Phosphine.A sulfonated phosphine having p-acceptor capability should co-ordinate at a trans Pt–N site but unexpectedly the anionic phosphine tppms P(C6H4SO3-m)3 32also bound at Fig. 1 Perspective view of compound 4 showing the atom numbering scheme. The possible hydrogen-bonding interaction is displayed as a dashed line. Table 2 Selected bond lengths (Å) and angles (8) for compound 4 Pt(1)–O(2) Pt(1)–S(1) Pt(1)–N(1) Pt(1)–C(3) O(2)–C(17) O(3)–C(17) C(17)–C(18) S(1)–O(1) S(1)–C(15) S(1)–C(16) N(1)–C(13) N(1)–C(14) N(1)–C(1) C(1)–C(2) O(2)–Pt(1)–S(1) O(2)–Pt(1)–N(1) O(2)–Pt(1)–C(3) S(1)–Pt(1)–N(1) S(1)–Pt(1)–C(3) 2.115(5) 2.188(2) 2.117(6) 1.976(8) 1.293(8) 1.218(8) 1.525(10) 1.473(5) 1.785(9) 1.771(7) 1.492(8) 1.490(8) 1.497(10) 1.477(10) 94.3(1) 88.6(2) 171.1(2) 175.4(2) 94.1(2) C(2)–C(3) C(2)–C(6) C(3)–C(4) C(4)–C(5) C(5)–C(6) C(8)–C(9) C(8)–C(12) C(9)–C(10) C(10)–C(11) C(11)–C(12) Fe(1)–C(2–6) Fe(1)–C(8–12) O(3) ? ? ? O(4) N(1)–Pt(1)–C(3) C(17)–O(2)–Pt(1) O(2)–C(17)–O(3) O(2)–C(17)–C(18) O(3)–C(17)–C(18) 1.468(11) 1.404(11) 1.416(9) 1.448(11) 1.422(9) 1.411(10) 1.428(11) 1.419(11) 1.426(11) 1.398(11) 2.06(2) (mean) 2.051(14) (mean) 2.837(7) a 83.3(3) 122.4(5) 124.9(7) 113.1(6) 122.0(7) a Translation 1 1 x, ��� 2 y, ��� 2 z.the trans Pt–C site. Direct addition of an aqueous solution of sodium salt of tris(m-sulfonatophenyl)phosphine to a CHCl3 solution of compound 1 at room temperature results in an immediate transfer of the orange colour to the aqueous layer due to the formation of monosubstituted 9 and the dominant bis-substituted 11 tppms complexes, eqn.(5); a similar mono- 10 and bis-tppms complex 12 were made from 3. The mono-tppms complexes 9 and 10 were only spectroscopically characterised in solutions of 11 and 12. This is the opposite of the behaviour found in reactions with PPh3.14 Compounds 9–12 rapidly oxidise in water and their syntheses required strictly anaerobic conditions.The formulation of 11 and 12 as bis-substituted adducts is predicated on the ES-MS and NMR spectra. Since they are highly charged species, cations are accumulated in the gas phase to give a net charge of 23. Thus the primary ion in the ES-MS for 11 is [11 2 4Na1 1 7H1]; the primary ion for 12 was likewise [12 2 8Na1 111H1]. The SMe2 resonances were absent in the 1H NMR of 11 and 12 although, from the NMe2 profile, planar chirality is maintained.dPt[11] = 23259 and dPt[12] = 23258, akin to those for chelated phosphine analogues (cf. d 23970 for the dppm complex).14 The 31P NMR also supported the cis orientation of the ligands. A smaller 1JPt–P is observed for the phosphorus trans to the Pt–C bond (3662/3690 Hz for 11 and 12 respectively) compared to that for phosphorus trans to the Pt–N bond z), as expected for a weaker Pt–P bond in the trans Pt–C site. Both coupling constants are larger than those for comparable chelates (1JPt–P =1510 and 3300 for the dppm analogue), but smaller than for P(OPh)3 (1JPt–P = 7153),14 and presumably reflect the high charge on the complex.For 9 and 10 a single 31P resonance, a typical dH for an SMe2 group in cyclometallated derivatives, and the coupling constants (1JPt–P = 3735, 3675 Hz for 9 and 10 respectively) characterised these unstable molecules as having a tppms ligand trans to the Pt–N bond. The anionic phosphine induces water solubility but also functions as both a hard and soft donor.This could be Pt NMe2 C Cl P(C6H4SO3)3 H H Pt NMe2 C P(C6H4SO3)3 P(C6H4SO3)3 H H (5) 1 + n(tppms3–) + Fe 3– Fe 9 11 5–1960 J. Chem. Soc., Dalton Trans., 1999, 1957–1965 important for biological activity and we therefore looked at other anions with this capability. Diethyldithiocarbamate/O-alkyl dithiocarbonate. In contrast to sodium carboxylates the direct reaction of sodium diethyldithiocarbamate with compounds 1 and 3 at room temperature gave good yields of the water-insoluble N,S chelates 13 and 14, eqn.(6). Parent ions were observed in both the FAB- and ESMS (at a cone voltage of 80 V); they are very stable species. Non-equivalence of the NMe and NEt protons and carbons was observed in the 1H and 13C NMR for 13 confirming the N,S chelate structure. The CS2 resonance dC 211 is typical of N,Schelate complexes. The NMR complexity increases further for 14 as the platinum(II) co-ordination sites are non-equivalent and individual dH and dC resonances are seen for each CH3 and CH2 group.The PtN2SC co-ordination sphere results in a 195Pt resonance (Table 1) at d 21974, for 13, and two at d 21981 and 22227 for 14, compared to 22070 (22075), 22140 (22136 and 22156) and 22550 (22557) for PtNOSC, PtNSClC and PtNPClC respectively (data for di-Pt compounds in italics). The diethylthiocarbamate ligand is a poor p acceptor and the anionic sulfur and tight ‘bite’ would contribute to the upfield shift but the 240 ppm diVerence between the two dPt, not seen in other bis-Pt cyclometallated complexes (Table 1), suggests that the co-ordination sphere in 14 is distorted.Given the ready formation of an N,S anionic chelate we anticipated a similar result for an O,S donor ligand but there was no NMR evidence for substitution by O-alkyl dithiocarbonate. Reactivity in aqueous solution Oxidation of compounds 4–6 by Ag1 in non-aqueous solvents to give green ferrocenium salts 7 has already been mentioned.What was unexpected was the facile oxidation of 4–12 in water by molecular oxygen, in all solvents, as manifested by the collapse of resonances in the NMR and the onset of ferrocenium absorption bands in the visible spectra. This facile oxidation had a marked influence on reactivity in aqueous solution; in particular, solutions of 4–6 and 8 were eYcient scavengers of Cl2 ion converting rapidly into 1–3.Electrochemical data were collected for all compounds but detailed spectroscopic studies were only undertaken on 4 and 8 as the oxidation process is extremely fast for 11 and 12. Electrochemistry. Cycloplatination shifts Fc1/0 approximately 0.2 V cathodic of ferrocene and compounds 4–6, 8 and 13 and 14 displayed typical reversible Nernstian behaviour for the [1/0] couple. There was nothing unusual in the E1/2 values except for the dimer 8, E1/2 = 0.06 V, which is ª 0.16 V more cathodic than comparable couples 13 (Table 1).Cyclic voltammetric and square wave responses for 11 and 12 were complicated by the lability of the tppms, particularly if traces of water were present, but in non-aqueous solvents Ep[11] at ª 0.10 V is comparable to E1/2 for the PMePh2 and dppm complexes of 2.13 In water E1/2[4–6] and E1/2[8] are apparently chemically Pt NMe2 CH2 S NEt2 C S S NEt2 C S CH2 NMe2 Pt Pt Et2N C S S (6) Fe 14 13 Fe 1 or 3 + dedtcreversible but the slow electrode kinetics results in large DEp of ª 100 mV.Taking cognisance of junction potentials there is a cathodic shift of ª 0.1 V from acetone to water. The electrochemical response for compound 4 was independent of pH, scan rate or solvent mix (e.g. methanol–water). However, a second cathodic wave is seen for 8 in water at scan rates > 800 mV s21 (Fig. 2), indicative of an ECE process. We suggest that this is due to dissociation of one end of the bridging malonate ligand on oxidation to give an mal-O analogue of 4 (there is evidence for this process in ES-MS, eqn.(7). Compounds 11 and 12 oxidised rapidly in water during the electrochemical measurement which, together with the ligand lability and co-ordination of water at the trans Pt–C site, led to very complex voltammetric data. When Cl2 was added to an aqueous solution of 4–6 or 8 the only redox process seen was that due to the respective 1–3. NMR. Provided the sample is sealed under argon, there is no change with time in the profile of the 195Pt resonance for compound 4 in any solvent.dPt[4] displays a large variation with solvent: 22122 in D2O, 22078 in CDCl3 22138 in MeOH and 22038 in acetone. This dependence on solvent is attributed to Fig 2 Cyclic voltammograms of compound 8 electrode at a platinum (a) in acetone, NEt4ClO4, 20 8C, repeat scans, 50, 100, 800 mV s21; (b) in water, NaClO4, 20 8C, 2 scans, 100 (dotted) and 800 mV s21. Pt Me2N CH2 NMe2 CH2 Pt OCCH2CO dmso Pt Me2N CH2 dmso solv NMe2 CH2 Pt OCCH2CO– + dmso (7) Fe Fe O O O Fe Fe 8 OJ.Chem. Soc., Dalton Trans., 1999, 1957–1965 1961 hydrogen bonding although the formation of another species could not be ruled out in aqueous solvents. Confirmation that a new species is formed in the presence of water came from the appearance of a new resonance at d 22073 when D2O was added to dry MeOH solutions of 4, the intensity being proportional to the relative amount of D2O added.A similar downfield shift and new resonances were found in acetone– D2O and CDCl3–D2O solvent mixes. Concomitant with this downfield shift in dPt, dH(OAc) changes to the position of an unco-ordinated OAc but planar chirality is maintained in the co-ordination sphere with only small shifts in the prochiral protons (SMe2, NMe2). These data are consistent with the formation of an aqua complex 15. However, immediately compound 4 is dissolved in D2O or ‘wet’ organic solvents in air the 195Pt resonance broadens and eventually collapses, as do the ferrocene proton resonances, and the solution has a green tinge.These spectral changes are faster at low pH and at pH > 9 spectral collapse due to the oxidation is relatively slow. Similar observations were made for aqueous solutions 5, 6 and 8. In acid the resonance attributed to 15 is the major species but at pH 6 15 and a new species (dPt 22257) coexist. At pH > 8 the only remaining species has dPt 22027.The addition of ClO4 2 to 4(aq) in D2O in air has no immediate eVect on dPt[4] but buVered PO4 32 (pH 7.4), OD2 (pH 9) and glycinate shift dPt to 22027, 22024 and 22209 respectively. The 1H NMR spectra show that the cyclometallated skeleton is retained but in the PO4 32 and OD2 solutions (but not glycinate) dH(SMe2) surprisingly disappeared. Since the dmso cannot be replaced in non-aqueous solutions by other than p acceptors the loss of dH(SMe2) suggests that another leaving group in the trans Pt–N position has been created.In halogenated solvent–water mixtures in air, or with Cl2 present, there is rapid formation of 1–3, clearly seen in the 195Pt NMR, particularly if a trace of acid is present (Scheme 1). Electronic spectra. The UV/visible spectra were run in conjunction with the NMR as they give an insight into the oxidation step. In dry organic solvents compounds 4–6 and 8 have the 1A1g æÆ 1E1g(1E2g) transition at ª450 nm. This oxidation in water gives rise to two new bands at ª 570(sh) nm and the major 2E1g æÆ 2E1u transition at 750 nm27 of a ferrocenium species (Fig. 3). There is a red-shift compared to the parent ferrocenylamine and an increase in oscillator strength, features which are common within ferrocene derivatives 28 but not usually seen in complexes with metal ions. Undoubtedly, this is a consequence of cyclometallation causing a mixing of the co-ordinated platinum(II) and ferrocenium orbitals. By monitoring the band at 750 nm it was found that oxidation of 4 to 41 is a pseudo-first order reaction, t1/2 = 16 min at pH 2 decreasing with increased pH (pH 6: t1/2 = 68 h) until, at pH 12, t1/2 = > 120 h; this substantiates the qualitative NMR results.The lmax of the product and the change in molar absorbance with time diVer at pH 2, 6 and 9 (Fig. 3) indicating that diVerent species are present. Equilibria in aqueous solution. These NMR and spectral data show that two distinct processes influence the aqueous solution chemistry of the water-soluble complexes (Scheme 1).First, there is an equilibrium which leads to a hydrated species 15 which provides a labile group trans to the Pt–C bond and subsequent co-ordination of weakly co-ordinating groups like the glycinate anion. Secondly, an oxidation process involving molecular oxygen leading to ferrocenium species. Consequently, the electrochemical investigations in water were with solutions containing both the original complex and 15.Aside from the oxidation process the equilibria proposed in Scheme 1 are familiar in cisplatin chemistry.10,29 At pH 2 the aqua species 15 (dPt 22122, 580/785 nm) dominates and, as the pH increases, hydroxo species 16 (dPt 22257, 575/750 nm) is formed. In strongly basic solutions a hydroxo-bridged species 17 may be produced which stabilises the ferrocenyl core of 4–6 to oxidation. This explains why dPt is the same for solutions buVered by PO4 32 and OD2. It is postulated that formation of a dimsyl species 18 at this pH provides a good leaving group and the impetus to create the necessary cis co-ordination site.Concurrent with the establishment of the equilibria incorporating the neutral species, oxidation gives a parallel series of products incorporating the ferrocenium analogues, the relative concentration being influenced by time and pH. It is well known that ferrocenium species are stabilised in acid solution, and clearly the proportion of oxidised species will decrease with pH, but under physiological conditions for biological testing ferrocenium species will dominate.Conclusion Incorporation of carboxylate moieties into the cyclometallated platinum(II) complexes based on ferrocenylamines induces the water solubility necessary for drug use. The trans influence and the preference for a p acceptor trans to the Pt–N bond dictate the range of ligands which can be co-ordinated, in particular chelating carboxylates.An additional factor is the steric conges- Scheme 1 Pt dmso NMe2 C R OC CH3 Pt dmso NMe2 C R OH2 Pt dmso NMe2 C R OH Pt NMe2 CH R OH OH Pt Me2N CH Pt NMe2 C R OH S O H2C CH3 R OAc– H2O H H H – Fe 17 Fe Fe + O2 4 15 [15]+ 16 18 Fe Fe + –H+ –H+ Fe O H1962 J. Chem. Soc., Dalton Trans., 1999, 1957–1965 tion around the PtII but the absence of malonato complexes of 2 and 3 is unexpected. Toxicity and anti-tumour data have been published for 4.15 Data now available for 5, 6 and 8 confirmed that this class of compound shows general hepatotoxicity with lower toxicity than the “free” ligands and there was less intestinal irritation with the water soluble compounds.Most signifi- cant, however, is that their cytotoxicities are virtually identical to those of the parent chloro complexes 1–3.21 The reason for this is now clear. In the presence of oxygen, when 4–6 or 8 encounter Cl2(aq) in vivo, they are converted into 1–3 and consequently in vivo biological testing, especially in saline solution, will always be of the chlorocycloplatinated species irrespective of the injected complex.The evidence strongly supports the formation of an aqua complex 15 at low pH, and hydroxo species at higher pH, in aqueous solutions of the carboxylate derivatives. In principle, 15 should have provided a route to complexes with amino acids and nucleotides (as with cisplatin 30) but there was no NMR evidence for substitution under strictly anerobic conditions; substitution in aqueous solution is complicated by the facile oxidation to ferrocenium species in air.Although molecular oxygen is definitely involved, there is insuYcient evidence to speculate whether oxidation involves a pH-dependent peroxo or radical oxidation mechanism. The oxidation is being thermodynamically driven by the lower E1/2 for the cycloplatinated complexes but the system is more subtle than this because the addition of Cl2 to solutions of the ferrocenium species gives neutral 1–3, not [1]1–[3]1.From a physiological perspective, the in vivo equilibria and biologically active complex will be diYcult to unravel. Experimental All synthetic work was performed in a fumehood as ferro- Fig 3 Electronic spectra of compound 4 in water, 20 8C, under argon, at various times after dissolution: (a) pH 2, intervals of 20 min, t1/2 = 16 min; (b) pH 6, intervals of ª 50 min, t1/2 = 68 h; (c) pH 12, over 400 h.cenylamines have acrid odours. All reactions were carried out in oven-dried glassware under an atmosphere of argon or oxygenfree nitrogen. The compounds 1, 2, 3,12 and TlX31 were prepared by literature methods. The IR and NMR spectra were recorded on Digilab FX60 and Varian VXR300 MHz /Gemini 200 MHz spectrometers respectively, with 195Pt referenced against K2PtCl4. Microanalyses were carried out by the Campbell Microanalytical Laboratory, University of Otago.Electrospray mass spectra were recorded on a VG Platform II spectrometer in a 1 : 1 v/v acetonitrile–water or methanol–water mobile phase (0.1 mM in compound) and FAB spectra on a Kratos MS80RFA instrument with an Iontech ZN11NF atom gun. Electrochemical measurements were performed with a three-electrode cell using a computer controlled EG & G PAR 273A potentiostat/galvanostat at scan rates 0.05–10 V s21. A polished platinum disc electrode was employed; the reference was SCE uncorrected for junction potentials ([ferrocene]1/0, E1/2 = 0.466 V in acetone), the supporting electrolyte 0.1 M (NEt4- ClO4) and the substrate ª 1 × 1023 M.Preparation of compounds 4–6 from thallium(I) acetate Compound 4. To a solution of compound 1 (52.8 mg, 0.96 mmol) in chloroform (5 ml) was added a solution of thallium(I) acetate (25.3 mg, 0.96 mmol) in ethanol (5 ml). The mixture was left standing at room temperature in the dark for six hours. The thallium(I) chloride which had precipitated and was removed by centrifuge.More precipitated when the supernatant solution was left overnight at room temperature. After all had precipitated and been filtered oV, the orange solution was evaporated to dryness and the residue recrystallised from acetone–hexane (1 : 3) to give orange-yellow crystals of 4 (68.3%) (Found: C, 35.63; H, 4.57; N, 2.36. C17H25FeNO3PtS requires C, 35.55; H, 4.39; N, 2.44%). dH(CDCl3) 2.04 (s, 3 H, CH3CO2); 2.83 (s, 3 H, JPt–H = 15.5, NCH3); 3.03 (s, 3 H, JPt–H = 14.2, NCH3); 3.37 (s, 3 H, JPt–H = 12.4, SCH3); 3.57 (s, 3 H, JPt–H = 13.5 Hz, SCH3) and 4.12–4.33 (m, 8 H, C8H8).dPt(CDCl3) 22076. n(KBr, cm21) 1614 (C]] O), 1319 (C–O) and 1139 (S]] O). lmax/nm(e/M21 cm21) (CHCl3) 455(332). Compound 6. This was prepared similarly, from compound 2 (26.2 mg, 0.29 mmol) and thallium(I) acetate (15.2 mg, 0.58 mmol). The orange residue was recrystallised from benzene– hexane (1 : 3) to give pale orange crystals of 6 (Found: C, 30.32; H, 4.12; N, 2.92.C24H40FeN2O6Pt2S2 requires C, 29.94; H, 4.19; N, 2.91%). dH(CD2Cl2) 1.93 (s, 6 H, CH3CO2); 2.73 (s, 6 H, JPt–H = 15.0, NCH3); 2.92 (s, 6 H, JPt–H = 13.2, NCH3); 3.33 (s, 6 H, JPt–H = 11.7, SCH3); 3.44 (s, 6 H, JPt–H = 12.3 Hz, SCH3); and 4.04–4.24 (m, 8 H). dPt(CD2Cl2) 22075. n(KBr, cm21) 1620 (C]] O), 1328 (C–O) and 1140 (S]] O). Compound 5. Compound 3 (43.7 mg, 0.77 mmol) in the minimum volume of chloroform was added to thallium(I) acetate (0.2032 g, 0.77 mmol) dissolved in ethanol (10 ml).The mixture was stirred for 10 mins and then left to stand at room temperature overnight in the dark. The precipitated thallium chloride was centrifuged, the supernatant solution filtered and then left to stand until precipitation had stopped. The orangeyellow residue obtained after the solvent was removed was recrystallised from acetone–methanol to give 5 as an orange solid (62%); mp 182 8C (Found: C, 36.45; H, 4.94; N, 2.41.C18H27FeNO3PtS requires C, 36.74; H, 4.63; N, 2.38%). ES-MS: m/z 571, [M 2 OAc 1 CH3CN]1; and 528, [M 2 OAc]1. dH(CDCl3) 1.23 (d, 3 H, J = 6.88, CHCH3), 2.03 (s, 3 H, O2CCH3), 2.50 (s, 3 H, 3JPt–H = 36.1, NCH3), 2.79 (s, 3 H, 3JPt–H = 32.8, NCH3), 3.38 (s, 3 H, 3JPt–H = 22.9, SCH3), 3.51 (s, 3 H, 3JPt–H = 30.2 Hz, SCH3), 4.03 (s, 1 H, one of h5-C5H3), 4.09 (s, 5 H, h5-C5H5), 4.26 (s, 1 H, one of h5-C5H3) and 4.38 (s, 1 H, one of h5-C5H3). dC (CDCl3) 11.15 (CCH3), 25.40 (CH3CO2), 29.72 (SCH3), 43.51 (SCH3), 46.14 (NCH3), 47.65 (NCH3),J.Chem. Soc., Dalton Trans., 1999, 1957–1965 1963 63.29 (CH), 65.72 (CH), 69.52 (h5-C5H5), 69.59 (CH), 70.65 (CH), 74.04 (quaternary carbon), 97.73 (quaternary carbon) and 177.58 (CH3CO2). dPt(CDCl3) 22091. n(KBr, cm21) 1602(C]] O), 1414(CH3CO2), 1130(C–O), 1022(S]] O) and 688(C–S). lmax/nm(e/M21 cm21) 451(339). Preparation of compound 8 A chloroform solution of compound 1 (0.4591 g, 0.83 mmol, 45 ml) was added to thallium malonate (0.4259 g 0.81mmol), in boiling distilled water–ethanol.Thallium chloride precipitated as the solution was stirred for 48 h in the dark. The liquid was centrifuged, filtered and solvent stripped to give a bright orange oil 8 which eventually solidified on pumping in a high vacuum (83%); mp 150 8C (decomp.) (Found: C, 33.96; H, 4.45; N, 2.31; S, 5.60. C33H48Fe2N2O6Pt2S2?2H2O requires C, 33.91; H, 4.31; N, 2.40; S, 5.49%). ES-MS: m/z 1055 [M1-dmso].dH(CDCl3) 2.85 (s, 3 H, 3JPt–H = 15.9, NCH3), 3.08 (s, 3 H, 3JPt–H = 14.7, NCH3), 3.31 (s, 2 H, C3H2O4), 3.41 (s, 3 H, 3JPt–H = 13.8, SCH3), 3.48 (s, 2 H, CH2), 3.59 (s, 3 H, 3JPt–H = 14.2 Hz, SCH3), 4.15 (s, 5 H, h5-C5H5Fe) and 4.32 (s, 3 H, h5-C5H3Fe). dC(CDCl3): 45.45 (SCH3), 46.22 (SCH3), 49.47 [(CO2)2CH2], 51.91 (NCH3), 52.31 (NCH3), 61.60 (CH2), 66.68 (CH2), 68.84 (C5H5Fe), 94.65 (quaternary C) and 174.76 [(CO2)2CH2]. dPt(CDCl3) 22091. n(KBr, cm21) 1662(C]] O), 1125(C–O) and 1015(S]] O).lmax/ nm(e/M21 cm21) (CHCl3) 455 (72). A similar reaction with compound 2 gave only starting material; other methods tried unsuccessfully were hot and cold acetone–water and chloroform–hot water solvent mixtures, and ultrasonic reactions. Reaction of compound 1 with other thallium(I) salts Thallium cyclobutane-1,1-dicarboxylate, a new salt, was synthesized as follows. Thallium(I) nitrate (0.500 g, 0.19 mmol), dissolved in the minimum amount of hot water, was added to a boiling aqueous solution of cyclobutane-1,1-dicarboxylic acid (0.271 g, 0.19 mmol) and the solution concentrated.White platelets of the salt deposited on cooling (86%); mp 208 8C (Found: C, 12.96; H, 1.01. C3H3O2Tl requires C, 13.08; H, 1.10%). n(KBr, cm21) 1703 (C]] O). dH(D2O) 1.95 (2 H, CH2B) and 2.48 (4 H, CH2A,A9). dC(D2O) 180.30. This salt was used in reactions with compounds 1 and 2, in a variety of solvent mixtures, without success. A similar result was obtained with thallium(I) oxalate and nitrate.Reaction of compound 1 with silver salts Silver acetate. Silver acetate (15.2 mg, 0.09 mmol) suspended in acetone (20 cm3) was added to compound 1 (50 mg, 0.09 mmol) and stirred for at least 5 h at room temperature, in the dark. The mixture was centrifuged, the yellow solution decanted and evaporated to dryness. The orange solid was recrystallised from acetone–hexane; yield 58% of 4 identical to that prepared from the thallium(I) salt.Silver nitrate. The nitrate (15.42 mg, 0.09 mmol) in water (10 cm3) was added to compound 1 (50 mg, 0.09 mmol) dropwise, resulting in a green solution. This was centrifuged, then filtered and evaporated to dryness to give green 7. Recrystallisation was unsatisfactory as 7 is extremely hygroscopic (Found: C, 29.46; H, 3.55; N, 5.43. C15H12ClFeN2O4PtS requires C, 29.38; H, 3.63; N, 4.57%). n(Nujol, cm21): 1385 (NO3 2) and 1126 (S]] O). Lmax(H2O) 53.5 W21 cm2 mol21.l/nm(e/M21 cm21) (acetone): 588(364) and 780(515). Other salts. The salt AgX(aq) [X = ClO4 2, NO3 2, SO4 22, BF4 2, PF6 2, ox, or Hmal] was added to compound 1 dissolved in acetone at which point the solutions changed from orange to green giving ferrocenyl derivatives. For non-co-ordinating anions the species produced was 151. Reactions of compound 1 with Pt(dmso)2X2 (X 5 ox or Hmal) The compound [Pt(dmso)2Cl2] (70.0 mg, 0.17 mmol) was dissolved in warm water (10 ml) and added to a solution of silver malonate (52.7 mg, 1.7 mmol) in HNO3 (1 mol dm23, 10 ml).The precipitated AgCl was removed and the solution left overnight during which time further AgCl precipitated. Evaporation of the filtered solution to dryness gave [Pt(dmso)2- (Omal)]. n(Nujol, cm21): 1736 (C]] O) and 1156 (S]] O). This was dissolved in acetone–methanol (2 : 1, 40 ml), 1 (115 mg, 4.7 mmol) added and the solution heated at 50–60 8C in the dark with stirring for three hours.It was then stirred overnight at 20 8C, the resulting pale yellow-orange solution centrifuged and the supernatant liquid evaporated to dryness to give pale yellow crystals of [FeCp(h-C5H4CH2NHMe2)] (Found: C, 50.09; H, 5.95; N, 9.08. C13H18FeN2O3 requires C, 51.00; H, 5.93; N, 9.15%). dH (CDCl3) 2.73 (6 H, CH3); 4.11 (2 H, CH3); 4.20 (5 H, C5H3); and 4.31–4.36 (4 H, C5H4). Similar results were obtained using silver oxalate and with 1 even if a base (e.g. K2CO3) was present in the final step.Preparation of compounds 9–12 Compounds 9 and 11. Compound 1 (0.414 g, 0.75 mmol) was dissolved in 2 ml of rigorously deoxygenated chloroform and added to the sodium salt of tris(m-sulfonatophenyl)phosphine (54.6 mg, 1.50 mmol) in 20 ml degassed distilled water. This solution was sealed under nitrogen and left stirring for 2 h. Once the aqueous layer had reached full orange colouration the water was evaporated and the product immediately (due to very rapid oxidation) chromatographed on a octadecylfunctionalised silica gel reversed-phase column with methanol– water (1 : 2).The solvent was removed and the solid dissolved in hot water, hot methanol added and the solution centrifuged. Removal of solvent and recrystallisation from methanol– acetone gave pure 11 as orange crystals (57%); mp 220 8C (decomp.) (Found: C, 38.21; H, 2.90; Cl, 0.00; N, 0.8; S, 12.13. C49H40FeNNa5O18P2PtS6 requires C, 37.94; H, 2.60; Cl, 0.00; N, 0.90; S, 12.40%) ES-MS: m/z 488 [(M 2 4Na1)2 1 7H1].dH(D2O) 2.72 (s, 3 H, 3JPt–H = 4.6, NCH3), 3.35 (s, 3 H, 3JPt–H = 5.2, NCH3), 4.11 (s, 1 H, one of h5-C5H3Fe), 4.22 (s, 5 H, h5-C5H5Fe), 4.33 (s, 1 H, one of h5-C5H3Fe), 4.38 (s, 1 H, one of h5-C5H3Fe) and 7.34–8.17 [m, 24 H, P(C6H4SO3)3]. dC(D2O) 38.72 (NCH3), 41.35 (NCH3), 57.34 (CH), 69.11 (h5-C5H5Fe), 70.09 (CH), 71.02 (CH) and 126.96–130.23 [P(C6H4SO3)3]. dP(D2O) 5.64 (d, 2JP–P = 18.3, 1JPt–PC = 3128) and 15.91 (d, 2JPt–P = 19.2, 1JPt–PN = 3748 Hz).Also characterised spectroscopically in aged solutions, 9: dp(D2O) 14.68 (s, 1JPt–PN = 3735 Hz, N–Pt–P product only); dPt(D2O) 23259 (d, 1JPt–PN = 4981, 1JPt–PC = 3662 Hz); n(KBr, cm21) 1466 (P–Ph), 993 (P–Ph) and 622 (C–S); lmax/nm (e/M21 cm21) water 480(162), 585(71) and 809(90). Compounds 10 and 12. A similar procedure to that for compound 11 using 3 gave 12 as orange crystals (54%); mp 264 8C (decomp.) Rapid oxidation and hygroscopic character resulted in poor microanalytical data (Found: C, 37.18; H, 3.44; N, 0.77; S, 12.83.C88H70FeN2Na10O36P4Pt2S12 requires C, 36.24; H, 2.40; N, 0.96; S, 13.18%). ES-MS: m/z 913 [(M 2 8Na1)2 1 11H1]. n(KBr, cm21) 621 (C–S). lmax/nm (e/M21 cm21): 407 (534), 504 (257) and 682 (534). dH(D2O) 2.64 (s, 3 H, 3JPt–H = 4.3, NCH3), 2.71 (s, 3 H, 3JPt–H = 4.6, NCH3), 2.88 (s, 3 H, 3JPt–H = 5.3, NCH3), 3.02 (s, 3 H, 3JPt–H = 5.6 Hz, NCH3), 3.92–4.04 (m, 6 H, h5-C5H3Fe) and 7.17–7.97 (m, 48 H, tppms).dC(D2O) 27.90 (NCH3), 38.71 (NCH3), 41.36 (NCH3), 57.86 (NCH3), 71.13 (h5-C5H5Fe), 71.74 (h5-C5H5Fe) and 124.84–143.49(tppms). dP(D2O) 20.29 (d, 2JPt–P = 18.3, 1JPt–PN = 4474) and 24.13 (d, 2JPt–P = 18.3, 1JPt–PC = 2478 Hz). Characterised spectroscopically in aged solutions, 12: dP(D2O) 12.92 (t, 2JP–P = 40.31, 1JPt–PN = 3675 Hz); dPt (D2O) 23258 (d, 1JPt–PN = 4995, 1JPt–PC = 3690).1964 J. Chem. Soc., Dalton Trans., 1999, 1957–1965 Preparation of compounds 13 and 14 Compound 13.Sodium diethyldithiocarbamate (dedtc) (6.4 mg 0.02 mmol) dissolved in 20 ml methanol was added to compound 1 (15.6 mg, 0.02 mmol) dissolved in the minimum volume of degassed chloroform. The solution was stirred for 2 h in the dark and the resulting brown-orange product extracted with hexane. The hexane solution was washed with water to remove the dmso and then solvent removed in vacuo. Chromatography on silica in chloroform removed all remaining impurities and recrystallisation of the residue from hot ethyl acetate gave 13 as orange-yellow crystals (67%); mp 95 8C (decomp.) (Found: C, 37.20; H, 5.14; N, 4.31.C18H26FeN2PtS2?2MeOH requires C, 36.93; H, 4.48; N, 4.79%). ES-MS: m/z 585 (M1). dH(CDCl3) 1.30 (t, 3 H, J = 7.3, CH2CH3), 1.34 (t, 3 H, J = 7.3, CH2CH3), 2.89 (s, 3 H, 3JPt–H = 18.4, NCH3), 3.24 (s, 3 H, 3JPt–H = 16.7, NCH3), 3.67 (q, 2 H, J = 6.9 Hz, CH2CH3), 3.70 (q, 2 H, J = 7.1 Hz, CH2CH3), 3.85 (s, 1 H, h5-C5H3Fe), 4.01 (s, 1 H, h5- C5H3Fe), 4.12 (s, 5 H, h5-C5H5Fe) and 4.23 (s, 1 H, h5-C5H3Fe). dC(CDCl3) 12.48 (CH2CH3)2), 43.94 (CH2CH3), 45.46 (CH2- CH3), 54.00 (CH3N), 54.93 (CH3N), 62.09 (CH, h5-C5H3Fe), 68.75 (CH, h-C5H3Fe), 69.23 (CH, h5-C5H3Fe) and 69.37 (5CH, h5-C5H5Fe).dPt(CDCl3) 21974. n(KBr, cm21): 1442, 1384 (C–N), 1279(C]] S) and 847(C–S). lmax/nm(e/M21 cm21) (CHCl3) 455(330) and 362(860). Compound 14. This was obtained as orange crystals (58%) by a similar route from compound 2; mp 112 8C (decomp.) (Found: C, 34.25; H, 4.41; N, 5.07.C26H42FeN4Pt2S4: C, 34.92; H, 4.30; N, 5.69%). ES-MS: m/z 985 (M1). dH(CDCl3) 1.24 (3 H, J = 9.9 Hz, CH2CH3), 1.27 (3 H, J = 9.9, CH2CH3), 1.28 (3 H, J = 9.4, CH2CH3), 1.30 (3 H, J = 9.3, CH2CH3), 2.87 (3 H, 3JPt–H = 13.8, NCH3), 2.89 (s, 3 H, 3JPt–H = 13.5, NCH3), 3.22 (s, 3 H, 3JPt–H = 16.2, NCH3), 3.24 (s, 3 H, 3JPt–H = 18.1, NCH3), 3.61 (q, 2 H, J = 7.2, CH2CH3), 3.65 (q, 2 H, J = 7.5, CH2CH3), 3.67 (q, 2 H, J = 7.2 Hz, CH2CH3), 3.70 (q, 2 H, J = 7.5 Hz, CH2CH3), 3.99 (2 H, h5-C5H3Fe), 4.04 (5 H, h5-C5H5Fe), 4.07 (2 H, h5-C5H3Fe) and 4.10 (2 H, h5-C5H3Fe).dC(CDCl3) 12.49 (CH2CH3), 12.62 (CH2CH3), 43.81 (CH2CH3), 43.95 (CH2CH3), 45.31 (CH2CH3), 45.43 (CH2CH3), 53.61 (NCH3), 53.85 (NCH3), 54.46 (NCH3), 54.92 (NCH3), 59.08, 59.46, 62.47, 67.13, 68.68 and 70.66 (CH, h5-C5H3)2Fe). dPt (CDCl3) 22227 and 21981. n(KBr, cm21): 1272(C]] S) and 844(C–S). lmax/nm(e/M21 cm21) (CHCl3) 470(75). Crystal structure determination of compound 4 Crystals of compound 4 were grown as yellow plates from acetone–hexane. Data were collected on a Nicolet, R3M dif- Table 3 Crystal data and structure refinement for compound 4 Empirical formula Formula weight T/K l/Å Crystal system Space group a/Å b/Å c/Å b/8 V/Å3 Z Dc/Mg m23 m/mm21 F(000) Crystal size/mm Reflections collected Independent reflections Data/parameters Final R,R9 [I > 2s(I)] Largest diVerence peak and hole/e Å23 C17H27FeNO4PtS 592.40 293(2) 0.71073 Monoclinic P21/c 10.066(2) 15.265(4) 12.997(3) 103.30(2) 1943.5(8) 4 2.025 8.065 1152 0.5 × 0.25 × 0.1 2640 2060 [R(int) = 0.0435] 2060/241 0.0278, 0.0323 0.918 and 21.080 fractometer using the w–2q scan technique.Details of the data collection and structure refinement are summarised in Table 3. The structure was solved by direct methods using SHELXS 86.32 The E map revealed the location of the Pt, Fe and S atoms with the remaining non-hydrogen atoms located in a series of least-squares refinement on F, Fourier diVerence cycles.Weighted refinement was performed using SHELX 76,33 with all non-hydrogen atoms refined anisotropically. A Fourierdi Verence synthesis following the location of all anticipated non-hydrogen atoms revealed electron density that could be sensibly assigned to a solvent water molecule. Inclusion of this in the refinement led to a significant improvement in R but the associated hydrogen atoms were not located.Other hydrogen atoms were included in the refinements as fixed contributions to Fc. CCDC reference number 186/1430. Acknowledgements We thank Professor B. K. Nicholson and Dr. W. Henderson (University of Waikato) for the ES-MS spectra and Professor W. Robinson (University of Canterbury) for the X-ray data collection. B. H. 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