DALTON FULL PAPER J. Chem. Soc., Dalton Trans., 1999, 1945–1949 1945 Synthesis of platinum(II) complexes of thymidine and 1-methylthymine (1-MeThy); crystal structure of cis-[PtCl(1-MeThy)- (PPh3)2] Lorenzo De Napoli,a Rosa Iacovino,b Anna Messere,a Daniela Montesarchio,a Gennaro Piccialli,*c Alessandra Romanelli,b Francesco RuVod and Michele Saviano b a Dipartimento di Chimica Organica e Biologica, Via Mezzocannone, 16, Università degli Studi di Napoli “Federico II”, I-80134 Napoli, Italy b Centro di studio di Biocristallografia del CNR, Via Mezzocannone 4, Università degli Studi di Napoli “Federico II”, I-80134 Napoli, Italy c Università degli Studi del Molise, Facoltà di Scienze, via Mazzini, 8, I-86170 Isernia, Italy.E-mail: picciall@unima.it d Dipartimento di Chimica, Via Mezzocannone, 4, Università degli Studi di Napoli “Federico II”, I-80134 Napoli, Italy Received 22nd February 1999, Accepted 20th April 1999 The reaction of 39,59-di-O-acetylthymidine with [Pt(PPh3)4] and KCl yielded a platinum(II) complex where the platinum is co-ordinated to the nucleobase through the N3 atom.In a similar reaction 1-methylthymine (1-MeThy) furnished the complex cis-[PtCl(1-MeThy)(PPh3)2], whose structure was determined by spectroscopic data and single crystal X-ray diVraction. When 1-MeThy was treated with [Pt(PPh3)4] in the absence of chloride ions the complex trans-[Pt(OH)(1-MeThy)(PPh3)2] was obtained. Introduction Platinum compounds, particularly cis-diamminedichloroplatinum( II) (cisplatin or cis-DDP) and several related derivatives, show important cytostatic eVects and are clinically used in the treatment of tumour diseases.1 Their biological activity is related to the ability to form covalent adducts with adjacent guanine bases in DNA.2 The synthesis of a plethora of diVerent platinum nucleobase or nucleoside complexes has largely contributed to clarifying the mechanism of these drugs.Some toxicological side-eVects of cisplatin and the drug resistance developed by some tumours further stimulated research towards the synthesis of new platinum derivatives.To the best of our knowledge, reported studies on the platination of nucleobases have been carried out using exclusively complexes of PtII or PtIV 3 as the starting material. In this framework we have investigated the reactivity of tetrakis- (triphenylphosphine)platinum(0) [Pt(PPh3)4] towards thymine or related nucleosides. This complex was chosen as a substrate by considering that some phosphines and a certain number of arylphosphine complexes have been found to be potent cytotoxic agents against tumour cells in culture or in vivo.4 In a previous paper 5 we have described the synthesis of complex 1, which is characterized by the rare s bond between PtII and C4 of the thymine base.This complex was obtained by reaction of [Pt(PPh3)4] with 39,59-di-O-acetyl-4-chlorothymidine I (Scheme 1) which proceeds by an oxidative addition mechanism.A careful analysis of this reaction showed that, together with 1 (85% yield), a minor product 2 (5–7% yield) was formed when equimolecular quantities of [Pt(PPh3)4] and I were refluxed under a nitrogen atmosphere in toluene for 2 h. Product 2 presented the well documented, for pyrimidine nucleobases, PtII–N3 co-ordination bond,6 the formation of which was not immediately explainable in our reaction system. In fact, as reported,6c,7 the N3 platination of thymine or uracil residues can easily be achieved only starting from their N3 deprotonated forms by reaction with appropriate platinum(II) complexes.Aiming at explaining the unexpected formation of complex 2 the reaction was reinvestigated. Herein we describe the results of our study which disclosed an alternative, straightforward route for the preparation of 2 in high yield. The structure of this complex has been assigned on the basis of its 1H, 31P and 13C NMR, IR and FAB MS data, as well as on single crystal X-ray diVraction studies carried out on the related complex cis- [PtCl(1-MeThy)(PPh3)2] (1-MeThy = 1-methylthyminate).Results and discussion By monitoring the reaction between I and [Pt(PPh3)4] by TLC Scheme 1 R = 3,5-Di-O-acetyl-2-deoxy-b-D-ribofuranosyl except in 3a,3b where it is 2-deoxy-b-D-ribofuranosyl.1946 J. Chem. Soc., Dalton Trans., 1999, 1945–1949 analysis, small amounts of 39,59-di-O-acetylthymidine II were detected, which disappeared in the final mixture.This suggested a possible intervention of II, obtained by an undesired hydrolysis of the very reactive 4-chloro derivative I, in the formation of complex 2. So we hypothesized an oxidative addition of the imidic N3 atom of II on [Pt(PPh3)4] generating a transient platinum hydride complex 4 [Scheme 1, eqn. (1)]. This reaction mechanism was suggested by the reported reactivity of some zerovalent platinum complexes which reacting with imides generated platinum(II) hydrides.8 Further reaction of 4 with water (probably due to trace amounts of water), followed by elimination of H2, furnished complex 5 which, by exchange with chloride ions, finally gave 2 [eqns.(2) and (3)]. To confirm this hypothesis we tested the reactivity of [Pt(PPh3)4] towards II in the presence of chloride ions. The reaction (4), performed under a nitrogen atmosphere in boiling benzene, gave complex 2 in high yield (80% after purification).The 1H and 13C NMR spectra of complex 2 showed two signals for each type of observed nucleus, thus indicating the presence of a mixture of two isomeric species (2a and 2b in 45 : 55 ratio). These isomers separated by HPLC on a silica gel column, are stable as solids but, when dissolved in CHCl3, they interconverted, re-establishing the original mixture in ca. 24 h. These results can be explained by assuming restricted rotation around the Pt–N3 bond in complex 2, inducing a further chirality in the molecule, which, associated with the presence of fixed configurations at the sugar carbons, gives rise to two diastereoisomeric forms.6a,d,9 For a better comprehension of the structure of 2 we then synthesized a similar complex using 1-methylthymine III as pyrimidine ligand, where the hindered rotation around the Pt–N3 bond was expected to generate two enantiomeric complexes.The reaction [Scheme 2, eqn. (5)], performed as described for 2, led smoothly to complex 6, recovered after silica gel chromatography in 82% yield.As expected, 6 exhibited only one signal for each observed nucleus in the 1H, 31P and 13C NMR spectra, closely related to the NMR data of 2. The 1H NMR spectrum of 6 in the presence of a chiral shift reagent confirmed its existence as two enantiomeric forms (see discussion on spectral data). The single-crystal structure of 6 is shown in Fig. 1 (see later). When the reaction of III with [Pt(PPh3)4] was carried out in the absence of chloride ions, eqn.(6), complex 7 was obtained in 85% yield. The structure and the trans geometry of 7 were ascertained by spectroscopic data and FAB MS analysis. Complex 6 could be alternatively prepared by treating 7 with potassium chloride in boiling benzene (2 h, 80% yield). Removal of the acetyl groups at the 59 and 39 positions of the sugar residues of the 2a,2b mixture was achieved by treatment Scheme 2 with concentrated aqueous ammonia for 2 h at 50 8C, giving 3a,3b (not separated, 90%), whose structure was confirmed by spectral data. This reaction, demonstrating the stability of the platinum–nucleobase linkage to basic conditions and furnishing a further derivatizable sugar compound, showed this new platinated nucleoside to be suitable for insertion into oligonucleotide chains by automated procedures.Spectroscopic data The IR spectrum of complex 2a shows strong bands at 1749, 1664 and 1588 cm21 attributed respectively to carbonyl functions of the acetyl groups and to carbonyls of the thymine base.The band at 1588 cm21 has been considered diagnostic for the N3 platinum co-ordinated thyminate ion.6a,c A weak band due to n(Pt–Cl) was observed at 305 cm21. An almost identical IR pattern was observed for isomer 2b. Analogously for complex 3, strong n(CO) bands were detected at 1653 and 1577 cm21. For complex 6 carbonyl resonances were found at 1655 and 1578 cm21, whereas only a weak signal, for n(Pt–Cl), was detected at 300 cm21.Similarly for 7 n(CO) gave strong bands at 1655 and 1579 cm21. The 31P NMR spectrum of complex 2a shows two nonequivalent phosphorus atoms due to two magnetically diVerent trans influences on each phosphine; 1J(Pt–P) values are 3265 and 3960 Hz, attributed respectively to phosphorus trans to N and trans to chloride.8 The 31P NMR spectrum of 2b is identical. For complex 6 the 31P NMR spectrum displayed the same pattern due to two cis phosphines having 1J(Pt–P) values of 3235 (trans to N) and 3984 Hz (trans to chloride).The spectrum of 7 showed a single phosphorus signal [1J(Pt–P) = 3091 Hz] which was attributed to two trans magnetically equivalent phosphines. In the 1H NMR spectrum of complex 2a protons H-6 and CH3-5 showed upfield shifts (Dd 0.92 and 0.33) compared to their resonances for free nucleoside II, suggesting N3 platination of the base.6d,10 Analogous upfield shifts were observed for complexes 2b, 6 and 7 for all the protons of the nucleobase. For 3a,3b the H-6 signals are submerged by the phosphine protons, whereas for CH3-5 signals upfield shifts of Dd 0.3 were observed.When the 1H NMR spectrum of 6 was recorded in the presence of the chiral shift reagent europium tris[3-(hepta- fluoropropylhydroxymethylene)(1)-camphorate] [Eu(hfc)3],- {camphor = (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one} a doubling and a downfield shift of the signals CH3-N1 (d 3.43 and 3.32) and CH3-5 (d 2.10 and 1.92) were observed.In 1H NMR experiments, performed on the diastereomeric mixture 2 dissolved in DMSO, increasing the temperature to 125 8C, no fluxionality was observed suggesting a high barrier to rotation around the Pt–N3 bond. In the 13C NMR spectra all the isolated complexes showed for the nucleobase carbons a downfield shift in comparison with the resonances of the “free” ligands. This eVect is particularly evident for C2, C4 and CH3-5 (Dd from 1 to 5), in agreement with literature data of similar platinum(II) nucleobase complexes.11 Molecular structure of cis-[PtCl(1-MeThy)(PPh3)2]?MeOH 6 The crystal structure of cis-[PtCl(1-MeThy)(PPh3)2]?MeOH 6 is illustrated in Fig. 1, which also gives the atom numbering scheme. Selected bond distances and angles are in Table 1. The platinum atom displays square planar co-ordination: two cis corners of the square plane are occupied by the P atoms of two triphenylphosphines and the chlorine atom and the amide nitrogen of the MeThy ligand are in cis position to each other.The four atoms co-ordinated to the metal lie in a plane with very small (less than 0.08 Å) deviation from it. The plane of the MeThy ligand is approximately perpendicular to the platinum co-ordination plane, as seen by the torsion angles Cl(1)–Pt–N(1)–C(1) and Cl(1)–Pt–N(1)–C(6) of 87.3(4)J. Chem. Soc., Dalton Trans., 1999, 1945–1949 1947 and 296.4(5)8, respectively. The P–Pt distances [P(1)–Pt 2.241(2), P(2)–Pt 2.268(2) Å] are diVerent, which is consistent with the amide [trans to P(2)] having a slightly larger trans influence than chloride.9,13,14 The analysis of the Pt–N co-ordination distances shows the trans eVect of the P atom.In fact, this distance [N(1)–Pt 2.072(5) Å] is longer (ª0.08 Å) than that observed in platinum(II) complexes with amide nitrogen ligands without co-ordinated P atoms.13 The remaining bond lengths and bond angles are normal.15,16 The analysis of the triphenylphosphine moiety in cis position with respect to the Cl(1) atom shows the Cl(1) atom in a staggered conformation with respect to the C(41), C(51), C(61) Fig. 1 An ORTEP12 projection of two molecules of cis-[PtCl(1- MeThy)(PPh3)2] 6. The thermal ellipsoids are drawn at 30% probability level. Table 1 Selected intramolecular bond distances (Å) and angles (8) for cis-[PtCl(1-MeThy)(PPh3)2] with estimated standard deviations in parentheses MeThy moiety Pt–N(1) Pt–P(1) Pt–P(2) Pt–Cl(1) N(1)–C(6) N(1)–C(1) N(2)–C(4) C(6)–N(1)–C(1) C(6)–N(1)–Pt C(1)–N(1)–Pt C(4)–N(2)–C(6) C(4)–N(2)–C(5) C(6)–N(2)–C(5) O(1)–C(1)–N(1) O(1)–C(1)–C(2) 2.072(5) 2.241(2) 2.268(2) 2.354(2) 1.356(8) 1.373(8) 1.336(10) 123.4(5) 121.7(4) 114.8(4) 119.9(6) 120.9(7) 119.1(7) 120.6(5) 122.4(6) N(2)–C(6) N(2)–C(5) O(1)–C(1) O(2)–C(6) C(1)–C(2) C(2)–C(4) C(2)–C(3) N(1)–C(1)–C(2) C(4)–C(2)–C(1) C(4)–C(2)–C(3) C(1)–C(2)–C(3) N(2)–C(4)–C(2) O(2)–C(6)–N(1) O(2)–C(6)–N(2) N(1)–C(6)–N(2) 1.406(9) 1.498(10) 1.220(8) 1.246(8) 1.406(9) 1.337(11) 1.490(11) 117.0(6) 119.7(6) 122.2(7) 118.0(7) 122.7(6) 120.3(6) 122.5(6) 117.2(6) Triphenylphosphine ligands N(1)–Pt–P(1) N(1)–Pt–P(2) P(1)–Pt–P(2) P(1)–Pt–Cl(1) P(2)–Pt–Cl(1) N(1)–Pt–Cl(1) C(21)–P(1)–C(11) C(21)–P(1)–C(31) C(11)–P(1)–C(31) 88.94(15) 171.22(14) 97.64(8) 175.10(5) 87.05(8) 86.54(15) 111.4(3) 102.5(3) 102.8(3) C(21)–P(1)–Pt C(11)–P(1)–Pt C(31)–P(1)–Pt C(51)–P(2)–C(41) C(51)–P(2)–C(61) C(41)–P(2)–C(61) C(51)–P(2)–Pt C(41)–P(2)–Pt C(61)–P(2)–Pt 113.4(2) 111.5(2) 114.4(2) 101.6(3) 107.3(3) 102.5(3) 114.9(2) 120.6(2) 108.7(2) atoms of the phenyl rings: the dihedral angles Cl(1)–Pt–P(2)– C(41), Cl(1)–Pt–P(2)–C(51) and Cl(1)–Pt–P(2)–C(61) are 2172.9(3), 65.0(2), and 255.2(2)8 respectively.In the crystal packing the molecules are characterized by one intermolecular hydrogen-bond between the oxygen of the methanol molecule and O(2) atom of the MeThy ligand [distance O–H ? ? ? O(2) 2.89(1) Å; angle O–H ? ? ? O(2)]] C(6) 153.2(5)8]. The crystal structure is further stabilized by van der Waals interactions involving the phenyl and the methyl groups.Experimental Material and methods The 1H and 13C-{1H} NMR spectra were recorded on a Bruker WM-400 spectrometer at 400 and 100.13 MHz respectively. All chemical shifts are expressed in ppm with respect to the signal of the protonated solvent (CDCl3: d 7.26 and 77.0. DMSO-d6: d 2.55 and 39.5.CD3OD: d 3.31 and 49.5). The 31P NMR spectra were run on a Bruker WM-400 spectrometer at 161.98 MHz, with external reference to 85% H3PO4 (d 0.0). The complex [Eu(hfc)3] was purchased from Aldrich. The IR spectra were recorded on a Perkin-Elmer 457 spectrophotometer, FAB mass spectra (positive) on a ZAB 2SE spectrometer. The HPLC analyses and purifications were carried out on a Beckman System Gold instrument equipped with a UV detector module 166 and a Shimadzu Chromatopac C-R6A integrator.Compound II was used as supplied by Sigma. Syntheses Complexes 2a,2b. A mixture of compound II (205 mg, 0.63 mmol), [Pt(PPh3)4] (783 mg, 0.63 mmol) and finely powdered KCl (68 mg, 1.26 mmol) was suspended in benzene (8 cm3) and refluxed with stirring under a nitrogen atmosphere for 2 h. After cooling, the mixture was filtered and the solid washed with benzene. The filtrates and washings, evaporated to dryness under reduced pressure, were chromatographed on a silica gel column (3 × 50 cm) eluted with increasing amounts of MeOH in CHCl3 (from 0 to 2%, v/v) to give 544 mg of the isomeric mixture 2a,2b (80%).TLC: Rf 0.4 (eluent CHCl3–MeOH 97: 3, v/v). The isomeric mixture was separated by HPLC on a silica gel column (Lichrosphere Si-60, 250 × 4 mm, 5 mm) eluted in CHCl3 (1 cm3 min21) to give pure 2a and 2b (ratio 45 : 55, retention times 5.1 and 5.7 min, respectively). FAB MS on mixture (195Pt, 35Cl): m/z 1044, [M 2 Cl]1 and 754 [M-nucleoside] 1.Complex 5a: IR (CHCl3) 1749, 1664, 1588 [strong, n(CO)], 305 cm21 [weak, n(Pt–Cl)]; 31P NMR (DMSO-d6) d 15.3 [d, PPh3 trans to Cl, 1J(Pt–P) = 3960] and 8.6 [d, PPh3 cis to Cl, 1J(Pt–P) = 3265 Hz]; 1H NMR (DMSO-d6) d 8.32–7.00 (30 H, m, phenyl protons), 6.67 (1H, s, H-6), 6.17 [1H, dd, J(H19H29) = 5.8 and 6.0, H-19], 5.14 (1H, m, H-39), 4.23 (2H, m, H-59), 4.10 (1H, m, H-49), 2.14 and 2.07 (3H each, s, CH3CO), 2.1–1.9 (2H, m, H-29) and 1.47 (3H, s, CH3-5); 13C-{1H} NMR (DMSO-d6): d 170.0 (CH3CO), 167.9 (C-4), 153.6 (C-2), 134.7–127.5 (phenyl carbons and C-6), 110.1 (C-5), 83.6 (C-49), 80.4 (C-19), 73.2 (C-39), 63.6 (C-59), 35.4 (C-29), 20.7 and 20.5 (2 CH3CO) and 13.3 (CH3-5).Complex 5b: IR (CHCl3) 1750, 1663, 1590 [strong, n(CO)], 308 cm21 [weak, n(Pt–Cl)]; 31P NMR (DMSO-d6) d 15.3 [d, PPh3 trans to Cl, 1J(Pt–P) = 3960] and 8.6 [d, PPh3 cis to Cl, 1J(Pt–P) = 3265 Hz]; 1H NMR (DMSO-d6) d 8.30–7.00 (30 H, m, phenyl protons), 6.64 (1H, s, H-6), 6.26 [1H, dd, J(H19H29) = 6.0 and 5.9, H-19], 5.19 (1H, m, H-39), 4.26 (2H, m, H-59), 4.13 (1H, m, H-49), 2.25 (2H, m, H-29), 2.14 and 2.11 (3H each, s, CH3CO) and 1.48 (3H, s, CH3-5); 13C-{1H} NMR (DMSO-d6) d 170.0 (CH3CO), 167.8 (C-4), 154.1 (C-2), 134.7–127.5 (phenyl carbons and C-6), 109.2 (C-5), 83.6 (C-49), 80.3 (C-19), 74.2 (C-39), 63.6 (C-59), 35.3 (C-29), 20.7 and 20.5 (2 CH3CO) and 13.3 (CH3-5).1948 J.Chem. Soc., Dalton Trans., 1999, 1945–1949 Complexes 3a,3b.Complex 2a,2b (150 mg, 0.14 mmol) was treated with aqueous concentrated NH3 (5 cm3, 35%) and MeOH (5 cm3) for 2 h at 50 8C. The resulting solution, dried under reduced pressure, was purified on a silica gel column (2 × 50 cm) eluted with increasing amounts of MeOH in CHCl3 (from 5 to 20%, v/v) to give 3a,3b (126 mg, 90%). Diastereomeric mixture: IR (CHCl3) 3667 [broad, n(OH)], 1653, 1577 cm21 [strong, n(CO)]; 31P NMR (CD3OD) d 13.5 [d, PPh3 trans to Cl, 1J(Pt–P) = 3971] and 6.8 [d, PPh3 cis to Cl, 1J(Pt– P) = 3305 Hz]; 1H NMR (CD3OD) d 7.80–7.10 (62H, m, phenyl protons and H-6), 6.19 and 6.01 (1H each, dd, H-19), 4.33 (2H, m, H-39), 3.87 (2H, m, H-49), 3.72 (4H, m, H-59) 2.30–2.00 (4H, m, H-29), 1.69 and 1.62 (3H each, s, CH3-5); 13C-{1H} NMR (CD3OD) d 172.7 (C-4), 156.9 (C-2), 137–128.0 (phenyl carbons and C-6), 111.9 and 108.7 (C-5), 88.8 (C-49), 87.5 and 86.9 (C-19), 72.5 and 72.4 (C-39), 63.2 (C-59), 41.8 and 41.4 (C-29) and 13.8 (CH3-5).cis-[PtCl(1-MeThy)(PPh3)2 6. From III. A mixture of compound III (200 mg, 1.44 mmol), [Pt(PPh3)4] (1.79 g, 1.44 mmol) and finely powdered KCl (155 mg, 2.88 mmol) was suspended in benzene (10 cm3) and refluxed with stirring under a nitrogen atmosphere for 2 h. After cooling, the mixture was filtered and the solid washed with benzene. The filtrate and washings, evaporated to dryness under reduced pressure, were chromatographed on a silica gel column (2.5 × 50 cm) eluted with increasing amounts of MeOH in CHCl3 (from 0 to 3%, v/v) to give pure complex 6 (1.05 g, 82%).TLC: Rf 0.44 (eluent CHCl3– MeOH 97: 3, v/v). From 7. A mixture of complex 7 (200 mg, 0.23 mmol), and finely powdered KCl (25 mg, 0.46 mmol) was suspended in benzene (5 cm3) and refluxed with stirring under a nitrogen atmosphere. After 2 h TLC analysis showed the disappearance of 7 and the formation of 6 (164 mg, 80%) which was purified as described above and identified by spectroscopic analyses. FAB MS (195Pt, 35Cl): m/z 893, [M 1 H]1 and 957 [M 2 Cl]1.IR (CHCl3) 1655, 1578 [strong, n(CO)], 300 cm21 [weak, n(Pt–Cl)]. 31P NMR (DMSO-d6): d 15.4 [d, PPh3 trans to Cl, 1J(Pt–P) = 3984] and 8.6 [d, PPh3 cis to Cl, 1J(Pt–P) = 3235 Hz]. 1H NMR (DMSO-d6): d 8.20–7.00 (30 H, m, phenyl protons); 6.31 (1H, s, H-6); 3.0 (3H, s, CH3-1); and 1.62 (3H, s, CH3-5). 13C-{1H} NMR (DMSO-d6): d 169.9 (C-4); 155.1 (C-2); 138.6 (C-6); 109.3 (C-5); 36.1 (CH3-1); and 12.1 (CH3-5).trans-[Pt(OH)(1-MeThy)(PPh3)2] 7. A solution of compound III (200 mg, 1.44 mmol) and [Pt(PPh3)4] (1.79 g, 1.44 mmol) was refluxed in benzene (8 cm3) under a nitrogen atmosphere for 2 h. After cooling, the mixture, evaporated to dryness under reduced pressure, was chromatographed on a silica gel column (2.5 × 50 cm) eluted with increasing amounts of MeOH in benzene (from 0 to 5%, v/v) to give pure complex 7 (107 mg, 85%). TLC: Rf 0.4 (eluent CHCl3–MeOH 95: 5, v/v).FAB MS (195Pt): m/z 875 [M 1 H]1; and 859, [M 2 OH]1. IR (CHCl3) 3334 [broad, n(OH)], 1655, 1579 cm21 [strong, n(CO)]. 31P NMR (CDCl3): d 18.6 [d, PPh3, 1J(Pt–P) = 3091]. 1H NMR (CDCl3): d 7.90–7.20 (30 H, m, phenyl protons); 5.93 (1H, s, H-6); 2.67 (3H, s, CH3-1); and 1.31 (3H, s, CH3-5). 13C-{1H} NMR (CDCl3): d 170.3 (C-4); 155.2 (C-2); 137.6 (C-6); 107.8 (C-5); 36.2 (CH3-1); and 13.2 (CH3-5). Crystallography Suitable crystals of cis-[PtCl(1-MeThy)(PPh3)2] 6 for X-ray analysis were obtained by slow evaporation of CHCl3–MeOH (9 : 1, v/v) at room temperature.Intensity data collection was performed using graphite-monochromated Cu-Ka radiation (l = 1.54178 Å) and a pulse-high discrimination on a CAD4 Enraf-Nonius automated diVractometer equipped with a MicroVax 3100 Digital computer of the “Centro di Studio di Biocristallografia del CNR” at Università di Napoli “Federico II”. The independent reflections were measured in the q range 1–708.Unit cell parameters were determined by least-squares refinement of the setting angles of 25 high angle reflections (18 < q < 228). Three standard reflections were monitored periodically and showed no significant change during data collection. A total of 7789 independent reflections were measured with a w–2q scan mode. Using a prescan speed of 4.128 min21, reflections with a net intensity I < 0.5s(I) were flagged as “weak”; those with I � 0.5s(I) were measured at lower speed depending on the value of s(I)/I. The structure was solved by direct methods using the SIR 97 program.17 The best E maps revealed all the non-H atoms and the methanol solvent molecule.Refinement by the full-matrix least-squares procedure on F2 (all data) used the SHELXL 93 program18 with anisotropic thermal factors for all non-hydrogen atoms. Hydrogen atom positions were calculated and allowed to ride on their attached atoms, with Uiso s = 1.2 Ueq of the attached atom.The scattering factors for all atomic species were calculated from Cromer and Waber.19 Crystal data. C42H34ClN2O2P2Pt?CH3OH, M = 923.23, triclinic, space group P1� (no. 2), a = 11.176(8), b = 13.892(9), c = 13,36(1) Å, a = 97.31(6), b = 91.32(6), g = 88.00(6)8, U = 2056(3) A3, T = 293 K, Z = 2, m(Cu-Ka) = 8.029 mm21, 7789 unique reflections (Rint = 0.0) used in all calculations. The final wR(F2) was 0.1334; R1 = 0.0515. CCDC reference number 186/1433. See http://www.rsc.org/suppdata/dt/1999/1945 for crystallographic files in .cif format.Acknowledgements We are grateful to Ministero dell’Università e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche for grants in support of this investigation and to Centro di Metodologie Chimico-Fisiche dell’Università degli Studi di Napoli “Federico II” for the NMR facilities. 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