DALTON FULL PAPER J. Chem. Soc., Dalton Trans., 1999, 175–182 175 Crystal structures of a protonated form of trans-[Pt(NH3)2(mura)2] and of a derivative containing three diVerent metal ions, Pt21, Ag1, and Na1 (mura 5 1-methyluracilate). Major diVerence in packing between heteronuclear pyrimidine nucleobase complexes of cis- and trans-(NH3)2PtII Felix Zamora,a,b Holger Witkowski,a Eva Freisinger,a Jens Müller,a Birgit Thormann,a Alberto Albinati *c and Bernhard Lippert *a a Fachbereich Chemie, Universität Dortmund, D-44221 Dortmund, Germany b Universidad Autonoma de Madrid, Departamento de Quimica Inorganica, Cantoblanco, E-28049 Madrid, Spain c Istituto Chimico Farmaceutico della Università di Milano, I-20131 Milano, Italy Received 24th June 1998, Accepted 16th November 1998 The complex trans-[Pt(NH3)2(mura)2] 1 (mura = 1-methyluracilate), a compound of very low water solubility, is markedly solubilised in the presence of acid or suitable metal salts due to protonation and metal binding to the exocyclic oxygen atoms, respectively.The perchlorate salt trans-[Pt(NH3)2(Hmura)2][ClO4]2?2H2O 2 has been characterised by X-ray analysis. With Ag1, 1 formed heteronuclear species of varying stoichiometries, e.g. Pt2Ag3 3, the composition of which can be further varied by the presence of alkali metal salts. The complex trans-[{Pt(NH3)2- (mura)2}2AgNa(H2O)4][ClO4]2?6.5H2O 4 appears to be the first structurally characterised example of a nucleobase complex containing three diVerent metal ions.Tetranuclear cations of 4 are arranged in the crystal in such a way as to permit both intermolecular hydrogen bonding between NH3 ligands and O2 sites of mura nucleobases and p stacking between adjacent trans-[Pt(NH3)2(mura)2] entities. This feature is radically diVerent from that observed in related diand tri-nuclear complexes derived from cis-(am)2PtII. With mercury(II) salts initially binding to exocyclic oxygen atoms of the mura ligand takes place, followed by metal binding to the C5 atoms of both uracil ligands of 1.Metal binding properties of cis-[Pt(am)2L2] [am = NH3 or (am)2 = diamine, L = mura = 1-methyluracilate or mthy = 1- methylthyminate] have been studied by us in detail,1 as has protonation, 2 which produces metal-stabilised forms of the rare pyrimidine nucleobase tautomers. The extremely low solubility of trans-[Pt(NH3)2(mura)2] 1 in any common solvent thus far has prevented a similar detailed study.Only with a large excess of Ag1, a solubilisation of this compound in water has been achieved as well as the isolation and crystal structure determination of a polymeric complex of PtAg2 stoichiometry.3 In contrast, with the structurally related complex trans-[Pt(am)2- (Hmcyt)2]21 (Hmcyt = 1-methylcytosine) a rich chemistry has been developed.4 It has been realised that as a consequence of diVerent metal orbitals interacting in dinuclear complexes of the two systems cis- and trans-(am)2PtII the types of metal– metal bonds utilised are also diVerent.5 This fact has pronounced consequences for Pt–M distances.For example, while PtII–PdII separations in the cis-(am)2PtII system are typically in the 2.8–2.9 Å range, they are around 2.5 Å in the case of compounds derived from trans-(am)2PtII. Here we report the crystal structure determinations of a protonated form of complex 1, trans-[Pt(NH3)2(Hmura)2][ClO4]2 2, as well as of a heteronuclear derivative of 1, trans-[{Pt(NH3)2- (mura)2}2AgNa(H2O)4][ClO4]2?6.5H2O which contains three different metal ions in a nucleobase complex and which represents the first example of its kind.In addition, limited solution studies with other metal ions leading to a solubilisation of 1 have been carried out. Experimental Preparation of compounds trans-[Pt(NH3)2(mura)2] 1. This complex was prepared by reaction of trans-[Pt(NH3)2Cl2] 6 (2 mmol in 20 cm3 water) with AgNO3 (3.98 mmol), filtration of AgCl, and addition of Hmura 7 (4 mmol) and NaOH (20 cm3, 0.2 mol dm23), and stirring the mixture for 2 h at 60 8C and for 3 d at 40 8C.The white precipitate formed was filtered oV, washed with water and dried. The solid (940 mg) was subsequently stirred in MeOH (500 cm3) for 1 d to dissolve unchanged Hmura, filtered oV, washed with more MeOH and dried at 100 8C. The yield of 1 was 94% (Found: C, 24.5; H, 3.5; N, 17.4. Calc. for C10H16- N6O4Pt : C, 25.05; H, 3.37; N, 17.53%).IR: 3349s (sp), 3204s, 3138s, 1640vs, 1620 (sh), 1580vs, 1550s, 1475m, 1450s, 1420m, 1365s, 1340s, 1305s, 1230m, 1200w, 1150s, 955w, 885w, 845m, 830w, 810w, 775s, 725s, 645m, 595m, 490s, 445s, 370w and 310w cm21. Partially (>50%) deuteriated complex 1 was obtained by keeping a sample of 1 (0.25 mmol) in D2O–NaOD (10 cm3, pD 9.9) for 24 h at 95 8C, filtering oV the precipitate and drying the sample for 2 h at 50 8C. Deuteriation of the ammine ligands was evident from the IR spectrum, which revealed characteristic shifts of the n(ND) modes (2495s, 2406s, 2297s cm21).trans-[Pt(NH3)2(Hmura)2][ClO4]2?2H2O 2. Complex 1 (0.2 mmol) was dissolved in aqueous HClO4 (8 cm3, 1 mol dm23), the solution filtered and kept for 1 week at 4 8C. Colourless crystals were filtered oV, washed with a small amount of ice– water and dried in air. The yield was 48% (Found: C, 16.5; H, 2.9; N, 11.8. Calc. for C10H22Cl2N6O14Pt: C, 16.77; H, 3.10; N, 11.73%).IR: 1639s, 1562s, 1481m, 1447s, 1371s, 1331s, 1094s, 806s, 775s, 625s, 482s, 443s and 365w cm21. trans-[{Pt(NH3)2(mura)2}2Ag3][ClO4]3 3. To a suspension of complex 1 (0.23 mmol) in water (10 cm3) was added NaClO4?H2O (1 mmol) and subsequently an aqueous solution176 J. Chem. Soc., Dalton Trans., 1999, 175–182 of AgNO3 (1023 mol dm23) until all solid had dissolved (0.69 mmol). After heating to 60 8C and filtration from a very little unidentified gray precipitate, the resulting solution was brought to room temperature and then allowed to evaporate at 4 8C.Microcrystalline 3 was isolated in 22% yield. Electron probe X-ray microanalysis (EPXMA) gave a Pt:Ag ratio of 2 : 3 (Found: C, 14.9; H, 2.0; N, 10.6. Calc. for C20H32Ag3Cl3- N12O20Pt2: C, 15.23; H, 2.05; N, 10.66%). Alternatively: to a suspension of 1 (0.21 mmol) in water (15 cm3) was added AgClO4 (0.69 mmol), the mixture warmed to 60 8C to prevent immediate formation of a precipitate, filtered, and the solution (pH 5.3) allowed to stand at 4 8C for a day.Microcrystalline 3 was then filtered oV (48% yield). IR: 3448vs (br), 3300 (sh), 3200 (sh), 1638vs, 1569s, 1525s, 1476m, 1447s, 1370s, 1329s, 1148s, 1120–1091vs, 810m, 774m, 723w, 627m, 493w and 451w cm21. trans-[{Pt(NH3)2(mura)2}2AgNa(H2O)4][ClO4]2?6.5H2O 4. This compound was obtained accidentally in the course of work concerned with the mixed mura/gly (gly = glycine anion) complex trans-[Pt(NH3)2(mura-N3)(gly-N)].A sample of the crude product, obtained from trans-[Pt(NH3)2(mura)Cl], AgNO3 and Hgly,8 had been kept at 60 8C for 6 h in the presence of an excess of NaClO4 and HClO4 at pH 3. Following filtration of some unidentified grayish precipitate, and slow evaporation at 4 8C, single crystals of 4 were obtained in low yield (<5%) besides other products. Compound 4 was characterised by X-ray analysis only. Its formation was rationalised by means of 1H NMR spectroscopy (see below).trans-[{Pt(NH3)2(mura 2 H)2}Hg3(CF3CO2)4]?2H2O 5. To a suspension of complex 1 (0.2 mmol) in water (1 cm3) was added solid Hg(CF3CO2)2 (0.8 mmol). Within a few minutes a clear, yellow solution formed, which was stirred at room temperature for 24 h. Then a colourless precipate of 5 was filtered oV, washed with water and dried in air. The yield was 88% (Found: C, 13.6; H, 1.2; N, 5.2. Calc. for C18H18F12Hg3N6O14Pt: C, 13.79; H, 1.16; N, 5.36%); EPXMA confirmed a Pt : Hg ratio of 3 : 1.Complex 5 is sparingly soluble in D2O, giving a strongly acidic reaction (pD 1.9). Only resonances due to H6 singlets are observed, at d 7.58, 7.39 and 7.34 (ca. 1 : 4 : 3), and four CH3 resonances (d 3.47, 3.42, 3.37, 3.30, ca. 1 : 15:2:4), showing that both uracil ligands are mercurated at C5. IR: 1663s, 1617s, 1558s, 1539s, 1209s, 1138s and 692m cm21. Spectroscopic studies The IR spectra (KBr pellets) were recorded on a Perkin-Elmer 580B and a Bruker IFS 28 spectrometer, 1H, 195Pt, and 199Hg NMR spectra (200.13, 42.95, 35.79 MHz) on a Bruker AC200 instrument.Chemical shifts are given in ppm and referenced to internal (Me3Si)CH2CH2CH2SO3Na (TSP) (D2O), tetramethylammonium tetrafluoroborate (D2O, d 3.1776 relative to TSP), external Na2PtCl6 (195Pt), and external HgCl2 in D2O (199Hg; to recalculate data referred to HgMe2 add 11228 ppm), respectively. For the 1H NMR spectra taken during the reaction of complex 1 with 5 equivalents HgII, a Gaussian window function (line broadening parameter = 24.5, Gaussian broadening parameter = 0.25) was applied prior to the Fourier transformation.The pD values (in D2O) were obtained by adding 0.4 to the pH meter reading. Crystallography The crystal structure of complex 2 was determined on a CAD4 diVractometer at 190 K. Unit cell dimensions were obtained by a least-squares fit of the 2q values of 25 high order reflections (9.5 £ q £ 16.78). Data were measured with variable scan speed to ensure constant statistical precision on the collected intensities.Three standard reflections were used to check the stability of the crystals and of the experimental conditions, and measured every hour. The collected intensities were corrected for Lorentz-polarisation factors 9 and empirically for absorption 10 by using the azimuthal (y) scans of 2 “high-c” (c > 878) reflections. The standard deviations on intensities were calculated in terms of statistics alone.The structures were solved by a combination of Patterson and Fourier methods and refined by full matrix least squares 9 (the function minimised being S[w(Fo 2 k21Fc 21)2]), using anisotropic displacement parameters for all atoms except for those of a counter ion (see below). No extinction correction was deemed necessary. The scattering factors used, corrected for the real and imaginary parts of the anomalous dispersion, were taken from the literature.11 The oxygen atoms of the two water molecules were refined anisotropically, however, it was not possible to locate the positions of the hydrogen atoms bonded to them.One of the two perchlorate counter ions is strongly disordered, even at low temperature. Therefore a model was constructed using the strongest peaks of a Fourier diVerence map. During the refinement, the positional parameters of the oxygen atoms were kept fixed and only their isotropic displacement parameters were allowed to vary, while the chlorine was refined anisotropically without constraints.The hydrogen atom bonded to atom O4 was located on a Fourier diVerence map, while the remaining hydrogen atoms were put in calculated positions, [C–H 0.95 Å, B(H) = 1.3B (Cbonded) Å2]; their contribution was taken into account but not refined. Upon convergence no significant features were found in the final Fourier diVerence map. All calculations were carried out using the Enraf-Nonius MOLEN package.9 Intensity data for complex 4 were collected on an Enraf- Nonius-KappaCCD diVractometer 12 with graphitemonochromated Mo-Ka radiation (l = 0.71069 Å) at room temperature.It covered the whole sphere of reciprocal space by measurement of 360 frames rotating about w in steps of 18 with 45 s scan time per frame. Preliminary orientation matrices and unit cell parameters were obtained from the peaks of the first ten frames and refined using the whole data set. Frames were integrated and corrected for Lorentz-polarisation eVects using DENZO.13 The scaling as well as the global refinement of crystal parameters was performed by SCALEPACK.13 Reflections, which were partly measured on previous and following frames, were used to scale these frames on each other.This empirical procedure in part eliminates absorption eVects and also considers a crystal decay if present. The structure was solved by standard Patterson methods 14 and refined by full matrix least squares based on F 2 using the SHELXTL-PLUS15 and SHELXL 93 programs.16a The scattering factors for the atoms were those given in the SHELXTLPLUS program.Transmission factors were calculated with SHELXL 97.16b Hydrogen atoms were placed in geometrical calculated positions and refined with a common isotropic thermal parameter, except for the ammine hydrogens and those of the methyl group C1 [U(H) = 1.5U(Nbonded)/U(Cbonded) Å2]. A part of the mura non-hydrogen ring atoms were only refined isotropically in order to save parameters as well as the partly disordered perchlorate anions and water molecules (except O1w) and the Na1.Thermal parameters for O atoms of ClO4 2 were applied to H2O molecules bound to Na1 and gave the occupation scheme. Crystal data and data collection parameters are summarised in Table 1. CCDC reference number 186/1251. See http://www.rsc.org/suppdata/dt/1999/175/ for crystallographic files in .cif format. Results and discussion Starting compound 1 and protonated form 2 Unlike cis-[Pt(NH3)2(mura)2]?2H2O,17 which is well soluble in water, trans-[Pt(NH3)2(mura)2] 1 represents an extremely poorlyJ.Chem. Soc., Dalton Trans., 1999, 175–182 177 soluble microcrystalline material. The IR spectrum of 1 in the 3000–3500 cm21 range is, unlike that of the cis isomer, very characteristic, however, with three prominent and sharp absorptions at 3349, 3204, and 3138 cm21. Upon deuteriation, these bands are shifted to 2495, 2406, and 2297 cm21, respectively, identifying them as n(NH) modes.The isotope shifts are 1.342, 1.332, and 1.366. Taken together, these values suggest involvement of the NH3 protons in weak hydrogen bonding.18 With trans-[Pt(NH3)2Cl2], the n(NH) modes occur at 3300 and 3220 cm21, the n(ND) modes at 2465 and 2341cm21, with wavenumber shifts of 1.339 and 1.375.19 We note that in the heteronuclear derivatives 3 and 4 this characteristic pattern of NH3 modes is lost and rather ill structured bands occur between 3500 and 3200 cm21.The 1H NMR resonances of complex 1 in D2O, pD 7.4 occur at d 7.46 (d, 3J 7.4 Hz) for H6, 5.72 (d) for H5, and 3.38 (s) for CH3. These resonances are downfield relative to those of the cis isomer (d 7.30; 5.52; 3.26), and reflect the situation that no intracomplex nucleobase stacking is possible in the case of the trans compound. Addition of acid to a suspension of 1 in D2O leads to formation of a clear solution, with 1H NMR resonances of the uracil ligands downfield from those of 1, e.g.at d 7.89 (H6), 6.15 (H5), and 3.52 (CH3) at pD 0 (1 mol dm23 DNO3). The 195Pt NMR shift (22458 ppm) is consistent with a PtN4 environment. As with neutral uracil and thymine ligands bound to cis-(am)2PtII,2 the Hmura ligands of 2 are susceptible to Pt–N3 bond cleavage, leading to complex decomposition and release of Hmura. The half-life of 2 at pD ª 0, 22 8C is approximately 25 h.Cation structure of complex 2 and packing pattern The cation structure of complex 2 is given in Fig. 1. Platinum is bound to the N3 positions of the two 1-methyluracil nucleobases, which are oriented head-head and are close to coplanar [dihedral angle 8(2)8]. Selected interatomic distances and angles of compound 2 are reported in Table 2. The two uracil rings in 2 do not display any significant diVerences in bond lengths and internal ring angles. Comparison of C–O bond lengths shows a lengthening of C4–O4 [1.326(16) Å] as compared to C2–O2 [1.237(18) Å] in the same base, which corresponds to 3.7 s [with e.s.d.calculated according to s = (s1 2 1 s2 2)� �� and s1 and s2 being the standard deviations of the two bonds] and suggests that O4 is protonated. In the second uracil ligand this diVerence [1.331(22) vs. 1.258(17) Å] corresponds to 2.6s only. Both O4 and O49 are involved in short hydrogen bonds to water molecules, distances being 2.56(2) Å for O4 ? ? ?Ow1 and 2.48(2) Å for O49 ? ? ?Ow2. This feature does not permit an unambiguous diVerentiation between the three possible forms [Pt(NH3)2- (Hmura)2][ClO4]2?2H2O, [H3O][Pt(NH3)2(Hmura)(mura)]- [ClO4]2?H2O, and [H3O]2[Pt(NH3)2(mura)2][ClO4]2, as discussed in similar cases,3a but we tentatively favor the first possibility, hence the pe of the rare 4-hydroxo, 2-oxo tautomeric form for the following reason: the IR spectrum of 2 gives no hint for the presence of two diVerent uracil ligands (Hmura, mura), but displays a pronounced shift of the intense 1580 cm21 Fig. 1 View of trans-[Pt(NH3)2(Hmura)2][ClO4]2 2 with atom numbering scheme. band of 1 to 1562 cm21 for 2, consistent with a loss in doublebond character of one of the CO groups. Moreover, the 1H NMR spectrum of 2 clearly indicates protonation of the mura ligands in solution. A section of the packing of the cation of complex 2 and the water molecules is presented in Fig. 2. As can be seen cations are arranged in pairs with stacking (ca. 3.5 Å) between the four bases and four hydrogen bonds involving the O2 oxygen atoms of the two bases and the N12 ammine groups. Distances and angles are included in Table 2. As a consequence of this packing, N11–Pt–N12 vectors are parallel, forming a 588 angle with the mean plane of the two uracil bases. The Pt ? ? ? Pt separation within the stacked pair is 4.046(1) Å. Pairs of stacked cations are interconnected by longer hydrogen bonds between N11 and O2.In addition there is hydrogen bonding between water molecules and the O4 sites, as mentioned above. The extent of base stacking between cations of complex 2 deserves some comment. As seen in a view perpendicular to the planes of the uracil ligands (Fig. 3), stacking is quite substantial and, as mentioned above, the stacking distance is only slightly longer than in unperturbed DNA (3.4 Å). With regard to crosslinking adducts of trans-(NH3)2PtII with two complementary bases in double-stranded DNA,20 this implies that the NH3 groups of a trans-(NH3)2PtII entity within the center of a DNA helix do not automatically disrupt base stacking by increasing the separation between the platinated base pair and the adjacent pairs.If the NH3 groups are not perpendicular to the mean plane of the two bases but held through hydrogen bonds in a position similar to that seen in 2, base stacking is expected strongly to depend on the flanking sequences.A model of a DNA dodecamer duplex containing a central guanine, cytosine Fig. 2 Detail of stacking pattern of cations of complex 2 with hydrogen bonds indicated. Fig. 3 Detail of stacking pattern of complex 2 with view perpendicular to the uracil rings to demonstrate the base overlap.178 J. Chem. Soc., Dalton Trans., 1999, 175–182 Table 1 Crystallographic data for compounds 2 and 4 Chemical formula M Crystal system Space group a/Å b/Å c/Å b/8 V/Å3 T/K Z m(Mo-Ka)/mm21 2q Range/8 No.reflections collected No. independent reflections [Fo 2 > 4s(F2)] Tmax/Tmin Rint R/R1 (obs. data) R9/wR2 (obs. data) 2 C10H22Cl2N6O14Pt 716.31 Monoclinic P21/c 8.210(2) 17.582(5) 15.511(5) 98.88(2) 2212(1) 190 4 6.728 5–50 3886 2873 1.097/0.7535 0.052 b 0.075 b 4 C10H26.5Ag0.5ClN6Na0.5O13.25Pt 738.84 Monoclinic C2/c 17.379(3) 20.590(4) 14.925(3) 108.52(3) 5064.1(17) 293(2) 8 6.085 6.3–46.4 55374 a 1760 0.700/0.115 0.085 0.0440 c 0.0922 c a Number of reflections after merging of the redundant data: 6765.b R = S Fo| 2 (1/k)|Fc /S|Fo|, R9 = [Sw(|Fo| 2 k21|Fc|)2/Sw|Fo|2]� �� . c R1 = S Fo| 2 |Fc /S|Fo|, wR2 = [Sw(Fo 2 2 Fc 2)2/Sw(Fo 2)2]� �� . cross-link and two diVerent pairs at either side and obtained by molecular mechanics, gives a mixed result, namely retention of base stacking on one side and a rise of base residues to 5 Å on the other.21 The packing pattern found in 2 is very similar to that of 4 (see below) and analogous to that in trans- [Pt(NH3)2(Hmcyt-N3)(dmgua-N1)]21 (Hmcyt = 1-methylcytosine, dmgua = 7,9-dimethylguanine),22 although in the latter case the base overlap is more reduced.Solubilisation of complex 1 by metal ions Heterometal ion (Ag1, Hg21, Cu21, Zn21, Tl1) binding to complex 1 in aqueous solution is immediately evident from the fact that 1 dissolves in part or fully and, with diamagnetic ions, leads to a significant improvement of the signal : noise ratio of the mura resonances in the 1H NMR spectra.With increasing amounts of the metal salt added, slight downfield shifts of the aromatic protons of the mura ligands of 1 are observed, with no indication of the formation of kinetically inert heterometallic species with Ag1, Zn21 and Tl1, however. Considering the rather modest eVects in the 1H NMR spectra, low formation constants seem likely. For example, with an excess of Ag1 (>5 equivalents) downfield shifts of H5 and H6 are ca. 0.05 ppm only (cPt ª 0.075 mol dm23, D2O).Likewise, the 195Pt NMR resonance (d 22405 of 3) is hardly aVected by an excess of Ag1. Mixed-metal complexes Pt2Ag3 3 and Pt2AgNa 4 The isolation and crystal structure analysis of a polymeric Table 2 Selected distances (Å) and angles (8) for trans-[Pt(NH3)2- (Hmura)2][ClO4]2?2H2O 2 a Pt–N(11) Pt–N(12) Pt–N(3) Pt–N(39) N(11)–Pt–N(12) N(11)–Pt–N(3) N(11)–Pt–N(39) O(4)–Ow(11) O(49)–Ow(2) N(11)–O(23) 2.06(1) 2.06(1) 2.05(1) 2.07(1) 177.7(5) 89.6(5) 91.2(5) 2.56(2) 2.48(2) 3.20(1) C(4)–O(4) C(2)–O(2) C(49)–O(49) C(29)–O(29) N(12)–Pt–N(3) N(12)–Pt–N(39) N(3)–Pt–N(39) N(12)–O(22) N(12)–O(292) 1.33(2) 1.24(2) 1.33(2) 1.26(2) 90.4(4) 88.8(5) 179.2(5) 2.90(2) 2.92(2) a Symmetry operations: 1 1 1 x, 0.5 2 y, 0.5 1 z; 2 2 x, 2 y, 1 2 z; 3 1 2 x, 2 y, 1 2 z.mixed PtAg2 complex of composition trans-[Pt(NH3)2(mura)2- Ag2(NO3)2(H2O)]?H2O has previously been reported by us.3 Applying only a slight modification, viz. addition of an excess of NaClO4 to a mixture of 1 and AgNO3, gave a compound of diVerent stoichiometry, [{Pt(NH3)2(mura)2}2Ag3][ClO4]3 3.It appears to be a member of a similar group of compounds of general composition PtxAgy(mura)z previously reported for the cis-Pt(NH3)2(mura)2/Ag1 system.23 As in the former system, and by no means restricted to Ag,17 it is not possible to predict complex stoichiometry in a rational way. Considering the large structural variety of mixed platinum–silver complexes found in the cis-[Pt(NH3)2L2] system (L = mura or mthy),24–28 it is not possible to assign a specific structure to 3.We had hoped that addition of NaClO4 to a mixture of complex 1 and AgNO3, rather than producing 3, would give in higher yield and in a rational way trans-[{Pt(NH3)2(mura)2}- AgNa(H2O)4][ClO4]2?6.5H2O 4, a compound which we had accidentally obtained in crystalline form but low yield in a rather diVerent way (cf. Experimental section). As we have clarified by 1H NMR spectroscopy,8 upon addition of HClO4 to trans-[Pt(NH3)2(mura-N3)(gly-N)] (and in the absence of Ag1 and Na1) a complicated rearrangement takes place, following initial protonation of the glycinate and the mura ligand.This situation parallels that seen for cis-[Pt(NH3)2(mura)(gly)].29 As a consequence, both Hgly and Hmura are partially displaced, but within 30 h at 40 8C, pH 3, there is clear evidence for formation of 1, both from 1H NMR spectroscopy and precipitation of 1.Considering the relatively low pH, formation of 1 from the mono(nucleobase) complex and free Hmura is remarkable. The tetranuclear cation of trans-[{Pt(NH3)2(mura)2}2AgNa- (H2O)4][ClO4]2?6.5H2O 4 (Fig. 4, Table 3) consists of two Pt21, a Ag1, and a Na1 ion, arranged in the form of a Y, with an angle of 146.9(1)8 between the two Pt–Ag bars. The Pt–Ag distances are 2.847(1) Å, in the normal range for mixed platinum–silver complexes of uracil and thymine, regardless if derived from cisor trans-(am)2PtII,3,24–28 or diVerent systems.30,31 The Ag1 and Na1 are 3.57(1) Å apart.All four mura nucleobases are arranged head-head and use their O4 oxygen atoms as heterometal (Ag, Na) binding sites. The cation has a C2 symmetry axis which passes through Ag and Na. Ignoring Pt21 and Na1 ions, Ag1 is bound to four oxygen atoms of four mura ligands, which form a distorted tetrahedron (Table 3). Distances to the bridging O49 oxygen a9) Å] are slightly longer than those to the O4 oxygen atoms [2.411(9) Å], which bind in a monodentate fashion, yet are in the normal range.3,32 The Ag1 is markedly out of theJ.Chem. Soc., Dalton Trans., 1999, 175–182 179 Fig. 4 View of the cation of trans-[{Pt(NH3)2(mura)2}2AgNa(H2O)4][ClO4]2?6.5H2O 4 with atom numbering scheme. plane of the chelating mura pairs (see below) because the two oxygens bridging Ag1 and Na1 are pulled together by Na1 [O49 ? ? ?O49a 3.20(1) Å]. In trans-[(NH2Me)2Pt(dmcyt)2Ag2]- [NO3]2 (dmcyt = 1,5-dimethylcytosinate), which represents a good structural model of a hypothetical trans-[(NH3)2- Pt(mura)2Ag]1 cation, the two Ag1 ions are essentially coplanar with the two bases.4f The Na1 ion is surrounded by two oxygens (O49) of the mura ligands and by four water molecules (O4w, O6wa) (Table 3). The Na–O distances are somewhat variable but not unusual.33 The quadrilateral formed by Na, Ag, and the two oxygen atoms O49 and O49a can be considered a mix of two similar quadrilaterals seen in the solid state structures of trans-[Pt(NH3)2(mura)2- Ag2(NO3)2(H2O)]?H2O3 (Ag2,O2) and cis-[Pd(en)(mthy)2Na2]- [NO3]2?H2O34 (Na2,O2), respectively.In all three cases the motif is identical, viz. exocyclic oxygen atoms of the pyrimidine bases function as bridges between the metal ions. The two mura bases within one half of the cation are close to planar [dihedral angle 4.9(8)8] and inclined by 638 (average) with respect to the PtN4 plane.As compared to other bis- (nucleobase) complexes of trans-(am)2PtII, where frequently almost perpendicular orientations are observed,22,35 this value is relatively low. It is the consequence of both intra- and intermolecular hydrogen bonding (see below). The Ag1 is markedly out of the planes of the mura ligands, by 1.05(2) Å from the ring containing N3, and by 1.38(2) Å from the ring containing N39. Packing pattern of complex 4. Cations of complex 4 form infinite zigzag arrays with repetitive Pt–Ag–Pt ? ? ? Pt–Ag–Pt units (Fig. 5) and intercationic Pt ? ? ? Pt separations of 4.271(2) Å.A detail of the packing is shown in Fig. 6. It demonstrates that adjacent cations interact both through stacking (3.5 Å) of four mura ligands and intermolecular hydrogen bonding between NH3 ligands and O2 oxygen atoms of the mura rings very much as in 2: N10 ? ? ?O2a 2.87(1); N10 ? ? ?O29a 2.95(1) Å; Pt1–N10–O2a 117.6(5); Pt1–N10–O2a9 116.8(5)8.This situation is reminiscent of that realised in related mixed nucleobase complexes (“metal-modified base pairs”) of trans-(am)2PtII.22,36 The packing pattern seen in complex 4 is completely diVerent from those of dinuclear Pt2 or multinuclear mixed PtxMy complexes of mura or mthy with cis-(am)2PtII.37 While in both systems strings of metal ions form, with intermolecular hydrogen bonding between the am(m)ine ligands of Pt and carbonyl oxygen atoms of the pyrimidine nucleobases, only in the trans- (am)2PtII complex 4 there is p stacking between the nucleobases.If intermolecular p stacking is observed in cis-(am)2PtII com- Fig. 5 Packing pattern of cations of complex 4.180 J. Chem. Soc., Dalton Trans., 1999, 175–182 plexes, it either involves aromatic amine ligands of the PtII, e.g. 2,29-bipyridine, yet not nucleobases,38 or it is intramolecular as a consequence of a stereoactive electron lone pair at a heterometal ion (TlI) bound to cis-(NH3)2Pt(mthy)2.39 As far as intercationic Pt ? ? ? Pt separations are concerned, they are rather variable with cis-(am)2PtII compounds, depending on relative nucleobase orientation (head-head or head-tail) and packing of the cationic units.37b They may be as low as 3.25 Å 25 and as long as 5.66 Å.37b The intermolecular distance seen in 4 [4.271(2) Å] is in between these two extremes and considerably shorter than in mononuclear complexes of trans-(am)2PtII displaying a similar stacking pattern.22,36 Reactions of complex 1 with HgX2 (X 5 NO3 or CF3CO2) Reactions of complex 1 with Hg(NO3)2 and Hg(CF3CO2)2 were Fig. 6 Detail of packing pattern of cations of complex 4, demonstrating hydrogen bonding and p-stacking interactions of platinum entities of adjacent cations. carried out in D2O and followed by 1H NMR spectroscopy. Addition of either salt to a suspension of 1 in D2O (1 £ pD £ 2) instantaneously leads to solubilisation of 1 and gives rise to new sets of resonances of mura, all of which are downfield with respect to those of 1.For example, at a 1 : 1 ratio r of HgII and 1, two sets of resonances of relative intensities of 3 : 1 are observed, viz. at d 7.57, 5.83, 3.45 (major species, A) and at 7.55, 5.88, 3.39 (minor species, B). Within hours, a new H6 singlet of low intensity at ca. d 7.45 grows in (C). The latter resonance forms more quickly and in higher yield as the ratio r is increased. With r = 5 (Fig. 7) this resonance represents the only one in the aromatic region after 2–3 h (pD 1, 22 8C).Application of a Gaussian window function to the FID of the spectra clearly Table 3 Selected bond lengths (Å) and angles (8) for the cation of complex 4 a Pt(1)–N(3) Pt(1)–N(39) Pt(1)–N(10) Pt(1)–N(109) Na(1)–O(49) Na(1)–O(4w2,3) N(3)–Pt(1)–N(39) N(3)–Pt(1)–N(10) N(3)–Pt(1)–N(109) N(39)–Pt(1)–N(10) N(39)–Pt(1)–N(109) N(10)–Pt(1)–N(109) O(49)–Na(1)–O(491) O(49)–Na(1)–O(6wa2) O(4)–Ag(1)–O(41) O(4)–Ag(1)–O(491) 2.049(9) 1.998(10) 2.044(9) 2.037(9) 2.318(13) 2.61(2) 179.1(4) 89.6(4) 90.9(4) 89.8(4) 89.7(4) 179.4(4) 86.6(6) 167.0(10) 130.9(5) 99.4(3) Pt(1)–Ag(1) Ag(1)–O(4) Ag(1)–O(49) Ag(1) ? ? ? Na(1) Na(1)–O(6wa2,3) O(49)–Na(1)–O(6wa3) O(49)–Na(1)–O(4w2) O(49)–Na(1)–O(4w3) O(6wa2)–Na(1)–O(6wa3) O(6wa2)–Na(1)–O(4w2) O(6wa2)–Na(1)–O(4w3) O(4w2)–Na(1)–O(4w3) O(4)–Ag(1)–O(49) O(49)–Ag(1)–O(491) 2.8474(11) 2.411(9) 2.462(9) 3.568(12) 2.44(4) 93.4(9) 82.9(6) 77.1(6) 90(2) 109.7(12) 90.0(11) 152.5(11) 118.1(3) 80.4(4) a Symmetry operations: 1 2x 1 1, y, 2z 1 1.5; 2 x 1 0.5, 2y 1 0.5, z 1 0.5; 3 2x 1 0.5, 2y 1 0.5, 2z 1 1.Fig. 7 Proton NMR spectra (H6, H5 and NCH3 protons) of mixtures of Hg(CF3CO2)2 and complex 1 (r = 5) at diVerent reaction times, recorded in D2O (pD 1–2).J. Chem. Soc., Dalton Trans., 1999, 175–182 181 Fig. 8 Possible di- and tri-nuclear, mixed Pt, Hgx (x = 1 or 2) complexes derived from head-head (hh) and head-tail (ht) rotamers of 1. The expected number ns of H5 and H6 doublets is given.reveals that the apparent singlet C consists of two components (C1, C2), as does the NCH3 resonance. In the initial state of the reaction, three H6 and H5 doublets of uneven intensities (A, B1, B2) are observed, unlike with r = 1 (two doublets). We propose that the species formed in the early stage of the reaction (A, B) represent heteronuclear PtHgx (x = 1 or 2) species with HgII binding to exocyclic oxygen atoms (O4, O2) of the mura ligands.Chemical shifts of the H6 and H5 doublets are neither consistent with protonated 1 nor with free Hmura. We are unable to assign these species, considering the multiplicity of products feasible, depending on the relative orientations of the two bases (Fig. 8). All we can tell is that the species formed are not in fast exchange and apparently depend on r. Species C and C1, C2, respectively, represent C5-mercurated species, since the disappearance of the H5 doublets of mura during the reaction is not due to an isotope exchange (2D vs. 1H) as clearly seen from the behaviour of the H6 doublets. The chemical shift of the H6 singlet is in the range expected for this kind of species.40–43 However, unlike in similar cases, we do not observe coupling between the 199Hg isotope and H6. Values of 3J of 100–170 Hz could have been expected.43 Likewise, a 199Hg NMR resonance is not detected. The 195Pt NMR resonance of the sample r = 5 containing only species C1 and C2 consists of an unusually broad (half width ca. 200 ppm) signal at an unexpected chemical shift (d 21808). This value compares with d 22830 for a complex of Hmura with a (dien)PtII entity at N3 and a HgII at Fig. 9 Chemical shifts of 195Pt NMR resonances for mixed Pt, Hgx species (a,b) and proposed structure of the compound formed at r = 5 (HgII : 1). C5,40 and d 22195 for a cyclic complex of 1-methylcytosine containing PtII at N3 and HgII both bound to N4 and C5 [Fig. 9(a), 9(b)].4b It suggests that in the present case PtII might be surrounded by two HgII, as schematically pointed out in Fig. 9(c). It is neither possible at present to assign a rotational state (head-head or head-tail) of the two uracil rings nor to determine the degree and kind of condensation (dimeric, polymeric, cyclic) via C5–Hg–C5 bonds. Attempts further to characterise complex 5, which was obtained in a preparative scale with r = 4, were unsuccessful. However, mercuration of both uracil ligands at C5 was clearly evident.Conclusion As shown in this work, trans-[Pt(NH3)2(mura-N3)2] 1 behaves as a ligand toward other metal ions (Ag1, Na1, Hg21). In this respect, 1 is very similar to the corresponding cis isomer, cis- [Pt(NH3)2(mura-N3)2].1 What is diVerent in the two systems, is essentially the relative orientations of the metal ions (Fig. 10) as well as the intercationic interactions. Thus, in dinuclear complexes derived from cis-[Pt(NH3)2(mura-N3)2], Pt and the second metal in general are facing each other [Fig. 10(a)], unless severe bulk of other ligands prevents it.44 If the second metal ion is likewise PtII in a cis geometry, this feature permits removal of electrons from the dz2 orbitals directed toward each other, hence oxidation. In 4, PtII and AgI are not at the closest possible distance [Fig. 10(b)], which they would be if AgI were linearly co-ordinated by two O4 oxygen atoms and coplanar with the two uracil rings [Fig. 10(c)]. As to the diVerences in intermolecular interactions between cations of 4, and likewise of 2, from those seen in related compounds of cis geometry, nucleobase stacking in the trans compounds appears to be a recurring motif 22 as opposed to mainly hydrogen bonding in cis complexes, with the latter sometimes reinforced by metal–metal bond formation.45 Fig. 10 Schematic representations of dinuclear Pt, M complexes derived from (a) cis-[Pt(NH3)2(mura-N3)2], (b) trans-[Pt(NH3)2(mura- N3)2] as observed in 4 and (c) trans-[Pt(NH3)2(mura-N3)2] with M coplanar with Pt and the two nucleobases.182 J.Chem. Soc., Dalton Trans., 1999, 175–182 Acknowledgements Support by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie and the European HCM project is gratefully acknowledged. References 1 B. Lippert, Prog. Inorg. Chem., 1989, 37, 1; E. Zangrando, F. Pichierri, L. Randaccio and B. Lippert, Coord. Chem. Rev., 1996, 156, 275 and refs.therein. 2 H. Schöllhorn, U. Thewalt and B. 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