Model of the Second Most Abundant Cisplatin-DNA Cross-Link: X-ray Crystal Structure and Conformational Analysis of cis-[(NH(3))(2)Pt(9-MeA-N7)(9-EtGH-N7)](NO(3)).2H(2)O (9-MeA = 9-Methyladenine; 9-EtGH = 9-Ethylguanine)

A model compound of the second most abundant DNA adduct of the antitumor agent cisplatin has been synthesized and structurally and spectroscopically characterized and its conformational behavior examined: cis-[(NH(3))(2)Pt(9-MeA-N7)(9-EtGH-N7)](NO(3))(2).2H(2)O (9-MeA = 9-methyladenine; 9-EtGH = 9-ethylguanine) crystallizes in the monoclinic system, space group P2(1)/n (No. 14) with a = 7.931(2), b = 11.035(3), c = 26.757(6) ?, beta = 94.94(2) degrees, and Z = 4. The two purine bases adopt a head-to-head orientation, with NH(2) of 9-MeA and CO of 9-EtGH being at the same side of the Pt coordination plane. A theoretical conformational analysis of the complex cis-[(NH(3))(2)Pt(Ade)(Gua)](2+) (Ade = adenine; Gua = guanine) based on molecular mechanics calculations of the nonbonded energy has revealed four minimum-energy zones similar to those derived previously for cis-[(NH(3))(2)Pt(Gua)(2)](2+) (Kozelka; et al. Eur. J. Biochem. 1992, 205, 895). This conformational analysis has allowed, together with the calculation of chemical shifts due to ring effects, the attribution of the two conformers observed for cis-[(NH(3))(2)Pt{d(ApG)}](+) by Dijt et al. (Eur. J. Biochem. 1989, 179, 344) to the two head-to-head conformational zones. The orientation of the two nucleobases in the crystal structure of cis-[(NH(3))(2)Pt(9-MeA)(9-EtGH)](2+) corresponds, according to our analysis, roughly to that preferentially assumed by the minor rotamer of cis-[(NH(3))(2)Pt{d(ApG)}](+).     

Platinum(II)-mediated coupling reactions of acetonitrile with the exocyclic nitrogen of 9-methyladenine and 1-methylcytosine. Synthesis, NMR characterization, and X-ray structures of new azametallacycle complexes

The hydroxo complex cis-[L2Pt(mu-OH)]2(NO3)2, (L = PMePh2, 1a), in CH3CN solution, deprotonates the NH2 group of 9-methyladenine (9-MeAd) to give the cyclic trinuclear species cis-[L2Pt[9-MeAd(-H)]]3(NO3)3, (L = PMePh2, 2a), in which the nucleobase binds the metal centers through the N(1), N(6) atoms. In solution at room temperature, 2a slowly reacts with the solvent to form quantitatively the mononuclear azametallacycle cis-[L2PtNH=C(Me)[9-MeAd(-2H)]]NO3 (L = PMePh2, 3a), containing as anionic ligand the deprotonated form of molecule N-(9-methyl-1,9-dihydro-purin-6-ylidene)-acetamidine. In the same experimental conditions, the hydroxo complex with PPh3 (1b) forms immediately the insertion product 3b. Single-crystal X-ray analyses of 3a and 3b show the coordination of the platinum cation at the N(1) site of the purine moiety and to the N atom of the inserted acetonitrile, whereas the exocyclic amino nitrogen binds the carbon atom of the same CN group. The resulting six-membered ring is slightly distorted from planarity, with carbon-nitrogen bond distances for the inserted nitrile typical of a double bond [C(3)-N(2) = 1.292(7) Angstroms in 3a and 1.279(11) Angstroms in 3b], while the remaining CN bonds of the metallocycle are in the range of 1.335(8)-1.397(10) Angstroms. A detailed multinuclear 1H, 31P, 13C, and 15N NMR study shows that the nitrogen atom of the inserted acetonitrile molecule binds a proton suggesting for 3a,b an imino structure in solution. In DMSO and chlorinated solvents, 3a slowly releases the nitrile reforming the trinuclear species 2a, whereas 3b forms the mononuclear derivative cis-[L2Pt[9-MeAd(-H)]]NO3 (L = PPh3, 4b), in which the adeninate ion chelates the metal center through the N(6) and N(7) atoms. Complex 4b is quantitatively obtained when 1b reacts with 9-MeAd in DMSO and can be easily isolated if the reaction is carried out in CH(2)Cl(2). In CH(3)CN solution, at room temperature, 4b slowly converts into 3b indicating that the insertion of acetonitrile is a reversible process. A similar metal-mediated coupling reaction occurs when 1a,b react with 1-methylcytosine (1-MeCy) in CH(3)CN. The resulting complexes, cis-[L(2)PtNH=C(Me)[1-MeCy(-2H)]]NO3, (L = PMePh2, 5a and PPh3, 5b), contain the deprotonated form of the ligand N-(1-methyl-2-oxo-2,3-dihydro-1H-pyrimidin-4-ylidene)-acetamidine. The X-ray analysis of 5a shows the coordination of the metal at the N(3) site of the pyrimidine cycle and to the nitrogen atom of the acetonitrile, with features of the six-membered metallocycle only slightly different from those found in 3a and 3b. In CD3CN/CH3(13)CN solution complexes 5a,b undergo exchange of the inserted nitrile, while in DMSO or chlorinated solvents they irreversibly release CH3CN to form species not yet fully characterized. No insertion of CH3CN occurs when the hydroxo complexes are stabilized by PMe3 and PMe2Ph.     

Role of the phosphine ligands on the stabilization of monoadducts of the model nucleobases 1-methylcytosine and 9-methylguanine in platinum(II) complexes

The addition of 1-methylcytosine (1-MeCy) or 9-methylguanine (9-MeGu) to solutions of cis-(PPh3)2P(ONO2)2 (1a), in a molar ratio of 1:1, affords the monoadducts cis-[(PPh3)2Pt(1-MeCy)(ONO2)]NO3 (2a) and cis-[(PPh3)2Pt(9-MeGu)(ONO2)]NO3 (3a) and only trace amounts of the bisadducts cis-[(PPh3)2Pt(1-MeCy)2](NO3)2 (4a) and cis-[(PPh3)2Pt(9-MeGu)2](NO3)2 (5a), respectively. The X-ray structural determination of 2a and 3a indicates a strong pi-pi stacking interaction between one of the PPh3 phenyl groups and the pyrimydinic N3-platinated cytosine or the imidazole part of the N7-coordinated guanine base. The addition of a further equiv of nucleobase to the monoadducts forms quantitatively the bisadducts that have been isolated as pure compounds 4a and 5a. Under the same experimental conditions, the dinitrato analogue cis-[(PMePh2)2Pt(ONO2)2] (1b) forms the monoadducts 2b and 3b in equilibrium with a relatively high concentration (20-30%) of the bisadducts cis-[(PMePh2)2Pt(1-MeCy)2](NO3)2 (4b) and cis-[(PMePh2)2Pt(9-MeGu)2](NO3)2 (5b), which have been structurally characterized by single-crystal X-ray analysis. The characterization of the isolated complexes by multinuclear NMR spectroscopy is also described.     

Mono- and polynuclear complexes of the model nucleobase 1-methylcytosine. Synthesis and characterization of cis-[(PMe2Ph)2Pt{(1-MeCy(-H)}]3(NO3)3 and cis-[(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)]NO3

The hydroxo complex cis-[L2Pt(mu-OH)]2(NO3)2 (L = PMe2Ph), in various solvents, reacts with 1-methylcytosine (1-MeCy) to give as the final product the cyclic species cis-[L2Pt{1-MeCy(-H),N 3N 4}]3(NO3)3 (1) in high or quantitative yield. X-ray analysis of 1 evidences a trinuclear species with the NH(2)-deprotonated nucleobases bridging symmetrically the metal centers through the N3 and N4 donors. A multinuclear NMR study of the reaction in DMSO-d6 reveals the initial formation of the dinuclear species cis-[L2Pt{1-MeCy(-H),N 3N 4}]2(2+) (2), which quantitatively converts into 1 following a first-order kinetic law (at 50 degrees C, t(1/2) = 5 h). In chlorinated solvents, the deprotonation of the nucleobase affords as the major product (60-70%) the linkage isomer of 1, cis-[L2Pt{1-MeCy(-H)}]3(3+) (3), in which three cytosinate ligands bridge unsymmetrically three cis-L2Pt(2+) units. In solution, 3 slowly converts quantitatively into the thermodynamically more stable isomer 1. No polynuclear adducts were obtained with the hydroxo complex stabilized by PPh3. cis-[(PPh3)2Pt(mu-OH)]2(NO3)2 reacts with 1-MeCy, in DMSO or CH2Cl2, to give the mononuclear species cis-[(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)](NO3) (4) containing one neutral and one NH2-deprotonated 1-MeCy molecule, coordinated to the same metal center at the N3 and N4 sites, respectively. X-ray analysis and NMR studies show an intramolecular H bond between the N4 amino group and the uncoordinated N3 atom of the two nucleobases.     

Metal-promoted synthesis of amidines containing the model nucleobases 1-methylcytosine and 9-methyladenine

The amidine complexes cis-[L(2)PtNH==C(R){1-MeCy(-2H)}]NO(3) (R = Me, 1a; Ph, 1b, Me(3)C, 1c; Ph(2)(H)C, 1d) and cis-[L(2)PtNH==C(R){9-MeAd(-2H)}]NO(3) (R = Me, 2a; Ph, 2b; Me(3)C, 2c; Ph(2)(H)C, 2d), are formed when cis-[L(2)Pt(μ-OH)](2)(NO(3))(2) (L = PPh(3)) reacts with 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) in solution of MeCN, PhCN, Me(3)CCN and Ph(2)(H)CCN. Reaction of 1a,b and 2a,b with HCl affords the protonated amidines [NH(2)==C(R){1-MeCy(-H)}]NO(3) (R = Me, 3a; Ph, 3b) and [NH(2)==C(R){9-MeAd(-H)}]NO(3) (R = Me, 4a; Ph, 4b) and cis-(PPh(3))(2)PtCl(2) in quantitative yield. Treatment of 3b and 4b with NaOH allows the isolation of the neutral benzimidamides NH(2)-C(Ph){1-MeCy(-2H)} (5b) and NH(2)-C(Ph){9-MeAd(-2H)} (6b). In the solid state 3b shows a planar structure with the hydrogen atom on N(4) cytosine position involved in a strong H-bond with the NO(3)(-) ion. Intermolecular H-bonds between the oxygen of the cytosine ring and one of the H atoms of the amidine-NH(2) group allow the dimerization of the molecule. A detailed analysis of the spectra of 3b in DMF-d(7) at -55 °C indicates the presence of an equilibrium between the species [NH(2)==C(R){1-MeCy(-H)}]NO(3) and [NH(2)==C(R){1-MeCy(-H)}](2)(NO(3))(2), exchanging with trace amounts of water at 25 °C. [(15)N,(1)H]-HMBC experiments for 5b and 6b indicate that the amino tautomer H(2)N-C(Ph){nucleobase(-2H)}, is the only detectable in solution and such structure has been confirmed in the solid state. The reaction of 5b and 6b with cis-L(2)Pt(ONO(2))(2) (L = PPh(3)), in chlorinated solvents, determines the immediate appearance of a pale yellow colour due to the coordination of the neutral amidine, likely in its imino form HN==C(Ph){nucleobase(-H)}, to give the adducts cis-[L(2)PtNH==C(Ph){nucleobase(-H)}](2+). In fact, addition of "proton sponge" leads to the immediate deprotonation of the amidine ligand with formation of the starting complexes 1b and 2b.     

Alkynyldiphenylphosphine d8 (Pt, Rh, Ir) complexes: contrasting behavior toward cis-[Pt(C6F5)2(THF)2

The synthesis and characterization of a series of mononuclear d(8) complexes with at least two P-coordinated alkynylphosphine ligands and their reactivity toward cis-[Pt(C(6)F(5))(2)(THF)(2)] are reported. The cationic [Pt(C(6)F(5))(PPh(2)C triple-bond CPh)(3)](CF(3)SO(3)), 1, [M(COD)(PPh(2)C triple-bond CPh)(2)](ClO(4)) (M = Rh, 2, and Ir, 3), and neutral [Pt(o-C(6)H(4)E(2))(PPh(2)C triple-bond CPh)(2)] (E = O, 6, and S, 7) complexes have been prepared, and the crystal structures of 1, 2, and 7.CH(3)COCH(3) have been determined by X-ray crystallography. The course of the reactions of the mononuclear complexes 1-3, 6, and 7 with cis-[Pt(C(6)F(5))(2)(THF)(2)] is strongly influenced by the metal and the ligands. Thus, treatment of 1 with 1 equiv of cis-[Pt(C(6)F(5))(2)(THF)(2)] gives the double inserted cationic product [Pt(C(6)F(5))(S)mu-(C(Ph)=C(PPh(2))C(PPh(2))=C(Ph)(C(6)F(5)))Pt(C(6)F(5))(PPh(2)C triple-bond CPh)](CF(3)SO(3)) (S = THF, H(2)O), 8 (S = H(2)O, X-ray), which evolves in solution to the mononuclear complex [(C(6)F(5))(PPh(2)C triple-bond CPh)Pt(C(10)H(4)-1-C(6)F(5)-4-Ph-2,3-kappaPP'(PPh(2))(2))](CF(3) SO(3)), 9 (X-ray), containing a 1-pentafluorophenyl-2,3-bis(diphenylphosphine)-4-phenylnaphthalene ligand, formed by annulation of a phenyl group and loss of the Pt(C(6)F(5)) unit. However, analogous reactions using 2 or 3 as precursors afford mixtures of complexes, from which we have characterized by X-ray crystallography the alkynylphosphine oxide compound [(C(6)F(5))(2)Pt(mu-kappaO:eta(2)-PPh(2)(O)C triple-bond CPh)](2), 10, in the reaction with the iridium complex (3). Complexes 6 and 7, which contain additional potential bridging donor atoms (O, S), react with cis-[Pt(C(6)F(5))(2)(THF)(2)] in the appropriate molar ratio (1:1 or 1:2) to give homo- bi- or trinuclear [Pt(PPh(2)C triple-bond CPh)(mu-kappaE-o-C(6)H(4)E(2))(mu-kappaP:eta(2)-PPh(2)C triple-bond CPh)Pt(C(6)F(5))(2)] (E = O, 11, and S, 12) and [(Pt(mu(3)-kappa(2)EE'-o-C(6)H(4)E(2))(mu-kappaP:eta(2)-PPh(2)C triple-bond CPh)(2))(Pt(C(6)F(5))(2))(2)] (E = O, 13, and S, 14) complexes. The molecular structure of 14 has been confirmed by X-ray diffraction, and the cyclic voltammetric behavior of precursor complexes 6 and 7 and polymetallic derivatives 11-14 has been examined.     

The reaction of Li[Al(OR)4] R = OC(CF3)2Ph, OC(CF3)3 with NO/NO2 giving NO[Al(OR)4], Li[NO3] and N2O. The synthesis of NO[Al(OR)4] from Li[Al(OR)4] and NO[SbF6] in sulfur dioxide solution

NO[Al(OC(CF(3))(2)Ph)(4)] 1 and NO[Al(OC(CF(3))(3))(4)] 2 were obtained by the metathesis reaction of NO[SbF(6)] and the corresponding Li[Al(OR)(4)] salts in liquid sulfur dioxide solution in ca 40% (1) and 85% (2) isolated yield. 1 and 2, as well as Li[NO(3)] and N(2)O, were also given by the reaction of an excess of mixture of (90 mol%) NO, (10 mol%) NO(2) with Li[Al(OR)(4)] followed by extraction with SO(2). The unfavourable disproportionation reaction of 2NO(2)(g) to [NO](+)(g) and [NO(3)](-)(g)[DeltaH degrees = +616.2 kJ mol(-1)] is more than compensated by the disproportionation energy of 3NO(g) to N(2)O(g) and NO(2)(g)[DeltaH degrees =-155.4 kJ mol(-1)] and the lattice energy of Li[NO(3)](s)[U(POT)= 862 kJ mol(-1)]. Evidence is presented that the reaction proceeds via a complex of [Li](+) with NO, NO(2)(or their dimers) and N(2)O. NO(2) and Li[Al(OC(CF(3))(3))(4)] gave [NO(3)(NO)(3)][Al(OC(CF(3))(3))(4)](2), NO[Al(OC(CF(3))(3))(4)] and (NO(2))[Al(OC(CF(3))(3))(4)] products. The aluminium complex [Li[AlF(OC(CF(3))(2)Ph)(3)]](2) 3 was prepared by the thermal decomposition of Li[Al(OC(CF(3))(2)Ph)(4)]. Compounds 1 and 3 were characterized by single crystal X-ray structural analyses, 1-3 by elemental analyses, NMR, IR, Raman and mass spectra. Solid 1 contains [Al(OC(CF(3))(2)Ph)(4)](-) and [NO](+) weakly linked via donor acceptor interactions, while in the SO(2) solution there is an equilibrium between the associated [NO](+)[Al(OC(CF(3))(2)Ph)(4)](-) and separated solvated ions. Solid 2 contains essentially ionic [NO](+) and [Al(OC(CF(3))(3))(4)](-). Complex 3 consists of two [Li[AlF(OC(CF(3))(2)Ph)(3)]] units linked via fluorine lithium contacts. Compound 1 is unstable in the SO(2) solution and decomposes to yield [AlF(OC(CF(3))(2)Ph)(3)](-), [(PhC(CF(3))(2)O)(3)Al(mu-F)Al(OC(CF(3))(2)Ph)(3)](-) anions as well as (NO)C(6)H(4)C(CF(3))(2)OH, while compound 2 is stable in liquid SO(2). The [small nu](NO(+)) in 1 and [NO](+)(toluene)[SbCl(6)] are similar, implying similar basicities of [Al(OC(CF(3))(2)Ph)(4)](-) and toluene.     

Cobalt(III) complexes of monodentate N9-bound adeninate (ade-), [Co(ade-kappaN9)Cl(en)2]+ (en = 1,2-diaminoethane): syntheses, crystal structures, and protonation behaviors of the geometrical isomers

In acidic aqueous solution, a cobalt(III) complex containing monodentate N(9)-bound adeninate (ade(-)), cis-[Co(ade-kappaN(9))Cl(en)(2)]Cl (cis-[1]Cl), underwent protonation to the adeninate moiety without geometrical isomerization or decomposition of the Co(III) coordination sphere, and complexes of cis-[CoCl(Hade)(en)(2)]Cl(2) (cis-[2]Cl(2)) and cis-[Co(H(2)ade)Cl(en)(2)]Cl(3) (cis-[3]Cl(3)) could be isolated. The pK(a) values of the Hade and H(2)ade(+) complexes are 6.03(1) and 2.53(12), respectively, at 20 degrees C in 0.1 M aqueous NaCl. The single-crystal X-ray analyses of cis-[2]Cl(2).0.5H(2)O and cis-[3]Cl(2)(BF(4)).H(2)O revealed that protonation took place first at the adeninate N(7) and then at the N(1) atoms to form adenine tautomer (7H-Hade-kappaN(9)) and cationic adeninium (1H,7H-H(2)ade(+)-kappaN(9)) complexes, respectively. On the other hand, addition of NaOH to an aqueous solution of cis-[1]Cl afforded a mixture of geometrical isomers of the hydroxo-adeninato complex, cis- and trans-[Co(ade-kappaN(9))(OH)(en)(2)](+). The trans-isomer of chloro-adeninato complex trans-[Co(ade-kappaN(9))Cl(en)(2)]BF(4) (trans-[1]BF(4)) was synthesized by a reaction of cis-[2](BF(4))(2) and sodium methoxide in methanol. This isomer in acidic aqueous solution was also stable toward isomerization, affording the corresponding adenine tautomer and adeninium complexes (pK(a) = 5.21(1) and 2.48(9), respectively, at 20 degrees C in 0.1 M aqueous NaCl). The protonated product of trans-[Co(7H-Hade-kappaN(9))Cl(en)(2)](BF(4))(2).H(2)O (trans-[2](BF(4))(2).H(2)O) could also be characterized by X-ray analysis. Furthermore, the hydrogen-bonding interactions of the adeninate/adenine tautomer complexes cis-[1]BF(4), cis-[2](BF(4))(2), and trans-[2](BF(4))(2) with 1-cyclohexyluracil in acetonitrile-d(3) were investigated by (1)H NMR spectroscopy. The crystal structure of trans-[Co(ade)(H(2)O)(en)(2)]HPO(4).3H(2)O, which was obtained by a reaction of trans-[Co(ade)(OH)(en)(2)]BF(4) and NaH(2)PO(4), was also determined.     

Supramolecular isomerism of 2,2'-bipyrazine complexes with cis-(NH(3))(2)Pt(II): ligand rotational state and sequential orientation determine the 3D shape of metallacycles

2,2'-Bipyrazine (2,2'-bpz) reacts with cis-(NH(3))(2)Pt(II) in water to give a variety of products, several of which were isolated and characterized by X-ray analysis: cis-[Pt(NH(3))(2)(2,2'-bpz-N4)(2)](NO(3))(2)·3H(2)O (1), [{cis-Pt(NH(3))(2)(2,2'-bpz-N4,N4')}(3)]-(PF(6))(5)NO(3)·7H(2)O (2a), [{cis-Pt(NH(3))(2)(2,2'-bpz-N4,N4')}(3)](BF(4))(2)-(SiF(6))(2)·15H(2)O (2b), and [{cis-Pt(NH(3))(2)(2,2'-bpz-N4,N4')}(4)]-(SO(4))(4)·22H(2)O (3). In 1, 2b, and 3 the 2,2'-bpz ligands adopt approximately C(2h) symmetries, hence the two pyrazine halves are in trans orientation, whereas in 2a all three 2,2'-bpz bridges are approximately C(2v) symmetric, with the pyrazine halves cis to each other. The topologies of the two triangular complexes 2a and 2b are consequently distinctly different, but nevertheless both cations act as hosts for anions. In 2a a PF(6)(-) and a NO(3)(-) anion are associated simultaneously with the +6 cation, whereas in 2b it is a BF(4)(-) anion and a water molecule, which are trapped in its cavity. There is no anion inclusion in case of the metallasquare 3. In principle, 3 can exist in a large number of stereoisomers, depending on the rotational states of the bridging 2,2'-bpz ligands. Isolation of a single rotamer form of 3 with C(2h) symmetric 2,2'-bpz ligands and an overall meso form is proposed to be a consequence of a highly efficient self-assembly process that starts from the precursor 1 and reaction with two cis-(NH(3))(2)Pt(II) units. This process leads to the isolated rotamer of 3 regardless of whether two cations 1 in head-head form react with two cis-(NH(3))(2)Pt(II), or whether the Δ enantiomer of the chiral head-tail form of 1 combines with its Λ enantiomer through two cis-(NH(3))(2)Pt(II) entities.     

7-Methylguanine: protonation, formation of linkage isomers with trans-(NH3)2Pt(II), and base pairing properties

Three protonated forms of 7-methylguanine (7-MeGH, 1) with different counter ions, [7-MeGH(2)]X (X = NO(3), 1a; ClO(4), 1b; BF(4), 1c) and two Pt(II) complexes, trans-[Pt(NH(3))(2)(7-MeGH-N9)(2)](ClO(4))(2) (4) and trans-[Pt(NH(3))(2)(7-MeGH-N9)(7-MeGH-N3)](ClO(4))(2)·3H(2)O (5) are described and their X-ray crystal structures are reported. 1a-1c form infinite ribbons via pairs of intermolecular hydrogen bonds between N1H···O6 and N3···N2H(2) sites, with anions connecting individual ribbons, thereby generating extended sheets. 4 and 5 do not display unusual features, except that 5 represents a rare case of a bis(nucleobase) complex of Pt(II) in which linkage isomers occur. Unlike in a previously reported compound, [Pt(dien)(7-MeGH-N9)](NO(3))(ClO(4)), the Pt coordination planes and the 7-MeGH planes are not coplanar in 4 and 5. The hydrogen bonding behaviour of 7-MeGH, free and when platinated at N9 (complex 4), was studied in Me(2)SO-d(6). It revealed the following: (i) there is no detectable self-association of 1 in Me(2)SO solution. (ii) 1 and 1-methylcytosine (1-MeC) form Watson-Crick pairs. (iii) 4 does not self-associate. (iv) 4 associates with 1-MeC in the Watson-Crick fashion. (v) 4 and 1 interact in solution, but no model can be proposed at present. (vi) Remarkable interaction shifts between 4 and 1 occur when NH(3) is liberated from trans-(NH(3))(2)Pt(II) to give NH(4)(+) in Me(2)SO-d(6). Feasible models, which imply the presence of deprotonated 7-MeG(-) species are proposed. Finally, DFT calculations were carried out to qualitatively estimate the effect of 7-MeGH acidity in [Pt(dien)(7-MeGH-N9)](2+) in dependence of the dihedral angle between the Pt coordination plane and the nucleobase.     

Pt(II)-promoted [2 + 3] cycloaddition of azide to cyanopyridines: convenient tool toward heterometallic structures

The [2 + 3] cycloaddition reactions (which are greatly accelerated by microwave irradiation) of the di(azido)platinum(II) compounds cis-[Pt(N(3))(2)(PPh(3))(2)] (1) with cyanopyridines NCR (2) (R = 4-, 3-, and 2-NC(5)H(4)) give the corresponding bis(pyridyltetrazolato) complexes trans-[Pt(N(4)CR)(2)(PPh(3))(2)] (3) [R = 4-NC(5)H(4) (3a), 3-NC(5)H(4) (3b), and 2-NC(5)H(4) (3c)]. Compound 3c has been characterized as the N(1)N(2)-bonded isomer in the solid state by X-ray crystallography and represents the first bis(tetrazolato) complex of this kind. Complexes 3a and 3b have been used as metallaligands to generate heteronuclear coordination polymers in the presence of copper nitrate. A one-dimensional supramolecular architecture was obtained as the exclusive product, {trans-[Pt(2)(N(4)CR)(4)(PPh(3))(4)Cu](n)(NO(3))(2n).nH(2)O (4.nH(2)O) (R = 4-NC(5)H(4)), when 3a was employed, whereas with 3b the heteronuclear square complex trans-[Pt(N(4)CR)(2)(PPh(3))(2)Cu(NO(3))(2)(H(2)O)](2) (5) (R = 3-NC(5)H(4)), composed of Pt/Cu ions, was obtained. All the isolated complexes were characterized by IR, elemental, and (for 3b, 3c, 4, and 5) X-ray structural analyses. Complexes 3 were additionally characterized by (1)H, (13)C, and (31)P {(1)H} NMR spectroscopies.     

Dinitrosyl iron complexes (DNICs) [L(2)Fe(NO)2]- (L = thiolate): interconversion among {Fe(NO)2}9 DNICs, {Fe(NO)2}10 DNICs, and [2Fe-2S] clusters, and the critical role of the thiolate ligands in regulating NO release of DNICs

Dinitrosyl iron complex [(-SC(7)H(4)SN)(2)Fe(NO)(2)](-) (1) was prepared by reaction of [S(5)Fe(NO)(2)](-) and bis(2-benzothiozolyl) disulfide. In synthesis of the analogous dinitrosyl iron compounds (DNICs), the stronger electron-donating thiolates [RS](-) (R = C(6)H(4)-o-NHCOCH(3), C(4)H(3)S, C(6)H(4)NH(2), Ph), compared to [-SC(7)H(4)SN](-) of complex 1, trigger thiolate-ligand substitution to yield [(-SC(6)H(4)-o-NHCOCH(3))(2)Fe(NO)(2)](-) (2), [(-SC(4)H(3)S)(2)Fe(NO)(2)](-) (3), and [(SPh)(2)Fe(NO)(2)](-) (4), respectively. At 298 K, complexes 2 and 3 exhibit a well-resolved five-line EPR signal at g = 2.038 and 2.027, respectively, the characteristic g value of DNICs. The magnetic susceptibility fit indicates that the resonance hybrid of {Fe(+)((*)NO)(2)}(9) and {Fe(-)((+)NO)(2)}(9) in 2 is dynamic by temperature. The IR nu(NO) stretching frequencies (ranging from (1766, 1716) to (1737, 1693) cm(-)(1) (THF)) of complexes 1-4 signal the entire window of possible electronic configurations for such stable and isolable {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-). The NO-releasing ability of {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) is finely tuned by the coordinated thiolate ligands. The less electron-donating thiolate ligands coordinated to {Fe(NO)(2)}(9) motif act as better NO-donor DNICs in the presence of NO-trapping agent [Fe(S,S-C(6)H(4))(2)](2)(2-). Interconversion between {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) and {Fe(NO)(2)}(10) [(Ph(3)P)(2)Fe(NO)(2)] was verified in the reaction of (a) [(RS)(2)Fe(NO)(2)](-), 10 equiv of PPh(3) and sodium-biphenyl, and (b) 2 equiv of thiol, [RS](-), and [(Ph(3)P)(2)Fe(NO)(2)], respectively. The biomimetic reaction cycle, transformation between {Fe(NO)(2)}(9) [(RS)(2)Fe(NO)(2)](-) and {Fe(NO)(2)}(9) [(R'S)(2)Fe(NO)(2)](-), reversible interconversion of {Fe(NO)(2)}(9) and {Fe(NO)(2)}(10) DNICs, and degradation/reassembly of [2Fe-2S] clusters may decipher and predict the biological cycle of interconversion of {Fe(NO)(2)}(9) DNICs, {Fe(NO)(2)}(10) DNICs, and the [Fe-S] clusters in proteins.     

Site selectivity in the reactions of the hexanuclear platinum cluster [Pt6(mu-PtBu2)4(CO)6][CF3SO3]2

The previously reported hexanuclear cluster [Pt(6)(mu-PtBu(2))(4)(CO)(6)](2+)[Y](2) (1-Y(2): Y=CF(3)SO(3) (-)) contains a central Pt(4) tetrahedron bridged at each of the opposite edges by another platinum atom; in turn, four phosphido ligands bridge the four Pt-Pt bonds not involved in the tetrahedron, and, finally, one carbonyl ligand is terminally bonded to each metal centre. Interestingly, the two outer carbonyls are more easily substituted or attacked by nucleophiles than the inner four, which are bonded to the tetrahedron vertices. In fact, the reaction of 1-Y(2) with 1 equiv of [nBu(4)N]Cl or with an excess of halide salts gives the monochloride [Pt(6)(mu-PtBu(2))(4)(CO)(5)Cl](+)[Y], 2-Y, or the neutral dihalide derivatives [Pt(6)(mu-PtBu(2))(4)(CO)(4)X(2)] (3: X=Cl; 4: X=Br; 5: X=I). Moreover, the useful unsymmetrically substituted [Pt(6)(mu-PtBu(2))(4)(CO)(4)ICl] (6) was obtained by reacting equimolar amounts of 2 and [nBu(4)N]I, and the dicationic derivatives [Pt(6)(mu-PtBu(2))(4)(CO)(4)L(2)](2+)[Y](2) (7-Y(2): L=(13)CO; 8-Y(2): L=CNtBu; 9-Y(2): L=PMe(3)) were obtained by reaction of an excess of the ligand L with 1-Y(2). Weaker nitrogen ligands were introduced by dissolving the dichloride 3 in acetonitrile or pyridyne in the presence of TlPF(6) to afford [Pt(6)(mu-PtBu(2))(4) (CO)(4)L(2)](2+)[Z](2) (Z=PF(6) (-), 10-Z(2): L=MeCN; 11-Z(2): L=Py). The "apical" carbonyls in 1-Y(2) are also prone to nucleophilic addition (Nu(-): H(-), MeO(-)) affording the acyl derivatives [Pt(6)(mu-PtBu(2))(4)(CO)(4)(CONu)(2)] (12: Nu=H; 13: Nu=OMe). Complex 12 is slowly converted into the dihydride [Pt(6)(mu-PtBu(2))(4)(CO)(4)H(2)] (14), which was more cleanly prepared by reacting 3 with NaBH(4). In a unique case we observed a reaction involving also the inner carbonyls of complex 1, that is, in the reaction with a large excess of the isocyanides R-NC, which form the corresponding persubstituted derivatives [Pt(6)(mu-tPBu(2))(4)(CN-R)(6)](2+)[Y](2), (15-Y(2): R=tBu; 16-Y(2) (2-): R=-C(6)H(4)-4-C triple bond CH). All complexes were characterized by microanalysis, IR and multinuclear NMR spectroscopy. The crystal and molecular structures of complexes 3, 5, 6 and 9-Y(2) are also reported. From the redox viewpoint, all complexes display two reversible one-electron reduction steps, the location of which depends both upon the electronic effects of the substituents, and the overall charge of the original complex.     

The [Sn(9)Pt(2)(PPh(3))](2)(-) and [Sn(9)Ni(2)(CO)](3)(-) complexes: two markedly different Sn(9)M(2)L transition metal zintl ion clusters and their dynamic behavior

[Sn(9)Pt(2)(PPh(3))](2)(-) (2) was prepared from Pt(PPh(3))(4), K(4)Sn(9), and 2,2,2-cryptand in en/toluene solvent mixtures. The [K(2,2,2-cryptand)](+) salt is very air and moisture sensitive and has been characterized by ESI-MS, variable-temperature (119)Sn, (31)P, and (195)Pt NMR and single-crystal X-ray diffraction studies. The structure of 2 comprises an elongated tricapped Sn(9) trigonal prism with a capping PtPPh(3), an interstitial Pt atom, a hypercloso electron count (10 vertex, 20 electron) and C(3)(v)() point symmetry. Hydrogenation trapping experiments and deuterium labeling studies showed that the formation of 2 involves a double C-H activation of solvent molecules (en or DMSO) with the elimination of H(2) gas. The ESI-MS analysis of 2 showed the K[Sn(9)Pt(2)(PPh(3))](1)(-) parent ion, an oxidized [Sn(9)Pt(2)(PPh(3))](1)(-) ion, and the protonated binary cluster anion [HSn(9)Pt(2)](1)(-). 2 is highly fluxional in solution giving rise to a single time-averaged (119)Sn NMR signal for all nine Sn atoms but the Pt atoms remain distinct. The exchange is intramolecular and is consistent with a rigid, linear Pt-Pt-PPh(3) rod embedded in a liquidlike Sn(9) matrix. [Sn(9)Ni(2)(CO)](3)(-) (3) was prepared from Ni(CO)(2)(PPh(3))(2), K(4)Sn(9), and 2,2,2-cryptand in en/toluene solvent mixtures. The [K(2,2,2-cryptand)](+) salt is very air and moisture sensitive, is paramagnetic, and has been characterized by ESI-MS, EPR, and single-crystal X-ray diffraction. Complex 3 is a 10-vertex 21-electron polyhedron, a slightly distorted closo-Sn(9)Ni cluster with an additional interstitial Ni atom and overall C(4)(v)() point symmetry. The EPR spectrum showed a five-line pattern due to 4.8-G hyperfine interactions involving all nine tin atoms. The ESI-MS analysis showed weak signals for the potassium complex [K(2)Sn(9)Ni(2)(CO)](1-) and the ligand-free binary ions [K(2)Sn(9)Ni(2)](1)(-), [KSn(9)Ni(2)](1)(-), and [HSn(9)Ni(2)](1)(-).     

Synthesis and reactivity of bridging and terminal hydrosulfido palladium and platinum complexes. Crystal structures of [NBu4]2[(Pt(c6F5)2(mu-SH)]2], [Pt(C6F5)2(PPh3)[S(H)AgPPh3]], and [Pt(C6F5)2(PPh3)[S(AuPPh3)2]

The reactions of the hydroxo complexes [M(2)R(4)(mu-OH)(2)](2)(-) (M = Pd, R = C(6)F(5), C(6)Cl(5); M = Pt, R = C(6)F(5)), [[PdR(PPh(3))(mu-OH)](2)] (R = C(6)F(5), C(6)Cl(5)), and [[Pt(C(6)F(5))(2)](2)(mu-OH)(mu-pz)](2-) (pz = pyrazolate) with H(2)S yield the corresponding hydrosulfido complexes [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-), [[PdR(PPh(3))(mu-SH)](2)], and [[Pt(C(6)F(5))(2)](2)(mu-SH)(mu-pz)](2-), respectively. The monomeric hydrosulfido complexes [M(C(6)F(5))(2)(SH)(PPh(3))](-) (M = Pd, Pt) have been prepared by reactions of the corresponding binuclear hydrosulfido complexes [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-) with PPh(3) in the molar ratio 1:2, and they can be used as metalloligands toward Ag(PPh(3))(+) to form the heterodinuclear complex [(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and toward Au(PPh(3))(+) yielding the heterotrinuclear complexes [M(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]]. The crystal structures of [NBu(4)](2)[[Pt(C(6)F(5))(2)(mu-SH)](2)], [Pt(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and [Pt(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]] have been established by X-ray diffraction and show no short metal-metal interactions between the metallic centers.     

Synthesis and Characterization of a Series of Triethylphosphine-Ligated Pt-Au Cluster Compounds. X-ray Crystal and Molecular Structure of [Pt(AuPEt(3))(9)](NO(3))(3)

The first triethylphosphine-stabilized Pt-Au cluster compounds, [Pt(AuPEt(3))(10)](2+) (2) and [Pt(AuPEt(3))(9)](3+) (3), were prepared by the direct reaction of Pt(PEt(3))(3) with AuPEt(3)NO(3) under a dihydrogen atmosphere. Cluster 2 is the highest-nuclearity homoleptic Pt(AuPR(3))(n)() cluster yet prepared. The reactivity and structures of these clusters are in agreement with the well-established electron-counting arguments. The 18-electron cluster 2 was converted into the 16-electron cluster 3 by oxidation with 2 equiv of ferricinium ion [Fe(eta(5)-C(5)H(5))(2)](+). Cluster 3 was converted into 2 by reduction with H(2) in the presence of [AuPEt(3)](+). Cluster 3 was also observed to cleanly add the 2-electron donors CO and PEt(3) to form the 18-electron clusters [(CO)Pt(AuPEt(3))(9)](3+) (4) and [(PEt(3))Pt(AuPEt(3))(9)](3+) (5), respectively. Single-crystal X-ray diffraction results show that 3 has a flattened, toroidal structure in which the PtAu(9) framework has a Pt-centered, tricapped trigonal prismatic geometry. Crystal data for [Pt(AuPEt(3))(9)](NO(3))(3) is as follows: hexagonal P6(3)/m, a = 15.134(5) ?, c = 23.48(1) ?, V = 4657 ?(3), Z = 2, residuals R = 0.056, and R(w)() = 0.053 for 1489 observed reflections and 81 variables, Mo Kalpha radiation. Compound 3 was found to reversibly add H(2) in solution to form the dihydride cluster [(H)(2)Pt(AuPEt(3))(9)](3+) (6). The equilibrium constant for this addition reaction is 1.1 x 10(3) M(-)(1) (CD(2)Cl(2) solution, 25 degrees C), slightly smaller than that for [Pt(AuPPh(3))(8)](2+). The rate of the addition is also slower than that with [Pt(AuPPh(3))(8)](2+). Cluster 3 is an excellent homogeneous catalyst for H(2)-D(2) equilibration giving a turnover rate for HD production of 0.13 s(-)(1) (nitrobenzene solvent, 30 degrees C, 1 atm). The PEt(3)-containing clusters give similar rates and follow the same general trends previously observed with PPh(3)-ligated clusters. The chemistry of these new clusters is explained by consideration of the steric and electronic properties of the PEt(3) ligand. These new compounds will be useful as models for hydrogen activation by Pt-Au clusters and as precursors for supported Pt-Au catalysts.     

The inducing NO-vasodilation by chemical reduction of coordinated nitrite ion in cis-[Ru(NO(2))L(bpy)(2)](+) complex

The synthesis of [Ru(NO(2))L(bpy)(2)](+) (bpy = 2,2'-bipyridine and L = pyridine (py) and pyrazine (pz)) can be accomplished by addition of [Ru(NO)L(bpy)(2)](PF(6))(3) to aqueous solutions of physiological pH. The electrochemical processes of [Ru(NO(2))L(bpy)(2)](+) in aqueous solution were studied by cyclic voltammetry and differential pulse voltammetry. The anodic scan shows a peak around 1.00 V vs. Ag/AgCl attributed to the oxidation process centered on the metal ion. However, in the cathodic scan a second peak around -0.60 V vs. Ag/AgCl was observed and attributed to the reduction process centered on the nitrite ligand. The controlled reduction potential electrolysis at -0.80 V vs. Ag/AgCl shows NO release characteristics as judged by NO measurement with a NO-sensor. This assumption was confirmed by ESI/MS(+) and spectroelectrochemical experiment where cis-[Ru(bpy)(2)L(H(2)O)](2+) was obtained as a product of the reduction of cis-[Ru(II)(NO(2))L(bpy)(2)](+). The vasorelaxation observed in denuded aortic rings pre-contracted with 0.1 mumol L(-1) phenylephrine responded with relaxation in the presence of cis-[Ru(II)(NO(2))L(bpy)(2)](+). The potential of rat aorta cells to metabolize cis-[Ru(II)(NO(2))L(bpy)(2)](+) was also followed by confocal analysis. The obtained results suggest that NO release happens by reduction of cis-[Ru(II)(NO(2))L(bpy)(2)](+) inside the cell. The maximum vasorelaxation was achieved with 1 x 10(-5) mol L(-1) of cis-[Ru(II)(NO(2))L(bpy)(2)](+) complex.     

Multinuclear platinum(II)-amine complexes containing bis(aminopropyl)dicarba-closo-dodecaborane(12) ligands

Treatment of the bridging bidentate 1,Z-bis(aminopropyl)-1,Z-dicarba-closo-dodecaborane(12)(1,Z-bis(aminopropyl)-1,Z-carborane) ligands of the type 1,Z-[H(2)N(CH(2))(3)](2)-1,Z-C(2)B(10)H(10)(L(1), Z= 7, 5) or (L(2), Z= 12, 6) with two equivalents of trans-[PtClI(2)(NH(3))](-), followed by halogen ligand metathesis with AgOTf and HCl((aq)) afforded the novel diplatinum(II)-amine species cis-[[PtCl(2)(NH(3))](2)L(n)](7(n= 1) or 8(n= 2), respectively). Similarly, the reaction of L(1) or L(2) with the labile trans-[PtCl(dmf)(NH(3))(2)](+) afforded trans-[[PtCl(NH(3))(2)](2)L(n)](OTf)(2)(9(n= 1) or 10(n= 2), respectively) in good yield and purity. However, isolation of the analogous 1,2-carborane complexes was not possible owing to decomposition reactions that led to extensive degradation of the carborane cage and reduction of the metal centre. The mixed dinuclear complex [cis-[PtCl(2)(NH(3))]-L(1)-trans-[PtCl(NH(3))(2)]]OTf (19) was prepared by treatment of the Boc-protected amine ligand 1-[(Boc)(2)N(CH(2))(3)]-7-[H(2)N(CH(2))(3)]-1,7-C(2)B(10)H(10)(L(3), 15) with trans-[PtCl(dmf)(NH(3))(2)](+) to yield trans-[PtCl(NH(3))(2)L(3)]OTf (16), followed by acid deprotection of the pendant amine group, complexation with trans-[PtClI(2)(NH(3))](-), and halogen ligand metathesis using AgOTf and HCl((aq)). A novel trinuclear species containing 5 was prepared by the addition of two equivalents of 15 to the labile precursor cis-[Pt(dmf)(2)(NH(3))(2)](2+) followed by acid deprotection of the pendant amine groups. Further complexation with two equivalents of trans-[PtClI(2)(NH(3))](-) followed by halogen ligand metathesis using AgOTf and HCl((aq)) afforded the triplatinum(II)-amine species [cis-[Pt(NH(3))(2)(L(1))(2)]-cis-[PtCl(2)(NH(3))](2)](OTf)(2)(23). Complexes 7-10, 19 and 23 represent the first examples of multinuclear platinum(ii)-amine derivatives containing carborane cages. Preliminary in vitro cytotoxicity studies for selected complexes are also reported.     

G-G base-pairing in nucleobase adducts of the anticancer drug cis-[PtCl2(NH3)(2-picoline)] and its trans isomer

cis-[PtCl2(NH3)(2-picoline)] (AMD473) is a sterically-hindered anticancer complex with a profile of chemical and biological activity that differs significantly from that of cisplatin. Adducts of AMD473 with neutral 9-ethylguanine (9-EtGH) and anionic (N1-deprotonated) 9-ethylguanine (9-EtG) as perchlorate and nitrate salts, and also a nitrate salt of the trans isomer (AMD443), were prepared and their structures determined by X-ray crystallography: cis-[Pt(NH3)(2-pic)(9-EtGH)2](ClO4)2 (1).2H(2)OMe(2)CO, cis-[Pt(NH3)(2-pic)(9-EtGH)2](NO3)2 (2).2H2O, cis-[Pt(NH3)(2-pic)(9-EtGH)(9-EtG)]NO3 (3),3.5 H2O, trans-[Pt(NH3)(2-pic)(9-EtGH)(9-EtG)]NO3 (4).8H2O. In all cases, platinum coordination is through N7 of neutral (1, 2) and anionic (3, 4) guanine. In each complex, the guanine bases are arranged in the head-to-tail conformation. In complex 1, there is an infinite array of six-molecule cycles, based on both hydrogen bonding and pi-pi stacking of the 2-picoline and guanine rings. Platinum(II) coordinated at N7 acidifies the N1 proton of neutral 9-ethylguanine (pKa = 9.57) to give pKa1 = 8.40 and pKa2 = 8.75 for complex 2, and pKa1 = 7.77 and pKa2 = 9.00 for complex 4. In complexes 3 and 4, three intermolecular hydrogen bonds are formed between neutral and deprotonated guanine ligands involving O6, N1 and N2 sites. Unusually, both of the platinated guanine bases of complexes 3 and 4 participate in this triple G triple bond G hydrogen bonding. This is the first report of X-ray crystal structures of nucleobase adducts of the promising anticancer drug AMD473.     

Reactions of acetonitrile coordinated to a nitrosylruthenium complex with H2O or CH(3)OH under mild conditions: structural characterization of imido-type complexes

The reaction of cis-[Ru(NO)(CH(3)CN)(bpy)(2)](3+) (bpy = 2,2'-bipyridine) in H(2)O at room temperature proceeded to afford two new nitrosylruthenium complexes. These complexes have been identified as nitrosylruthenium complexes containing the N-bound methylcarboxyimidato ligand, cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](2+), and methylcarboxyimido acid ligand, cis-[Ru(NO)(NH=C(OH)CH(3))(bpy)(2)](3+), formed by an electrophilic reaction at the nitrile carbon of the acetonitrile coordinated to the ruthenium ion. The X-ray structure analysis on a single crystal obtained from CH(3)CN-H(2)O solution of cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](PF(6))(3) has been performed: C(22)H(20.5)N(6)O(2)P(2.5)F(15)Ru, orthorhombic, Pccn, a = 15.966(1) A, b = 31.839(1) A, c = 11.707(1) A, V = 5950.8(4) A(3), and Z = 8. The structural results revealed that the single crystal consisted of 1:1 mixture of cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](2+) and cis-[Ru(NO)(NH=C(OH)CH(3))(bpy)(2)](3+) and the structural formula of this single crystal was thus [Ru(NO)(NH=C(OH(0.5))CH(3))(bpy)(2)](PF(6))(2.5). The reaction of cis-[Ru(NO)(CH(3)CN)(bpy)(2)](3+) in dry CH(3)OH-CH(3)CN at room temperature afforded a nitrosylruthenium complex containing the methyl methylcarboxyimidate ligand, cis-[Ru(NO)(NH=C(OCH(3))CH(3))(bpy)(2)](3+). The structure has been determined by X-ray structure analysis: C(25)H(29)N(8)O(18)Cl(3)Ru, monoclinic, P2(1)/c, a = 13.129(1) A, b = 17.053(1) A, c = 15.711(1) A, beta = 90.876(5) degrees, V = 3517.3(4) A(3), and Z = 4.