Sulfur-Assisted Phenyl Migration from Phosphorus to Platinum in PtW2 and PtMo2 Clusters Containing Thioether-Functionalized Short-Bite Ligands of the Bis(diphenylphosphanyl)amine-Type.

The reactivity of dichloroplatinum(II) complexes containing thioether-functionalized bis(diphenylphosphanyl)amines of formula (Ph2P)2N(CH2)2SR (R = (CH2)5CH3, CH2Ph) toward group 6 carbonylmetalates Na[M(CO)3Cp] (M = Mo or W, Cp = cyclopentadienyl) was explored. Reactions with two or more equivalents of Na[M(CO)3Cp] (M = Mo or W) afforded the trinuclear complexes of general formula [PtPh{M(CO)3Cp}{µ-P(Ph)N(CH2CH2SR)(PPh2)-κ(3)P,P,S}M(CO)2Cp] (3 M = Mo, R = (CH2)5CH3; 4 M = Mo, R = CH2Ph; 9 M = W, R = (CH2)5CH3; 10 M = W, R = CH2Ph), the structure of which consists of a six-membered platinacycle condensed with a four-membered M-P-N- P cycle, together with small amounts of isomeric PtM2 clusters [PtM2(CO)5Cp2{(Ph2P)2N(CH2CH2SR)-κ(2)P,P}] (5 M = Mo, R = (CH2)5CH3; 6 M = Mo, R = CH2Ph; 11 M = W, R = (CH2)5CH3; 12 M = W, R = CH2Ph) in which the ligand (Ph2P)2NR solely chelates the Pt atom or bridges an M-Pt bond as in [PtM2(CO)5Cp2{µ-(Ph2P)2N(CH2CH2SR)-κ(2)P,P}] (7 M = Mo, R = (CH2)5CH3; 8 M = Mo, R = CH2Ph; 13 M = W, R = (CH2)5CH3; 14 M = W, R = CH2Ph). The synthesis of the trinuclear complexes 3, 4, 9, and 10 entails an unexpected P-phenyl bond cleavage reaction and phenyl migration onto Pt. When only 1 equiv of Na[M(CO)3Cp] (M = Mo or W) was used, the heterodinuclear products of monosubstitution [PtCl{M(CO)3Cp}{Ph2PN(R)PPh2-P,P}] (15 M = Mo, R = (CH2)5CH3; 16 M = Mo, R = CH2Ph; 17 M = W, R = (CH2)5CH3; 18 M = W, R = CH2Ph) were obtained, which are the precursors to the bicyclic products 3, 4, 9, and 10, respectively. Density functional calculations were performed to study the thermodynamics of the formation of all the new complexes, to evaluate the relative stabilities of the isomeric chelated and bridged forms, and to trace the mechanism of formation of the phosphanido-bridged products 3, 4, 9, and 10. It was concluded that Pt(II) complexes containing a thioether-functionalized short-bite ligand, [PtCl2{Ph2PN(R)PPh2}], react with Na[M(CO)3Cp] to yield first heterodinuclear Pt-M and then heterotrinuclear PtM2 complexes resulting from the activation of a P-C bond in one of the PPh2 groups and phenyl migration to Pt. The critical role of an intramolecular thioether group was demonstrated.

Pt-Mo and Pt-W mixed-metal clusters with chelating or bridging diphosphine short-bite ligands (Ph2P)2NH and (Ph2P)2N(CH2)9CH3: a combined synthetic and theoretical study.

The reactivity of the complexes [PtCl(2){Ph(2)PN(R)PPh(2)-P,P}] (R = -H, 3; R = -(CH(2))(9)CH(3), 8) toward group 6 carbonylmetalates Na[MCp(CO)(3)] (M = W or Mo, Cp = cyclopentadienyl) was explored. When R = H, the triangular clusters [PtM(2)Cp(2)(CO)(5)(µ-dppa)] (M = W, 4; M = Mo, 5), in which the diphosphane ligand bridges a Pt-M bond, were obtained as the only products. When R = -(CH(2))(9)CH(3), isomeric mixtures of the triangular clusters [PtM(2)Cp(2)(CO)(5){Ph(2)PN(R)PPh(2)-P,P}], in which the diphosphane ligand chelates the Pt center (M = W, 11; M = Mo, 13) or bridges a Pt-M bond (M = W, 12; M = Mo, 14), were obtained. Irrespective of the M/Pt ratio used when R = -(CH(2))(9)CH(3), the reaction of [PtCl(2){Ph(2)PN(R)PPh(2)-P,P}] with Na[MCp(CO)(3)] in acetonitrile stopped at the monosubstitution stage with the formation of [PtCl{MCp(CO)(3)}{Ph(2)PN(R)PPh(2)-P,P}] (R = -(CH(2))(9)CH(3), M = W, 9; M = Mo, 10), which are the precursors to the trinuclear clusters formed in THF when excess carbonylmetalate was used. The dynamic behavior of the dppa derivatives 4 and 5 in solution as well as that of their carbonylation products 6 and 7, respectively, is discussed. Density functional calculations were performed to study the thermodynamics of formation of 4 and 5 and 11-14, to evaluate the relative stabilities of the chelated and bridged forms and to trace a possible pathway for the formation of the trinuclear clusters.

Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.

The pathological form of prion protein (PrP(Sc)), as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrP(Sc) extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90-231 (hPrP90₋231) increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrP(Sc). In the present study we demonstrate that hPrP90₋231, pre-incubated with 10 mM Ca⁺⁺ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP90₋231 bearing pathogenic mutations (D202N and E200K). We also report that Ca⁺⁺ binding to hPrP90₋231 induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP90₋231 cytotoxicity. Finally, by in silico structural analysis, we propose that Ca⁺⁺ binding to hPrP90₋231 modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity.

Hydrido phosphanido bridged polynuclear complexes obtained by protonation of a phosphinito bridged Pt(I) complex with HBF4 and HF.

The protonation of the phosphinito-bridged Pt(I) complex [(PHCy(2))Pt(µ-PCy(2)){κ(2)P,O-µ-P(O)Cy(2)}Pt(PHCy(2))](Pt-Pt) (1) by aqueous HBF(4) or hydrofluoric acid leads selectively to the hydrido-bridged solvento species syn-[(PHCy(2))(H(2)O)Pt(µ-PCy(2))(µ-H)Pt(PHCy(2)){κP-P(OH)Cy(2)}](Y)(2)(Pt-Pt) ([2-H(2)O]Y(2)) {Y = BF(4), F(HF)(n)} when an excess of acid was used. On standing in halogenated solvents, complex [2-H(2)O](BF(4))(2) undergoes a slow but complete isomerization to [(PHCy(2))(2)Pt(µ-PCy(2))(µ-H)Pt{κP-P(OH)Cy(2)}(H(2)O)](BF(4))(2)(Pt-Pt) ([4-H(2)O][BF(4)](2)) having the P(OH)Cy(2) ligand trans to the hydride. The water molecule coordinated to platinum in [2-H(2)O][BF(4)](2) is readily replaced by halides, nitriles, and triphenylphosphane, and the acetonitrile complex [2-CH(3)CN][BF(4)](2) was characterized by XRD analysis. Solvento species other than aqua complexes, such as [2-acetone-d(6)](2+) or [2-CD(2)Cl(2)](2+) were obtained in solution by the reaction of excess etherate HBF(4) with 1 in the relevant solvent. The complex [2-H(2)O](Y)(2) [Y = F(HF)(n)] spontaneously isomerizes into the terminal hydrido complexes [(PHCy(2))Pt(µ-PCy(2)){κ(2)P,O-µ-P(O)Cy(2)}Pt(H)(PHCy(2))](Y)(Pt-Pt) ([6](Y)). In the presence of HF, complex [6](Y) transforms into the bis-phosphanido-bridged Pt(II) dinuclear complex [(PHCy(2))(H)Pt(µ-PCy(2))(2)Pt{κP-P(OH)Cy(2)}](Y)(Pt-Pt) ([7](Y)). When the reaction of 1 with HF was carried out with diluted hydrofluoric acid by allowing the HF to slowly diffuse into the dichloromethane solution, the main product was the linear 60e tetranuclear complex [(PHCy(2)){κP-P(O)Cy(2)}Pt(1)(µ-PCy(2))(µ-H)Pt(2)(µ-PCy(2))](2)(Pt(1)-Pt(2)) (8). Insoluble compound 8 is readily protonated by HBF(4) in dichloromethane, forming the more soluble species [(PHCy(2)){κP-P(OH)Cy(2)}Pt(1)(µ-PCy(2))(µ-H)Pt(2)(µ-PCy(2))](2)(BF(4))(2)(Pt(1)-Pt(2)) {[9][BF(4)](2)}. XRD analysis of [9][BF(4)](2)·2CH(2)Cl(2) shows that [9](2+) is comprised of four coplanar Pt atoms held together by four phosphanido and two hydrido bridges. Both XRD and NMR analyses indicate alternate intermetal distances with peripheral Pt-Pt bonds and a longer central Pt···Pt separation. DFT calculations allow tracing of the mechanistic pathways for the protonation of 1 by HBF(4) and HF and evaluation of their energetic aspects. Our results indicate that in both cases the protonation occurs through an initial proton transfer from the acid to the phosphinito oxygen, which then shuttles the incoming proton to the Pt-Pt bond. The different evolution of the reaction with HF, leading also to [6](Y) or 8, has been explained in terms of the peculiar behavior of the F(HF)(n)(-) anions and their strong basicity for n = 0 or 1.