Coordination Sphere Of Platinum Research Articles

PtOx Cly (OH)z (H2 O)n Complexes under Oxidative and Reductive Conditions: Impact of the Level of Theory on Thermodynamic Stabilities.

Platinum-based catalysts with Cl- , OH- , O2- and H2 O ligands, are involved in many industrial processes. Their final chemical properties are impacted by calcination and reduction applied during the preparation and activation steps. We investigate their stability under these reactive conditions with density functional theory (DFT). We benchmark various functionals (PBE-dDsC, optPBE, B3LYP, HSE06, PBE0, TPSS, RTPSS and SCAN) against ACFDT-RPA. PBE-dDsC is well adapted, although hybrid functionals are more accurate for redox reactions. Thermodynamic phase diagrams are determined by computing the chemical potential of the species as a function of temperature and partial pressures of H2 O, HCl, O2 and H2 . The stability and nature of the Pt species are highly sensitive to the activation conditions. Under O2 , high temperatures favour PtO2 while under H2 , platinum is easily reduced to Pt(0). Chlorine modifies the coordination sphere of platinum during calcination by stabilizing PtCl4 and shifts the reduction of platinum to higher temperatures under H2 .

Idiosyncratic Ag7Pt2O7: An Electron Imprecise yet Diamagnetic Small Band Gap Oxide

AbstractThe seminal qualitative concepts of chemical bonding, as presented by Walter Kossel and Gilbert Newton Lewis back in 1916, have lasting general validity. These basic rules of chemical valence still serve as a touchstone for validating the plausibility of composition and constitution of a given chemical compound. We report on Ag7Pt2O7, with a composition that violates the basic rules of chemical valence and an exotic crystal structure. The first coordination sphere of platinum is characteristic of tetravalent platinum. Thus, the electron count corresponds to Ag7Pt2O7*e−, where excess electrons are associated with the silver substructure. Such conditions given, it is commonly assumed that the excess electrons are either itinerant or localized in Ag−Ag bonds. However, the material does not show metallic conductivity, nor does the structure feature Ag‐Ag pairs. Instead, the excess electrons organize themselves in 2e−4c bonds within the silver substructure. This subvalent silver oxide reveals a new general facet pertinent to silver chemistry.

Idiosyncratic Ag7Pt2O7: An Electron Imprecise yet Diamagnetic Small Band Gap Oxide.

The seminal qualitative concepts of chemical bonding, as presented by Walter Kossel and Gilbert Newton Lewis back in 1916, have lasting general validity. These basic rules of chemical valence still serve as a touchstone for validating the plausibility of composition and constitution of a given chemical compound. We report on Ag7Pt2O7, with a composition that violates the basic rules of chemical valence and an exotic crystal structure. The first coordination sphere of platinum is characteristic of tetravalent platinum. Thus, the electron count corresponds to Ag7Pt2O7*e−, where excess electrons are associated with the silver substructure. Such conditions given, it is commonly assumed that the excess electrons are either itinerant or localized in Ag−Ag bonds. However, the material does not show metallic conductivity, nor does the structure feature Ag‐Ag pairs. Instead, the excess electrons organize themselves in 2e−4c bonds within the silver substructure. This subvalent silver oxide reveals a new general facet pertinent to silver chemistry.

Interaction of Platinum Compounds PtenCl2 and [Pten Cl SO(CH3)2] NO3 with DNA Molecule in Solution

It was demonstrated that the replacement of chlorine ion on dimethyl sulfoxide (DMSO) in the first coordination sphere of platinum changes the result of compound interaction with DNA. DMSO molecule blocks one of the active centers of the platinum compound participating in the formation of coordination bonds with macromolecule, and DNA does not substitute DMSO molecule in the platinum first coordination sphere.

Dehydrogenative B−H/C(sp3)−H Benzylic Borylation within the Coordination Sphere of Platinum(II)

AbstractThe first examples of stoichiometric dehydrogenative B−H/C(sp3)−H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2‐P,N)Pt(η3‐benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ‐bond metathesis steps, whereby a PtII−H intermediate engages in C(sp3)−H bond activation‐induced dehydrogenation.

Dehydrogenative B-H/C(sp3 )-H Benzylic Borylation within the Coordination Sphere of Platinum(II).

The first examples of stoichiometric dehydrogenative B-H/C(sp3 )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2 -P,N)Pt(η3 -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a PtII -H intermediate engages in C(sp3 )-H bond activation-induced dehydrogenation.

Stepwise isolation of low-valent, low-coordinate Sn and Pb mono- and dications in the coordination sphere of platinum.

Synthetic access to low-coordinate Pb mono- and dications is in general impeded due to their poor solubility and highly electrophilic nature. However, the electrophilicity of these cations can be tamed by attaching them to electron-rich transition metals. Following this principle we have isolated low-valent Pb mono- ([(Cy3P)2Pt-PbCl]2[AlCl4]2, 8a) and dications ([(Cy3P)2Pt(Pb)][AlCl4]2, 11) in the coordination sphere of platinum. The same approach then has been implemented for the isolation of analogous low-valent Sn mono- (7a) and dications (10). An energy decomposition analysis (EDA-NOCV) was performed to investigate the nature of Pt-Pb and Pb-Cl bonding in [(Cy3P)2Pt(PbCl2)] (2), 8a and 11. The results show that the Pt-Pb bonds in 8a and 11 are electron-sharing in nature, whereas that of the precursor 2 is a dative bond. The breakdown of attractive interactions in 2, 8a and 11 reveals that the ionic interactions in the analyzed Pt-Pb and Pb-Cl bonds are always stronger than the covalent interactions, except for the Pb-Cl bond in 8a. The calculated D3 dispersion energies show that dispersion interactions play a key role in the thermodynamic stability of 2, 8a and 11.

Cisplatin Binding to Proteins: Molecular Structure of the Ribonuclease A Adduct

The crystal structure of the main adduct formed in the reaction between cisplatin and bovine pancreatic ribonuclease is reported here. Notably, in both of the protein molecules present in the asymmetric unit, platinum(II) binding takes place exclusively at the level of Met29. In one of the two molecules, the Gln28 side chain completes the platinum coordination sphere, anchoring the cisplatin fragment to the protein in a bidentate fashion. These results contain interesting implications for understanding the biological chemistry of this important drug.

H/D exchange at sp3 carbons in the coordination sphere of platinum(ii)

The [PtCl(η(1)-CH2CH2OR)(Me2phen)], Me2phen = 2,9-dimethyl-1,10-phenanthroline, complex is indefinitely stable in the solid state; however, when dissolved in protic deuterated solvents at basic pH, it undergoes H-D exchange at the Me2phen Me's. An analogous H-D exchange process takes place in the related [PtCl2(Me2phen)] complex which is sterically strained and very easily can detach one nitrogen of Me2phen yielding a T-shaped species. In contrast, the H-D exchange is considerably slower in the [Pt(OR)2(Me2phen)] complex characterized by smaller size and lower trans-labilizing effect of the oxygen donor ligands. It is suggested that the formation of a T-shaped intermediate could foster the C-H activation via oxidative addition to the metal centre. In accord with this hypothesis, the H/D exchange was found to be considerably slower in analogous complexes with 6,6'-dimethyl-2,2'-bipyridyl (Me2bpy), where the greater flexibility of Me2bpy, as compared to Me2phen, reduces the strain in the four coordinate substrate and hence the propensity to dissociate one end of the bidentate ligand.

Calculations of microconstants and equilibrium formation constants for platinum(II) and palladium(II) halide complexes in solution

Distribution diagrams and formation functions for halide complexes [M(H2O)4 − nCln]2 − n (M = Pt(II) or Pd(II)) and [PdCl4 − nBrn]2− (n = 0–4) in solution are analyzed in terms of the matrix model. Equilibrium constants for binding the first ligand \(\left( {\bar K} \right)\) and corrections for the mutual influence between ligands (ω) in the course of complex formation in solution are calculated. In examples analyzed, the substitution of chloride ion for water in the coordination sphere of platinum(II) and palladium(II) is an anti-cooperative process. The substitution of bromide ion for chloride ion in the coordination sphere of [PdCl4]2− is weakly cooperative. Quantum-chemical calculations show that platinum(II) and palladium(II) cis-bisaquadichloro complexes in the gas phase are thermodynamically less stable than trans-isomers. The cis-trans isomerization constants in the gas phase calculated by the DFT method and those found for solutions using the matrix model have the same order of magnitude.

Synthesis and DNA Interaction of Platinum Complex/Peptide Chimera as Potential Drug Candidates

AbstractModification and optimization of the anticancer drug cisplatin is of interest with respect to selective cell targeting and DNA binding efficiency. Attractive approaches contain both, modification of the platinum coordination sphere and design of hybrid molecules of the cisplatin binding moiety including peptide motifs. Peptides with cell penetrating, directing or recognizing properties can be implemented. In this study, positively charged peptide sequences were investigated with the potential of inducing DNA structural distortions caused by charge neutralization of the dsDNA helix. Association of charged peptides is likely to increase the flexibility of the DNA thereby facilitating platinum binding. The synthesis and DNA interaction of five new cisplatin–peptide hybrids with enhanced solubility and potential antitumor activity is presented. Propylenediamine or bisimidazole units were used as bisdentate platinum ligands and were coupled to a peptide sequence in the final elongation step of the solid‐phase peptide synthesis (SPPS). Agarose and polyacrylamide gel electrophoresis, fluorescence intercalation, and thermal UV melting studies, all support the presence of covalently formed platinum DNA adducts in a reaction mediated by the positively charged peptide.

ChemInform Abstract: Oxoboryl Complexes: Boron—Oxygen Triple Bonds Stabilized in the Coordination Sphere of Platinum.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New platinum(II) complexes containing both an O, O′-chelated acetylacetonate ligand and a sulfur ligand in the platinum coordination sphere induce apoptosis in HeLa cervical carcinoma cells

We report the cytotoxic effects obtained in HeLa cells of three newly synthesized platinum complexes containing both an O, O′-chelated acetylacetonate ligand and a sulfur ligand in the platinum coordination sphere, which show, by 1H NMR, negligible reactivity with purine bases. These compounds induce cell death with [Pt( O, O′-acac)(γ-acac)(DMS)] being the most effective (IC 50 = 0.98 ± 0.056 and 1.82 ± 0.023 μM for [Pt( O, O′-acac)(γ-acac)(DMS)] and cisplatin, respectively). About 50% of cells died after 5 h treatment with 100 μM [Pt( O, O′-acac)(γ-acac)(DMS)] whilst a 16 h incubation was required to get the same results using 100 μM cisplatin. Cellular accumulation measurements, after treatment with equimolar drug concentrations, indicated the major lipophilicity and cellular uptake of the new compounds. While the cytotoxicity of cisplatin was due to both intracellular accumulation and DNA binding, that of [Pt( O, O′-acac)(γ-acac)(DMS)] was associated with intracellular Pt accumulation only, since it has low reactivity to DNA in intact cells and in vitro. The reaction of the new complexes with guanosine and 5′-GMP was negligible, whereas the l-methionine instantly reacted with the initial Pt complexes. Both cisplatin and [Pt( O, O′-acac)(γ-acac)(DMS)] induced apoptosis in HeLa cells. [Pt( O, O′-acac)(γ-acac)(DMS)] provoked the early signs of apoptosis induction (cleavage of PARP and activation of caspases-9, -3 and -7) only 1 h after addition of the drug. However, in cisplatin-treated cells, cleavage of PARP was seen after 9 h with activation of caspases also proceeding more slowly. In conclusion, these results indicate that the newly synthesized platinum(II) complexes have high and rapid cytotoxic activity in vitro, and suggest that DNA may not be their primary target.

Crystal structure and infrared analysis of a new trinuclear platinum(II) complex with L-cysteine

A new trinuclear platinum(II) complex with cysteine of composition [Pt(C3H6NO2S)Cl]3·(C2H6SO)3 was obtained and structurally characterized by X-ray diffraction and infrared analysis. The compound crystallizes in the trigonal system, space group R3, and is described in a hexagonal cell with a=17.739(1), c=9.531(1) and Z=3. Cysteine is coordinated to Pt(II) through the nitrogen and sulphur atoms. Each cysteine sulphur bridges between two metal atoms. A square planar coordination sphere of platinum is completed by a chlorine atom. The complex is soluble in dimethyl sulfoxide.

Peculiarities of interactions between the DNA molecule and different isomers and modifications of binuclear coordination compounds of platinum(II)

A comparison has been made of conformational changes in the DNA molecule during its interaction in solution with different binuclear coordination compounds of platinum [Pt(NH3)2Cl-R-Pt(NH3)2Cl]Cl2 in cis and trans conformations, which contain cytosine, pyrazine, and carboxypyrazine as the common ligand (R). The influence of concentration of the components, and in particular, of ionic strength of the solution on the complexation process was studied. The influence of the nature of the common ligand, and of cis and trans conformations of coordination compounds on the character of their interaction with DNA was considered. A comparison was made between the structures of DNA complexes with mono-and binuclear compounds with the same set of ligands in the platinum coordination sphere.

Platinum(II) Complexes with Antitumoral/Antiviral Aromatic Heterocycles: Effect of Glutathione upon in Vitro Cell Growth Inhibition

The compounds [Pt(Me(2)phen)(acy)(2)](NO(3))(2) (1), [Pt(Me(2)phen)(pen)(2)](NO(3))(2), [Pt(phen)(acy)(2)](NO(3))(2) (2), and [Pt(phen)(pen)(2)](NO(3))(2), containing the bidentate 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (Me(2)phen, neocuproine) and the antiviral agents acyclovir (acy) or penciclovir (pen), show different in vitro toxicity, the Me(2)phen complexes being appreciably more toxic than the phen complexes. To explain the different behavior, we investigated the reaction of complexes 1 and 2 with glutathione (gamma-glutamylcysteinylglycine, GSH), a peptide believed to play an important role in driving the cellular effects of platinum drugs. The reaction led to different products, the phen complexes forming a stable binuclear mu-thiol-bridged species still containing the phenanthroline and the Me(2)phen complexes releasing the neocuproine ligand and forming an insoluble material. In vitro tests confirmed that the greater cell toxicity of complex 1 is due to the displacement of the neocuproine ligand by GSH. The results highlight the great dependence of the glutathione reactivity upon relatively small changes in the platinum coordination sphere.

First Examples of β‐Diketonate Platinum(II) Complexes with Sulfoxide Ligands

AbstractNew platinum(II) complexes have been prepared as models for explaining the coordination of multiple β‐diketonate li‐gands to give [Pt(O,O′‐acac)(γ‐acac)L] species. The new com‐pounds containing both an O,O′‐chelated acetylacetonate ligand and a sulfoxide in the platinum coordination sphere, [PtCl(O,O′‐acac)(DMSO)] (1) and [Pt(O,O′‐acac)(γ‐acac)(DMSO)] (2), have been synthesised and characterised by 1H, 13C, 195Pt 1‐D and 2‐D NMR heteronuclear correlation spectroscopy and, in the case of 2, by X‐ray crystal structure analysis also. Moreover, a new synthetic pathway to obtain the previously reported complex K[Pt(O,O′‐acac)(γ‐acac)2] (3) has been developed. The data presented herein are consistent with a reaction mechanism which explains the subsequent steps of the coordination of multiple β‐diketonate li‐gands to platinum(II) complexes, where the first species formed contains one O,O′‐chelated acac group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Vinylic Deprotonation in the Coordination Sphere of Platinum(II): Regioselective Formation of Alkenyl Complexes

AbstractReaction of [PtCl(η2‐CH2=CHAr)(tmeda)](ClO4) (1) [Ar = C6H5 (1a), 4‐CH3OC6H4 (1b), 3‐NO2C6H4 (1c); tmeda = N,N,N′,N′‐tetramethylethylenediamine) with triethylamine, or even with inorganic carbonate, leads to the abstraction of a vinylic proton and formation of the (alkenyl)platinum species [PtCl{(E)‐CH=CHAr}(tmeda)] (2) in high yield. The initially formed (E) isomer, in solution of chlorinated solvents, partly isomerizes into the (Z) form [equilibrium ratio (E)/(Z) ≈︁ 4:1]; the isomerization reaction is rather slow and is catalyzed by visible light. The nature of the phenyl substituent (electron donor OMe or electron‐withdrawing NO2 group) does not appear to affect the rate of deprotonation. The nature and stereochemistry of the formed (alkenyl)platinum species has been elucidated through 1D and 2D 1H and 13C NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Trifunctional dinuclear platinum complexes as DNA-protein cross-linking agents.

The trifunctional dinuclear platinum compounds 1,2/c,c [[cis-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) and 1,2/t,c [[trans-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) contain a monofunctional platinum coordination sphere linked to a cis-[PtCl(2)(amine)(2)] moiety. The compounds have been examined for their DNA binding and ability to induce covalent ternary DNA-protein cross-links. Comparison was made with representative bifunctional dinuclear platinum compounds [[PtCl(NH(3))(2)](2)mu-H(2)N(CH(2))(n)NH(2)](2+). DNA modified by the trifunctional compounds is able to bind and cross-link BamHI, a sequence-specific DNA-binding protein that recognizes the palindromic sequence GGATCC and also very efficiently binds and cross-links SP1, a sequence-specific Zn finger protein that induces a bend in the DNA upon binding. Two representative nonsequence-specific DNA-binding proteins, the Klenow fragment from DNA polymerase I and Klenow exonuclease minus (which has been mutated to remove the 3'-5' proofreading domain), both bind modified DNA and effectively cross-link to the DNA. Data from circular dichroism, inhibition of ethidium bromide fluorescence, interstrand cross-linking and unwinding assays are all consistent with (Pt,Pt) interstrand cross-links as the dominant lesion of trifunctional compounds and the most likely structure to form the ternary DNA-protein cross-links. In vitro transcription of RNA is inhibited by the platinum compounds and indicate G residues as primary binding sites. Binding to calf thymus DNA as assessed by differential pulse polarography is rapid and essentially quantitative. An increase in melting temperature of CT DNA adducted by the platinum compounds is observed at low salt concentrations but at high salt, modification results in a decrease of t(m). In summary, the trifunctional agents may find use as protein-targeting drugs and as probes for conformational effects on DNA-protein interactions.

Structure–activity relationships in platinum–acridinylthiourea conjugates: effect of the thiourea nonleaving group on drug stability, nucleobase affinity, and in vitro cytotoxicity

The synthesis, cytotoxicity, and nucleoside binding of some platinum-acridinylthiourea conjugates derived from the prototypical compound [PtCl(en)(ACRAMTU)](NO3)2 ("PT-ACRAMTU"; en=ethane-1,2-diamine, ACRAMTU=1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, protonated form) are reported. To establish structure-activity relationships within this class of compounds, systematic changes were made to the thiourea nonleaving group, which links the intercalator to platinum. Three new derivatives of ACRAMTU, one di-, one tri-, and one tetraalkylated, were generated, where the degree of alkylation indicates the number of alkyl groups attached to the SCN2 framework. Subsequent reaction of the tri- and tetraalkylated derivatives with activated [PtCl2(en)] yielded the corresponding platinum conjugates. The dialkylated thiourea gave an unstable complex, which was not included in the studies. The crystal structure of PT-ACRAMTU x MeOH has been determined. In the solid state, one axial position of the square-planar platinum coordination sphere is partially shielded by the bulky thiourea group, providing a strong rationale for the kinetic inertness of the compound. The cytotoxicity of the prototype, the two new conjugates, and cisplatin was assessed in ovarian (A2780, A2780/CP), lung (NCI-H460), and colon (RKO) cancer cell lines using clonogenic survival assays. The derivatives containing trialkylated thiourea groups showed activity similar or superior to cisplatin, with IC50 values in the low micromolar concentration range. The complex modified with the tetraalkylated (bulkiest) thiourea was significantly less active, possibly due to the greatly decreased rate of binding to nucleobase nitrogen (1H NMR spectroscopy), but was most efficient at overcoming cross resistance to cisplatin in A2780/CP. Possible consequences of the reported structural modifications for the mechanism of action of these agents are discussed.