Synthesis and X-ray structure of an octahedral platinum-silver cluster [(Ph3P)2N]2[Pt2Ag4Cl2(C2Ph)8] with disordered silver atoms

Variable-temperature X-ray structural study of the complex [(Ph₃P)₂N]₂[Pt₂Ag₄Cl₂(C₂Ph)₈] prepared by the reaction of cis-[PtCl₂(AsPh₃)₂] and [(Ph₃P)₂N][Ag(C₂Ph)₂] in 1:2 M ratio, revealed isolated (non-polymerised) [Pt₂Ag₄Cl₂(CCPh)₈]²⁻ anions with a pseudo-octahedral arrangement of metal atoms. The Pt atoms (in mutually trans vertices) are each σ-bonded to four alkynyl ligands in a square planar arrangement; these moieties are bridged by four Ag atoms; each silver atom being η²-bonded to two alkynyl groups. Chloride ligands are asymmetrically bridging two opposite Ag-Ag edges. Silver atoms show strong and unusual temperature-dependent disorder.     

Synthesis of the donor-acceptor ligand 2-(4-dimethylaminobenzylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (dbpcd) and X-ray diffraction structure of the platinum(II) compound PtCl2(dbpcd)·1.5CH2Cl2

Knoevenagel condensation of 4-(dimethylamino)benzaldehyde with 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) gives the donor-acceptor ligand 2-(4-dimethylaminobenzylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (dbpcd). The reaction of dbpcd with PtCl₂(cod) affords the platinum(II) complex PtCl₂(dbpcd) in high yield. The free dbpcd ligand and PtCl₂(dbpcd) have been isolated and fully characterized in solution by IR and NMR spectroscopies, and the solid-state structure of PtCl₂(dbpcd) determined by X-ray diffraction analysis. PtCl₂(dbpcd), as the 1.5CH₂Cl₂ solvate, crystallizes in the triclinic space group , a = 11.7412(7) Å, b = 12.0486(7) Å, c = 14.4781(9) Å, α = 82.866(1), β = 75.049(1), γ = 83.905(1), V = 1957.6(2) Å³, Z = 2, and D_calc = 1.678 mg/m³, R = 0.0291 and wR₂ = 0.0723 for 8315 reflections with I > 2σ(I). The molecular structure of PtCl₂(dbpcd)·1.5CH₂Cl₂ consists of a square-planar platinum architecture containing two chlorines and the ancillary dbpcd diphosphine ligand. The redox properties of the dbpcd ligand and PtCl₂(dbpcd) have been explored by cyclic voltammetry, and these data are discussed with respect to extended Hückel MO calculations.     

Palladium(II) and platinum(II) complexes of 2-hydroxy acetophenone N(4)-ethylthiosemicarbazone - crystal structure and description of bonding properties

Reaction of H₂PtCl₄ and K₂PdCl₄ with 2-hydroxyacetophenone N(4)-ethylthiosemicarbazone, H₂Ap4Et, afforded [Pt(Ap4Et)(H₂Ap4Et)] and [Pd(Ap4Et)(H₂Ap4Et)]. Their crystal and molecular structures are reported and represent the first 1:2 thiosemicarbazone complexes with ligands having both different formal charge and denticity. The dianion, Ap4Et²⁻, coordinates in a planar conformation to palladium(II) or platinum(II) via the phenolato O, imine N and thiolato S atoms, while the neutral molecule exhibits monodentate coordination by the thione S atom. Intra-, intermolecular hydrogen bonds and C-H?π contacts lead to aggregation and a supramolecular assembly. Electronic, IR, and NMR spectral data, as well as electrochemical measurements, are included. The pK_a values of the poorly water soluble H₂Ap4Et were obtained spectrophotometrically in aqueous solutions of constant ionic strength.     

Methimazole complexes of platinum(II): Synthesis, characterization and redox behavior

A variety of platinum(II) complexes of methimazole (2-mercapto-1-methylimidazole; HImS = neutral form and ImS = thiolate form), coordinated in both thione and thiolate forms, have been isolated by reacting methimazole with [PtCl(terpy)]Cl (terpy = 2,2′:6′,2″ terpyridine), [PtCl₂(bipy)] (bipy = bipyridine), [PtCl₂(o-phen)] (o-phen = o-phenanthroline), [PtCl₂(CH₃CN)₂] and [PtCl₂(COD)] (COD = 1,5-cyclooctadiene). These complexes were characterized by electronic absorption, IR and NMR (¹H, ¹³C, ¹⁹⁵Pt) spectroscopies. Molecular structure of [Pt(bipy)(HImS)₂]Cl₂·3H₂O (3a·3H₂O) has been established by single crystal X-ray crystallography. Platinum thiolate complex, [Pt(ImS)₂(HImS)₂] (5), could be obtained by treatment of [Pt(HImS)₄]Cl₂ with sodium methoxide in methanol. The solution of 5 in organic solvents yielded bi- and tri-nuclear platinum complexes. The effect of diimine ligands on oxidation of methimazole moiety in the complexes has been studied by electrochemical oxidation and pulse radiolytic oxidation employing specific one-electron oxidant, radical.     

Synthesis and X-ray structure of the dinuclear platinum(II) complex with saccharin {K[Pt(sac)3(H2O)] · H2O}2: Studies on its antiproliferative activity in aqueous solution

Synthesis and X-ray structure of a dinuclear platinum(II) complex with the ligand saccharin(sac) are described. The structure shows two approximately square-planar platinum centers. Each platinum atom is coordinated to one water molecule and three N-bonded saccharinate ligands. The two centers are linked through two potassium atoms. Each potassium atom interacts with six oxygen atoms from hydration and coordinated water molecules and from carbonyl and sulfonate groups of the ligands. It is suggested that, in aqueous solution, the dimeric structure of the complex is dissociated and the monomeric species K[Pt(sac)₃(H₂O)] is formed. The complex was dissolved in water and submitted to in vitro cytotoxic analyses using HeLa cells (human cervix cancer). It was shown that the monomeric complex elicited a potent cytotoxic activity when compared to the vehicle-treated cells. The IC₅₀ value for the monomeric complex is 6.8 μM, a little bit higher than that obtained for cisplatin.     

Synthesis of new platinum(II) complexes containing hybrid thioether-pyrazole ligands: Structural analysis by H and C{H} NMR spectroscopy and X-ray crystal structures

Treatment of the ligands 1,8-bis(3,5-dimethyl-1-pyrazolyl)-3,6-dithiaoctane (bddo), 1,9-bis(3,5-dimethyl-1-pyrazolyl)-3,7-dithianonane (bddn), and 1,6-bis(3,5-dimethyl-1-pyrazolyl)-2,5-dithiahexane (bddh) with several platinum starting materials as K₂PtCl₄, PtCl₂, [PtCl₂(CH₃CN)₂] and [PtCl₂(PhCN)₂] was developed under different conditions. The reactions did not yield pure products. The ratio of the NSSN, NS, SS, NN, and 2NS isomers has been calculated through NMR experiments. Treatment of the mixtures of complexes with NaBPh₄ affords [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn). These Pt(II) complexes have been characterised by elemental analyses, conductivity measurements, IR and ¹H and ¹³C NMR spectroscopy. The X-ray structures of the complexes [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn) have also been determined. In these complexes, the metal atom is tetracoordinated by the two azine nitrogen atoms of the pyrazole rings and two thioether sulfur atoms. When the [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn) complexes were heated under reflux in a solution of Et₄NBr in CH₂Cl₂/CH₃OH (1:1), a mixture of isomers was obtained.     

Synthesis of new platinum(II) compounds with several bidentate and tridentate nitrogen-donor ligands. Structural analyses by H, C{H} and Pt{H} NMR spectroscopy and X-ray crystal structure

The reaction of the N-alkylaminopyrazole (NN′) ligands 1-[2-(ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[2-(tert-butylamino)ethyl]-3,5-dimethylpyrazole (deat), or (NN′N) ligands bis[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae) and bis[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) with [PtCl₂(CH₃CN)₂] affords a series of square-planar Pt(II) complexes with formula [PtCl₂(NN′)] (NN′ = deae (1); deat (2)), [PtCl₂(bdmae)] (3), or [PtCl(ddae)]Cl (4). Treatment of complex 4 in the presence of AgBF₄ in CH₂Cl₂/methanol (3:1) gives [PtCl(ddae)](BF₄) (5). These Pt(II) complexes have been characterised by elemental analyses, conductivity measurements and IR, ¹H, ¹³C{¹H}, and ¹⁹⁵Pt{¹H} NMR spectroscopies. The ¹H NMR spectroscopic studies of the complexes prove the rigid conformation of the ligands when they are complexed. The solid-state structure of complex 1 was determined by single crystal X-ray diffraction methods. The deae ligand is coordinated through the N_pz and N_amino atoms to the metallic centre, which completes its coordination with two chlorine atoms in cis disposition.     

Hydrogen bonding patterns in pyrazole Pt(II- and IV) chloride complexes

The solid-state packing arrays of the platinum(II) trans- and cis-[PtCl₂(PzH)₂] (1 and 2) and platinum(IV) trans- and cis-[PtCl₄(PzH)₂] (3 and 4) complexes have been examined and the occurrence of N-H ? Cl hydrogen-bonding associations in those structures has been discussed. Although different packing motifs are observed, in all cases molecules are interacting mostly via NH ? Cl and CH ? Cl associations. The square planar 1 and 2 form stacked arrays of PtCl₂(PzH)₂, which are supported by NH ? Cl and CH ? Cl hydrogen bonding. The isomeric structure of the complexes and orientation of the PzH rings determine NH ? Cl bonding mode (intermolecular or intramolecular) and also the extent of the platinum-platinum interaction. The synthetic procedures for the preparation of 1-4 along with elemental and X-ray analyses, TG/DTA, FAB⁺-MS, IR, and ¹H and ¹³C{¹H} NMR data are also given in this article.     

The crystal and molecular structures of dichloro [N,O-(D,L)-diaminopropionic acid] platinum(II) and Dichloro [N,O-(L)-lysine] platinum(II) monohydrate

K₂PtCl₄ reacts with L-lysine and with D,L-diaminiopropionic acid (Dap) forming the neutral complexes [PtCl₂(N,O-Lys)]·H₂0 (1) and [PtCl₂(N,O-Dap)], (2) respectively.Compound 1 is monoclinic, space group P2₁ with a = 11.262(3), b = 11.041(2), c = 9.690(2) Å, β = 102.07(5)°, V = 1178(1) ų and Z = 4. Compound 2 is monoclinic, space group P2₁/n with a = 8.777(1), b = 10.615(2), c = 7.947(1) Å, β = 94.98(3)°, V = 738(1) ų and Z = 4. In both compounds, the zwitterionic ligands form an N,O-five membered chelate with the platinum atom. Structures 1 and 2 were refined to R values of 3.3% and 6.3% respectively.     

Mixed-ligand silver(I) complexes containing bis[2-(diphenylphosphino)phenyl]ether and pyridyl ligands

The reaction of [Ag₂(κ²-P,P′-DPEphos)₂(μ-OTf)₂] (1) (DPEphos = bis(2-(diphenylphosphino)phenyl]ether) with 1,10-phenanthroline (phen) and 4,4′-bipyridine in equimolar ratios afford, respectively, the mononuclear complex [Ag(κ²-P,P′-DPEphos)(phen)][OTf] (2) and the coordination polymer [Ag(κ²-P,P′-DPEphos)(μ-4,4′-bpy)]_n[OTf]_n (3). In complex 3, the silver atoms are bridged by 4,4′-bipyridine units to form a zigzag metallopolymer.     

Synthesis, spectroscopical characterization and the biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5-triazine derivatives and dimethylsulfoxide

A series of platinum(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one (6,8-DiMe-4-O-IMT) (I) and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo[1,5-a]-1,3,5-triazin-4(1H)-one (6,8-DiMe-4-O-2-S-IMT) (II) of formula trans-[PtCl₂(dmso)(6,8-DiMe-4-O-IMT)] (1a) and trans-[PtCl₂(dmso)(6,8-DiMe-4-O-2-S-IMT)] (2a) have been prepared and characterized with ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR and IR. Significant ¹⁵N NMR upfield coordination shifts (81-96 ppm) of N(7) atom indicate this nitrogen atom as a coordination site. The multinuclear NMR and IR spectra indicate the square planar geometry with N(7) bonded heterocycles, S-bonded dimethylsulfoxide and two trans chloride anions. The platinum(II) complexes were tested for their antiproliferative activity in vitro against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The activity of (1a, 2a) was lower than that of cisplatin.     

Synthesis, spectroscopic properties and structural characterisation of Pd(II) and Pt(II) complexes with 1,3,5-pyrazole derived ligands. Rotation around the metal-N bond

Reactions of ligands 1-ethyl-5-methyl-3-phenyl-1H-pyrazole (L¹) and 5-methyl-1-octyl-3-phenyl-1H-pyrazole (L²) with [PdCl₂(CH₃CN)₂ and K₂PtCl₄ gave complexes trans-[MCl₂(L)₂] (L = L¹, L²). The new complexes were characterised by elemental analyses, conductivity measurements, infrared, ¹H and ¹³C{¹H} NMR spectroscopies and X-ray diffraction. The NMR study of the complex [PdCl₂(L¹)₂], in CDCl₃ solution, is consistent with a very slow rotation of ligands around the Pd-N bond, so that two conformational isomers can be observed in solution (syn and anti). Different behaviour is observed for complexes [PdCl₂(L²)₂] and [PtCl₂(L)₂] (L = L¹, L²), which present an isomer in solution at room temperature (anti). The crystal structure of [PdCl₂(L¹)₂] complex is described, where the Pd(II) presents a square planar geometry with the ligands coordinated in a trans disposition.     

Kinetics and mechanism for reduction of halo- and haloam(m)ine platinum(IV) complexes by l-ascorbate

Reduction of the model platinum(IV) complexes cis-[PtCl₄(NH₃)₂] (1), trans-[PtCl₄(NH₃)₂] (2), trans-[PtCl₂(en)₂]²⁺ (3), trans-[PtBr₂(NH₃)₄]²⁺ (4), [PtCl₆]²⁻ (5), and [PtBr₆]²⁻ (6) with l-ascorbic acid (H₂Asc) in 1.0 M aqueous medium at 25 °C in the region 1.75≤pH≤7.20 has been investigated using stopped-flow spectrophotometry. The redox reactions follow the rate law: −d[Pt(IV]/dt=k[H₂Asc]_tot[Pt(IV)] where k is a pH-dependent second-order rate constant and [H₂Asc]_tot, the total concentration of ascorbic acid. The pH-dependence of k is attributed to parallel reduction of Pt(IV) by the protolytic species HAsc⁻ and Asc²⁻. Analysis of the kinetics data reveals that the ascorbate anion Asc²⁻ is up to seven orders of magnitude more reactive than HAsc⁻ while H₂Asc is unreactive. Electron transfer from HAsc⁻/Asc²⁻ to the Pt(IV) compounds is suggested to take place by a mechanism involving a reductive attack on any one of the mutually trans-halide ligands by Asc²⁻ and/or HAsc⁻ forming a halide-bridged activated complex. The rapid reduction of these complexes supports the assumption that ascorbate Asc²⁻ might be an important reductant at physiological conditions for anticancer active Pt(IV) pro-drugs capable of undergoing reductive trans elimination. The parameters ΔH^≠ and ΔS^≠ for reduction of Pt(IV) with Asc²⁻ have been determined from the study of the temperature dependence of k.     

Syntheses and structures of heterobimetallic complexes derived from [Ga(edt)2] as a metalloligand (edt = SC2H4S): Potential precursors for ternary materials MGaS2 (M = Cu or Ag)

Metathesis reaction between equimolar amount of [Et₄N][GaCl₄] and Na₂edt in methanol resulted in the formation of the dichloro complex [Et₄N][Ga(edt)Cl₂] (1), whereas reaction of [Et₄N][GaCl₄] with two equivalents of Na₂edt in methanol gave the complex [Et₄N][Ga(edt)₂] (2) which can act as a metalloligand. Treatment of 2 with M(PPh₃)₂NO₃ in DMF/CH₂Cl₂ afforded the heterobimetallic complexes [Ga(edt)₂M-(PPh₃)₂] (M = Cu 3, Ag 4) in moderate yields. The structures of 1-4 were determined by single-crystal X-ray diffraction analyses. Both [Ga(edt)Cl₂]⁻ and [Ga(edt)₂]⁻ anions have a distorted tetrahedral geometry. The former consists of one five-membered ring formed by chelating dithiolate and two terminal chloride atoms while the latter consists of two five-membered rings formed by two the chelating dithiolates. Complexes 3 and 4 consist of metalloligand [Ga(edt)₂]⁻ anion chelated to [M(PPh₃)₂]⁺via the sulfur atoms. Both tetrahedrally coordinated Ga and Cu(Ag) atoms are bridged by two sulfur atoms, forming a planar “GaS₂M” (M = Cu, Ag) core. Thermogravimetry analysis revealed that heterobimetallic complexes 3 and 4 decomposed to give the corresponding ternary metal sulfide materials.     

Platinum(IV) isocyanide complexes

Neutral and cationic platinum(IV) isocyanide complexes of the type [PtCl₄(CNR)₂], [PtCl₄(CNR) (PMe₂Ph)], [PtCl₃(CNR)(PMe₂Ph)₂]⁺, [PtCl₂(CNR)₂ (PMe₂Ph)₂]²⁺, where R = methyl, t-butyl, cyclohexyl, p-tolyl, have been prepared by chlorine addition to the corresponding platinum(II) derivatives. The complexes [PtCl₂(CN)₂(CNR)₂] and [PtCl₂(CN)(CNR) (PMe₂Ph)₂]⁺ (R = t-butyl), are also reported. The cationic t-butylisocyanide derivatives are noteworthy in the way they readily lose the t-butyl cation at room temperature to give the corresponding cyano complexes. The compounds have been characterized by elemental analysis, molecular weights and conductivity measurements, and their i.r. and n.m.r. data are discussed in relation to structures and to the nature of the platinum-isocyanide bond.     

Synthesis, structure and antimicrobial activities of meso silver(I) histidinate [Ag2(D-his)(L-his)]n (Hhis = histidine) showing different self-assembly from those of chiral silver(I) histidinates

An achiral coordination polymer, [Ag₂(D-his)(L-his)]_n, DL-1 (Hhis = histidine), was prepared by slow diffusion of two aqueous solutions of chiral complexes, {[Ag(D-his)]₂}_n (D-2) and {[Ag(L-his)]₂}_n (L-2).¹ The crystal structure of DL-1 consists of a linkage of meso-form dimer units through two kinds of Ag?Ag contacts. Crystals of the achiral silver(I) histidinate complex DL-1 exhibited different self-assembly from those of chiral helical polymers (D-3 and L-3). The formation of DL-1 from the two aqueous solutions indicated that ligand exchange around silver(I) atoms took place in water. The antimicrobial activities of DL-1 against selected bacteria, yeasts and molds were evaluated by minimum inhibitory concentration (MIC).     

cis-Dichloroplatinum (II) complexes with aminomethylnicotinate and -isonicotinate ligands

6-Aminomethylnicotinic acid (1a) and 2-aminomethylisonicotinic acid (1b) were each reacted with K₂PtCl₄ in aqueous 1 M HCl to give the corresponding N,N-chelated cis-dichloroplatinum(II) complexes 2. These were converted into amides 3 via their mixed anhydrides by treating them first with ethyl chloroformate and then with the respective 1° or 2° amine. The analogous 6-aminomethylnicotinic acid ester complexes 7 were obtained by reaction of the preformed ligands with K₂PtCl₄.     

Effects of diethyldithiocarbamate (ddtc) on the plasma biotransformations of tetrachloro(d,i-trans)-1,2-diaminocyclohexaneplatinum(iv) (tetraplatin) in fischer 344 rats

We have studied the effects of diethyldithiocarbamate (DDTC) on the biotransformations of toxic doses of tetrachloro (d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) in Fischer 344 rats. In animals not treated with DDTC, tetraplatin was rapidly converted to dichloro(d,I-trans)1,2-diaminocyclohexaneplatinum(II) [PtCl₂(dach]. Subsequent biotransformations included the transient formation of the (d,I-trans)1,2-diaminocyclohexane-aquachloroplatinum(II) [Pt(H₂O)(Cl)(dach)]+ complex, followed by formation of the platinum (Pt)-methionine and either Pt-cysteine or Pt-ornithine complexes. Significant amounts of free (d,I-trans) 1,2-diaminocyclohexane (dach) were observed in plasma as a result of intracellular trans-labilization reactions. DDTC caused a marked decrease in both total and protein-bound platinum in the circulation. A significant increase in the plasma concentration of free dach was also observed as a result of formation of the Pt(DDTC)₂ complex. Some of the free dach could have arisen from intracellular reactions with DDTC, but the displacement of platinum from plasma proteins was more than sufficient to account for the increase in free dach in the circulation. DDTC treatment also decreased plasma concentrations of tetraplatin, PtCl₂(dach), [Pt(H₂O)(Cl)(dach)]⁺, the Pt-methionine complex, and one unidentified biotransformation product, but had no effect on the Pt-cysteine (or Pt-ornithine) complex. These effects of DDTC on protein-bound platinum and low-molecular-weight biotransformation products in plasma may contribute to the decrease in tetraplatin toxicity seen in DDTC-treated rats.     

Pt(IV) complexes as prodrugs for cisplatin

The antitumor effects of platinum(IV) complexes, considered prodrugs for cisplatin, are believed to be due to biological reduction of Pt(IV) to Pt(II), with the reduction products binding to DNA and other cellular targets. In this work we used pBR322 DNA to capture the products of reduction of oxoplatin, c,t,c-[PtCl₂(OH)₂(NH₃)₂], 3, and a carboxylate-modified analog, c,t,c-[PtCl₂(OH)(O₂CCH₂CH₂CO₂H)(NH₃)₂], 4, by ascorbic acid (AsA) or glutathione (GSH). Since carbonate plays a significant role in the speciation of platinum complexes in solution, we also investigated the effects of carbonate on the reduction/DNA-binding process. In pH 7.4 buffer in the absence of carbonate, both 3 and 4 are reduced by AsA to cisplatin (confirmed using ¹⁹⁵Pt NMR), which binds to and unwinds closed circular DNA in a manner consistent with the formation of the well-known 1, 2 intrastrand DNA crosslink. However, when GSH is used as the reducing agent for 3 and 4, ¹⁹⁵Pt NMR shows that cisplatin is not produced in the reaction medium. Although the Pt(II) products bind to closed circular DNA, their effect on the mobility of Form I DNA is different from that produced by cisplatin. When physiological carbonate is present in the reduction medium, ¹³C NMR shows that Pt(II) carbonato complexes form which block or impede platinum binding to DNA. The results of the study vis-à-vis the ability of the Pt(IV) complexes to act as prodrugs for cisplatin are discussed.