Efficient intraliposomal entrapment of hydrophilic platinum oligonuclear complexes

A simple method for intraliposomal entrapment of platinum complexes is presented, where hydrophilic platinum oligonuclear complexes, 1-methyluracil green (MeUG), uridine green (UdG) and uridine blue (UdB), are included inside liposomes and allowed to react with bilayer lipids. The liposomes prepared in this method exhibit higher entrapment efficiency and higher distribution to organs (liver, kidney, spleen, lung) and blood (but not B16 cancer cells) than those prepared from mononuclear Pt complexes [cis-diamminedichloroplatinum, cis-diammine-1,1′-dicarboxylatocyclobutaneplatinum, and cis-dichloro-cis-dihydroxy-trans-bis(isopropylamine)platinum)].     

Carbon‐Carbon Double Bond versus Carbonyl Group Hydrogenation: Controlling the Intramolecular Selectivity with Polyaniline‐Supported Platinum Catalysts

The use of polyaniline (PANI) as catalyst support for heterogeneous catalysts and their application in chemical catalysis is hitherto rather poorly known. We report the successful synthesis of highly dispersed PANI‐supported platinum catalysts (particle sizes between 1.7 and 3.7 nm as revealed by transmission electron microscopy, TEM) choosing two different approaches, namely (i) deposition‐precipitation of H₂PtCl₆ onto polyaniline, suspended in basic medium (DP method) and, (ii) immobilization of a preformed nanoscale platinum colloid on polyaniline (sol‐method). The PANI‐supported platinum catalysts were applied in the selective hydrogenation of the α,β‐unsaturated aldehyde citral. In order to benchmark their catalytic performance, citral hydrogenation was also carried out by using platinum supported on the classical support materials silica (SiO₂), alumina (Al₂O₃), active carbon and graphite. The relations of the structural characteristics and surface state of the catalysts with respect to their hydrogenation properties have been probed by EXAFS and XPS. It is found that the DP method yields chemically prepared PtO₂ on polyaniline and, thus, produces a highly dispersed and immobilized Adams catalyst (in the β‐PtO₂ form) which is able to efficiently hydrogenate the conjugated CC bond of citral (selectivity to citronellal=87%), whereas reduction of the CO group occurs with polyaniline‐supported platinum (selectivity to geraniol/nerol=78%) prepared via the sol‐method. The complete reversal of the selectivity between the preferred hydrogenation of the conjugated CC or CO group is not only particularly useful for the selective hydrogenation of α,β‐unsaturated aldehydes but also unveils the great potential of conducting polymer‐supported precious metals in the field of hitherto barely investigated chemical catalysis.     

Synthesis,Cytotoxicity, Induction of Apoptosis,and Interaction with DNA of Dinuclear Platinum(II) Complexes

Six dicarboxylato‐bridged dinuclear platinum(II) complexes S1 – S6 , with a newly designed chiral ligand, 2‐{[(1R,2R)‐2‐aminocyclohexyl]amino}propanoic acid ( HL ), were prepared and spectrally characterized. The in vitro cytotoxicity of all resulting platinum(II) complexes was evaluated against human HCT‐116, MCF‐7, and HepG‐2 tumor cell lines. The results show that all compounds exhibit positive biological activity toward HCT‐116 and MCF‐7 cell lines, of which complexes S3 , S4 , and S5 , with succinate and its derivatives as bridges, showing better activity than the positive controls. Moreover, double‐dyeing flow cytometric resection experiments indicate that the target compounds inhibit tumor cell growth by inducing apoptosis; gel electrophoresis experiments demonstrate the compounds′ ability to prompt pET22b plasmid DNA degradation in almost the same way as oxaliplatin.     

A New Class of Luminescent Platinum(II) Complexes of 1,3-Bis(N-alkylbenzimidazol-2′-yl)benzene-Type Ligands and Their Application Studies in the Fabrication of Solution-Processable Organic Light-Emitting Devices

A novel class of luminescent platinum(II) bzimb (1,3-bis(N-alkylbenzimidazol-2′-yl)benzene) complexes has been designed and synthesized. With the incorporation of various substituents on the anionic phenyl ring of the bzimb ligand, the emission color can be readily tuned. Their photophysical, electrochemical and electroluminescence properties have been studied. These platinum(II) bzimb complexes have been demonstrated to be capable of serving as phosphorescent dopants. Efficient solution-processable OLEDs (organic light-emitting devices), with a maximum external quantum efficiency of up to 4.85 %, can be achieved. This class of platinum(II) bzimb complexes represents a promising class of phosphorescent dopants for solution-processable OLEDs.     

Stereochemistry and Circular Dichroism of Chiral Internal Olefin-Platinum(II) Complexes

A series of cis- and trans-dichloro(benzylamine) (chiral olefin) platinum(II) complexes, containing (Z) and (E) isomers of the internal chiral olefins R-CH=CH-R', has been prepared by ethylene displacement from the corresponding ethylene containing complexes. The particular stereochemical features of the complexes allow one to interpret the CD on the basis of the individual contributions coming from the chiral centres already present in the free olefin and from the chiral centres formed in the complexation of the double bond. Evidence is reported showing that the aforementioned contributions are additive and that the chiral centre(s) bound to the metal dominates the CD at about 400 nm, its chirality type being reflected in the sign and its chirality prevalence in the Δϵ value.     

Distributions of hydroperoxide positional isomers generated by oxidation of 1-palmitoyl-2-arachidonoyl-<Emphasis Type="Italic">sn</Emphasis>-glycero-3-phosphocholine in liposomes and in methanol solution

The differences in distribution of geometric isomers of unsaturated PC hydroperoxides generated by free radical oxidation were compared, as corresponding hydroxy analogs, in heterogeneous liposomes and in a homogeneous methanol solution by using HPLC with UV detection due to the presence of conjugated dienes. Identification of fractionated peak components was carried out by GC-MS. When the oxidation of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, PC(16∶0/18∶2), was initiated in liposomes by a hydrophilic azo radical initiator, and in a methanol solution by a hydrophobic azo radical initiator, there was no significant difference in the relative percentages of 1-palmitoyl-2-(9-hydroxy-trans-10,trans-12-octadecadienoyl)-sn-glycero-3-phosphocholine (9-t,t-OH PC) and 1-palmitoyl-2-(13-hydroxy-trans-9,trans-11-octadecadienoyl)-sn-glycero-3-phosphocholine (13-t,t-OH PC) between the PC oxidized in liposomes and in the methanol solution. For the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, PC(16∶0/20∶4), the relative percentage of 1-palmitoyl-2-(5-hydroxy-trans-6,cis-8,11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (5-OH PC) was significantly higher (P<0.01) than that of 1-palmitoyl-2-(15-hydroxy-cis-5,8,11,trans-13-eicosatetraenoyl)-sn-glycero-3-phosphocholine (15-OH PC) in liposomes. For the homogeneous methanol solution of PC(16∶0/20∶4), the relative percentage of 5-OH PC was close to that of 15-OH PC. For the PC(16∶0/20∶4) oxidized in bulk with added pentamethylchromanol, the individual amount of 15-OH PC, 1-palmitoyl-2-(11-hydroxy-cis-5,8trans-12,cis-14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (11-OH PC), 1-palmitoyl-2-(12-hydroxy-cis-5,8,trans-10,cis-14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (12-OH PC), 1-palmitoyl-2-(8-hydroxy-cis-5,trans-9,cis-11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (8-OH PC), 1-palmitoyl-2-(9-hydroxy-cis-5,trans-7,cis-11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (9-OH PC), and 5-OH PC were close to each other compared to the corresponding values in liposomes and in methanol solution. The results obtained by gel permeation chromatography of the PC liposomes containing hydrophilic 2,2′-azobis-2-amidinopropane) dihydrochloride (AAPH) suggest that the AAPH added to the liposomes of PC(16∶0/20∶4) was partitioned into the water phase and out of the hydrophobic region of the fatty acyl moieties of the PC. These results confirm that the distance that exists in the bis-allylic carbons of the unsaturated fatty acyl moieties of PC from the interface between the hydrophilic region of PC and the water phases played an important role in influencing hydrogen abstraction to form a symmetrical distribution of hydroperoxide isomers in both the heterogeneous liposomes and the homogeneous methanol solution.     

Heterogeneous reductions of (homohypostrophene)dialkylplatinum(II) complexes provide a useful system for the study of intermediate surface alkyls on platinum [1]

This paper reports a comparison of the ethyl moieties generated on the surface of platinum black during the heterogeneous, platinum-catalyzed hydrogenations of (1,5-cyclooctadiene)diethylplatinum(II) ((COD)PtEt₂), of (homohypostrophene)diethylplatinum(II) ((HOP)PtEt₂), and of ethylene using D₂ in ethyl alcohol-d. In reductions of the platinum complexes, the -olefin and -alkyl organic ligands are converted to alkanes by reaction of the intermediate surface alkyls with surface hydrides, and the platinum(II) becomes part of the platinum(0) surface. These reductions are characterized by two kinetic regimes: one in which the rate of reaction is limited by the mass transport of hydrogen to the surface of the catalyst (the mass transport limited regime, MTL), and one in which the rate is limited by a reaction on the surface of the catalyst (the reaction rate limited regime, RRL). In the RRL regime, the isotopic compositions of the ethanes-d _n produced from the reductions of the platinum complexes and of ethylene suggest that the surface ethyls (Et *) generated from each precursor have similar relative rates of isotopic exchange (and thus of C-H bond activation) and of reductive elimination as ethane. In the MTL regime, the Et * derived from each precursor have different reactivities: the Et* generated from (HOP)PtEt₂ have reactivities that are more similar to the Et * generated from ethylene than do the Et * generated from (COD)PtEt₂.     

Antiproliferative Activity of Polymer-Bound, Monoamine-Coordinated Platinum Complexes Against LNCaP Human Metastatic Prostate Adenocarcinoma Cells

The chemotherapeutic treatment of secondary, i.e., disseminated cancers, has until now remained an unsatisfactory modality. The LNCaP human metastatic prostate adenocarcinoma cell line lends itself as a useful tool to probe the efficaciousness of novel antineoplastic agents for the control of metastatic cell growth. In this paper we report on a series of cell culture tests assessing the antiproliferative activity of several water-soluble polymer–platinum conjugates in which the metal is tied (anchored) to various polymeric carriers through coordination by a single carrier-attached primary amine ligand. The conjugates are based on polyaspartamide carriers composed, within the backbone, of a majority fraction of subunits bearing water-solubilizing tertiary amine side-group functions and a minority fraction of subunits featuring side chain-terminating primary amino groups for metal binding. Two similarly structured conjugates in which the platinum center is coordinated by two amine ligands in cisoid orientation mimicking the structural skeleton of cisplatin are included in the study for comparison. In all structures cleavage of a side-chain segment is required for release of the monomeric bioactive platinum complex. The growth of LNCaP human metastatic prostate adenocarcinoma cells in RPMI 1640 medium in the presence and absence of the conjugates in a range of concentrations is assessed by a protein assay, and the IC₅₀ values, representing the drug concentrations required for 50% cell growth inhibition relative to untreated control, are determined. The results show both classes of conjugates, those comprising monoamine-coordinated platinum and those featuring cis-diamine-coordinated metal, to be well comparable in antiproliferative activity. A major program of synthesis and evaluation of polymer-bound monoamineplatinum complexes, prompted by these findings, is forthcoming in this laboratory.     

Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity

Continuing our studies on the mechanisms underlying the cytotoxicity of potential drugs, we have described several aspects of the in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with bioactive, synthetic aminoflavone ligands. We examined the mechanism of proapoptotic activity of cis-dichlorobis(3-imino-2-methoxyflavanone)ruthenium(II), cis-dichlorobis(3-imino-2-ethoxyflavanone)ruthenium(II), and trans-dichlorobis(3-aminoflavone)platinum(II). Cisplatin was used as a reference compound. The cytotoxicity was investigated by MTT assay. The mechanism of proapoptotic activity of the tested compounds was investigated by evaluation of caspase-8 activity, cytometric analysis of annexin-V positive cells, and mitochondrial potential loss measurement. The results showed that ruthenium compounds break partially or completely the cisplatin resistance by activating the caspase 8-dependent apoptosis pathway and loss of mitochondrial membrane potential. Platinum compounds also have a cytostatic effect, but their action requires more exposure time. Potential mechanisms underlying drug resistance in the two pairs of cancer cell lines were investigated: total glutathione content, P-glycoprotein activity, and differences in the activity of DNA repair induced by nucleotide excision. Results showed that cisplatin-resistant cells have elevated glutathione levels relative to sensitive cells. Moreover, they indicated the mechanisms enabling cells to avoid apoptosis caused by DNA damage. Pg-P activity has no effect on the development of cisplatin resistance in the cell lines described.     

Kinetics and Mechanism of the Platinum(II)-Catalyzed Hydroarylation of Vinyl Arenes with 1,2-Dimethylindole

The mechanism of the intermolecular hydroarylation of vinyl arenes ( 1 ) with 1,2-dimethylindole ( 2 ) catalyzed by PtCl₂ has been evaluated through a combination of kinetic analysis, deuterium labeling studies, and stereochemical analysis. The results of these and additional experiments are consistent with a mechanism for hydroarylation involving rapid and reversible complexation of vinyl arene to the catalytically inactive platinum mono(vinyl arene)complex trans-PtCl₂(H₂C=CHAr)(solvent) to form the reactive platinum bis(vinyl arene) complex trans-PtCl₂(H₂C=CHAr)₂, which undergoes turnover-limiting, outer-sphere attack of indole. Rapid protodemetallation of the resulting platinum alkyl complex releases product and regenerates the equilibrating mixture of platinum π-vinyl arene complexes.     

Platinum Nanoparticles Supported on Ionic Liquid‐Modified Magnetic Nanoparticles: Selective Hydrogenation Catalysts

A method for supporting platinum nanoparticles on magnetite nanoparticles is described. The method requires modification of the surface of the magnetic nanoparticles with ionic liquid groups. Before modification, the magnetic nanoparticles are not stable and easily aggregate and, after modification, the magnetite nanoparticles become highly stable and soluble in polar or non‐polar organic solvents depending on the alkyl group of the linked ionic liquids. The supporting of platinum nanoparticles on the modified magnetic nanoparticles was achieved by adsorbing platinum salts (K₂PtCl₄) on the surface of the magnetite nanoparticles via ion exchange with the linked ionic liquid groups and then reducing them by hydrazine. The supported platinum nanoparticles were applied in the catalytic hydrogenation of alkynes in which cis‐alkenes were selectively produced, and in the hydrogenation of α,β‐unsaturated aldehydes where the allyl alcohols were obtained as the exclusive products. The new catalyst can be easily separated from the reaction mixtures by applying an external magnetic field and recycled.     

On the role of adsorbed atomic oxygen and CO2 in copper based methanol synthesis catalysts

The reactions of cyclohexane (6.7 kPa) andn-hexane (13.3 kPa) in H₂ (450 kPa) were studied on platinum-rhenium model catalysts in the range 570–740 K. The catalysts were prepared by depositing rhenium on a platinum foil or platinum on a rhenium foil. The catalyst total area was 0.5–1.0 cm². The surfaces were pre-sulfided before reaction and thiophene added to the feed to maintain the surface sulfided under reaction conditions. Sulfur binds with rhenium forming a catalytically inactive rhenium-sulfur compound. As the concentration of rhenium-sulfur on the surface is increased and the platinum ensembles become smaller, only dehydro-genation-hydrogenation activity is observed. However, the catalyst becomes more resistant to deactivation.     

Diplatinum(III) [Cl2(μ2-amidinate)4] compound derived from air oxidation of mononuclear cis-[Pt(NH3)2(amidine-κ)2] complex

The dinuclear platinum(III) complex [Pt₂Cl₂{μ₂-N(H)C(Et)N(H)}₄] (2) has been prepared by heating cis-[Pt(NH₃)₂{NHC(NH₂)Et}₂](Cl)₂ (cis-1) under aeration conditions in an EtOH/H₂O mixture at 70 °C for 2 d and it was characterized by elemental analyses (C, H, N), ESI⁺-MS, IR, ¹H and ¹³C NMR spectroscopies and also by X-ray diffraction. Complex 2 represents the second Pt^III dimer stabilized by the amidinate ligand ever known and it has a lantern-type structure with four amidinate ligands bridging two Pt^III centers with Pt–Pt distance of 2.4809(2) Å.     

Methods for correction of selectivity of N-(2-sulfoethyl)chitosan-based materials towards platinum(IV) and palladium(II) ions

In this paper, we report methods for correction of selectivity of sorbents based on N-(2-sulfoethyl)chitosan towards platinum(IV) and palladium(II) in HCl solutions. The common method for correction of selectivity of the sorbents is variation of their modification degree with complexing groups. An increase in the degree of sulfoethylation of the chitosan leads to the significant increase in selectivity of sorption of palladium(II) over platinum(IV). Application of the N-(2-sulfoethyl)chitosan with the highest degree of sulfoethylation allows for selective separation palladium(II) from platinum(IV) (рН = 5.0). Palladium is quantitatively desorbed from the surface of the N-(2-sulfoethyl)chitosans by 3.5 mol/dm³ solution of HCl.     

Cyclometalated N‐Heterocyclic Carbene‐Platinum Catalysts for the Enantioselective Cycloisomerization of Nitrogen‐Tethered 1,6‐Enynes

Platinum(II) complexes which combine six‐membered N‐heterocyclic carbene‐containing metallacyclic units and monodentate chiral phosphines have been prepared. The key step of their synthesis is the intramolecular oxidative addition of N‐2‐iodobenzylimidazolylidene‐platinum(0)‐diene complexes in the presence of the chiral phosphorus ligands. The platinum(II) metallacycles have been used as well‐defined pre‐catalysts for the enantioselective cycloisomerization of nitrogen‐tethered 1,6‐enynes into 3‐azabicyclo[4.1.0]hept‐4‐enes. High enantiomeric excesses have been obtained with either Monophos or phenyl‐Binepine based catalysts (ees=82–96%), although phenyl‐Binepine outperforms Monophos in these reactions. The absolute configuration of the final 3‐azabicyclo[4.1.0.]heptenes has been established by X‐ray diffraction studies. The method has been extended then to the cycloisomerization of dienynes with enantiotopic vinyl groups. An (S)‐phenyl‐Binepine‐platinum(II) complex allows total diastereoselectivity and high enantioselectivity levels to be attained in these reactions (ees up to 95%) which represent the first enantioselective desymetrizations achieved via enyne cycloisomerizations.     

Regeneration of platinum-metal-based catalysts with carboxyphosphines as extractants

Separation of platinum-metal-based homogeneous catalysts was achieved by their conversion to complexes of functionalized phosphines of the general formulae R_3-n P[(CH₂) _x CO₂H)] _n , R = Me, Et, Ph,n = 1, 2, 3,x = 1, 2, and [(HO₂CCH₂)PCH₂]₂, followed by extraction of the complexes into aqueous phase. This approach to regeneration of platinum metals from reaction mixtures after carrying out homogeneously catalyzed reactions was demonstrated on 11 examples of various types of reactions with Ru, Rh, Pd, Os, Ir and Pt compounds as catalysts.     

Cell Growth-Inhibiting Properties of Selected Carrier-Bound, Monoamine-Coordinated Platinum(II) Compounds

In contradistinction to the ligand arrangement in coordination compounds of the square-planar cis-diamminedichloroplatinum(II) type as represented by the prototype anticancer drug cisplatin, scant attention has been paid in cancer research to those platinum complexes in which only a single amino group (in addition to different ligands) is coordinated to the metal. In continuation of earlier research in this laboratory focused on macromolecular compounds containing monoamine-coordinated platinum, we have now synthesized a series of such polymeric platinum conjugates and assessed their antiproliferative activity in cell culture tests conducted against several human cancer cell lines. Conjugates containing hydroxylated side groups as hydrosolubilizing entities are found to exhibit poor, or no, activity up to the highest drug concentration tested (50 g Pt/mL). In contrast, those conjugates in which the solubilizing units are characterized by the presence of potentially cationic tert-amine side chain terminals show remarkably high cell-killing activity, with IC₅₀ in the range of 1–6 g Pt/mL against the HeLa cervical epitheloid carcinoma line. Two selected samples tested against the A-2780 human ovarian cancer line and its cisplatin-resistant A-2780-cis counterpart shows lack of cross-resistance with cisplatin (resistance factor 1). These findings augur well for the development of polymer-conjugated monoamine-coordinated platinum compounds with carcinostatic properties.     

烯丙基硅(氧)烷铂配合物硅氢加成催化剂的研究

通式为（ＣＨ２ ＣＨＣＨ２） ｎＳｉＲ（４－ ｎ） （ ｎ ＝ ２ ,３ ,４ ;Ｒ＝ Ｍｅ ,Ｐｈ） 的烯丙基硅烷以及１ ,３ 二烯丙基 四甲基二硅氧烷（ＤＡＴＭ） 经由Ｇｒｉｇｎａｒｄ 反应制备,它们再与氯铂酸反应制备出相应的标题配合物,这种配合物可用做硅氢加成催化剂。研究发现在氯丙烯与硅氯仿的加成反应中,ＴＡＳ（ ｎ ＝ ４） 、ＤＭＤＡ（ｎ ＝ ２ ,Ｒ＝ Ｍｅ） 、ＭＴＡ（ ｎ ＝ ３ ,Ｒ＝ Ｍｅ） 和ＤＡＴＭ 的铂配合物的活性都比氯铂酸大。同时还讨论了几种铂配合物催化剂对含氢硅油与乙烯基硅橡胶的加成反应活性,发现不同催化剂的活性各不相同。     

Homogeneous hydrogenation of methylcis-9,cis-15-octadecadienoate catalyzed by platinum-tin,palladium and nickel complexes

Methylcis-9,cis-15-octadecadienoate was used as a model for the hydrogenation of methyl linolenate. Homogeneous catalysis by platinum, palladium and nickel complexes produced a mixture of isomeric monoenes similar to that from the hydrogenation of methyl linolenate. These catalysts are, therefore, capable of promoting isomerization of isolated double bonds and of producing conjugated dienes which are necessary for the formation of monoenes. N. Market, and Nutr. Res. Div., ARS, USDA.