Bifunctional Platinum Research Articles

Comparative study of Pt/zeolites for n-hexadecane hydroisomerization: EU-1, ZSM-48, ZSM-23, ZSM-22, and ZSM-12

The hydroisomerization of n-hexadecane was investigated using bifunctional platinum catalysts supported on EU-1, ZSM-48, ZSM-23, ZSM-22, and ZSM-12 zeolites. These one-dimensional microporous zeolites were synthesized at 160 ℃ with an Si/Al molar ratio of 60, and 0.5 wt% Pt was loaded onto them using the impregnation method. The findings indicate that Brønsted acidity predominantly influences the conversion to n-hexadecane over 10 membered ring zeolites. Additionally, ZSM-12, characterized by a 12-ring channel, exhibits preferential activity in this regard. The apparent activation energy for the reactions increased from 81 kJ/mol (Pt/ZSM-23) to 134 kJ/mol (Pt/ZSM-48) across all tested catalysts. Pt/ZSM-22 demonstrated high selectivity towards mono-branched isomers, whereas Pt/ZSM-12 favored the formation of multi-branched isomers. The isomer selectivity trend was Pt/ZSM-22 > Pt/ZSM-12 > Pt/EU-1 > Pt/ZSM-48 > Pt/ZSM-23. Moreover, TG analysis of spent catalysts unveiled that coke formation on these zeolites was chiefly influenced by zeolite channel structure and Brønsted acid content. The average coke selectivity followed this order: Pt/EU-1 > Pt/ZSM-12 > Pt/ZSM-48 > Pt/ZSM-22 > Pt/ZSM-23.

Production of jet fuel by hydrorefining of Fischer-Tropsch wax over Pt/Al-TUD-1 bifunctional catalyst

TUD-1 supported bifunctional platinum catalysts were prepared and characterized for structural and textural properties, acidity, and platinum dispersion. The acidity of TUD-1 was varied by isomorphous substitution of Al and Ti in the framework. The TUD-1 supports possess a three-dimensional amorphous structure as shown by XRD. BET-N2 adsorption and pyridine FTIR studies revealed that the incorporation of Al in the TUD-1 framework enhances the surface area and generates Brønsted acidity. The catalysts were screened for hydrorefining of Fischer-Tropsch wax with C8-C44 n-paraffins. The catalysts prepared with Si-TUD-1 and Ti-TUD-1 supports were not active for hydrocracking and hydroisomerization due to the absence of Brønsted acid sites, which was verified by pyridine FTIR. Increasing the amount of Al in the framework gradually increased the Brønsted acid sites and thus promoted hydrocracking and hydroisomerization of F-T wax. Pt/Al-TUD-1 catalyst with a Si/Al ratio of 10 produced more jet fuel range hydrocarbons. Hydrorefining of F-T wax was evaluated over an optimal Pt/Al-TUD-1 (Si/Al = 10) catalyst at different pressures and temperatures. Hydroisomerization was favored at low hydrogen pressure. Increasing the temperature shifted the hydrocarbon distribution more towards gasoline due to severe cracking. The temperature of 330 °C and a hydrogen pressure of 5 MPa were found to be optimum to produce jet fuel range hydrocarbons that meet the ASTM specification of cold flow properties. This study proves the feasibility of the production of renewable jet fuel that is directly compatible with fossil-based aviation engines, through hydrorefining of F-T waxes using a mesoporous bifunctional catalyst.

Mustards-Derived Terpyridine-Platinum Complexes as Anticancer Agents: DNA Alkylation vs Coordination.

The development of bifunctional platinum complexes with the ability to interact with DNA via different binding modes is of interest in anticancer metallodrug research. Therefore, we report platinum(II) terpyridine complexes to target DNA by coordination and/or through a tethered alkylating moiety. The platinum complexes were evaluated for their in vitro antiproliferative properties against the human cancer cell lines HCT116 (colorectal), SW480 (colon), NCI-H460 (non-small cell lung), and SiHa (cervix) and generally exhibited potent antiproliferative activity although lower than their respective terpyridine ligands. 1H NMR spectroscopy and/or ESI-MS studies on the aqueous stability and reactivity with various small biomolecules, acting as protein and DNA model compounds, were used to establish potential modes of action for these complexes. These investigations indicated rapid binding of complex PtL3 to the biomolecules through coordination to the Pt center, while PtL4 in addition alkylated 9-ethylguanine. PtL3 was investigated for its reactivity to the model protein hen egg white lysozyme (HEWL) by protein crystallography which allowed identification of the Nδ1 atom of His15 as the binding site.

Optimization of Supports in Bifunctional Supported Pt Catalysts for Polystyrene Hydrocracking to Liquid Fuels

A series of bifunctional platinum catalysts were prepared, supported on alumina or different zeolites, some of which were submitted to either desilication or dealumination in order to modify their acidic properties. The catalysts were characterized for their structural and textural properties, their acidic properties, including distribution of acid strength and Bronsted and Lewis acidity, their metallic properties, and used in the hydrocracking of polystyrene under kinetic control, where activity in end-of-chain scission and random scission of the polymer has been quantified as well as the distribution of products. Activation energies and pre-exponential factors have been calculated from the kinetic data, and analyzed in terms of compensation effect, in order to extract conclusions on activity, active centers and reaction pathways. Finally, activation energies, both of end-of-chain and random scissions, yield to gasoline fraction and percentage of aromatics in the gasoline fraction have been correlated with catalytic properties in order to extract conclusions on the major catalytic properties affecting catalytic performance in this process, from the point of view of catalytic design.

Synthesis, antiproliferative activity in cancer cells and DNA interaction studies of [Pt(cis-1,3-diaminocycloalkane)Cl2] analogs

The search for more effective platinum anticancer drugs has led to the design, synthesis, and preclinical testing of hundreds of new platinum complexes. This search resulted in the recognition and subsequent FDA approval of the third-generation Pt(II) anticancer drug, [Pt(1,2-diaminocyclohexane)(oxalate)], oxaliplatin, as an effective agent in treating colorectal and gastrointestinal cancers. Another promising example of the class of anticancer platinum(II) complexes incorporating the Pt(1,n-diaminocycloalkane) moiety is kiteplatin ([Pt(cis-1,4-DACH)Cl2], DACH = diaminocyclohexane). We report here our progress in evaluating the role of the cycloalkyl moiety in these complexes focusing on the synthesis, characterization, evaluation of the antiproliferative activity in tumor cells and studies of the mechanism of action of new [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes wherein the cis-1,3-diaminocycloalkane group contains the cyclobutyl, cyclopentyl, and cyclohexyl moieties. We demonstrate that [Pt(cis-1,3-DACH)Cl2] destroys cancer cells with greater efficacy than the other two investigated 1,3-diamminocycloalkane derivatives, or cisplatin. Moreover, the investigated [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes show selectivity toward tumor cells relative to non-tumorigenic normal cells. We also performed several mechanistic studies in cell-free media focused on understanding some early steps in the mechanism of antitumor activity of bifunctional platinum(II) complexes. Our data indicate that reactivities of the investigated [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes and cisplatin with glutathione and DNA binding do not correlate with antiproliferative activity of these platinum(II) complexes in cancer cells. In contrast, we show that the higher antiproliferative activity in cancer cells of [Pt(cis-1,3-DACH)Cl2] originates from its highest hydrophobicity and most efficient cellular uptake.

Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs.

Aquation free energy profiles of neutral cisplatin and cationic monofunctional derivatives, including triaminochloroplatinum(II) and cis-diammine(pyridine)chloroplatinum(II), were computed using state of the art thermodynamic integration, for which temperature and solvent were accounted for explicitly using density functional theory-based canonical molecular dynamics (DFT-MD). For all the systems, the "inverse-hydration" where the metal center acts as an acceptor of hydrogen bond has been observed. This has motivated to consider the inversely bonded solvent molecule in the definition of the reaction coordinate required to initiate the constrained DFT-MD trajectories. We found that there exists little difference in free enthalpies of activation, such that these platinum-based anticancer drugs are likely to behave the same way in aqueous media. Detailed analysis of the microsolvation structure of the square-planar complexes, along with the key steps of the aquation mechanism, is discussed.

Hydrogen generation from ammonia electrolysis on bifunctional platinum nanocubes electrocatalysts

Abstract The ammonia electrolysis is a highly efficient and energy-saving method for ultra-pure hydrogen generation, which highly relies on electrocatalytic performance of electrocatalysts. In this work, high-quality platinum (Pt) nanocubes (Pt-NCs) with 4.5 nm size are achieved by facile hydrothermal synthesis. The physical morphology and structure of Pt-NCs are exhaustively characterized, revealing that Pt-NCs with special {100} facets have excellent uniformity, good dispersity and high crystallinity. Meanwhile, the electrocatalytic performance of Pt-NCs for ammonia electrolysis are carefully investigated in alkaline solutions, which display outstanding electroactivity and stability for both ammonia electrooxidation reaction (AEOR) and hydrogen evolution reaction (HER) in KOH solution. Furthermore, a symmetric Pt-NCs||Pt-NCs ammonia electrolyzer based on bifunctional Pt-NCs electrocatalyst is constructed, which only requires 0.68 V electrolysis voltage for hydrogen generation. Additionally, the symmetric Pt-NCs||Pt-NCs ammonia electrolyzer has excellent reversible switch capability for AEOR at anode and HER at cathode, showing outstanding alternating operation ability for ammonia electrolysis.

Bifunctional Platinum Tetrapods: High‐Performance Catalyst for Hydrogenation of Aromatic Nitro Compounds and Electrochemical Sensor for Hydrazine.

AbstractPrecise engineering of platinum as nanostructured platinum tetrapods (Pt TPs) is achieved via a facile one‐step hydrothermal synthesis using KCl and KBr as structure directing agents. Heavily influenced by its size and shape, Pt TPs exhibits excellent catalytic activity, selectivity and recyclability in hydrogenation of nitroarenes and acts as an electrochemical sensor for hydrazine. This enhanced activity is attributed to the surface structure of Pt with high‐index facets.

Direct Synthesis of Al-B-SBA-15 and Its Application in Preparing of Bifunctional Platinum Catalyst for Hydrogenation of Tetralin

In this work, the mesoporous material Al-B-SBA-15 has been obtained by direct synthesis method with Si : B : Al ratio of 10 : 0.5 : 0.5. Wetness impregnation (WI) method was used to load platinum on Al-B-SBA-15. The prepared support and catalyst were characterized by nitrogen adsorption–desorption measurement (BET), XRD, TEM, and TPD-NH3 to investigate the influence of boron and aluminium on characteristics of the catalyst. The activity of the bifunctional catalyst was tested for hydrogenation of tetralin at 180–220°C, hydrogen pressure of 1.5–2.5 MPa for 3 h.

Direct Synthesis of Al-B-SBA-15 and its Application in Рreparing of Bifunctional Platinum Catalyst for Hydrogenation of Tetralin

In this work, the mesoporous material Al-B-SBA-15 has been obtained by direct synthesis method with Si : B : Al ratio of 10 : 0.5 : 0.5. Wetness impregnation (WI) method was used to load platinum on Al-B-SBA-15. The prepared support and catalyst were characterized by nitrogen adsorption-desorption measurement (BET), XRD, TEM, and TPD-NH3 to investigate the influence of aluminium and boron on characteristics of the catalyst. The activity of the bifunctional catalyst was tested for hydrogenation of tetralin at 180–220 °C, hydrogen pressure of 1.5–2.5 MPa for 3 h.

Mechanistic Insights into the Hydrogenolysis of Levoglucosanol over Bifunctional Platinum Silica–Alumina Catalysts

Herein, we report on the hydrogenolysis of the biorenewable intermediate levoglucosanol (Lgol) over bifunctional platinum catalysts supported on silica–alumina in tetrahydrofuran solvent. 13C radiolabeling is used to confirm the ring rearrangement forming tetrahydrofurandimethanol. The reaction rate and product selectivity are comparable between 1.1 and 5.3 wt % Pt loadings, indicating that, at these metal loadings, the rate-limiting step is acid catalyzed. The measured zero-order dependence in hydrogen indicates that a non-rate-determining hydrogenation step follows an acid-catalyzed irreversible rate-determining step. The measured first-order dependence in Lgol indicates that the acid sites are not highly covered by Lgol. A physical mixture of Pt/SiO2 and SiAl catalysts displayed product selectivity similar to that of the Pt/SiAl catalyst, indicating that nanoscale proximity of metal and acid sites is not required to carry out Lgol hydrogenolysis selectively. As the Pt loading in Pt/SiAl catalysts is de...

Bifunctional Platinum(II) Complexes with Bisphosphonates Substituted Diamine Derivatives: Synthesis and In vitro Cytotoxicity

A series of N,N'-dibisphosphonate-containing 1,3-propanediamine derivatives (L1 - L6) and their corresponding dichloridoplatinum(II) complexes (1 - 6) have been synthesized and characterized by elemental analysis, 1 H-NMR, 13 C-NMR, 31 P-NMR and HR-MS spectra. The in vitro antitumor activities of compounds L1 - L6 and 1 - 6 were tested by WST-8 assay with Cell Counting Kit-8, indicating that platinum-based complexes 1 - 6 showed higher cytotoxicity than corresponding ligands L1 - L6 against A549 and MG-63, especially complex 2 which displayed comparable cytotoxicity to those of cisplatin and zoledronate after 48 h incubation. In addition, complexes 1 - 6 were more active in vitro on osteosarcoma cell line MG-63 than normal osteoblast cell line hFOB 1.19. The structure-activity relationship has been summarized based on the in vitro cytotoxicity of three series of platinum complexes from this and our previous studies. The in vitro bone affinity of platinum complexes was also tested by hydroxyapatite (HAP) chromatography in terms of capacity factor K'. Besides, in this paper, representative complex 2, which has been proved to be a promising antitumor agent with high cytotoxicity and bone HAP binding property, was investigated for its mechanism of action producing cell death against MG-63.

The role of annular nitrogen in tuning the reactivity of bifunctional platinum(II) complexes appended to pyridyl spacers; A kinetic and mechanistic investigation

A kinetic and mechanistic study on ligand substitution reactions of pyridine functionalized dinuclear Pt(II) complexes visa-viz., N,N,N’,N’-tetrakis(2-pyridyl)-2,3 pyridinediaminetetraquaplatinum(II) (PtL1); N,N,N’,N’-tetrakis(2-pyridyl)-2,4-pyridinediaminetetraquaplatinum(II) (PtL2); N,N,N’,N’-tetrakis(2-pyridyl)-2,6-pyridinediaminetetraquaplatinum(II) (PtL3); N,N,N’,N’-tetrakis(2-pyridyl)-2,5-pyridinediaminetetraquaplatinum(II) (PtL4) and N,N,N’,N’-tetrakis(2-pyridylaminomethyl)-2,6-pyridinediaminetetraquaplatinum(II) (PtL5) complexes with thiourea (TU), N,N’-dimethylthiourea (DMTU) and N,N,N’N’-tetramethylthiourea (TMTU) as the entering nucleophiles was carried out under pseudo-first-order conditions by stopped-flow and UV–Vis spectrophotometric techniques. Substitution reactions proceeds via a two-step pathway with the rate law kobs(1,2) = k2(1st/2nd)[Nu]. The first substitution step is attributed to simultaneous displacement of one water molecule at each platinum(II) center. The second step is attributed to the slow phase substitution of the second water molecule occurring concurrently with the slow displacement of the bridging linker. The steps were confirmed by 1H and 195Pt NMR spectroscopy. The reactivity of the complexes is governed by the position of the annular nitrogen in the pyridine spacer. The Low positive values of enthalpy of activation and significantly large negative values of entropy of activation parameters for both steps indicate an associative mechanism of substitution.

Dynamics of the Activity and Physicochemical Characteristics of Pt/WO4 2−–ZrO2 Catalysts in the Hydroisomerization of Heptane and Heptane–Benzene Mixtures

The dynamics of the activity and selectivity of bifunctional platinum tungstated zirconia PtWZ catalyst in the hydroisomerization of n-heptane and heptane–benzene mixture is discussed in the paper. The change in the properties of the catalyst before and after reaction were characterized using different techniques. The catalyst showed high efficiency for the hydroisomerization of heptane and heptane–benzene mixture, however, deactivation occurred with time on stream, more significantly when benzene was present in the reaction mixture. The carbonaceous matter was deposited on the catalyst (up to 0.8%) during the hydroisomerization reaction. Predominantly aliphatic carbonaceous «poly-CxHy» species, much less oxidized and little aromatic «graphite-like» species were identified by XPS spectra on the catalyst after the heptane isomerization. In the presence of benzene, the formation of «graphite-like» matter increased progressively as temperature increased. However, no appreciable changes in the bulk properties of the t-ZrO2 matrix (phase composition, specific surface area, pore volume, pore size distribution) and in the state of platinum component were revealed, though an increased extent of W6+ to W5+ reduction was detected by XPS spectra irrespectively of the reaction conditions. The deactivation of the PtWZ catalyst was suggested to result from the blocking the active centers by carbonaceous deposits, the deactivation of the acidic centers being more pronounced as compared to metallic ones. All the carbonaceous deposits were burned-off completely below 450–500 °C.

A Novel Platinum(II)-Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F-Conjugated Trastuzumab.

Greater control is desirable in the stochastic conjugation technology used to synthesize antibody-drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable "semifinal" products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257-67. ©2016 AACR.

Pros and cons of bifunctional platinum(iv) antitumor prodrugs: two are (not always) better than one

This article evaluates the efficacy and applicability of bifunctional prodrugs consisting of a six-coordinate Pt(iv) octahedral core and one or more bioactive molecules. The platinum(iv) complexes release upon reduction the corresponding cytotoxic Pt(ii) agents and the bioactive molecules, able to inhibit some biochemical mechanisms of cancer growth and/or prevent the deactivation of the Pt(ii) metabolites.

Speciation of oxaliplatin adducts with DNA nucleotides

This paper describes a set of fast and selective high performance liquid chromatography (HPLC) methods coupled to electro-spray ionisation linear ion trap mass spectrometry (ESI-MS), sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) and UV detection for in vitro studies of the bifunctional adducts of oxaliplatin with mono-nucleotides, di-nucleotides and cellular DNA. The stationary phases and the optimised conditions used for each separation are discussed. Interaction of oxaliplatin with A and G mono-nucleotides resulted in the formation of five bifunctional platinum diaminocyclohexane (DACHPt) adducts. These were two isomers of the A-DACHPt-A and A-DACHPt-G adducts, and one G-DACHPt-G adduct, as confirmed by MS/MS spectra obtained by collision induced dissociation. These adducts were also characterised by UV absorption data and SF-ICP-MS elemental (195)Pt and (31)P signals. Further, interaction of oxaliplatin with AG and GG di-nucleotides resulted in the formation of three adducts: DACHPt-GG and two isomers of the DACHPt-AG adduct, as confirmed by ESI-MS and the complementary data obtained by UV and SF-ICP-MS. Finally, a very sensitive LC-ICP-MS method for the quantification of oxaliplatin GG intra-strand adducts (DACHPt-GG) was developed and used for monitoring the in vitro formation and repair of these adducts in human colorectal cancer cells. The method detection limit was 0.14 ppb Pt which was equivalent to 0.22 Pt adduct per 10(6) nucleotides based on a 10 μg DNA sample. This detection limit makes this method suitable for in vivo assessment of DACHPt-GG adducts in patients undergoing oxaliplatin chemotherapy.

Kinetic Studies on the Reactions of Different Bifunctional Platinum(II) Complexes with Selected Nucleophiles

AbstractSubstitution reactions of the complexes cis‐[Pt(NH3)2Cl2], [Pt(SMC)Cl2]–, [Pt(en)Cl2], and [Pt(dach)Cl2], where SMC = S‐methyl‐L‐cysteine, en = ethylenediamine and dach = 1,2‐diaminocyclohexane, with selected biologically important ligands, viz. guanosine‐5′‐monophosphate (5′‐GMP), L‐histidine and 1,2,4‐triazole, were studied. All reactions were studied in aqueous 25 mM Hepes buffer in the presence of 5 mM NaCl at pH = 7.2 under pseudo‐first‐order conditions as a function of concentration at 310 K by using UV/Vis spectrophotometry. Two consecutive reaction steps, which both depend on the nucleophile concentration, were observed in all cases. The second‐order rate constants for both reaction steps indicate a decrease in the order [Pt(SMC)Cl2]– > cis‐[Pt(NH3)2Cl2] > [Pt(en)Cl2] > [Pt(dach)Cl2]. DFT calculations (B3LYP/LANL2DZp) showed that the Pt–N7(Guo) adduct is more stable than the Pt–S(thioether) adduct for the studied complexes cis‐[Pt(NH3)2Cl2], [Pt(SMC)Cl2]–, and [Pt(en)Cl2]. The calculations collectively support the experimentally observed substitution of thioethers bound to PtII complexes by N7(5′‐GMP). Finally, this result could be the first to clearly show how much the Pt–N7(Gua) adduct is more stable than the Pt–S(thioether).

A novel link to base excision repair?

DNA interstrand crosslinks (ICLs) can arise from reactions with endogenous chemicals, such as malondialdehyde - a lipid peroxidation product - or from exposure to various clinical anti-cancer drugs, most notably bifunctional alkylators and platinum compounds. Because they covalently link the two strands of DNA, ICLs completely block transcription and replication, and, as a result, are lethal to the cell. It is well established that proteins that function in nucleotide excision repair and homologous recombination are involved in ICL resolution. Recent work, coupled with a much earlier report, now suggest an emerging link between proteins of the base excision repair pathway and crosslink processing.

Hydroisomerization of <i>n</i>-Hexadecane over Pt/Beta and Pt/USY Zeolite Catalysts

Bifunctional platinum (0.8 wt%) catalysts containing beta and USY zeolites were tested for the hydroisomerization of n-hexadecane. The Pt/Beta(SiO2/Al2O3 = 40) catalyst with moderate acid strength showed better isomerization selectivity than the Pt/USY(SiO2/Al2O3 = 11) catalyst which showed higher n-hexadecane conversion but higher hydrocracking activity due to their strong acid sites. The Pt/Beta(SiO2/Al2O3 = 40) catalyst showed high isomerization selectivity and improvement in cold flow property even under more than 90% conversion of n-hexadecane.