Palladium Compounds Research Articles

Thiosemicarbazone Derivatives as Inhibitors of Amyloid-β Aggregation: Effect of Metal Coordination.

Three thiosemicarbazone derivatives, namely 4-(dimethylamino)benzaldehyde 4,4-dimethylthiosemicarbazone (HL1), 4-(dimethylamino)benzaldehyde thiosemicarbazone (HL2), and 4-(dimethylamino)benzaldehyde 4-methylthiosemicarbazone (HL3), have been synthesized and characterized. The three palladium(II) complexes 1-3 were prepared respectively from HL1, HL2, and HL3. The crystal structures of two coordination compounds, namely Pd(L2)2 (2) and Pd(L3)2 (3), were obtained, which showed the expected square-planar environment for the metal centers. The ligand HL3 and the Pd(II) complexes 1-3, which are stable in buffered solutions containing up to 5% DMSO, exhibit remarkable inhibitory properties against the aggregation of amyloid-β, reducing the formation of fibrils. HL1, HL3, 2, and 3 display IC50 values (i.e., the concentrations required to reduce Aβ fibrillation by 50%) below 1 μM, lower that of the reference compound catechin (IC50 = 2.8 μM). Finally, in cellulo studies with E. coli cells revealed that the palladium(II) compounds are significantly more efficient than the free ligands in inhibiting Aβ aggregation inside bacterial inclusion bodies, thus illustrating a beneficial effect of metal coordination.

First Polynuclear Palladium Compounds [(C5H12NO)(PdCl3)]n and [(C10H16NO)2(Pd2Cl6)] with High Antitumor and Radioprotective Activity

Polymeric palladium complexes [(C5H12NO)(PdCl3)]n (I) and [(C10H16NO)2(Pd2Cl6)] (II) were synthesized for the first time and studied by X-ray diffraction. Complexes I and II were found to have moderate toxicity (3rd class of toxicity) and high antitumor and radioprotective activities. Treatment of Lewis lung carcinoma (LLC) with I and II induced statistically significant antitumor and antimetastatic effects exceeding those of cisplatin: the use of I and II retarded the growth of LLC by 60.0%, while cisplatin retarded it by 48.0%. The decrease in the LLC metastasis was 75% upon the action of I, 91.0% in the case of II, and 69.0% for cisplatin. It was shown that II has a clear-cut radioprotective action. On single exposure of mice to a dose of 8.2 Gy, their survival rate was 58.0% versus 4.5% for the control. Fractional exposure to increasing doses (2.5, 3, and 3.5 Gy) resulted in 75.0% survival rate versus 33.0% for the control.

Biological Potential and Structure Activity Relationships in Organotin (IV) and Pd(II) Compounds

Organotin(IV) and palladium(II) complexes are mainly synthesized by treating a N,O or S donor ligand with an organotin halide and PdCl2, respectively. The structures of the complexes can be elucidated by various characterization techniques such as microanalysis (CHNS), FTIR spectroscopic analysis, UV-Visible spectroscopy, NMR (1H & 13C) and single crystal XRD. Organotin compounds are applied in numerous biocidal formulations as wood preservatives, surface disinfectants, antitumor agents, insecticides, marine antifouling paints, mollucides, miticides and fungicides. The biochemical activity is mainly affected by coordination number of tin, number and nature of the organic group bonded to tin and the chain length of an alkyl groups. Organotin(IV) dithiocarbamates are famous for their acaricidal, antifungal, tuberculostatic, antibacterial and anticarcinogenic activities. Cisplatin which is a famous Pt(II) drug, is successfully applied either alone or in various combinations to treat cancer. However, There is also a growing interest in the discovery of alternate drugs with palladium(II) because there are considerable similarities between the coordination chemistry of palladium(II) and platinum(II) compounds. However, the palladium complexes dissociate readily and form reactive species which could not reach their pharmacological targets. This drawback can be overcome by synthesizing Pd(II) complexes with chelating ligands such as dithiocarbamates. Pd(II) and Pt(II) compounds with bioactive ligands are of special interest due to their possibility of oral administration, lower toxicity and their ability to coordinate with DNA. Organotin(IV) derivatives possess strong antibacterial and antifungal potential while palladium(II) complexes are chiefly famous for their antitumor and anticancer activities. The nature of a metal coordinated to the ligand, has a decisive role in biological activities of both kinds of compounds.

Complementary methods for characterization of the corrosion products on the surface of Ag60Cu26Zn14 and Ag58.5Cu31.5Pd10 brazing alloys

AbstractCorrosion products formed on the surface of two silver brazing alloys after the potentiostatic polarization in 3.5% sodium chloride solution were characterized by the standard methods such as, the X-ray diffraction, micro-Raman spectroscopy, and scanning electron microscopy with energy-dispersive spectroscopy. This paper presents the results of a laser desorption/ionization mass spectrometry (LDI MS) analysis as a new approach to the characterization of corrosion products. The potential of the anodic polarization was 0.5 V versus saturated calomel electrode, and the process duration was 300 s. The corrosion layers on both investigated alloys were similar in composition with cuprous chloride and silver chloride as the main components and had strong indications of cuprous oxide formation. The major difference between these two layers was the existence of zinc hydroxychloride as the corrosion product of Ag-Cu-Zn alloy. Palladium compounds were not found in the case of Ag-Cu-Pd alloy. The results of different methods have shown a good consistency. Complementarity between the used methods was useful in the interpretation of the results for each used method. This study has demonstrated that LDI MS can be used as an efficient additional method together with the traditional ones.

A series of (NHC)Pd(N˄O)(OAc) complexes: synthesis, characterization and catalytic activities towards desulfinative Sonogashira coupling of arylsulfonyl hydrazides with arylalkynes

A series of well‐defined N‐heterocyclic carbene palladium (II) complexes with general formula (NHC)Pd(N˄O)(OAc) were prepared through reaction of Pd (NHC)(OAc)2(H2O) with 1‐methyl‐1H‐pyrazole‐3‐carboxylic acid or 1‐methyl‐1H‐indazole‐3‐carboxylic acid in the presence of K2CO3. These complexes were then used for desulfinative Sonogashira coupling of arylsulfonyl hydrazides with terminal alkynes. With low catalyst loading, all synthesized palladium compounds exhibited moderate to high catalytic activities for the reactions.

Crystal Structure, Antitumour and Antibacterial Activity of Imidazo[1, 2‐α]pyridine Ligand Containing Palladium Complexes

AbstractDue to similar coordination chemistry of palladium with platinum, a lot of palladium compounds investigated for their anticancer activity after the discovery of cisplatin. Imidazo[1, 2‐α]pyridine is a drug precursor scaffold and has already been successfully utilized to come up with a number of clinical drugs against various diseases. In this present study anticancer and antimicrobial activity of three palladium complexes e. g. [PdL4]2Cl (coded as NH4), PdL2Cl2 (coded as NH5) and [PdL4]2Cl.(4H2O).L (coded as NH6) where L=imidazo[1,2‐α]pyridine ligand has been described. All of the synthesized palladium complexes have been characterized by elemental microanalysis and spectral techniques. [PdL4]2Cl and [PdL4]2Cl.(4H2O).L were also characterized by single crystal X‐ray diffraction method. MTT reduction assay was used to determine the anticancer activity against three human ovarian tumour models and three colorectal tumour models. PdL2Cl2 has shown moderate anticancer activity with lower resistance factor value against ovarian cancer model compared to clinical standard cisplatin. The same complex also exhibited significant antitumour activity in all colorectal tumour models. The rest of the complexes did not show significant anticancer activity but one of the complexes displayed promising antibacterial activity against Staphylococcus aureus. PdL2Cl2 could act at least as a lead to develop new anticancer agent.

Redox, transmetalation, and stacking properties of tetrathiafulvalene-2,3,6,7-tetrathiolate bridged tin, nickel, and palladium compounds.

Here we report that capping the molecule TTFtt (TTFtt = tetrathiafulvalene-2,3,6,7-tetrathiolate) with dialkyl tin groups enables the isolation of a stable series of redox congeners and facile transmetalation to Ni and Pd. TTFtt has been proposed as an attractive building block for molecular materials for two decades as it combines the redox chemistry of TTF and dithiolene units. TTFttH4, however, is inherently unstable and the incorporation of TTFtt units into complexes or materials typically proceeds through the in situ generation of the tetraanion TTFtt4−. Capping of TTFtt4− with Bu2Sn2+ units dramatically improves the stability of the TTFtt moiety and furthermore enables the isolation of a redox series where the TTF core carries the formal charges of 0, +1, and +2. All of these redox congeners show efficient and clean transmetalation to Ni and Pd resulting in an analogous series of bimetallic complexes capped by 1,2-bis(diphenylphosphino)ethane (dppe) ligands. Furthermore, by using the same transmetalation method, we synthesized analogous palladium complexes capped by 1,1′-bis(diphenylphosphino)ferrocene (dppf) which had been previously reported. All of these species have been thoroughly characterized through a systematic survey of chemical and electronic properties by techniques including cyclic voltammetry (CV), ultraviolet-visible-near infrared spectroscopy (UV-vis-NIR), electron paramagnetic resonance spectroscopy (EPR), nuclear magnetic resonance spectroscopy (NMR) and X-ray diffraction (XRD). These detailed synthetic and spectroscopic studies highlight important differences between the transmetalation strategy presented here and previously reported synthetic methods for the installation of TTFtt. In addition, the utility of this stabilization strategy can be illustrated by the observation of unusual TTF radical–radical packing in the solid state and dimerization in the solution state. Theoretical calculations based on variational 2-electron reduced density matrix methods have been used to investigate these unusual interactions and illustrate fundamentally different levels of covalency and overlap depending on the orientations of the TTF cores. Taken together, this work demonstrates that tin-capped TTFtt units are ideal reagents for the installation of redox-tunable TTFtt ligands enabling the generation of entirely new geometric and electronic structures.

СИНТЕЗ И СТРУКТУРА КОМПЛЕКСА ПАЛЛАДИЯ (II) С 2-ЭТИЛ, - 6 МЕТИЛ - 3 - ГИДРОКСИПИРИДИНОМ

New complex compounds of palladium (II) with biologically active ligand 2-ethyl6 methyl-3-hydroxy-pyridine-mexidol in acidic medium (pH=5.3) of the following composition have been synthesized – 8 12 2 4 (C H ON) PdCl ⊕     . In this case, the ligand is protonated and as a single-charged cation occupies an external coordination sphere. The structure of the complex is proved by X-ray structure analysis. It is shown that the structure is constructed of an isolated complex anion – [PdCl4]2- and cation C H ON 8 12 ⊕ . The square planar coordination of the palladium atom is formed from three chlorine atoms and the formed tetraacidoanion ligand forms a hydrogen bond. The average length of Pd-Cl bond is 2.3030 0 A, there are no deviations from 900 valence angles of Cl-Pd-Cl. The palladium atom is not shifted from the plane coordination polyhedron (square) and therefore trance angles of Cl-Pd-Cl are 1800. Two different lengths -2.289 0 A and 2.713 0 A of hydrogen bonds are related to the geometric location of the ligand functional group. The obtained 2-ethyl-6-methyl-3-hydroxypyridinetrachloro - palladium - mexidazole was tested for radioprotective properties. Toxicity of the preparation is LD50 - 240 mg/kg of animal weight. Toxicological studies of mexidazole in mice, rats and dogs did not reveal cardiotoxic, immunotoxic, embryonic, nephrotoxic, hematoxic and other types of side effects. Mexidazole is removed from the body with urine 5-8 hours after intravenous injection. The carried out biological test showed that the compound, along with radioprotective properties, has some antitumor activity.

Reactivity of metallic palladium in a K2CO3-K2O-B2O3-Al2O3 melt

The reactivity of metallic palladium in a K2CO3-K2O-B2O3 melt is investigated as a function of heating temperature and time. The aqueous solubility of heat-treated palladium is enhanced by controlling the heating conditions leading to an optimum palladium extraction of 53% from the heat-treated product. The alumina crucible used as a reactor partially dissolves during the heating of metallic Pd, which requires the analysis of palladium solubilization to be discussed in terms of K2CO3-K2O-B2O3-Al2O3 system. Oxidized palladium combines with boron and aluminum oxyanions as ligands in the molten medium to form water-soluble palladium compounds. Information regarding water-soluble palladium compounds was obtained by analyzing the precipitate collected from the palladium-containing solution produced by water-leaching of the heat-treated product. The precipitate contained Pd (0.19 wt%), Al (0.74 wt%), B (2.6 wt%), and K (45 wt%). Raman spectroscopy confirmed the presence of oxidized palladium in the precipitate. Aluminum oxyanions with AlO4 and AlO6 structures and boron oxyanions as diborate groups also were detected in the precipitate.

EXTH-17. TREATMENT OF MALIGNANT GLIOMAS WITH DRUG-LOADED MICROBUBBLES: CONCEPTION OF A PROMISING FUTURE THERAPEUTIC STRATEGY

Abstract The major obstacles for an effective chemotherapy of glioblastomas (GBM) are the blood-brain barrier (BBB) and serious systemic side effects of the cytotoxic drugs. A new promising strategy could be the delivery of the chemotherapeutics across the BBB to the tumor site encapsulated in microbubbles. The microbubbles will shield the drug from detrimental systemic effects. Low intensity focused ultrasound (LIFU) allows opening of the BBB and a targeted release of the drugs within the brain tumor. We synthesized microbubbles ≤ 2 µm in diameter by thin-film hydration of lipids, which could be disintegrated applying LIFU. The toxicity was tested on GBM cell lines and neither the intact bubbles nor the lipids alone showed any toxic effects. Additionally, these cells were treated with 6 platinum(II) and palladium(II) complexes conjugated to lipophilic side chains of different length (C1, C8, C10) for 72 h. Cell viability was evaluated with MTT assay and in real-time utilizing the impedance-based xCELLigence DP-System. EC50 values were calculated from both assays and all six drugs were highly effective. Especially the palladium(II) compound with the C1-chain had a very low EC50 value (< 10 µM), while the longer chains and the platinum(II) compounds were less effective (EC50 10 - 30 µM). The real time proliferation assay of the drugs revealed an early and concentration-dependent onset of the cytotoxic effect, about 30 h after application. The lipophilic side chains of the drugs should allow encapsulating them into the microbubbles to develop an effective drug-delivery system for the treatment of GBM.

Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species.

The in chemico Direct Peptide Reactivity Assay (DPRA) was developed as a non-animal, relatively high throughput, screening tool for skin sensitization potential. Although the Adverse Outcome Pathway (AOP) for respiratory sensitization remains to be fully elucidated, it is recognized that the molecular initiation event for both skin and respiratory sensitization to low molecular weight chemicals involves haptenation with proteins. The DPRA examines the reactivity of a test compound to two model peptides (containing either cysteine or lysine) and consequently is able to screen for both skin and respiratory sensitization potential. The DPRA was primarily developed for and validated with organic compounds and assessment of the applicability of the assay to metal compounds has received only limited attention. This paper reports the successful application of the DPRA to a series of platinum compounds, including hexachloroplatinate and tetrachloroplatinate salts, which are some of the most potent chemical respiratory sensitizers known. Eleven platinum compounds were evaluated using the DPRA protocol as detailed by Lalko et al., with only minor modification. Two palladium compounds with structures similar to that of the platinum species studied and cobalt chloride were additionally tested for comparison. The hexachloroplatinate and tetrachloroplatinate salts showed exceptionally high reactivity with the cysteine peptide (EC15 values of 1.4 and 14 μM, respectively). However, for platinum compounds (e.g. hydrogen hexahydroxyplatinate and tetraammineplatinum) where clinical and epidemiological evidence indicates limited sensitization potential, the cysteine DPRA showed only minor or no reactivity (EC15 values of 24 600 and >30 000 μM, respectively). The outcomes of the lysine peptide assays were less robust and where EC15 was measurable, values were substantially higher than the corresponding results from the cysteine assay. This work supports the value of in chemico peptide reactivity as a metric for assessment of platinum sensitization potential and therefore in screening of new platinum compounds for low or absent sensitization potential. Additional studies are required to determine whether the DPRA may be successfully applied to other metals. We provide details on method modifications and precautions important to the success of the DPRA in the assessment of metal reactivity.

Improved Synthesis, Anticancer Activity and Electrochemical Characterization of Unusual Zwitterionic Palladium Compounds with a Ten‐Term Coordinative Ring.

AbstractA new improved synthetic protocol for the preparation of uncommon zwitterionic palladium(II) complexes with a ten‐term coordinative ring is reported. A suitable combination of reaction solvent and temperature allows to drastically reduce the reaction time and increase the yield. A detailed kinetic study, implemented by theoretical DFT calculations, clarifies and quantifies this solvent effect. The antiproliferative activity of the synthesized complexes was tested toward eight different cancer cell lines. The mesityl derivative showed potent and selective cytotoxicity toward several types of cancer cell lines, with IC50 values lower than cisplatin. Additionaly, the anticancer activity against cisplatin‐sensitive and cisplatin‐resistant ovarian cancer cells suggested a different mechanism of action with respect to traditional platinum chemotherapeutics. Aiming to easily determine these promising metallo‐drugs, a voltammetric study of their electrochemical fingerprint was carried out. For both compounds a suitable signal, ascribed to the reduction of the metallic center from palladium(II) to palladium(0), was identified and further investigated by Differential Pulse Voltammetry.

Electrochemical evaluation of intermediate reduction of p-nitrophenol to nitroso derivative at palladium-phosphate electrode

ABSTRACT A novel voltammetric sensor for the determination of p-nitrophenol has been developed using carbon paste electrode (CPE) modified by metallic palladium (Pd) supported onto natural phosphate (NP). The proposed protocol demonstrates the successful application of palladium compounds in the electrochemical determination of p-nitrophenol (p-NP) in acetate buffer (pH 4.7). Indeed, the palladium displayed a strong catalytic action towards p-nitrophenol reduction. Electrochemical methods including square wave voltammetry (SWV) and chronoamperometry have been used to evaluate the electrochemical behaviour of the palladium towards the catalytic reduction of p-NP. In addition, the proposed electrode was able to catalyse and visualise the intermediate reaction of the nitro group reduction to nitroso group.

P11.44 Conception of a promising future therapy: Drug loaded-microbubbles against glioblastoma

Abstract BACKGROUND Major obstacles for an effective chemotherapy of glioblastomas (GBM) are the blood-brain-barrier (BBB) and serious systemic side effects of the cytotoxic drugs. A new promising strategy could be the delivery of microbubbles, encapsulating the chemotherapeutics, across the BBB to the tumor site. This will shield the drug from detrimental systemic effects. Low intensity focused ultrasound (LIFU) is able to open the BBB and triggers targeted release of the drugs within the tumor. First data on the synthesis of microbubbles, specifically designed new drugs and the targeted rupture of microbubbles by LIFU are presented. MATERIAL AND METHODS Thin-film hydration of lipids was utilized to prepare microbubbles, which were tested for toxicity on the GBM cell lines GaMG, U87, U138 and U343. In addition these cells were treated with 6 platinum(II) and palladium(II) complexes conjugated to lipophilic side chains of different length (C1, C8, C10) for 72h. To evaluate cell viability and calculate EC50 values MTT assays and a real-time proliferation assay using the impedance-based xCELLigence DP-System were executed. RESULTS Microbubbles ≤ 2µm in diameter were synthesized and could be disintegrated by applying LIFU. Neither the intact bubbles nor the lipids alone had any toxic effects on the GBM cells. In contrast, all six drugs were highly effective with EC50 values far below those of Temozolomide (67µM) and in the range of the reference drug cisplatin (3µM). Especially the palladium(II) compound with the C1-chain displayed a very low EC50 value (<10µM), while the longer chains and the platinum(II) compounds were less effective (EC50 10–40µM). An early and concentration-dependent onset of the cytotoxic effect of drugs with C1 and C8 side chains was revealed in the real time proliferation assay. CONCLUSION All components for a new microbubble-based therapeutic strategy are in place. Microbubbles were synthesized without having toxic effects in cell culture. New highly potent palladium(II) and platinum(II) compounds with low EC50 values were developed. The next step will be their encapsulation into the microbubbles via their lipophilic side chains to develop an effective drug-delivery system for the treatment of GBM in combination with LIFU. This will allow increasing the local concentration of chemotherapeutic agents at the tumor site, irrespectively of their molecular size and BBB penetration capacity.

Synthesis, crystal structure and intermolecular contacts in trans-bis(ethylamine) dichloro platinum(II) and palladium(II) complexes

The methods of synthesis of trans-bis(ethylamine)dichloro platinum(II) (trans-[Pt(C2H5NH2)2Cl2]) and palladium(II) (trans-[Pd(C2H5NH2)2Cl2]) complexes for obtaining monophase products were developed. For substance characterizations FTIR spectroscopy, thermogravimetric and X-ray diffraction analysis were used. The crystal structures of the synthesized compounds were determined using X-ray powder diffraction technique. The neutral complexes had specific system of intermolecular contacts in the crystals that allowed distinguishing two forms, A and B. Despite of the similar structure and sizes, trans-[Pt(C2H5NH2)2Cl2] and trans-[Pd(C2H5NH2)2Cl2] complexes created different hydrogen bond networks and crystal structures. The first had a grid topology of 36 with the cells from three and the second - 44 from four complexes. It resulted in different thermal behavior. Trans- [Pt(C2H5NH2)2Cl2]-A demonstrated irreversible solid state transition into B-form at 165 °C and got new H-bond system with the topology similar to the palladium analog (44), however, the realized complex arrangement was significantly different. The structure of B-form was stable until the decomposition at 220°С. High-temperature X-ray diffraction demonstrated high elasticity of the H-bond network in trans-[Pd(C2H5NH2)2Cl2]-A. Notwithstanding significant alterations during heating, the H-bond system returns the structure to its initial state.The interpretation of structural transformation was proposed. The H-bond network formation was influenced by the dynamic properties of the molecules. For the platinum compound, the option with more dense molecular packing occurred. For palladium, the atomic mass distribution was responsible for a larger molecular volume and for a more symmetrical packing. Thermal decomposition of both compounds occurred with simultaneous separation of the halogen and amminoalkyl particles resulting in a low-temperature reduction of the metal and the formation of nanoparticles with sizes in the range of 5–10 nm. For the palladium compound, the decay in vacuum had a noticeable rate already at 100 °C.

The system thorium-palladium-boron: A DFT study on the stability and properties of Th2Pd15B5

Phase relations in the Th-Pd-B system were determined via electron microprobe and X-ray powder diffraction analyses of ∼20 ternary alloys. Phase equilibria are dominated by the two high-melting thorium borides ThB4, Th1-yB6 and one ternary compound, namely τ1-Th2Pd14+xB5, with a structure deriving from the Sc4Ni29B10-type. Th1-yB6 is the binary starting point of a continuous solid solution up to ThPd0.53B4.28 closely corresponding to the superconducting phase Th1-yPdxB6-2x (x ≤ 0.65; 0 ≤ y ≤ 0.22 at x = 0; TC = 21 K), which was described by Zandbergen et al. in 1995 for x = 0.65 from high resolution electron microscopy. All thorium-rich palladium compounds from 0 to 75 at.% Pd form stable two-phase equilibria with ThB4 without any significant mutual solid solubilities. The solubility of Th in βB has been determined for the first time from a single crystal X-ray study of ThB99: Th atoms occupy sites A1 (occ. = 13%), D (occ. = 11%), and a rather small amount of 2.9% resides in site 18f (Dd-hole).To shed light on the physical properties of the ternary compound, DFT (density functional theory) calculations were performed for two idealized representatives of the τ1-phase, namely for Th2Pd14B5 and Th2Pd15B4. The calculations cover ionic relaxation, electron density of states, band structure and Fermi surfaces, elastic constants (computed via the linear response method) and the phonon density of states. Furthermore the thermodynamic stability (energy of formation) as well as the phonon contribution of the thermodynamic properties, such as the specific heat have been calculated clearly indicating Th2Pd15B4 as the composition thermodynamically more stable than Th2Pd14B5. At the Fermi energy the Pd-d contribution is dominant for both structures, but the number of states is higher for Th2Pd15B4 with DOS(EF) = 13 states/eV/f.u. than for Th2Pd14B5 with DOS(EF) = 8.5 states/eV/f.u. The corresponding Sommerfeld constants, γe = DOS(EF)kBπ2/3 = 30.55 mJ/molK2 for Th2Pd15B4 and 19.98 mJ/molK2 for Th2Pd14B5, clearly indicate metallic behavior of the τ1-phase. In addition, mechanical properties were measured for Th2Pd15B5 and compared with calculated values and data from the literature. Th2Pd15B5 on account of its high content of Pd is only slightly harder than the rather soft and almost ductile binary Pd-borides.

Catalytic cyclopropanation of spiro[2.4]hepta-4,6-diene with diazomethane

Catalytic cyclopropanation of spiro[2.4]hepta-4,6-diene with diazomethane in the presence of copper or palladium compounds results in mono- and dicyclopropanation products, namely, spiro[bicyclo[3.1.0]hex-3-ene-2,1′-cyclopropane] and spiro[cyclopropane-1,5′-tricyclo[4.1.0.02,4]heptane], with different efficiency. The use of Pd compounds as catalysts allows the cyclopropanation to be performed under conditions of simultaneous generation and decomposition of diazomethane.

NMR-Based Metabolomics in Metal-Based Drug Research

Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.

Синтез производных 1-фенилиндолов

The growing needs of medicine and pharmacology induce synthetic organic chemistry to constantly be in the process of modernizing existing methods of synthesis and developing new ones. Since ancient times, the high physiological activity of indole derivatives has been widely known. Indole is a heterocyclic condensed aromatic compound that is part of the molecules of a multitude of compounds with biochemical and physiological value. A large number of drugs of the indole group obtained synthetically are derivatives of arylindols. One of the most common methods of obtaining arylindoles is the use of Ulman reaction conditions. However, this technique involves the use of high temperatures and a large amount of aryl halide to obtain optimal yields. Some classical methods suggest the use of palladium compounds as a catalyst, which are highly prices and require inert conditions, which limits their uses in the syntheses and reduces the overall synthetic attraction. In order to mitigate the conditions of the Ulman reaction and increase the reaction yields, methods have been proposed for the synthesis of 1-phenylindole derivatives based on the introduction of phenyldiodide by arylating the nitrogen atom in position 1 of the 5-methoxyindole indole ring in the presence of monovalent copper chloride using phenanthroline and anthracene as ligands, followed by heteroarylation the compounds obtained quinoline and isoquinoline in the presence of benzoyl chloride and 2-bromo-3-methylbutanoyl chloride. The physical and chemical characteristics of the compounds obtained were determined. Installed using 1H NMR spectroscopy and elemental analysis of the structure of the obtained derivatives are in good agreement with the proposed structural formulas. According to a review of literature data, the obtained structures can be supposedly used to research their physiological activity.

Synthesis, characterization and cytotoxic activity of tioconazole coordination compounds with nickel(II), palladium(II) and platinum(II)

Coordination compounds of nickel(II), palladium(II) and platinum(II) with tioconazole (tcnz) were synthesized and characterized by infrared, UV-Vis-NIR, elemental analysis, molar conductivity, magnetic susceptibility, mass spectrometry, NMR spectroscopy and X- ray diffraction. Tioconazole presented a monodentate coordination mode, through the nitrogen atom of the imidazolic ring. The NiII compounds stabilized an octahedral geometry. In [Ni(tcnz)2(NO3)2].H2O the coordinated nitrate presented a bidentate coordination mode, while for the [Ni(tcnz)2(OAc)2].3H2O compound, the acetate behaves as a bridging ligand. When different molar ratios were used on the reaction synthesis, three or six ligands were coordinate to the nickel(II) atom, [Ni(tcnz)3Br2(H2O)], [Ni(tcnz)6]Cl2 and [Ni(tcnz)6]Br2. The palladium(II) and platinum(II) compounds, [Pd(tcnz)2Cl2], [Pt(tcnz)2Cl2].2H2O and [Pd(tcnz)2(OAc)2], stabilized a trans-square planar geometry. The compounds [Ni(tcnz)6]X2 give place to 3D supramolecular arrangements through hydrogen bonding (X∙∙∙H, X = Cl and Br) and p∙∙∙p stacking interactions, between the six membered rings of neighbouring molecules. The in vitro cytotoxic activity of the synthesized compounds was studied in four different human carcinoma cell lines: HCT-15 (colon), HeLa (cervix-uterine), MCF-7 (breast) and PC-3 (prostate).