Gold dithiocarbamate derivatives as potential antineoplastic agents: design, spectroscopic properties, and in vitro antitumor activity

At present, cisplatin (cis-diamminodichloroplatinum(II)) is one of the most largely employed anticancer drugs as it is effective in the treatment of 70-90% of testicular and, in combination with other drugs, of ovarian, small cell lung, bladder, brain, and breast tumors. Anyway, despite its high effectiveness, it exhibits some clinical problems related to its use in the curative therapy, such as a severe normal tissue toxicity (in particular, nephrotoxicity) and the frequent occurrence of initial and acquired resistance to the treatment. To obtain compounds with superior chemotherapeutic index in terms of increased bioavailability, higher cytotoxicity, and lower side effects than cisplatin, we report here on some gold(I) and gold(III) complexes with dithiocarbamate ligands (DMDT = N,N-dimethyldithiocarbamate; DMDTM = S-methyl-N,N-dimethyldithiocarbamate; ESDT = ethylsarcosinedithiocarbamate), which have been synthesized, purified, and characterized by means of elemental analyses, conductivity measurements, mono- and bidimensional NMR, FT-IR, and UV-vis spectroscopy, and thermal analyses. Moreover, the electrochemical properties of the designed compounds have been studied through cyclic voltammetry. All the synthesized gold complexes have been tested for their in vitro cytotoxic activity. Remarkably, most of them, in particular gold(III) derivatives of N,N-dimethyldithiocarbamate and ethylsarcosinedithiocarbamate, have been proved to be much more cytotoxic in vitro than cisplatin, with IC50 values about 1- to 4-fold lower than that of the reference drug, even toward human tumor cell lines intrinsically resistant to cisplatin itself. Moreover, they appeared to be much more cytotoxic also on the cisplatin-resistant cell lines, with activity levels comparable to those on the corresponding cisplatin-sensitive cell lines, ruling out the occurrence of cross-resistance phenomena and supporting the hypothesis of a different antitumor activity mechanism of action.     

Liquid flame: combustion of metal suspensions in liquid sulfur

Thermodynamic calculations show that some metals can react with sulfur without the formation of gaseous products at normal pressure and yet demonstrate sufficiently high flame temperatures to support the propagation of stable flames. For example, a stoichiometric ternary mixture of iron, manganese, and sulfur demonstrates gasless combustion at an equimolar concentration of iron and of manganese with an adiabatic flame temperature of about 2000 °C. Differential thermal analysis of the mixture shows no exothermic reactions below 280 °C. Therefore, sulfur in the mixture can be safely melted (m.p. 119 °C), converting a powder blend into a liquid suspension that is free from gas bubbles. Symmetrical cylindrical flames in shallow pools of suspensions of Fe and Mn powders in liquid sulfur and combustion of the same liquid mixtures in preheated narrow steel tubes have been studied to determine flame propagation speeds as a function of mixture composition. It was found that, contrary to the behavior of the calculated flame temperature, flame speed decreases with the increase of the manganese content in the mixture and is not affected by mixture dilution with the combustion product. Direct measurements of the flame temperatures by thermocouples indicated a weak dependence of the peak flame temperature on mixture composition and revealed a two-stage flame structure. The existence of the two distinct reaction zones in the mixture of two reactive metals with sulfur is in accordance with qualitative theoretical predictions by the theory of flame with parallel reactions existing in the literature. According to theory, the reaction with the higher flame speed in a corresponding binary single-metal–sulfur mixture will form the leading stage of the complex flame front and will govern the flame propagation speed in the ternary composition. The speed of flame propagation in pure Fe–S mixture is almost three times higher than the flame speed in Mn–S mixture. As a result, the iron–sulfur reaction dominates the flame propagation mechanism in Fe–Mn–S suspension.     

Complexation of quercetin with three kinds of cyclodextrins: an antioxidant study

The slightly water-soluble flavonoid quercetin (QUE) and its inclusion with either beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HP-betaCD) or sulfobutyl ether-beta-cyclodextrin (SBE-betaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in all cases type-A(L) diagrams have been obtained (soluble 1:1 complexes). The results showed that the inclusion ability of betaCD and its derivatives was the order: SBE-betaCD>HP-betaCD>betaCD. Kinetic studies of DPPH with QUE and CDs complexes were done. The results obtained indicated that the QUE-SBE-betaCD complex was the most reactive form. The scavenging capability of QUE and CDs complexes with DPPH and galvinoxyl was studied using ESR spectroscopy. All complexes showed a higher scavenging capability with both radicals, compare quercetin in water. Beside, these results indicated that the complexes formed maintained the quercetin antioxidant activity.     

Synthesis of Weinreb amides via Pd-catalyzed aminocarbonylation of heterocyclic-derived triflates

The direct transformation of lactam-, lactone-, and thiolactone-derived triflates into N-methoxy-N-methyl or morpholine Weinreb amides has been realized using Pd-catalyzed aminocarbonylation under CO atmospheric pressure and at room temperature. The carbonylative coupling can be efficiently carried out with 2% of catalyst in the presence of Xantphos as a ligand. The amides smoothly react with nucleophiles to afford acylated aza-, oxa-, and thio-heterocycles. The proposed methodology could be advantageously exploited for the synthesis of dienones in which one of the double bonds is embedded in a heterocyclic moiety, as useful substrates for Nazarov cyclization.     

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl‐derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one‐carbon coupling partners can be employed, thereby generating cyclopentenes which bear a fully substituted stereocenter [either all‐carbon or heteroatom‐substituted (sulfur and phosphorus)]. Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four‐carbon coupling partner is not the turnover‐limiting step of the catalytic cycle.     

Copper Bromide–Catalyzed C-Alkylation of 2-Amino-1,4-Naphthoquinone: New Synthesis of 1-Azaanthraquinones

Copper(I) bromide catalyzes the regioselective Michael addition reaction of 2-amino-1,4-naphthoquinone (5) with methyl vinyl ketone and 2-propenal to provide easy access to C-alkylated quinone derivatives, useful precursors of 1-azaanthraquinones.     

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.     

Horseradish peroxidase-screen printed biosensors for determination of Ochratoxin A

This work summarizes the manufacturing procedure of Horseradish peroxidase (HRP) based biosensors for the determination of the mycotoxin Ochratoxin A (OTA). The biosensors have been fabricated using the single technology of screen-printing. That is to say, an HRP containing ink has been directly screen-printed onto carbon electrodes, which offers a higher rapidity and simplicity in the manufacturing process of biosensors for OTA determination. The formal redox potential of the Fe(III/II) moiety of HRP has been used to demonstrate the effective loading of enzyme into the ink. The chronoamperometric oxidation current registered has been successfully related to the concentration of OTA in solution from different samples, including beer ones. Under the optimum conditions of the experimental variables, precision in terms of reproducibility and repeatability has been calculated in the concentration range from 23.85 to 203.28 nM. A relative standard deviation for the slopes of 10% (n = 4) was obtained for reproducibility. In the case of repeatability, the biosensor retained a 30% of the initial sensitivity after the third calibration. The average capability of detection for 0.05% probabilities of false positive and negative was 26.77 ± 3.61 nM (α = 0.05 and β = 0.05, n = 3).