Potent 5-nitrofuran derivatives inhibitors of Trypanosoma cruzi growth: electrochemical, spectroscopic and biological studies

Cyclic voltammetry and electron spin resonance techniques were used in the investigation of several potential antiprotozoal containing thiosemicarbazone and carbamate nitrofurans. In the electrochemical behaviour, a self-protonation process involving the nitro group was observed. The reactivity of the nitro anion radical for these derivatives with glutathione, a biological relevant thiol, was also studied in means of cyclic voltammetry. These studies demonstrated that glutathione could react with radical species from 5-nitrofuryl system. Furthermore, from the voltammetric results, some parameters of biological significance as E(7)(1) (indicative of the biological nitro anion radical formation), and [Formula: see text] (thermodynamic indicator the of oxygen redox cycling) have been calculated. We also evaluated the stability of the nitro anion radical in terms of the dimerization constant (k(d)). The nitrofuran-free radicals from cyclic voltammetry were characterized by electron spin resonance. A clear dependence between both the thiosemicarbazone or carbamate substructure and the length of the linker, furyl- or furylpropenyl-spacer, and the delocalization of the unpaired electron was observed. Through of biological assays we obtained important parameters that account for the selective anti-trypanosomal activity of these derivatives. The trypomastigote viability study showed that all derivatives are as active as in the epimastigote form of the parasite in a doses dependent manner.     

Basicity of bisperhalophenyl aurates toward closed-shell metal ions: metallophilicity and additional interactions

The interaction of bisperhalophenyl aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂, and C₆Cl₅) with the closed-shell Ag⁺, Cu⁺, and Tl⁺ ions has been studied theoretically and compared with the experimentally known X-ray diffraction crystal structures. Initially, the aurates have been fully optimized at MP2 level of theory in a D _2h symmetry. The analysis of the basicity of the three aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂ and C₆Cl₅) against Ag⁺ ions in a C _2v symmetry has been calculated in point-by-point bsse-corrected interaction energy analysis at HF and MP2 levels of theory. Taking into account the experimental observation of additional interactions between the heterometals and C _ipso atoms at the perhalophenyl rings or halogen atoms at the ortho position of the perhalophenyl rings, dinuclear models of the type [AuR₂]^?···Ag⁺ (R?=?C₆Cl₅, and C₆F₅); [AuR₂]^?···Cu⁺ (R?=?C₆F₅, and C₆Cl₅) and [AuR₂]^?···Tl⁺ (R?=?C₆F₅, and C₆Cl₅) with a C _2v , C ₂ , and C _s symmetries have been optimized at DFT-B3LYP level. The interaction energies have been computed through bsse-corrected single point HF and MP2 calculations. The energy stabilization provided and the heterometal preference have been analyzed and compared with the experimental results.     

Relaxation of microparticles exposed to hydrodynamic forces in microfluidic conduits

The behavior of microparticles exposed to gravitational and lift forces and to the velocity gradient in flow velocity profile formed in microfluidic conduits is studied from the viewpoint of the transient period (the relaxation) between the moment at which a particle starts to be transported by the hydrodynamic flow and the time at which it reaches an equilibrium position, characterized by a balance of all active forces. The theoretical model allowing the calculation of the relaxation time is proposed. The numerical calculus based on the proposed model is compared with the experimental data obtained under different experimental conditions, namely, for different lengths of microfluidic channels, different average linear velocities of the carrier liquid, and different sizes and densities of the particles used in the study. The results are important for the optimization of microfluidic separation units such as microthermal field-flow fractionation channels in which the separation or manipulation of the microparticles of various origin, synthetic, natural, biological, etc., is performed under similar experimental conditions but by applying an additional thermodynamic force.

Lanthanide dota-like complexes containing a picolinate pendant: structural entry for the design of Ln(III)-based luminescent probes

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ? Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.     

Assessment and formation mechanism of laser-induced periodic surface structures on polymer spin-coated films in real and reciprocal space

In this work we evaluate the potential of grazing incidence X-ray scattering techniques in the investigation of laser-induced periodic surface structures (LIPSSs) in a series of strongly absorbing model spin-coated polymer films which are amorphous, such as poly(ethylene terephthalate), poly(trimethylene terephthalate), and poly(carbonate bisphenol A), and in a weaker absorbing polymer, such as semicrystalline poly(vinylidene fluoride), over a narrow range of fluences. Irradiation was performed with pulses of 6 ns at 266 nm, and LIPSSs with period lengths similar to the laser wavelength and parallel to the laser polarization direction are formed by devitrification of the film surface at temperatures above the characteristic glass transition temperature of the polymers. No crystallization of the surface is induced by laser irradiation, and crystallinity of the material prevents LIPSS formation. The structural information obtained by both atomic force microscopy and grazing incidence small-angle X-ray scattering (GISAXS) correlates satisfactorily. Comparison of experimental and simulated GISAXS patterns suggests that LIPSSs can be well described considering a quasi-one-dimensional paracrystalline lattice and that irradiation parameters have an influence on the order of such a lattice.     

Rational design of a Tn antigen mimic

A novel Tn antigen mimic, in which the natural underlying amino acid has been replaced by the non-natural α-methylserine analogue, is reported. This derivative exhibits a similar affinity for a natural lectin as for the natural Tn and retains the bioactive conformation observed in the Tn-containing glycopeptides with anti-MUC1 antibodies.     

Syntheses, crystal structures, transport properties and first-principles electronic structure study of the (tTTF)2X (X=Br, I) low-dimensional antiferromagnets

An efficient synthetic procedure for the preparation of unsymmetrically substituted tetrathiafulvalene (TTF) donors has been used to obtain the trimethylene-tetrathiafulvalene (tTTF) donor with high purity. Good quality crystals of the two (tTTF)(2)X (X = Br, I) salts have been obtained by electrocrystallization. The two salts are isomorphous and contain tTTF layers which are built from (tTTF)(2) dimeric units. Both systems are low-dimensional antiferromagnets with the highest Ne?el temperatures for TTF based radical cation salts: ≈ 35 K (Br salt) and ≈43 K (I salt). The resistivity is found to substantially decrease with pressure although both salts still have activated conductivity at 25 kbar. First-principles Density Functional Theory (DFT) calculations have been used to investigate the relative strength of the three different types of magnetic interactions in the tTTF layers as well as the potential magnetic ground states. These calculations successfully predict the nature of the ground state and suggest a possible correlation between structural details and Ne?el temperatures for the bromine and iodine salts. Remarkably, the calculated antiferromagnetic ground state can be predicted from the nesting properties of the Fermi surface for the hypothetical Pauli paramagnetic metallic state.     

Extended viologen as a source of electric oscillations

A long organic molecule 1 with five bipyridinium functions separated by benzene rings (extended viologen) undergoes a reversible multi-step electron transfer. Here we show that this decacation accepts electrons at the heterogeneous interface with the occurrence of the periodically changing electric reduction currents. According to the applied bias voltage the observed current-time dependence changes from chaotic through periodic and irregular to sinusoidal and finally to monotonous. A careful choice of the controlling parameters yields the sustained periodic sinusoidal currents lasting for a prolonged time. Oscillations stem from a mutual interplay of the heterogeneous supply of electrons and the homogeneous redox reactions (disproportionation) between the transient redox forms. In difference to many other electrochemical oscillating systems the described oscillations do not require any additional external impedance. The principle of these oscillatory currents may serve as a model of a truly 'molecular oscillator'.     

Recent advances in [2+2+2] cycloaddition reactions

The [2+2+2] cycloaddition is an elegant, atom-efficient and group tolerant process for the synthesis of carbo- and heterocycles, mostly aromatic, involving the formation of several C-C bonds in a single step. Cyclotrimerisation is catalyzed by a variety of organometallic complexes, including more than 15 different metals. The aim of this tutorial review is to point out the most recent advances in this field and to encourage the use of this reaction enroute to complex molecules. After summarizing the most common catalysts and reaction conditions generally used, we survey the mechanistic features currently accepted for this reaction. Section 4 covers the scope of the different [2+2+2] cycloaddition versions starting with the cyclotrimerisation of three triple bonds, including nitriles, with especial emphasis on asymmetric reactions that create central, axial or planar chirality. Then, reactions that use double bonds are addressed. Finally, the most outstanding examples of natural products synthesis using [2+2+2] cycloadditions as a key step reported recently are shown.