Study of benznidazole–cyclodextrin inclusion complexes, cytotoxicity and trypanocidal activity

The current chemotherapy for Chagas disease is still based on benznidazole, which has low solubility, but complexation with cyclodextrins provides a way of increasing the solubility. The objective of this work was to characterize the inclusion complexes formed between benznidazole (BNZ) and randomly 2-methyled-β-cyclodextrin (RM-β-CD) in aqueous solution and study cytotoxicity and trypanocidal. BNZ:RM-β-CD solution complex systems were prepared and characterized using the phase solubility diagram, nuclear magnetic resonance and a photostability assays, also to investigate the in vitro trypanocidal activity with epimastigote forms of Trypanossoma cruzi and the study of cytotoxicity against mammal cells. The phase-solubility diagram displayed an A _L-type feature, providing evidence of the formation of soluble inclusion complexes. The continuous variation method showed the existence of a complex with 1:1 stoichiometry. Toxicity assays demonstrated that inclusion complexes were able to reduce the toxic effects caused by benznidazole alone and that this did not interfere with the trypanocidal activity of the benznidazole. The use of inclusion complexes benznidazole:cyclodextrin is thus a promising alternative for the development of a safe and stable liquid formulation and a new option for the treatment of Chagas disease.     

Expanding the Scope of Arylsulfonylacetylenes as Alkynylating Reagents and Mechanistic Insights in the Formation of Csp2?Csp and Csp3?Csp Bonds from Organolithiums

We describe the unexpected behavior of the arylsulfonylacetylenes, which suffer an “anti‐Michael” addition of organolithiums producing their alkynylation under very mild conditions. The broad scope, excellent yields, and simplicity of the experimental procedure are the main features of this methodology. A rational explanation of all these results can be achieved by theoretical calculations, which suggest that the association of the organolithiums to the electrophile is a previous step of their intramolecular attack and is responsible for the unexpected “anti‐Michael” reactions observed for substituted sulfonylacetylenes.     

Organozinc Pivalate Reagents: Segregation,Solubility, Stabilization,and Structural Insights

The pivalates RZnOPiv⋅Mg(OPiv)X⋅n LiCl (OPiv=pivalate; R=aryl; X=Cl, Br, I) stand out amongst salt‐supported organometallic reagents, because apart from their effectiveness in Negishi cross‐coupling reactions, they show more resistance to attack by moist air than conventional organometallic compounds. Herein a combination of synthesis, coupling applications, X‐ray crystallographic studies, NMR (including DOSY) studies, and ESI mass spectrometric studies provide details of these pivalate reagents in their own right. A p‐tolyl case system shows that in [D₈]THF solution these reagents exist as separated Me(p‐C₆H₄)ZnCl and Mg(OPiv)₂ species. Air exposure tests and X‐ray crystallographic studies indicate that Mg(OPiv)₂ enhances the air stability of aryl zinc species by sequestering H₂O contaminants. Coupling reactions of Me(p‐C₆H₄)ZnX (where X=different salts) with 4‐bromoanisole highlight the importance of the presence of Mg(OPiv)₂. Insight into the role of LiCl in these multicomponent mixtures is provided by the molecular structure of [(THF)₂Li₂(Cl)₂(OPiv)₂Zn].     

Synthesis and Photochromic Properties of Configurationally Varied Azobenzene Glycosides

Spatial orientation of carbohydrates is a meaningful parameter in carbohydrate recognition processes. To vary orientation of sugars with temporal and spatial resolution, photosensitive glycoconjugates with favorable photochromic properties appear to be opportune. Here, a series of azobenzene glycosides were synthesized, employing glycoside synthesis and Mills reaction, to allow “switching” of carbohydrate orientation by reversible E/Z isomerization of the azobenzene N=N double bond. Their photochromic properties were tested and effects of azobenzene substitution as well as the effect of anomeric configuration and the orientation of the sugars 2-hydroxy group were evaluated.     

Large deflection of a non-linear,elastic, asymmetric Ludwick cantilever beam subjected to horizontal force,vertical force and bending torque at the free end

The investigated cantilever beam is characterized by a constant rectangular cross-section and is subjected to a concentrated constant vertical load, to a concentrated constant horizontal load and to a concentrated constant bending torque at the free end. The same beam is made by an elastic non-linear asymmetric Ludwick type material with different behavior in tension and compression. Namely the constitutive law of the proposed material is characterized by two different elastic moduli and two different strain exponential coefficients. The aim of this study is to describe the deformation of the beam neutral surface and particularly the horizontal and vertical displacements of the free end cross-section. The analysis of large deflection is based on the Euler–Bernoulli bending beam theory, for which cross-sections, after the deformation, remain plain and perpendicular to the neutral surface; furthermore their shape and area do not change. On the stress viewpoint, the shear stress effect and the axial force effect are considered negligible in comparison with the bending effect. The mechanical model deduced from the identified hypotheses includes two kind of non-linearity: the first due to the material and the latter due to large deformations. The mathematical problem associated with the mechanical model, i.e. to compute the bending deformations, consists in solving a non-linear algebraic system and a non-liner second order ordinary differential equation. Thus a numerical algorithm is developed and some examples of specific results are shown in this paper.     

Ground-state correlation properties of charged bosons trapped in strongly anisotropic harmonic potentials

We study systems of a few charged bosons contained within a strongly anisotropic harmonic trap. A detailed examination of the ground-state correlation properties of two-, three-, and four-particle systems is carried out within the framework of the single-mode approximation of the transverse components. The linear correlation entropy of the quasi-1D systems is discussed in dependence on the confinement anisotropy and compared with a strictly 1D limit. Only at weak interaction the correlation properties depend strongly on the anisotropy parameter.