Preyssler catalyst-promoted rapid,clean, and efficient condensation reactions for 3H-1,5-benzodiazepine synthesis in solvent-free conditions

A simple, convenient, and environmentally benign synthesis of 1,5-benzodiazepines is developed by condensing different o-phenylenediamines and 1,3-aryl-1,3-propanodiones. The reaction is catalyzed by a Preyssler (NaH₁₄P₅W₃₀O₁₁₀, HPA) heteropolyacid as a safe, clean, and recyclable catalyst. The method is operationally simple and provides access to a variety of 1,5-benzodiazepines in good to excellent yields.     

Diphenylalanine Motif Drives Self-Assembling in Hybrid PNA-Peptide Conjugates

Peptides and nucleic acids can self-assemble to give supramolecular structures that find application in different fields, ranging from the delivery of drugs to the obtainment of materials endowed with optical properties. Forces that stabilize the “suprastructures” typically are hydrogen bonds or aromatic interactions; in case of nucleic acids, Watson-Crick pairing drives self-assembly while, in case of peptides, backbone hydrogen bonds and interactions between aromatic side chains trigger the formation of structures, such as nanotubes or ribbons. Molecules containing both aromatic peptides and nucleic acids could in principle exploit different forces to self-assemble. In this work we meant to investigate the self-assembly of mixed systems, with the aim to understand which forces play a major role and determine formation/structure of aggregates. We therefore synthesized conjugates of the peptide FF to the peptide nucleic acid dimer “gc” and characterized their aggregates by different spectroscopic techniques, including NMR, CD and fluorescence.     

Transport properties and current inversion by white Gaussian noise in a coupled ratchet model

We have found, by varying two parameters, several stationary trajectories in a system consisting in many elastically coupled particles that are placed in a periodic ratchet potential on a ring. The system is assumed to be over-damped and driven by an external potential that is periodic both in space and time. The transport properties of these orbits are quite different and their values are quantified. The symmetries allow us to study the orbits with and without the presence of thermal fluctuations and there is found current inversions due to the addition of white Gaussian noise.     

β-Hairpin stabilization through an interstrand triazole bridge

β-Hairpin peptides were conformationally stabilized through a 1,4 disubstituted 1,2,3-triazole interstrand linkage. A NMR conformational analysis revealed that the β-hairpin content depends on the number and position of substituent methylene units of the 1,2,3-triazole ring. These results will allow the design of metabolically stable peptidomimetic analogs of bioactive β-hairpin peptides.     

Transport and dynamical properties of inertial ratchets

In this paper we discuss the dynamics and transport properties of a massive particle in a ratchet type potential immersed in a dissipative environment. The directional currents and characteristics of the motion are studied as the specific frictional coefficient varies, finding that the stationary regime is strongly dependent on this parameter. The maximal Lyapunov exponent and the current show large fluctuations and inversions, therefore for some range of the control parameter, this inertial ratchet could originate a mass separation device. Also an exploration of the effect of a random force on the system is performed.     

Hydrogen mean force and anharmonicity in polycrystalline and amorphous ice

The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitivity to anharmonicity in the hydrogen-nucleus effective potential. The shape of the mean force for amorphous and polycrystalline ice is primarily determined by the anisotropy of the underlying quasi-harmonic effective potential. The data from amorphous ice show an additional curvature reflecting the more pronounced anharmonicity of the effective potential with respect to that of ice Ih.     

Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives

As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-yn-19′-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-ynyl)butanolide (2), from the seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound 1 showed an IC₅₀ value of 29.9 μM against the intracellular amastigote forms of Leishmania (L.) infantum, whereas compound 2 was inactive. These results suggested that the terminal double bond plays an important role in the activity. This effect was also observed for the semisynthetic acetylated (1a and 2a) and eliminated (1b and 2b) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC₅₀ values of 43.3 μM (1a) and 23.1 μM (1b). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds 1 + 2 was subjected to catalytic hydrogenation to afford a compound 3 containing a saturated side chain. The antiparasitic assays performed with compound 3, acetylated (3a), and eliminated (3b) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds 1, 1a, and 1b in order to investigate their physicochemical parameters, pharmacokinetics, and drug-likeness. Despite the reduced effect against amastigote forms of the parasite to the purified compounds, different mixtures of compounds 1 + 2, 1a + 2a, and 1b + 2b were prepared and exhibited IC₅₀ values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC₅₀ > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of Porcelia macrocarpa are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.     

Degenerate Second Order Differential Operators Generating Analytic Semigroups in Lp and W1,p

We deal with the problem of analyticity for the semigroup generated by the second order differential operator Au ≔ αu″ + βu′ (or by some restrictions of it) in the spaces L^p(0, 1), with or without weight, and in W^1,p(0, 1), 1 < p < ∞. Here α and β are assumed real‐valued and continuous in [0, 1], with α(x) > 0 in (0, 1), and the domain of A is determined by the generalized Neumann boundary conditions and by Wentzell boundary conditions.