Vat Photopolymerization 3D Printing of Hydrogels with Re-Adjustable Swelling.

Vat photopolymerization typically prints highly crosslinked networks. Printing hydrogels, which are also networks but with a high swelling capacity in water and therefore with low crosslinking density, is a challenge for this technique. However, it may be of interest in medicine and in other areas, since it would allow for the preparation of this type of 3D-shaped material.

Evaluation of Poly(-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells.

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects.

Study of the Addition Mechanism of 1-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions.

The reaction of -indazoles with formaldehyde in aqueous hydrochloric acid has been experimentally studied by solution and solid-state nuclear magnetic resonance (NMR) and crystallography. The mechanism of the formation of -CHOH derivatives was determined. For the first time, 2-substituted derivatives have been characterized by multinuclear NMR.

The use of DOSY experiments to determine the solution structures of coinage metal pyrazolates: The case of {[3,5-(CF ) Pz]Ag}.

A series of DOSY experiments have been carried out to determine the solution stoichiometry of silver(I) 3,5-bis (trifluoromethyl)pyrazolate species. This compound exists as a trimer in the solid state (n = 3) but in solutions of chlorinated solvents, the DOSY data suggest the presence of a mixture of solvent stabilized monomer (n = 1) and dimer (n = 2) in equilibrium. Different approximations have been used including the Stokes-Einstein and the Stokes-Einstein-Gierer-Wirtz equations.

Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles.

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC = 74.

A static and dynamic NMR study of 10-hydrazino-BODIPY.

10-Hydrazino-BODIPY, BoNHNH , presents slow rotation about the C10-NH bond that results in anisochronous H and C NMR signals. The assignment of the different signals has been made using traditional two-dimensional methods as well as spin-spin coupling constants and confirmed by DFT calculations (B3LYP) using the 6-311++G(d,p) basis set. The rotational barrier has been determined in three pairs of proton signals and compared with the calculated barrier.

A GIPAW versus GIAO-ZORA-SO study of C and N CPMAS NMR chemical shifts of aromatic and heterocyclic bromo derivatives.

Theoretical simulation of NMR parameters in compounds bearing heavy atoms generally requires the application of relativistic corrections. We report herein the theoretical characterization of C and N CPMAS NMR of known bromo-derivative crystals by using both the GIPAW and the combined GIAO-ZORA-SO approximation methods. Several statistical analyses were performed to compare both approaches, with non-relativistic GIPAW method being more useful to predict the C and N chemical shifts.

The synergy of different solid-state techniques to elucidate the supramolecular assembly of two 1H-benzotriazole polymorphs.

1H-Benzotriazole crystallizes as two different polymorphs, namely 4aα and 4aβ. One polymorph is chiral and it resolves spontaneously as conglomerates. The other polymorph crystallizes in a centrosymmetric space group and it is therefore achiral.

Bond Length Alternation Observed Experimentally: The Case of 1H-Indazole.

Bond length alternation is a chemical phenomenon in benzene rings fused to other rings, which has been mainly predicted theoretically. Its physical origin is still not clear and has generated discussion. Here, by using a strategy that combines microwave spectroscopy, custom-made synthesis and high-level ab initio calculations, we demonstrate that this phenomenon is clearly observed in the prototype indazole molecule isolated in the gas phase.

An Example of Polynomial Expansion: The Reaction of 3(5)-Methyl-1-Pyrazole with Chloroform and Characterization of the Four Isomers.

The reaction in phase-transfer catalyzed conditions of 3(5)-methyl-1-pyrazole with chloroform affords four isomers , , and in proportions corresponding to the polynomial expansion (a + b)³, with a = 0.6 and b = 0.4, a and b being 3-methyl and 5-methyl proportions.

A theoretical NMR study of polymorphism in crystal structures of azoles and benzazoles.

The NMR chemical shifts of two azoles and one benzazole whose crystal structures present polymorphism have been computed using the GIPAW approach. N and C nuclei have been studied. Statistical analysis of the computed C and N chemical shifts indicates that the GIPAW chemical shifts reproduce with a high degree of accuracy those experimentally reported.

Simple dialkyl pyrazole-3,5-dicarboxylates show in vitro and in vivo activity against disease-causing trypanosomatids.

The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.

Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles.

Two series of new 5-nitroindazole derivatives, 1-substituted 2-benzylindazolin-3-ones (6-29, series A) and 3-alkoxy-2-benzyl-2H-indazoles (30-37, series B), containing differently functionalized chains at position 1 and 3, respectively, have been synthesized starting from 2-benzyl-5-nitroindazolin-3-one 5, and evaluated against the protozoan parasites Trypanosoma cruzi and Trichomonas vaginalis, etiological agents of Chagas disease and trichomonosis, respectively. Many indazolinones of series A were efficient against different morphological forms of T. cruzi CL Brener strain (compounds 6, 7, 9, 10 and 19-21: IC50 = 1.

The (1) H NMR spectrum of pyrazole in a nematic phase.

The experimental (1) H nuclear magnetic resonance (NMR) spectrum of 1H-pyrazole was recorded in thermotropic nematic liquid crystal N-(p-ethoxybenzylidene)-p-butylaniline (EBBA) within the temperature range of 299-308 K. Two of three observable dipolar DHH -couplings appeared to be equal at each temperature because of fast prototropic tautomerism. Analysis of the Saupe orientational order parameters using fixed geometry determined by computations and experimental dipolar couplings results in a situation in which the molecular orientation relative to the magnetic field (and the liquid crystal director) can be described exceptionally by a single parameter.

In vitro leishmanicidal activity of 1,3-disubstituted 5-nitroindazoles.

The antiprotozoal activity of some indazole-derived amines (2, 3, 5-8) as well as that of some simple structurally related 3-alkoxy-1-alkyl-5-nitroindazoles (1, 4) against promastigote and amastigote forms of Leishmania infantum and Leishmania braziliensis is reported. In some cases, these compounds showed in vitro activities against the different morphological forms of Leishmania similar to or higher than those of the reference drug glucantime; this fact, along with low unspecific cytotoxicities against macrophages shown by some of them, led to good selectivity indexes (SI). The high efficiency of some 5-nitroindazoles against the mentioned protozoa was confirmed by further in vitro studies on infection rates.

Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.

Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells.

Static and dynamic properties of 1,1'-bi-2-naphthol and its conjugated acids and bases.

Several convergent techniques were used to characterize 1,1'-bi-2-naphthol (BINOL) and some of its properties. Its acidity in the gas-phase, from neutral species to monoanion, was measured by mass spectrometry. The conformation and structure of BINOL in the gas phase was determined by microwave rotational spectroscopy.

New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5-nitroindazoles.

The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1, 4) and 3-alkoxy-1-(ω-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different morphological forms of Trypanosoma cruzi are reported. These compounds were prepared using simple alkylation reactions and, usually, taking advantage of the reactivity of some indazole-derived betaines previously studied by us. Most indazole derivatives showed in vitro activities similar or higher than those of the reference drug benznidazole; this fact, along with low unspecific cytotoxicities against Vero cells shown by some of them, led to very good selectivity indexes (SI).

Cyclic [4]rotaxanes containing two parallel porphyrinic plates: toward switchable molecular receptors and compressors.

Twenty years ago, researchers considered the synthesis of simple rotaxanes a challenging task, but with the rapid development of this field, chemists now view these interlocking molecules as accessible synthetic targets. In a major advance for the field, researchers have developed transition metals or organic molecules as templating structures, making it easier to construct these molecular systems. In addition, chemists have found ways to introduce new functional groups, which have given these compounds new properties.

The structures of two aldazines: [1,1'-(1E,1'E)-hydrazine-1,2-diylidenebis(methan-1-yl-1-ylidene)dinaphthalen-2-ol] (Lumogen) and 2,2'-(1E,1'E)-hydrazine-1,2-diylidenebis(methan-1-yl-1-ylidene)diphenol (salicylaldazine) in the solid state and in solution.

A combination of NMR spectroscopy and theoretical methods Density functional theory including dispersion corrections (DFT-D) was used to study the structures of Lumogen and salicylaldazine. In the solid state, Lumogen exists as the dihydroxy tautomer 1a (an azine, C=N-N=C) as was already known from an X-ray determination. In a deuterated dimethyl sulfoxide solution, another tautomer is observed besides 1a; its structure corresponds to the hydroxy-oxo tautomer 1b (a hydrazone, C=N-NH-Csp(2)).

The structure of azines derived from C-formyl-1H-imidazoles in solution and in the solid state: tautomerism, configurational and conformational studies.

The structures of three azines derived from 2-formylimidazole, 4(5)-formylimidazole, and 4(5)-formyl-5(4)-methylimidazole have been determined in solution and in the solid state. Density Functional Theory (DFT) Polarizable Continuum Model (PCM) calculations (geometries, energies, and chemical shifts), NMR [solution and cross polarization magic-angle spinning (CPMAS)], and X-ray crystallography [azine of 4(5)-formylimidazole] have been used. The configuration around the central C = N bonds has been determined and some insights about prototropic tautomerism and conformation have been gained.

NIR emission of cyclic [4]rotaxanes containing π-extended porphyrin chromophores.

The photophysical properties of a Cu(I) [4]rotaxane 4(4+) and of the demetalated [4]rotaxane 3 have been determined and compared to those of the component Zn porphyrin 2. All samples emit in the NIR region (700-1200 nm). The luminescence from the interlocked structures is bathochromically shifted with respect to 2 and displays a lower emission quantum yield, much lower for 4(4+) than for 3.

Hydrogen-bond-mediated self-assembly of 26-membered diaza tetraester crowns of 3,5-disubstituted 1H-pyrazole. Dimerization study in the solid state and in CDCl3 solution.

By using an improved synthetic method reported earlier, the cyclic stannoxanes obtained from RN-diethanolamine (R = Me, Bu) and dibutyltin oxide have been reacted with 1H-pyrazole-3,5-dicarbonyl dichloride to afford 26-membered diaza tetraester crowns (1, R = Me; 3, R = Bu) and 39-membered triaza hexaester crowns (2, R = Me; 4, R = Bu). The new structures were identified from their analytical and spectroscopic ((1)H and (13)C NMR, FAB-MS, and/or ESI-MS) data. Both diaza tetraester crowns (1 and 3), containing two 1H-pyrazole units, self-assemble into dimeric species through the formation of four hydrogen bonds involving the two NH pyrazole groups and the two tertiary amine groups of both crowns, as proved by X-ray crystallography and NMR analysis.

Synthesis, complexation and NMR relaxation properties of Gd3+ complexes of Mes(DO3A)3.

Medium sized molecules endowed with multiple Gd(3+) complexes are efficient high magnetic field MRI contrast agents. The novel ligand Mes(DO3A)(3), presenting three DO3A (1,4,7,10-tetraazacyclododecane-N,N',N''-triacetatic acid) units grafted on the methyl positions of a central mesitylene (1,3,5-trimethylbenzene), has been synthesized. Designed as an MRI contrast agent, this ligand is complexed with Gd(3+) and its efficiency is characterized by variable field (1)H-NMR and variable temperature (17)O-NMR.