Gustavo A. Echeverría

1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development.

Cellulose-derived chiral pyrrolidines were synthesized in excellent yields, regioselectivities, and stereoselectivities via a 1,3-dipolar cycloaddition reaction between levoglucosenone and azomethine ylides. An unprecedented isomerization event led to a new family of pyrrolidines with an unusual relative stereochemistry. Preliminary results showed that these compounds are promising organocatalysts for iminium ion-based asymmetric Diels-Alder reactions.

Optimization of antitrypanosomatid agents: identification of nonmutagenic drug candidates with in vivo activity.

Chagas disease, caused by Trypanosoma cruzi parasite, was described thousands of years ago. Currently, it affects millions of people, mostly in Latin America, and there are not suitable drugs for treating it. As an attempt to find appropriate drugs to deal with this problem, we report here on the design, synthesis, and characterization of 82 new compounds. Trypanosomicidal behavior in vitro showed more than 20 outstanding derivatives with anti-Trypanosoma cruzi activity. Furthermore, we studied the nonspecific toxicity against mammalian cells determining their selectivity and also performed mutagenicity studies. Proof of concept, in vivo studies, was conducted with two of the most promising derivatives (77 and 80). They were identified as candidates because they have (i) very simple and cost-effective syntheses; (ii) activity against different stages and strains of the parasite showing excellent in vivo behavior during the acute phase of Chagas disease; and (iii) neither nonspecific toxicity nor mutagenic activity.

A substituted sulfonamide and its Co (II), Cu (II), and Zn (II) complexes as potential antifungal agents

Abstract A sulfonamide 1-tosyl-1-H-benzo(d)imidazol-2-amine (TBZA) and three new complexes of Co(II), Cu(II), and Zn(II) have been synthesized. The compounds have been characterized by elemental analyses, FTIR, 1H, and 13C-NMR spectroscopy. The structure of the TBZA, and its Co(II) and Cu(II) complexes, was determined by X-ray diffraction methods. TBZA and its Co(II) complex crystallize in the triclinic P-1 space group, while the Cu(II) complex crystallizes in the monoclinic P21/c space group. Antifungal activity was screened against eight pathogenic yeasts: Candida albicans (DMic 972576), Candida krusei (DMic 951705), Candida glabrata (DMic 982882), Candida tropicalis (DMic 982884), Candida dubliniensis (DMic 93695), Candida guilliermondii (DMic 021150), Cryptococcus neoformans (ATCC 24067), and Cryptococcus gattii (ATCC MYA-4561). Results on the inhibition of various human (h) CAs, hCA I, II, IV, VII, IX, and XII, and pathogenic beta and gamma CAs are also reported.

Antitumoral, Antihypertensive, Antimicrobial, and Antioxidant Effects of an Octanuclear Copper(II)-Telmisartan Complex with an Hydrophobic Nanometer Hole

A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16]·24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and electron paramagnetic resonance spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16]·24H2O crystallizes in the tetragonal P4/ncc space group with a = b = 47.335(1), c = 30.894(3) Å, Z = 4 molecules per unit cell giving a macrocyclic ring with a double helical structure. The Cu(II) ions are in a distorted bipyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole, and their crystal packing defines nanochannels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimic with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3, and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis, an apoptotic mechanism was established for the latter cell line. Telmisartan and CuTlm show antibacterial and antifungal activities in various strains, and CuTlm displays improved activity against the Staphylococcus aureus strain as compared with unbounded copper(II).

Molecular structure of 4-hidroxy-3-(3-methyl-2-butenyl) acetophenone, a plant antifungal, by X-ray diffraction, DFT calculation, and NMR and FTIR spectroscopy.

The molecular structure of two mixed and closely related conformers of the title compound, C13H16O2, found in the solid with unequal occupancies has been determined by X-ray diffraction methods. The substance crystallizes in the monoclinic Pca2(1) space group with a=17.279(2), b=5.1716(7), c=12.549(2)Å, and Z=4 molecules per unit cell. The structure was solved from 1314 reflections with I>2σI and refined to an agreement R1-factor of 0.049. The minor conformer (34.7%) is nearly mirror-related to and extensively overlapped with the major one. The skeleton of the 4-hydroxyacetophenone molecular fragment and the prenyl group, (CH2)(CH)C(CH3)2, pendant arm attached to it are both planar and perpendicular to each other. A strong intermolecular O-H⋯O bond links neighboring molecules in the lattice to produce a polymeric structure. The conformational structures of the compound in the gas phase have been calculated by the DFT method and the geometrical results have been compared with the X-ray data. These data allow a complete assignment of vibration modes in the solid state FTIR and Raman spectra. The calculated 1H and 13C chemicals shifts are in good agreement with the corresponding experimental NMR spectra of the compound in solution.

Ethyl acetate: X-ray, solvent and computed structures.

Ethyl acetate (ethyl ethanoate) was crystallized in situ and the crystal structure was determined. In the solid, the molecule is flat with trans conformation. The geometric details of ethyl acetate as a solvate are analyzed statistically using the Cambridge Structural Database, uncovering a high degree of hidden disorder. Despite the disorder, they exhibit a preference of the trans over the gauche isomer, with a negligible contribution of the cis isomer. These results are compared to ab initio calculations on both solid-state and molecular level. For the molecular structures, the computed energy differences of the isomers match the statistics found as a solvent. Several DFT-D2 methods used to calculate the solid state yield results that differ significantly from the experiment.

1-[2-(1-Hydroxy­cyclo­hexyl)-2-(4-methoxy­phenyl)­ethyl]­di­methyl­ammon­ium chloride (venlafaxine hydro­chloride)

The crystal structure of racemic Venlafaxine hydrochloride, C(17)H(28)NO(2)(+).Cl(-), consists of two types of parallel chains formed by translated Venlafaxine(+) cations, hydrogen bonded by Cl(-) anions, and characterized by the opposite chirality of their constituent molecules. These chains organize in two different types of broad layers of opposite handedness, related by a glide plane.

Layered crystal structure, conformational and vibrational properties of 2,2,2-trichloroethoxysulfonamide: an experimental and theoretical study.

The molecular structure of 2,2,2-trichloroethoxysulfonamide, CCl3CH2OSO2NH2, has been determined in the solid state by X-ray diffraction data and in the gas phase by ab initio (MP2) and DFT calculations. The substance crystallizes in the monoclinic P21/c space group with a = 9.969(3)Å, b = 22.914(6)Å, c = 7.349(2)Å, β = 91.06(3)°, and Z = 8 molecules per unit cell. There are two independent, but closely related molecular conformers in the crystal asymmetric unit. They only differ in the angular orientation of the sulfonamide (SO2NH2) group. The conformers are arranged in the lattice as center-symmetric NH · · · O(sulf)-bonded dimers. Neighboring dimers are linked through further NH · · · O(sulf) bonds giving rise to a crystal layered structure. The solid state infrared and Raman spectra have been recorded and the observed bands assigned to the molecular vibration modes. Also, the thermal behavior of the substance was investigated by TG-DT analysis. The stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using natural bond (NBO) analysis.

COORDINATION BINDING MODES FOR POLYMERIC CADMIUM DICARBOXYLATE HYDRATE COMPLEXES

Abstract Single crystal X-ray crystal diffraction, IR and TGA-DTA data and searches in the Cambridge Structural Database (CSD) have been used to analyze coordination binding modes of Cd(II) in dicarboxylate complexes with anions of different length. The results, discussed in this paper, show that Cd(II) presents a range of coordination geometries. Six, seven and eight coordination with different degrees of departure from regular polyhedra are observed. The length of the ions influences the availability of donor oxygens and induces bidentate, six or four member chelating rings, and monodentate binding, which produces polymerization of different dimensionality.

Conformational studies of trans-1,4-substituted cyclohexanes. I: Trans-1,4-cyclohexanedicarbonitrile

The molecules of the title compound (C 8 H 10 N 2 ), which each adopt a chair conformation with the CN substituents equatorially bonded, lie on crystallograpbic inversion centres and are linked by CN...CN intermolecular interactions to form (101) sheets. The sheets are additionally stabilized by short C-H...N contacts