Spectral Characteristics Related to Chemical Substructures and Structures Indicative of Organic Precursors from Fulvic Acids in Sediments by NMR and HPLC-ESI-MS.

The aim of this work was to determine Fulvic Acids (FAs) in sediments to better know their composition at the molecular level and to propose substructures and structures of organic precursors. The sediment samples were obtained from a priority area for the conservation of ecosystems and biodiversity in Mexico. FAs were extracted and purified using modifications to the International Humic Substances Society method. The characterization was carried out by 1D and 2D nuclear magnetic resonance (NMR) and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) in positive (ESI+) and negative (ESI-) modes. Twelve substructures were proposed by the COSY and HSQC experiments, correlating with compounds likely belonging to lignin derivatives obtained from soils as previously reported. The analysis of spectra obtained by HPLC-ESI-MS indicated likely presence of compounds chemically similar to that of the substructures elucidated by NMR. FAs studied are mainly constituted by carboxylic acids, hydroxyl, esters, vinyls, aliphatics, substituted aromatic rings, and amines, presenting structures related to organic precursors, such as lignin derivatives and polysaccharides.

Supramolecular arrangement and photophysical properties of a dinuclear cyanophenylboronic acid ester.

Boronic esters are useful building blocks for crystal engineering and the generation of supramolecular architectures, including macrocycles, cages and polymers (one-, two- and three-dimensional), with potential utility in diverse fields such as separation, storage and luminescent materials. The novel dinuclear cyanophenylboronic ester described herein, namely 4,4'-(2,4,8,10-tetraoxa-3,9-diboraspiro[5.5]undecane-3,9-diyl)dibenzonitrile, C19H16B2N2O4, was prepared by condensation of 4-cyanophenylboronic acid and pentaerythritol and fully characterized by elemental analysis, IR and NMR (1H and 11B) spectroscopy, single-crystal X-ray diffraction analysis and TG-DSC (thermogravimetry-differential scanning calorimetry) studies. In addition, the photophysical properties were examined in solution and in the solid state by UV-Vis and fluorescence spectroscopies. Density functional theory (DFT) calculations with ethanol as solvent reproduced reasonably well the HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) of the title compound. Hirshfeld surface and fingerprint plot analyses are presented to illustrate the supramolecular connectivity in the solid state.

Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis.

We synthesized four 5-nitrothiazole (1-4) and four 6-nitrobenzothiazole acetamides (5-8) using an easy two step synthetic route. All compounds were tested in vitro against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis, showing excellent antiprotozoal effects. IC50's of the most potent compounds range from nanomolar to low micromolar order, being more active than their drugs of choice. Compound 1 (IC50=122 nM), was 44-times more active than Metronidazole, and 10-fold more effective than Nitazoxanide against G. intestinalis and showed good trichomonicidal activity (IC50=2.24 µM). This compound did not display in vitro cytotoxicity against VERO cells. The in vitro inhibitory effect of compounds 1-8 and Nitazoxanide against G. intestinalis fructose-1,6-biphosphate aldolase (GiFBPA) was evaluated as potential drug target, showing a clear inhibitory effect over the enzyme activity. Molecular docking of compounds 1, 4 and Nitazoxanide into the ligand binding pocket of GiFBPA, revealed contacts with the active site residues of the enzyme. Ligand efficiency metrics of 1 revealed optimal combinations of physicochemical and antiprotozoal properties, better than Nitazoxanide.

2,6-Dihy-droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate.

The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol-ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra-hedral coordination environments, with B-O and B-C bond lengths of 1.446 (4)-1.539 (3) and 1.590 (5)-1.609 (5) Å, respectively. In the crystal, the ester and water mol-ecules are linked into a three-dimensional network by a large number of O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. The crystal packing is further accomplished by π-π inter-actions, with centroid-centroid distances of 3.621 (4)-3.787 (4) Å.

Substituent effects and pH profiles for stability constants of arylboronic acid diol esters.

Stability constants of boronic acid diol esters in aqueous solution have been determined potentiometrically for a series of meta-, para-substituted phenylboronic acids and diols of variable acidity. The constants ß(11-1) for reactions between neutral forms of reactants producing the anionic ester plus proton follow the Hammett equation with ρ depending on pKa of diol and varying from 2.0 for glucose to 1.29 for 4-nitrocatechol. Observed stability constants (K(obs)) measured by UV-vis and fluorometric titrations at variable pH for esters of 4,5-dihydroxy-1,3-benzenedisulfonate (Tiron) generally agree with those expected on the basis of ß(11-1) values, but the direct fitting of K(obs) vs pH profiles gives shifted pKa values both for boronic acids and diol as a result of significant interdependence of fitting parameters. The subsituent effects on absorption and fluorescence spectra of Tiron arylboronate esters are characterized. The K(obs) for Tiron determined by (11)B NMR titrations are approximately 1 order of magnitude smaller than those determined by UV-vis titrations under identical conditions. A general equation, which makes possible an estimate of ß(11-1) for any pair of boronic acid and diol from their pKa values, is proposed on the basis of established Brönsted-type correlation of Hammett parameters for ß(11-1) with acidity of diols. The equation allows one to calculate stability constants expected only on basis of acid-base properties of the components, thus permitting more strict evaluation of contributions of additional factors such as steric or charge effects to the ester stability.

Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent.

A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10 µM), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11ß-HSD1. In this model, compound 1 binds into the catalytic site of 11ß-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+).

4-[(E)-2-(Pyridin-2-yl)ethen-yl]pyridine-terephthalic acid (2/1).

The title 2:1 co-crystal, 2C12H10N2·C8H6O4, crystallizes with one mol-ecule of 4-[(E)-2-(pyridin-2-yl)ethen-yl]pyridine (A) and one half-mol-ecule of terephthalic acid (B) in the asymmetric unit. In the crystal, the components are linked through heterodimeric COOH⋯Npyridine synthons, forming linear aggregates of composition -A-B-A-B-. Further linkage through weak C-H⋯O and C-H⋯π inter-actions gives two-dimensional hydrogen-bonded undulating sheets propagating in the [100] and [010] directions. These layers are connected through additional weak C-H⋯O contacts, forming a three-dimensional structure.

Solvent-solvent and solvent-solute interactions in a 3D chloroform clathrate with diorganotin macrocycles in the nano-sized pores.

A 3D clathrate of deuterochloroform molecules was formed in the presence of nano-sized macrocyclic molecules.

Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.

We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.

Relative acidities and structure analysis of cis and trans isomers of 1,5-oxazaspiro[5.5] undecane derivatives by multinuclear magnetic resonance.

The relative acidities of the cis and trans isomers of a series of 1,5-oxazaspiro[5.5]undecane derivatives were determined by measuring DeltapK in acid-base titrations followed by (1)H NMR. Relative structural stabilities were determined by measuring substituent chemical shift and gamma-gauche effects in (13)C, (15)N, and (17)O NMR. Crystallographic characterization of a model spiro[5.5]undecane is presented to support the basicity in solid state.

3-Pyridineboronic acid --> boroxine --> pentadecanuclear boron cage --> 3D molecular network: a sequence based on two levels of self-complementary self-assembly.

A pentadecanuclear boroxine-cage has been generated through a single-component self-assembly process, and serves as a twofold concave-convex self-complementary tecton for the assembly of a complex 3D molecular network.

Macrocyclic diorganotin complexes of gamma-amino acid dithiocarbamates as hosts for ion-pair recognition.

The dimethyl-, di-n-butyl-, and diphenyltin(IV) dithiocarbamate (dtc) complexes [{R2Sn(L-dtc)}x] 1-7 (1, L = L1, R = Me; 2, L = L1, R = n-Bu; 3, L = L2, R = Me, x = infinity; 4, L = L2, R = n-Bu; 5, L = L3, R = Me, x = 2; 6, L = L3, R = n-Bu, x = 2; 7, L = L3, R = Ph, x = 2) have been prepared from a series of secondary amino acid (AA) homologues as starting materials: N-benzylglycine (alpha-AA derivative = L1), N-benzyl-3-aminopropionic acid (beta-AA derivative = L2), and N-benzyl-4-aminobutyric acid (gamma-AA derivative = L3). The resulting compounds have been characterized by elemental analysis, mass spectrometry, IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy, thermogravimetric analysis, and X-ray crystallography, showing that in all complexes both functional groups of the heteroleptic ligands are coordinated to the tin atoms. By X-ray diffraction analysis, it could be shown that [{Me2Sn(L2-dtc)}x] (3) is polymeric in the solid state, while the complexes derived from L3 (5-7) have dinuclear 18-membered macrocyclic structures of the composition [{R2Sn(L3-dtc)}2]. For the remaining compounds, it could not be established with certainty whether the structures are macrocyclic or polymeric. A theoretical investigation at the B3LYP/SBKJC(d,p) level of theory indicated that the alpha-AA-dtc complexes might have trinuclear macrocyclic structures. The macrocyclic complexes 5-7 have a double-calix-shaped conformation with two cavities large enough for the inclusion of aliphatic and aromatic guest molecules. They are self-complementary for the formation of supramolecuar synthons that give rise to 1D molecular arrangements in the solid state. Preliminary recognition experiments with tetrabutylammonium acetate have shown that the [{R2Sn(L3-dtc)}2] macrocycles 6 and 7 might interact simultaneously with anions (AcO(-)), which coordinate to the tin atoms, and organic cations (TBA(+)), which accommodate within the hydrophobic cavity (ion-pair recognition).

Theoretical study of the experimental coordination behavior of N-(2-aminophenyl)-D-glycero-D-gulo-heptonamide to Hg(II) ion.

The reactivity of N-(2-aminophenyl)-d-glycero-d-gulo-heptonamide (adgha), with the group 12 cations, Zn(II), Cd(II), and Hg(II), was studied in DMSO-d(6) solution. The studied system showed a selective coordination to Hg(II), and the products formed were characterized by (1)H and (13)C NMR in DMSO-d(6) solution and fast atom bombardment (FAB(+)) mass spectra. The expected coordination compounds, [Hg(adgha)](NO(3))(2) and [Hg(adgha)(2)](NO(3))(2), were observed as unstable intermediates that decompose to bis-[2-(d-glycero-d-gulo-hexahydroxyhexyl)-benzimidazole-κN]mercury(II) dinitrate, [Hg(ghbz)(2)](NO(3))(2). The chemical transformation of the complexes was followed by NMR experiments, and the nature of the species formed is sustained by a theoretical study done using DFT methodology. From this study, we propose the structure of the complexes formed in solution, the relative stability of the species formed, and the possible role of the solvent in the observed transformations.

Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids.

A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)<1 microM) against the first four protozoa, which make them significantly more potent than either standard. 1,5-bis[4-(5-methoxy-1H-benzimidazole-2-yl)phenoxy]pentane (2) was 3- and 9-fold more potent againstG. lamblia than metronidazole and pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.

Assignment of the relative configuration of spiro[4.5]decanes by 13C, 15N and 17O NMR.

The relative configuration of 11 1,4-diazaspiro[4.5]decanes (1a-1j and 1m), 15 1,4-oxazaspiro[4.5]decanes (2a-2o) and 10 1,4-dioxaspiro[4.5]decanes (3a-3n) substituted at the 2-, 6-, 7- or 8-position by a methyl group or using the tert-butyl group as a model for the ananchomeric structure is reported. The relative stereochemistry was analyzed by 1H, 13C, 15N and 17O NMR and all isomers present were characterized spectroscopically. Compounds with a methyl group in the six-membered ring show a chair conformation preference with the methyl group in the equatorial position. Compounds with one or two nitrogens exhibit a tautomeric equilibrium between the imine-diazolidine forms, as demonstrated by IR and 13C NMR.