RESUMEN
Theoretical simulation of NMR parameters in compounds bearing heavy atoms generally requires the application of relativistic corrections. We report herein the theoretical characterization of 13C and 15N 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 13C and 15N chemical shifts. The problem of applying GIPAW to crystal structures showing static or dynamic crystalline disorder of the special class resulting in half-protons will be discussed in detail.
RESUMEN
The reaction in phase-transfer catalyzed conditions of 3(5)-methyl-1H-pyrazole with chloroform affords four isomers 333, 335, 355 and 555 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. The up (u) and down (d) conformation of the pyrazolyl rings with regard to the Csp³â»H atom was established by X-ray crystallography and by ¹H-, 13C- and 15N-NMR in solution combined with gauge-including atomic orbitals (GIAO)/B3LYP/6-311++G(d,p) calculations. A comparison with other X-ray structures of tris-pyrazolylmethanes was carried out.
Asunto(s)
Cloroformo/química , Pirazoles/química , Cristalografía por Rayos X , Isomerismo , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Modelos Teóricos , Conformación Molecular , Estructura MolecularRESUMEN
A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe+2 chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H2O2 induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (ΔΨm). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases.
Asunto(s)
Antioxidantes/farmacología , Quelantes del Hierro/farmacología , Cetonas/farmacología , Fármacos Neuroprotectores/farmacología , Quinonas/farmacología , Antioxidantes/síntesis química , Apoptosis/efectos de los fármacos , Benzotiazoles/antagonistas & inhibidores , Compuestos de Bifenilo/antagonistas & inhibidores , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/farmacología , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Concentración 50 Inhibidora , Quelantes del Hierro/síntesis química , Cetonas/síntesis química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/síntesis química , Estrés Oxidativo/efectos de los fármacos , Picratos/antagonistas & inhibidores , Quinonas/síntesis química , Relación Estructura-Actividad , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
A series of new (E)-3(5)-[ß-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding ß-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (¹H, (13)C, (19)F and (15)N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[ß-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.
Asunto(s)
Curcumina/química , Flúor/química , Óxido Nítrico Sintasa/antagonistas & inhibidores , Pirazoles/síntesis química , Pirazoles/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Pirazoles/química , Relación Estructura-Actividad , Difracción de Rayos X/métodosRESUMEN
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.
Asunto(s)
Hidrazinas/química , Imidazoles/química , Hidrazinas/síntesis química , Espectroscopía de Resonancia Magnética/normas , Estructura Molecular , Teoría Cuántica , Estándares de Referencia , SolucionesRESUMEN
The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino)carbonyl] aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug, has been studied both in solution and in the solid state by a combination of NMR spectroscopy and theoretical calculations. The possibility that glibenclamide suffers a tautomerization under melting to afford a desmotrope was rejected.
Asunto(s)
Gliburida/química , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética/normas , Modelos Moleculares , Estructura Molecular , Teoría Cuántica , Estándares de ReferenciaRESUMEN
We report a theoretical approach, at the M05-2x/6-311+G(d) level, to explain the affinity of indazoles for nitric oxide synthases using a simplified model of porphyrin. The theoretical E(rel)=E(i) stacking-E(i) apical values correlate with the experimental inhibition percents allowing to predict that 3,7-dinitro-1H-indazole should be a good NOS inhibitor.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Indazoles/farmacología , Metaloporfirinas/metabolismo , Modelos Moleculares , Óxido Nítrico Sintasa/metabolismo , Metaloporfirinas/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Teoría CuánticaRESUMEN
Using solid-state NMR spectroscopy, we have detected and characterized ultrafast intramolecular proton tautomerism in the N-H-N hydrogen bonds of solid N, N'-diphenyl-6-aminofulvene-1-aldimine ( I) on the microsecond-to-picosecond time scale. (15)N cross-polarization magic-angle-spinning NMR experiments using (1)H decoupling performed on polycrystalline I- (15)N 2 and the related compound N-phenyl- N'-(1,3,4-triazole)-6-aminofulvene-1-aldimine ( II) provided information about the thermodynamics of the tautomeric processes. We found that II forms only a single tautomer but that the gas-phase degeneracy of the two tautomers of I is lifted by solid-state interactions. Rate constants, including H/D kinetic isotope effects (KIEs), on the microsecond-to-picosecond time scale were obtained by measuring and analyzing the longitudinal (15)N and (2)H relaxation times of I- (15)N 2, I- (15)N 2- d 10, and I- (15)N 2- d 1 over a wide temperature range. In addition to the microcrystalline modification, a novel amorphous modification of I was found and studied. In this modification, proton transfer is much faster than in the crystalline form. For both modifications, we observed large H/D KIEs that were temperature-dependent at high temperatures and temperature-independent at low temperatures. These findings are interpreted in terms of a simple quasiclassical tunneling model proposed by Bell and modified by Limbach. We obtained evidence that a reorganization energy is necessary in order to compress the N-H-N hydrogen bond and achieve a molecular configuration in which the barrier for H transfer is reduced and tunneling or an over-barrier reaction can occur.
RESUMEN
Three bis(amino acids) linked by the amino groups have been prepared and structurally characterized. We have named them Gly-Gly, Ala-Ala and Gly-Ala (or Ala-Gly). These compounds have been characterized by NMR both in solution and in the solid state. They exist as zwitterions with the ammonium group proximal to the carboxylate anion. In the case of Gly-Ala, a dynamic situation is observed by CPMAS NMR ((13)C and (15)N) corresponding to a double proton migration between two proximal tautomers.
Asunto(s)
Aminoácidos/química , Espectroscopía de Resonancia Magnética , Alanina , Isótopos de Carbono , Glicina , Isótopos de NitrógenoRESUMEN
Schiff bases of 3-hydroxypyridin-4-carboxaldehyde and L-alpha-amino esters as well as those derived from the structurally related amines lacking the ester function have been synthesised. In two cases a tetrahydro-1H-imidazo[4,5-c]pyridine was formed as a by-product. (1)H, (13)C, (15)N-NMR spectral data and density functional theory (DFT) calculations established the structure of all compounds.
Asunto(s)
Aminoácidos/química , Ésteres/química , Isoxazoles/química , Espectroscopía de Resonancia Magnética/métodos , Bases de Schiff/química , Isoxazoles/síntesis química , Espectroscopía de Resonancia Magnética/normas , Modelos Químicos , Estructura Molecular , Estándares de Referencia , Bases de Schiff/síntesis química , Sensibilidad y Especificidad , EstereoisomerismoRESUMEN
New Schiff bases have been prepared by reacting 3-hydroxy-4-pyridine- carboxaldehyde with various amines. NMR spectroscopic methods provided clear evidence that the Schiff bases exist in the solid state and in solution as hydroxyimino tautomers with the E-configuration. A study of the stabilities of the tautomeric forms and the different conformers has been carried out using density functional calculations at the B3LYP/6-31G** level.
Asunto(s)
Bases de Schiff/química , Bases de Schiff/síntesis química , Enlace de Hidrógeno , Isomerismo , Espectroscopía de Resonancia MagnéticaRESUMEN
The introduction of poly(1H-pyrazolyl)borate anions, better known as scorpionates, as negatively charged ligands for a great diversity of metal cations has had a tremendous influence in coordination chemistry. The structures of two salts of tetrakispyrazolylborate, namely [tetrakis(3-phenyl-1H-pyrazol-1-yl)borato]thallium(I), [Tl(C36H28BN8)], and catena-poly[potassium-[µ2-tetrakis(3-cyclopropyl-1H-pyrazol-1-yl)borato]], [K(C24H28BN8)]n, have been determined at 296â K in the monoclinic P21/c and C2/c space groups, respectively. In their crystal structures, the thallium salt presents discrete molecular motifs, while the potassium salt shows infinite polymeric chains. The 13C and 15N CPMAS (cross polarization magic angle spinning) NMR spectra of these compounds were recorded and the chemical shifts compared with theoretically calculated ones at the GIAO/B3LYP/6-311++G(d,p) level. Both techniques are complementary and mutually consistent.
RESUMEN
A series of aminotroponimine and aminotropone derivatives were studied by electrospray mass spectrometry. MS and MS/MS data were acquired according to automated procedures. In the case of mono- and di-halogenated compounds, their specific behavior upon collisionally-activated dissociation conditions provided rapid structural assignments through inexpensive isotopic labeling MS/MS experiments.
RESUMEN
An unusually substantial coupling is observed across the hydrogen bond of fully 15 N-labeled compound 1 when it is studied by 1 H and 15 N NMR spectroscopy. The structure was determined by X-ray diffraction and shown to correspond to tautomer 1 a (both in the solid state and in solution). These results open up a new field of hydrogen-bond research by NMR spectroscopic methods.
RESUMEN
A 2hJNN intermolecular spin-spin coupling constant (SSCC) of 10.2±0.4 Hz has been measured for the powdered tetrachlorogallate salt of pyridinium solvated by pyridine (pyridine-H+â¯pyridine cation 3). Density Functional Theory (DFT) calculations at the B3LYP/6-311++G(d,p) level reproduced this value and two others reported in the literature for 2hJ intermolecular SSCCs, which were measured for complexes in solution.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Modelos Químicos , Radioisótopos de Nitrógeno/análisis , Radioisótopos de Nitrógeno/química , Compuestos de Piridinio/química , Simulación por Computador , Enlace de HidrógenoRESUMEN
Multinuclear magnetic resonance spectroscopy together with GIAO-DFT calculations allowed establishment of the structure of the products obtained by condensation of 3(5)-amino-4-phenyl-1H-pyrazole and beta-dicarbonyl compounds bearing a trifluoromethyl group. They are 3-phenyl-5-(R)-7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
RESUMEN
Three N-substituted pyrazoles and three N-substituted indazoles [1-(4-nitrophenyl)-3,5-dimethylpyrazole (1), 1-(2,4-dinitrophenyl)-3,5-dimethylpyrazole (2), 1-tosyl-pyrazole (3), 1-p-chlorobenzoylindazole (4), 1-tosylinda-zole (5) and 2-(2-hydroxy-2-phenylethyl)-indazole (6)] have been studied by NMR spectroscopy in solution (1H, 13C, 15N) and in the solid state (13C, 15N). The chemical shifts have been compared with GIAO/DFT calculated absolute shieldings. Some discrepancies have been analyzed.