A theoretical and experimental NMR study of the prototropic tautomerism of tris(tetrabutylammonium) hydrogen pyrophosphate salt in solution and in the solid-state

The structure of tris(tetrabutylammonium)hydrogen pyrophosphate(HPP) has been studied in solution and in the solid-state by 31P NMR. GIAO/DFT calculations of the isolated molecule in its open and closed conformations, of their water complexes and the solvent effects (continuum model) have been useful to discuss the experimental NMR data. Contrary to literature reports, the 31P NMR spectra of HPP in solution have a single band, that broadenedconsiderably when the temperature is lowered till 193 K without reaching the coalescence. In the solid-state, two very close signals are observed that the calculations do not reproduce adequately

Curcumina y curcuminoides: química, estudios estructurales y propiedades biológicas

Esta revisión versa sobre la curcumina, una molécula fascinante, cuyas propiedades medicinales cubren campos como cáncer y Alzheimer. Se describen sus propiedades químicas y fisicoquímicas así como las de algunos de sus derivados (los curcuminoides y hemicurcuminoides), en particular aquellos que contienen un heterociclo. Las propiedades biológicas y farmacológicas más relevantes serán también mencionadas. Para concluir, se presenta brevemente nuestra contribución a este camp

The Structure of N-Benzylazoles from Pyrrole to Carbazole: Geometries and Energies

International audienceThe complete series of 18 parents N-benzylazoles (10 azoles and 8 benzazoles) have been calculated at the B3LYP/6-311++G(d,p) level. The geometries have been compared with the X-ray structures reported in the literature for six derivatives (1H-imidazole, 1H-1,2,3-triazole, 1H-1,2,3,4-tetrazole, 1H-benzimidazole, 1H-benzotriazole, and 9H-carbazole). Only one minimum has been found for the 18 molecules, but several transition states connecting them have been located. The calculated geometries agree well with those reported by X-ray crystallography

Structural studies of two Tinuvin® P analogs: 2-(2,4-Dimethylphenyl)- 2H-benzotriazole and 2-phenyl-2H-benzotriazole

2-(2,4-Dimethylphenyl)-2H-benzotriazole (1) has been synthesized in a three step procedure starting from 2,4-dimethyl-N-(2-nitrophenyl)benzamide via a 5-(2,4-dimethylphenyl)-1-(2-nitrophenyl)-1H-tetrazole intermediate. Its structure and those of Tinuvin® P and 2-phenyl-2H-benzotriazole (5) have been studied by multinuclear NMR (1H-, 13C- and 15N-) in solution and in the solid state. X-ray diffraction analysis of 1 and 5 allowed to us establish the molecular conformation around the single bond connecting the two aromatic systems, in agreement with the conclusions drawn from the NMR study. In the case of 1 ab initio geometry optimization was achieved at the Hartree-Fock HF/6-31G** and DFT B3LYP/6-31G ** levels. © 2007 by MDPI.Peer Reviewe

Insights into the control of taxane metabolism: Molecular, cellular, and metabolic changes induced by elicitation in Taxus baccata cell suspensions

More knowledge is needed about the molecular/cellular control of paclitaxel (PTX) production in Taxus spp. cell cultures. In this study, the yield of this anticancer agent in Taxus baccata cell suspensions was improved 11-fold after elicitation with coronatine (COR) compared to the untreated cells, and 18-fold when co-supplemented with methyl-β-cyclodextrins (β-CDs). In the dual treatment, the release of taxanes from the producer cells was greatly enhanced, with 81.6% of the total taxane content being found in the medium at the end of the experiment. The experimental conditions that caused the highest PTX production also induced its maximum excretion, and increased the expression of taxane biosynthetic genes, especially the flux-limiting BAPT and DBTNBT. The application of COR, which activates PTX biosynthesis, together with β - CDs, which form inclusion complexes with PTX and related taxanes, is evidently an efficient strategy for enhancing PTX production and release to the culture medium. Due to the recently described role of lipid droplets (LDs) in the trafficking and accumulation of hydrophobic taxanes in Taxus spp. cell cultures, the structure, number and taxane storage capacity of these organelles was also studied. In elicited cultures, the number of LDs increased and they mainly accumulated taxanes with a side chain, especially PTX. Thus, PTX constituted up to 50-70% of the total taxanes found in LDs throughout the experiment in the COR + β - CD-treated cultures. These results confirm that LDs can store taxanes and distribute them inside and outside cells. Keywords: Taxus baccata; cell cultures; coronatine; gene expression; lipid droplets; paclitaxel; taxane accumulation

Fast degenerate double proton transfer in the solid state between two indazolinone tautomers

The neutral dimer formed by 4,6-difluoro-1H,2H-indazolin-3-one and 3-hydroxy-4,6-difluoro-1H-indazole linked by two hydrogen bonds presents a very fast intermolecular double proton transfer in the solid state (ISSPT). The combined use of crystallography, solid state NMR and DFT [B3LYP/6-311++G(d,p)] calculations supports this interesting observation and allows us to estimate a barrier of about 20 kJ mol-1. © 2010 The Royal Society of Chemistry.Peer Reviewe

Exploring the Metabolic Stability of Engineered Hairy Roots after 16 Years Maintenance

Plants remain a major source of new drugs, leads and fine chemicals. Cell cultures deriving from plants offer a fascinating tool to study plant metabolic pathways and offer large scale production systems for valuable compounds - commercial examples include compounds such as paclitaxel. The major constraint with undifferentiated cell cultures is that they are generally considered to be genetically unstable and cultured cells tend to produce low yields of secondary metabolites especially over time. Hairy roots, a tumor tissue caused by infection of Agrobacterium rhizogenes is a relevant alternative for plant secondary metabolite production for being fast growing, able to grow without phytohormones, and displaying higher stability than undifferentiated cells. Although genetic and metabolic stability has often been connected to transgenic hairy roots, there are only few reports on how a very long-term subculturing effects on the production capacity of hairy roots. In this study, hairy roots producing high tropane alkaloid levels were subjected to 16-year follow-up in relation to genetic and metabolic stability. Cryopreservation method for hairy roots of Hyoscyamus muticus was developed to replace laborious subculturing, and although the post-thaw recovery rates remained low, the expression of transgene remained unaltered in cryopreserved roots. It was shown that although displaying some fluctuation in the metabolite yields, even an exceedingly long-term subculturing was successfully applied without significant loss of metabolic activity

A Spectroscopic study of colchicine in the solid state and in solution by multinuclear magnetic resonance and vibrational circular dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.Peer Reviewe

Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H, 13C, 19F and 15N) 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)-[β-(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.This work has been financed by Ministerio de Ciencia e Innovación (CTQ2010-16122) and Ministerio de Economía y Competitividad of Spain (CTQ2014-56833-R, RD12/0043/0005, and PI13-00981) and Comunidad Autónoma de Madrid (Project MADRISOLAR2, ref. S2009/PPQ-1533). One of us (C. I. Nieto) is indebted to UNED for a predoctoral fellowship (FPI “Grupos de Investigación” UNED)