CSIC - Institute of Advanced Chemistry of Catalonia

Barcelona, Spain

CSIC - Institute of Advanced Chemistry of Catalonia

Barcelona, Spain
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Messeguer A.,CSIC - Institute of Advanced Chemistry of Catalonia
Chemico-Biological Interactions | Year: 2011

The Toxic Oil Syndrome (TOS) was an epidemic disease appeared in central Spain in 1981, causing over 400 deaths and affecting more than 20,000 people, mainly women and children. The disease was linked to the consumption of rapeseed oil denatured with aniline, illegally refined at the ITH oil refinery in Seville, mixed with other oils and sold as edible olive oil. Among the aniline derivatives detected in the oil batches generated by an uncontrolled deodorisation procedure during the refining process, fatty acid anilides were first postulated as the causal agents. Nevertheless, compounds identified as 3-(N-phenylamino)propane-1,2-diol (PAP) and its mono-, di-, and triacyl derivatives (mPAP, dPAP and tPAP, respectively), were subsequently considered better biomarkers of toxic oils and the best candidates for causing the intoxication. In this account, we will discuss the results obtained in recent years by our group concerning: (a) The effect of different variables intervening in the deodorisation process that could influence the formation of PAP derivatives. To this end we decided to take the aniline derivatives linked to oleic acid as compound models since this is the fatty acid present in highest amounts in rapeseed oil. The study was focused on the influence of different parameters on the formation of the diester PAP derivative (OOPAP) the monoester derivative (OPAP) and the corresponding amide (oleanilide, OA), and the interactions between any two of these variables. Of particular interest was the interaction observed between OOPAP and OA, due to its potential relevance to the final composition of the toxic oil model. (b) Xenobiochemical aspects of PAP derivatives, specifically: the stereospecific hydrolysis of OPAP and OOPAP by human pancreatic lipase, the in vitro activation of PAP by human and rat liver microsomes as well as by recombinant 450 enzymes, and the formation and stability of GSH and N-acetylcysteine adducts of a highly reactive iminoquinone intermediate generated in the biotransformation of PAP. © 2010 Elsevier Ireland Ltd. All Rights Reserved.

Luis S.V.,Jaume I University | Alfonso I.,CSIC - Institute of Advanced Chemistry of Catalonia
Accounts of Chemical Research | Year: 2014

For years researchers have tried to understand the molecular behavior of complex biomolecules through the development of small molecules that can partially mimic their function. Now researchers are implementing the reverse approach: using the structural and mechanistic knowledge obtained from those complex systems to design small molecules with defined properties and for specific applications. One successful strategy for constructing bioinspired, minimalistic molecules is to combine natural building blocks that provide functional elements with abiotic fragments that serve as structural scaffolds. Therefore pseudopeptidic compounds, most of them based on C2 symmetric structures, represent a unique opportunity to explore and evaluate this approach. Some of these molecules are as simple as two amino acids connected by a diamino spacer.The results in this Account show how bioinspired minimalistic pseudopeptides can form ordered structures, participate in the recognition and transcription of information events in molecular devices, and catalyze reactions. This strategy allows researchers to design and prepare a variety of open-chain and macrocyclic compounds leading to systems that can self-aggregate to form hierarchically ordered micro- and nanostructures. In addition, small changes in the molecule or external stimuli can regulate the self-aggregation pattern. In the same way, researchers can also tune the molecular movements of simple pseudopeptides through environmental factors, providing a means to control new molecular devices. In addition, some of the prepared model compounds have shown interesting properties in molecular recognition and even as sensors for several targets of interest. Finally we have observed remarkable catalytic activities from these types of molecules, although those results are still far from the efficiency shown by natural peptides. This family of pseudopeptidic compounds offers the opportunity for the more elaborate design of relatively simple abiotic but bioinspired systems that display specific properties. In addition, the results can provide additional information that will increase the molecular understanding of the basic principles that underlie the extraordinary behavior of natural systems. © 2013 American Chemical Society.

Alfonso I.,CSIC - Institute of Advanced Chemistry of Catalonia | Quesada R.,University of Burgos
Chemical Science | Year: 2013

The control of ion transport and homeostasis is a critical function of living organisms. In this perspective, an overview of different synthetic systems capable of facilitating the transmembrane transport of ions along with the biological activity exerted by these compounds is presented. Examples of both cation selective and anion selective transporters are highlighted. The potential future applications of these systems in the treatment of conditions derived from the dysregulation of natural ion transport mechanisms and the development of new antimicrobials and anticancer drugs are discussed. © 2013 The Royal Society of Chemistry.

Torrent-Sucarrat M.,CSIC - Institute of Advanced Chemistry of Catalonia | Francisco J.S.,Purdue University | Anglada J.M.,CSIC - Institute of Advanced Chemistry of Catalonia
Journal of the American Chemical Society | Year: 2012

Sulfuric acid can act as a catalyst of its own formation. We have carried out a computational investigation on the gas-phase formation of H 2SO4 by hydrolysis of SO3 involving one and two water molecules, and also in the presence of sulfuric acid and its complexes with one and two water molecules. The hydrolysis of SO3 requires the concurrence of two water molecules, one of them acting as a catalyzer, and our results predict an important catalytic effect, ranging between 3 and 11 kcal·mol-1 when the catalytic water molecule is substituted by a sulfuric acid molecule or one of its hydrates. In these cases, the reaction products are either bare sulfuric acid dimer or sulfuric acid dimer complexed with a water molecule. There are broad implications from these new findings. The results of the present investigation show that the catalytic effect of sulfuric acid in the SO3 hydrolysis can be important in the Earth's stratosphere, in the heterogeneous formation of sulfuric acid and in the formation of aerosols, in H2SO4 formation by aircraft engines, and also in understanding the formation of sulfuric acid in the atmosphere of Venus. © 2012 American Chemical Society.

Torrent-Sucarrat M.,CSIC - Institute of Advanced Chemistry of Catalonia | Anglada J.M.,CSIC - Institute of Advanced Chemistry of Catalonia
Journal of Chemical Theory and Computation | Year: 2011

The infrared anharmonic spectra for the H +(H 2O) 3, H +(H 2O) 4, and H +(H 2O) 21 water clusters have been reported using vibrational second-order perturbation theory at the B3LYP level with 6-31+G(d) and 6-311++G(3df,3pd) basis sets. The anharmonicity results crucial for the evaluation of the protonated water clusters and the anharmonic corrections can be larger than 500 cm -1, resulting in a shift of the H 3O + asymmetric stretchings near the region of 2000 cm -1. © 2010 American Chemical Society.

Garcia-Urdiales E.,University of Oviedo | Alfonso I.,CSIC - Institute of Advanced Chemistry of Catalonia | Gotor V.,University of Oviedo
Chemical Reviews | Year: 2011

Various developments made towards the use of biocatalysts for the desymmetrization of meso and prochiral compounds are reviewed. Studied have found that the hydrolysis of meso epoxides generally displays low enantioselectivities. Fukuyama and co-workers reported the total synthesis of Leustroducsin, a potent colonystimulating factor inducer isolated from the culture broth of Streptomyces platensis SANK 60191. Prati and co-workers have carried out the Amano PS lipasecatalyzed desymmetrization of aziridine, whose monoacetylated derivative, obtained in high yield and ee, is related to a key intermediate used in the total synthesis of the already mentioned antibiotic FR-900482. Sugai and co-workers have investigated the substrate specificity of the reduction of different triketones with the yeast strain Torulaspora delbrueckii IFO10921.

Perez-Jimenez J.,CSIC - Institute of Advanced Chemistry of Catalonia | Torres J.L.,CSIC - Institute of Advanced Chemistry of Catalonia
Journal of Agricultural and Food Chemistry | Year: 2011

More than 500 phenolic compounds have been reported as present in foodstuffs, and their intake has been related to the prevention of several chronic diseases. Most of the literature on phenolic compounds focuses on those present in the supernatant of aqueous-organic extractions: extractable phenolics. Nevertheless, significant amounts of phenolic compounds remain in the solid residues after such extractions. These nonextractable phenolics are mostly proanthocyanidins, phenolic acids, and hydrolyzable tannins that are closely associated with the food matrix. Studies of this fraction of dietary phenolic compounds are scarce, and the few there are usually refer to particular types of phenolics rather than to the fraction as a whole. The present review reports the state-of-the-art methods that currently exist for analyzing nonextractable phenolic compounds in foods. © 2011 American Chemical Society.

Clapes P.,CSIC - Institute of Advanced Chemistry of Catalonia | Garrabou X.,CSIC - Institute of Advanced Chemistry of Catalonia
Advanced Synthesis and Catalysis | Year: 2011

Biocatalytic carbon-carbon bond formation by means of aldolases offers an exceptionally stereoselective and green tool for this strategic reaction in synthetic organic chemistry. Recent developments have shown that aldolases are particularly suitable catalysts for asymmetric framework construction and preparation of innovative molecules, which are valuable for investigations in drug discovery. Finding novel carboligases with unprecedented activities and engineering those available for improved substrate tolerance and stereoselectivity towards new synthetic challenges are fostering the advances in this field. Extensive knowledge of the precise reaction mechanism and the enzyme-substrate interactions arising from biochemical and structural studies are leading to the development of novel catalysts by rational strategies, as well as to de novo computational design of enzymes. Besides, a number of industrially-oriented processes with aldolases have been developed towards the production of drug precursors and dietary commodities. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trapero A.,CSIC - Institute of Advanced Chemistry of Catalonia | Llebaria A.,CSIC - Institute of Advanced Chemistry of Catalonia
Future Medicinal Chemistry | Year: 2013

Gaucher disease is a progressive lysosomal storage disorder caused by a deficiency in the activity of γ-glucocerebrosidase and is characterized by the accumulation of the glycosphingolipid glucosylceramide in the lysosomes of macrophages that leads to dysfunction in multiple organ system. An emerging strategy for the treatment of Gaucher disease is pharmacological chaperone therapy, based on the use of γ-glucocerebrosidase inhibitors that are capable of enhancing residual hydrolytic activity at subinhibitory concentrations. In this article, the most common lysosomal storage disorder, Gaucher disease, is introduced and the current therapeutic strategies based on the use of enzyme inhibitors to ameliorate this disease are discussed, with a focus on the efforts being made toward finding and optimizing novel molecules as pharmacological chaperones for Gaucher disease that offer the promise to remedy this malady. © 2013 Future Science Ltd.

Alfonso I.,CSIC - Institute of Advanced Chemistry of Catalonia
Current Organic Synthesis | Year: 2010

This review highlights the development of new receptors based on enantiopure trans-cyclohexane-1,2-diamine, a chiral building block presenting unique structural and conformational properties. Different architectures sharing this structural motif, which were prepared following several synthetic approaches, have been summarized from the recent literature. © 2010 Bentham Science Publishers Ltd.

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