Cristina Minguillón

Identification of a Novel Metabolite in the Degradation of Pyrene by Mycobacterium sp. Strain AP1: Actions of the Isolate on Two- and Three-Ring Polycyclic Aromatic Hydrocarbons

ABSTRACT Mycobacterium sp. strain AP1 grew with pyrene as a sole source of carbon and energy. The identification of metabolites accumulating during growth suggests that this strain initiates its attack on pyrene by either monooxygenation or dioxygenation at its C-4, C-5 positions to give trans- orcis-4,5-dihydroxy-4,5-dihydropyrene, respectively. Dehydrogenation of the latter, ortho cleavage of the resulting diol to form phenanthrene 4,5-dicarboxylic acid, and subsequent decarboxylation to phenanthrene 4-carboxylic acid lead to degradation of the phenanthrene 4-carboxylic acid via phthalate. A novel metabolite identified as 6,6′-dihydroxy-2,2′-biphenyl dicarboxylic acid demonstrates a new branch in the pathway that involves the cleavage of both central rings of pyrene. In addition to pyrene, strain AP1 utilized hexadecane, phenanthrene, and fluoranthene for growth. Pyrene-grown cells oxidized the methylenic groups of fluorene and acenaphthene and catalyzed the dihydroxylation andortho cleavage of one of the rings of naphthalene and phenanthrene to give 2-carboxycinnamic and diphenic acids, respectively. The catabolic versatility of strain AP1 and its use ofortho cleavage mechanisms during the degradation of polycyclic aromatic hydrocarbons (PAHs) give new insight into the role that pyrene-degrading bacterial strains may play in the environmental fate of PAH mixtures.

Covalently bonded polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography

Polysaccharide derivatives have been extensively used as chromatographic chiral selectors in chiral stationary phases (CSPs) for the separation of enantiomers by HPLC. When coated onto a silica matrix, they represent nowadays one of the most popular type of CSPs. However, they are only compatible with a limited choice of solvents. The main drawback of these CSPs is related to the solubility of the chiral selector in a number of solvents, which limits their applicability. The different attempts which have been described up to now to overcome this problem by covalently fixing the chiral selector to a matrix are reviewed in this paper.

Chiral Chromatographic Discrimination Ability of a Cellulose 3,5-Dimethylphenylcarbamate/10-Undecenoate Mixed Derivative Fixed on Several Chromatographic Matrices

Abstract The properties as chiral selector in HPLC chiral stationary phases (CSPs) of a cellulose derivative bearing simultaneously 3,5-dimethylphenylamino carbonyl and 10-undecenoyl groups are described. This polysaccharide is reticulated (or bonded) on chromatographic supports such as silica gel, previously treated or not, graphite or alumina. The chiral stationary phases thus obtained are resistant to the usual solvents used in liquid chromatography and can be used on normal or reversed phase conditions. The results obtained on the resolution of racemic compounds with these stationary phases depend on the nature of the support. The best results were obtained with the chiral stationary phase in which the cellulose derivative is bonded on allyl silica gel.

Bonded cellulose-derived high-performance liquid chromatography chiral stationary phases I. Influence of the degree of fixation on selectivity

Four mixed 10-undecenoyl-3,5-dimethylphenylaminocarbonyl derivatives of cellulose, with an increasing proportion of alkenoyl groups, were synthesized and chemically bonded on allylsilica gel. The influence of the degree of fixation of the cellulose derivative on the matrix for the four resulting chiral stationary phases on their selectivity is discussed.

3,5-Dimethylphenylcarbamates of amylose, chitosan and cellulose bonded on silica gel: Comparison of their chiral recognition abilities as high-performance liquid chromatography chiral stationary phases

Mixed 10-undecenoyl/3,5-dimethylphenylaminocarbonyl derivatives of amylose and chitosan were prepared and immobilized on allylsilica gel. The enantioselectivities of the resulting supports were compared to those of an analogous cellulose-derived chiral stationary phase previously prepared.

Chitosan derivatives as chiral selectors bonded on allyl silica gel: preparation, characterisation and study of the resulting high-performance liquid chromatography chiral stationary phases

Abstract Several mixed 10-undecenoyl/phenylaminocarbonyl or benzoyl derivatives of chitosan, differently substituted in the aromatic ring, were prepared, characterized and immobilized on allylsilica gel. The resulting high-performance liquid chromatography (HPLC) chiral supports were tested chromatographically. The influence of the starting polysaccharidic material, as well as that of the solvents used as mobile phase modifiers, on the preparation and performance of the resulting chiral stationary phases (CSPs) is discussed.

Huprine–Tacrine Heterodimers as Anti-Amyloidogenic Compounds of Potential Interest against Alzheimer’s and Prion Diseases

A family of huprine-tacrine heterodimers has been developed to simultaneously block the active and peripheral sites of acetylcholinesterase (AChE). Their dual site binding for AChE, supported by kinetic and molecular modeling studies, results in a highly potent inhibition of the catalytic activity of human AChE and, more importantly, in the in vitro neutralization of the pathological chaperoning effect of AChE toward the aggregation of both the β-amyloid peptide (Aβ) and a prion peptide with a key role in the aggregation of the prion protein. Huprine-tacrine heterodimers take on added value in that they display a potent in vitro inhibitory activity toward human butyrylcholinesterase, self-induced Aβ aggregation, and β-secretase. Finally, they are able to cross the blood-brain barrier, as predicted in an artificial membrane model assay and demonstrated in ex vivo experiments with OF1 mice, reaching their multiple biological targets in the central nervous system. Overall, these compounds are promising lead compounds for the treatment of Alzheimers and prion diseases.

Multiple dual-mode countercurrent chromatography applied to chiral separations using a (S)-naproxen derivative as chiral selector.

Countercurrent chromatography (CCC) is a liquid-liquid chromatographic technique without a solid support. Several alternative elution modes can be applied to take advantage of the special nature of the liquid stationary phase. Among these dual-mode (DM) and multiple dual-mode (MDM) consist of switching alternatively between Reversed and Normal Phase operation during the experiment (once for DM and several times for MDM). In this paper, MDM has been applied to the chiral CCC separations of two racemic mixtures, (+/-)-N-(3,4-cis-3-decyl-1,2,3,4-tetrahydrophenanthren-4-yl)-3,5-dinitrobenzamide and N-(3,5-dinitrobenzoyl)-(+/-)-leucine, using (S)-naproxen N,N-diethylamide as chiral selector (CS). Although the behaviour of the two analytes differed, improved resolution factors were successfully obtained. Results are rationalized on the basis of the distinct partition behaviour of the CS/enantiomer complexes in the biphasic system.

Solvent versatility of bonded cellulose-derived chiral stationary phases for high-performance liquid chromatography and its consequences in column loadability

The chromatographic behaviour of a 10-undecenoate/3,5-dimethylphenylcarbamate of cellulose bonded on allylsilica gel is tested using four organic mobile-phase modifiers (2-propanol, chloroform, tetrahydrofuran and ethyl acetate). The advantages of the broad choice of solvents offered by this kind of chiral stationary phases and their resistance are discussed. The loadability of the column and its dependence both on the racemate to be resolved and on the solvent used as mobile phase are also discussed.

Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

Abstract Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane β-amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded β-amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-β-amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from d -glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected.