J. Manuel López-Romero

Isoquinoline alkaloids from Berberis Vulgaris subsp. Australis

Abstract Sixteen isoquinoline alkaloids were isolated from Berberis vulgaris subsp. australis . In addition to quaternary protoberberines and bisbenzylisoquinolines, a new seco - bis benzylisoquinoline, (-)-tejedine, is reported.

Synthesis of theophylline derivatives and study of their activity as antagonists at adenosine receptors

The synthesis of oligo(ethylene glycol)-alkene substituted theophyllines in positions 7 and/or 8 is described. The binding activity at adenosine receptors of selected derivatives was studied. Compound 2 showed high affinity for human A(2B) receptor (K(i) = 4.16 nM) with a selectivity K(iA2A)/K(iA2B) of 24.1, and a solubility in water of 1 mM. The alkenyl substituent in some of the theophylline derivatives allows for covalent attachment of them onto hydrogen-terminated silicon substrate surfaces via hydrosilylation. Alternatively, an azido group was incorporated to an oligo(ethylene glycol)theophylline derivative as an anchor for tethering the molecules on ethynyl presenting surfaces via click reaction.

Membrane surface functionalization via theophylline derivative coating and streptavidin immobilization.

Poly(vinylidene fluoride) (PVDF) and regenerated cellulose (RC) membranes were surface-modified by the adsorption of one adenosine receptor antagonist: the theophylline-oligo(ethylene glycol)-alkene derivative, Theo1. Surface modification was carried out by immersion of the membrane in a dichloromethane solution of Theo1 (PVDF+Theo1 and RC+Theo1 samples). Membrane surfaces with partial coverage by theophylline and/or its inclusion in the membrane structures were studied by X-ray photoelectron spectroscopy (XPS), solid-state nuclear magnetic resonance (SNMR), impedance spectroscopy (IS) and contact angle (CA) measurements. The Theo1 orientation was inferred from the data. Streptavidin (SA) was immobilized onto the membrane/Theo1 hybrid material. The protein-theophylline Theo1 interaction was visualized with bright field microscopy (BFM).

Synthesis of new mannosyl, galactosyl and glucosyl theophylline nucleosides with potential activity as antagonists of adenosine receptors. DEMA-induced cyclization of glycosylideneiminouracils

The synthesis of D-mannosyl, D-galactosyl and D-glucosyl theophylline nucleosides by diethoxymethyl acetate (DEMA)-induced cyclization of 4-amino-5-glycosylideneimino-1,3-dimethyluracil is reported. 8-Methyltheophylline derivatives of the same sugars were also prepared by Ac(2)O/H(+)-induced cyclization of their imine precursors. This approach has allowed beta-D-mannopyranosyl-, alpha-D-galactofuranosyl- and beta-D-glucofuranosyltheophylline nucleosides to be synthesized for the first time. The inhibition of specific binding at A(1), A(2A), A(2B) and A(3) adenosine receptors in the mannose derivatives is also reported.

Functionalized Lipid Nanoparticles–Cellophane Hybrid Films for Molecular Delivery: Preparation, Physicochemical Characterization, and Stability

Lipid nanoparticles functionalized with the sunscreen 2,4-dihydroxybenzophenone (FLNPs) have been prepared by the ultrasound method and embedded in highly hydrophilic cellophane supports (regenerated cellulose, RC), creating biocompatible hybrid films (RC-FLNPs samples). The morphology of the FLNPs was studied with transmission microscopy, whereas the surface and interior chemical composition was analyzed by micro-Raman spectroscopy. RC-FLNPs hybrid films were prepared from the immersion of two cellophane supports with different thicknesses and water uptake properties (RC-3 and RC-6) in an aqueous dispersion of FLNPs. The structure of this hybrid material was visualized with bright-field microscopy, which clearly showed the inclusion of the FLNPs in the cellophane matrix. The stability of the RC-FLNPs films with respect to both aqueous environments and time was demonstrated by NaCl diffusion measurements. The reduction in the diffusion coefficient through the nanoparticle-modified films compared with the original supports confirms the presence of nanoparticles for concentration gradients of up to 0.4 M (osmotic pressure around 10 bar), indicating the stability of the hybrid hydrophilic material, even in aqueous environments and under matter flow conditions for a period of 21 days.

Preparation, characterization, and protein-resistance of films derived from a series of α-oligo(ethylene glycol)-ω-alkenes on H–Si(111) surfaces

A series of oligo(ethylene glycol) (OEG)-terminated monolayers were prepared by photo-activated grafting of OEG-alkenes with the general formula CH2CH(CH2)m(OCH2CH2)nOCH3 (abbreviated as Cm+2EGn, m = 8, 9; n = 3–7) on hydrogen-terminated silicon (111) surfaces using different deposition conditions. The films were characterized by contact-angle goniometry, ellipsometry, X-ray photoelectron spectroscopy (XPS) and tested for protein resistance. Films prepared under a higher vacuum showed a higher thickness and exhibited better protein resistance with increasing ethylene glycol (EG) units. Remarkably, the films prepared from C10EGn were generally thicker than those from their corresponding homologues C11EGn, and displayed better resistance to protein adsorption, which were probably due to the odd–even effect from the alkyl chain. Prepared under high vacuum conditions (∼10−5 mbar), the C10EG7 films with a thickness of 40 A adsorbed <0.8% (the detection limit of N 1s XPS) monolayer of fibrinogen in a standard assay. The films remained protein-resistant (adsorbed <3% monolayer of fibrinogen) even after 28 days in phosphate buffered saline (PBS) at 37 °C or 17 days in MC3T3-E1 cell culture with 10% fetal bovine serum at 37 °C. Therefore, the C10EG7 films prepared under high vacuum conditions represent the most protein-resistant and stable films on non-oxidized silicon substrates.