Jesús Hierrezuelo

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.

Inclusion of silver nanoparticles for improving regenerated cellulose membrane performance and reduction of biofouling

The preparation of silver nanoparticles (AgNPs) and their incorporation into the structure of a regenerated cellulose membrane by dip coating is presented. Morphological characterization of the AgNPs (average diameter of 20±2nm) was carried out by SEM/TEM, while elastic, electrical and antimicrobial properties of the hybrid membrane were also analyzed. The presence of silver nanoparticles in the membrane seems to increases its rigidity and its chemical stability against oxidation, but it only induces small changes in the transport parameters. As expected, AgNPs provide antimicrobial properties to the membrane and consequently the reduction of biofouling without affecting significantly other characteristic parameters, opening the application of the modified membrane to wastewaters treatment.

DMABI tripod structures with sensing capabilities: synthesis, characterization and fluorescence analysis

We present herein the synthesis, and the structural and spectroscopic analysis of a non-planar tripod-shaped p-(N,N′-dimethylamino)benzyliden-1,3-indandione (DMABI) chromophore. This novel molecule is composed of a Si core with three incorporated arms, each of them contains a 1,3-indandione derivative with an electron donating (−NMe2) group, thus providing fluorescence capabilities. We prepared a DMABI arm by coupling a p-(N,N′-dimethylamino)benzaldehyde (DMAB) tripod substituted molecule with 1,3-indandione via aldol condensation. The structures of DMAB-tripods were confirmed by spectroscopic data and studied by quantum chemical calculations. Fluorescence spectroscopy was used for optical characterization. Quantum yields and the corresponding lifetimes reveal typical characteristics of conjugated derivatives. Finally, we monitored the enhancement in fluorescence intensity of compound 1 in the presence of 4-chloro-2,6-dinitroaniline (4CDNA) in the range between 0 and 20 mg L−1. We justify this enhancement by calculated energies and the distribution of the HOMO and the LUMO for DMABI-tripod and 4CDNA.