Synthesis and Characterization of a Luminescent Cyclic Poly(ethylene oxide)-Polypyridyl Ruthenium Complex.

We report the synthesis of a macrocyclic poly(ethylene oxide) (PEO) connected by one [Ru(bpy)3]2+ unit (where bpy = 2,2'-bipyridine), a photoactive metal complex that provides photosensitivity and potential biomedical applications to this polymer structure. The PEO chain provides biocompatibility, water solubility, and topological play. The macrocycles were successfully synthesized by copper-free click cycloaddition between a bifunctional dibenzocyclooctyne (DBCO)-PEO precursor and 4,4'-diazido-2,2'-bipyridine, followed by complexation with [Ru(bpy)2Cl2]. The cyclic product accumulated efficiently in MCF7 cancer cells and exhibited a longer fluorescence lifetime than its linear analogue, likely due to differences in the accessibility of the ligand-centered/intraligand states of Ru polypyridyls in both topologies.

Linear and Cyclic Depsipeptidomimetics with ß-Lactam Cores: A Class of New αv ß3 Integrin Receptor Inhibitors.

The αv ß3 integrin receptor plays an important role in tumor metastasis and tumor-induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe-(Me)Val dipeptide by a ß-lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond ß-lactam-NH-Asp linkage by a ß-lactam-O-Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open-chain compounds of the form Asp-ß-lactam-Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.

Mechanistic insights on the magnesium(II) ion-activated reduction of methyl benzoylformate with chelated NADH peptide beta-lactam models.

Mechanistic details of the Mg(2+) ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a beta-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg(2+)/ArCOCO(2)R ternary complexes 3 and the corresponding transition states leading to enantiomeric methyl mandelates. Thus, ternary complexes showed the dihydronicotinamide moiety placed quasiequatorial to a seven-membered chelation pseudoplane including the two amide carbonyls and the Mg(2+) cation, whereas productive transition states were strongly deformed with the dihydronicotinamide group oriented quasiaxial to the chelation pseudoplane. This chelation model was further applied to acyclic nonrigidified NADH models and, based on the fluxional mobility of the peptide chain bonds, experimental enantioselectivities were correctly predicted. Parallel experiments were also conducted in deuterated acetonitrile, using NMR techniques, to study the structure of the binary complexes 2 (NADH/Mg(2+)) and ternary complexes 3 (NADH/Mg(2+)/PhCOCO(2)Me). Finally, owing to the incorporation of two diastereotopic trimethylsilyl NMR-tags in the beta-lactam-NADH peptidomimetics, a nonproductive ternary complex predicted by calculations could be observed and its structure characterized on the basis of ROESY experiments and molecular modeling.

Meningioma del surco olfatorio / Olfactory groove meningioma

Los meningiomas del surco olfatorio son tumores intracraneales infrecuentes. Suelen alcanzar gran tamaño antes de manifestarse clínicamente, siendo los síntomas más frecuentes los relacionados con la alteración de funciones corticales superiores. Es esencial llegar a un diagnóstico precoz cuando el tumor es relativamente pequeño (3 a 4 cm), para reducir su alta morbi-mortalidad, puesto que el avance en las técnicas de neuro-imagen no han sido suficientes para mejorar el pronóstico. Los signos precoces como edema de papila y/o cambios mentales, la anosmia permanente y la cefalea, desde el punto de vista del especialista de ORL, nos deben hacer sospechar una patología orgánica, descartando la presencia de una masa ocupante de espacio.

Meningiomas of the olfactory sulcus are rare intracranial tumors. They tend to reach a large size before showing clinically. Their most frequent symptoms are related to superior cortical functions. Early diagnose is essential when the tumor is still relatively small (3 to 4 cm), in order to reduce its high morbid-mortality rate, since the advance in neuro-image techniques has not been good enough to improve its prognosis. Early signs such as papilladema and/or cognitive changes and permanent anosmia and headache, from the ENT point of view should make us suspect an organic pathology, ruling out the presence of a space occupying mass.