Carlos Cativiela

Nanoparticle-induced vascular blockade in human prostate cancer

The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.

HYDROTALCITE-PROMOTED EPOXIDATION OF ELECTRON-DEFICIENT ALKENES WITH HYDROGEN PEROXIDE

A synthetic anionic clay, hydrotalcite (MgAl = 2.8), promotes the epoxidation of electron-deficient alkenes with H2O2. With open-chain, α,β-unsaturated carbonyl compounds 3-hydroxy-1,2-dioxolanes are also obtained.

Synthesis, characterization and catalytic activity in Heck-type reactions of orthometallated PdII and PtII complexes derived from (1R, 2R)-1,2-diaminocyclohexane

The chiral bis-imine (1R,2R)-C6H10-[ENCHC6H33,4-(OMe)2]21 (LH) reacts with [Pd(OAc)2] (1:1 molar ratio; OAc=acetate) giving the orthometallated [Pd(OAc)(C6H24,5-(OMe)22-CHN-(1R,2R)-C6H10NCHC6H3-3′,4′-(OMe)2-κ-C,N,N)] 2 (abbreviated as [Pd(OAc)(L-κ-C,N,N)]), through CH bond activation on only one of the aryl rings and N,N-coordination of the two iminic N atoms. 2 reacts with an excess of LiCl to give [Pd(Cl)(L-κ-C,N,N)] 3. The reaction of 3 with AgClO4 and neutral or anionic ligands L′ (1:1:1 molar ratio) affords [Pd(L-κ-C,N,N)(L′)](ClO4) (L′=PPh34a, NCMe 5, pyridine 6, p-nitroaniline 7) or [Pd(I)(L-κ-C,N,N)] 8. Complex 4a reacts with wet CDCl3 giving [Pd(C6H24,5-(OMe)22-CHN-(1R,2R)C6H10NH2-κ-C,N,N)(PPh3)](ClO4) 4b as a result of the hydrolysis of the CN bond not involved in the orthometallated ring. The molecular structure of 4b·CH2Cl2 has been determined by X-ray diffraction methods. Cleavage of the PdN bond trans to the Caryl atom can be accomplished by coordination of strongly chelating ligands, such as acetylacetonate (acac) or bis(diphenylphosphino)ethane (dppe), forming [Pd(acac-O,O′)(L-κ-C,N)] 9 and [Pd(L-κ-C,N)(dppe-P,P′)](ClO4) 12, while classical N,N′-chelating ligands such as 1,10-phenantroline (phen) or 2,2′-bipyridyl (bipy) behave as monodentate N-donor ligands yielding [Pd(L-κ-C,N,N)(κ1-N-phen)](ClO4) 10 and [Pd(L-κ-C,N,N)(κ1-N-bipy)](ClO4) 11. Treatment of 1 with PtCl2(DMSO)2 (1:1 molar ratio) in refluxing 2-methoxyethanol gives Cl2Pt[(NH2)2C6H10N,N′] 13a and [Pt(Cl)(C6H24,5-(OMe)22-CHN-(1R,2R)C6H10NH2-κ-C,N,N)] 13b, while [Pt(Cl)(L-κ-C,N,N)] 14 can be obtained by reaction of [Pt(μ-Cl)(η3-2-MeC3H4)]2 with 1 in refluxing CHCl3. Complexes 2 and 3 catalyzed the arylation of methyl acrylate giving good yields of the corresponding methyl cinnamates and TON up to 847 000. Complex 3 also catalyzes the hydroarylation of 2-norbornene, but with lower yields and without enantioselectivity.

Factors influencing the k10 montmorillonite-catalyzed diels-alder reaction between methyl acrylate and cyclopentadiene

Experimental factorial design has been used to study several factors that are assumed to affect the results of the K10-catalyzed Die] s-Alder reaction between methyl acrylate and cyclopentadiene. The results obtained were complemented by physical characterization of the solid catalysts using X-ray diffraction, FTIR studies of adsorption of pyridine, methyl acrylate, and solvents, and BET measurements. Among the factors studied, the nature of the solvent is the most important one influencing the reaction results. Complementary studies have shown that solvents miscible with water give rise to low yields and endo/exo selectivities, very close to those obtained without clay in the same solvent. In these solvents the clay does not play any catalytic role and the reaction takes place in the bulk of the solvent. In general, excellent results are obtained with solvents nonmiscible with water, but a close relationship exists between the nature of the solvent and the cation exchanged into the K10 montmorillonite. In particular, anisole is the best solvent for Zn2+-doped K10 montmorillonite-catalyzed reaction, but it is not so good when the exchanged cation is Fe3+ In this case a radical-promoted Friedel-Crafts reaction of cyclopentadiene with anisole and oligomerization of cyclopentadiene take place. The presence of radicals has been confirmed by ESR experiments. Furthermore, in methylene chloride as solvent, catalytic activity is related to strength of Lewis acidity, and Zn2+-K10 is a better catalyst than Fe3+-K10.

Mesogenic behaviour in some pyrazole and isoxazole derivatives

Abstract Several aromatic β-diketones with a different number of alkyloxy groups in the aromatic rings and their derived pyrazoles, isoxazoles and thallium (I) complexes have been synthesized. The potential mesomorphic properties of these compounds have been investigated by optical microscopy, DSC and X-ray diffraction. The pyrazoles and isoxazoles with one chain in each aromatic ring are mesogenic, showing smectic A and smectic C mesophases, whereas the pyrazoles and isoxazoles with two chains per ring and the β-diketones and thallium complexes are not. The mesogenic potentiality is shown to be related to the molecular linearity and to the number of alkyloxy groups. To the best of our knowledge, this is the first time liquid crystal properties have been described for pyrazole and isoxazole derivatives.

Comparison of the catalytic properties of protonic zeolites and exchanged clays for Diels-Alder synthesis

Abstract Zn 2+ - and Fe 3+ -exchanged K10 montmorillonites have been compared to HY and HBEA zeolites for Diels-Alder condensation of methyl and (−)-menthyl acrylates with cyclopentadiene. In the case of clays, the endo/exo and diastereofacial selectivities of the reaction increase with the temperature of dehydration of the solid. The catalysts dried at 393 K show lower selectivities and some deactivation as a function of time. The initial selectivity of the zeolitic catalysts is good but decreases rapidly with time. This decrease is attributed to the formation of polymers of cyclopentadiene, which deactivate the catalyst. FT-IR studies ofpyridine adsorption on the catalysts showed that this polymerization reaction increases when the proportion of Bronsted acid sites increases.

A new titanium-silica catalyst for the epoxidation of alkenes

Abstract Silica gel treated with Ti(O i Pr) 4 is an efficient catalyst for the TBHP epoxidation of non-functionalized alkenes, dienes, and allylic alcohols. This catalyst is more efficient than those obtained from other titanium precursors; it must be activated at 140°C prior to use, it can be recovered and stored in the open air. The reactivity of different olefinic substrates is compared and is shown to be dependent on the structure, which allows the selective epoxidation of compounds containing different kinds of double bonds.

Study of the reaction of imines derived from (R)-glyceraldehyde with Danishefsky's diene

Abstract N-Benzylimines derived from conveniently protected (R)-glyceraldehyde underwent diastereoselective tandem Mannich-Michael reaction with Danishefskys diene in the presence of Lewis acids. The temperature, catalyst and solvent dependence of the product ratio is described. Under zinc iodide-catalysed conditions in acetonitrile at −20°C, double stereodifferentiation using (R)-2,3-di-O-benzylglyceraldehyde (S)-N-α-(methylbenzyl)imine as starting material was successful and the reaction occurred with good yield and complete diastereoselectivity.

Proton-conducting supramolecular metallogels from the lowest molecular weight assembler ligand: a quote for simplicity.

Oxalic acid has been proven to be the lowest molecular weight organic ligand able to form robust supramolecular metallogel networks in the presence of metal salts. In particular, two novel multifunctional metallogels were readily prepared at room temperature by simple mixing of stock solutions of Cu(II) acetate monohydrate or Cu(II) perchlorate hexahydrate and oxalic acid dihydrate. Formation of different polymorphs and unprecedented proton conduction under anhydrous conditions were also demonstrated with some of these materials.

Metal complexes of biologically important ligands: Synthesis of amino acidato complexes of PdII containing a C,N-cyclometallated group as an ancillary ligand

Abstract New amino acidato complexes of Pd II of stoichiometry [Pd(CN)(Aa)] (CN C , N -cyclometallated ligand, Aa = N , O -amino acidato ligand) have been obtained by reaction of [Pd(CN)(acac)] (CN N , N -dimethylbenzylamine- C 2 , N (dmba) ( 1 ) or N , N -dimethyl( S - α -phenylethyl)amine- C 2 , N ( S -dmphea) ( 2 )) with glycine, chiral amino acids (alanine, phenylalanine and valine), and amino acid derivatives ( N -acetylglycine and N -acetyl- α , β -dehydroalanine) in MeOH. The compounds are characterized by IR, 1 H and 13 C NMR. The geometry of these complexes has been unambiguously determined by NOE difference experiments and NOESY measurements.