Ester Weiss

High Antitumor Activity of Highly Resistant Salan–Titanium(IV) Complexes in Nanoparticles: An Identified Active Species†

A nanoformulated trinuclear hydrolysis product of a bis(alkoxo) salan-Ti(IV) complex shows high antitumor activity, which identifies it as an active species in cells. Additional highly stable mononuclear derivatives also show high activity, when formulated into nanoparticles, thus evincing that biologically friendly Ti(IV) can provide high cytotoxicity with controlled biological function.

Design, synthesis, and evaluation of quinazoline T cell proliferation inhibitors.

We report here on a class of quinazoline molecules that inhibit T cell proliferation. The most potent compound N-p-tolyl-2-(3,4,5-trimethoxyphenyl)quinazolin-4-amine (S101) and its close analogs were found to inhibit the proliferation of T cells from human peripheral blood mononuclear cells (PBMC) and Jurkat cells, with IC(50) in the sub-micromolar range. The inhibitor induced G2 cell cycle arrest but did not inhibit IL-2 secretion. The anti-proliferative effect correlated with inhibition of the tyrosine phosphorylation of SLP-76, a molecular element in the signaling pathway of the T cell receptor (TCR). The inhibitor restrained proliferation of lymphocytes with much higher potency than non-hematopoietic cells. This new class of specific T cell proliferation inhibitors may serve as lead molecules for the development of agents aimed at diseases in which T cell signaling plays a role and agents to induce tolerance to grafted tissues or organs.

Palladium nanoparticles encapsulated in magnetically separable polymeric nanoreactors

A method for immobilization of palladium nanoparticles in magnetically separable polymeric nanocapsules is presented. The method is based on co-encapsulation of palladium nanoparticles stabilized by hyperbranched polyamidoamine (H-PAMAM-C15) modified with palmitoyl groups and hydrophobic magnetite nanoparticles within polyurea nanospheres. The synthesis of these polyurea nanospheres is based on nanoemulsification of chloroform, containing magnetic nanoparticles and palladium acetate, in water using suitable surfactants or dispersants. Then, the chloroform nano-droplets are confined in a polyurea shell formed by interfacial polycondensation between isocyanate and amine monomers. The palladium acetate was reduced with hydrogen to create palladium nanoparticles dispersed in the core of the polyurea nanocapsules. These catalytic polymeric nanoreactors were utilized in hydrogenation of alkenes and alkynes in water. The nanoreactors were easily separated from the reaction mixture via application of external magnetic field. The recyclability of these nanoreactors was examined in hydrogenation of styrene; no significant change was observed in their reactivity for up to four cycles.

Anti‐proliferative Activity of Nano‐Formulated Phenolato Titanium(IV) Complexes Against Cancer Cells

Nanoparticles of titanium(IV) complexes of phenolato ligands were formed and evaluated for cytotoxicity toward human HT‐29 colon cancer, murine T‐25 lymphoma, and murine HU‐2 multidrug‐resistant (MDR) cells. The nano‐formulation, besides increasing the complexes′ shelf lives, is particularly efficient in overcoming limitations in solubility and cell‐penetration, thus enhancing biological accessibility; large complexes that were inactive when measured in a non‐formulated form showed marked activity when nano‐formulated. For active and accessible small complexes, the effect of the formulation was negligible. Most complexes showed similar activity toward MDR cells and their drug‐sensitive analogues, further increasing their therapeutic potential. An exception is a particularly hydrophobic complex, which is presumably more accessible to interaction with the membrane ABCB1 (MDR1) transporter active in the multidrug resistance of HU‐2 cells. The most efficient compound is a mononuclear complex of a single hexadentate ligand, combining particularly high activity and hydrolytic stability with accessibility aided by the nano‐formulation.

Ionic liquid-based polymeric microreactors and their applicability

This work examines the applicability of encapsulated 1-methyl-3-butylimidazolium hexafluorophosphate within a polyurea shell (BMIm[PF6]@polyurea) to act as microreactors by dissolving platinum acetylacetonate or cinchonine in the ionic liquid phase pre-emulsification. Their applicability was tested in hydrosilylation and Michael addition reactions, respectively. The capsules crack within the first catalytic cycle indicating a fragile shell is formed. In addition, the development of particulated BMIm[PF6] within polyurethane is described. These BMIm[PF6]@polyurethane capsules were characterized and analyzed using scanning electron microscopy, X-ray diffraction, solid-state NMR, infrared and thermal gravimetric analysis. Finally, their ability to act as microreactors in the Michael addition reaction was tested. The capsules morphology does not undergo any changes after the reaction.

Functional Particulated Ionic Liquid-Based Silica Microcapsules

A method for the preparation of functional silica microcapsules containing 1-butyl-3-methylimidazolium hexafluorophosphate (BMIm[PF6]) is described. This method is based on emulsification of ionic liquid in water, and interfacial polycondensation of tetraethoxysilane (TEOS) and 3-aminopropyltrimethoxysilane (APTMS) using the sol-gel technique. The microcapsules were characterized by scanning electron microscopy, transition electron microscopy, thermal gravimetric analysis, infrared and solid state NMR. The resulted material was utilized efficiently in the Knoevenagel condensation.