Renato Noto

New ionic liquid-modified silica gels as recyclable materials for L-proline- or H–Pro–Pro–Asp–NH2-catalyzed aldol reaction

L-proline and the tripeptide H–Pro–Pro–Asp–NH2 (1) have been supported, by adsorption, onto the surface of modified silica gels functionalized with a monolayer of covalently attached 1,2-dimethyl-imidazolium chloride, tetrafluoroborate or hexafluorophosphate ionic moieties, respectively. Three different linkers were used to attach the ionic liquid moiety to the surface of these supports. The resulting materials have been used as catalysts for the aldol reaction between acetone and several substituted benzaldehydes. Good yields and enantioselectivities, comparable to or better than those obtained under homogeneous conditions, were obtained. These materials are easily recovered by filtration, and studies regarding their re-use have been carried out. Studies performed using L-proline-supported materials have shown that the re-use of these materials is dependent on the nature of the linker. The supported tripeptide H–Pro–Pro–Asp–NH2 gave higher enantioselectivities than those obtained with supported-proline. Recycling investigations using tripeptide-supported materials showed continued good selectivities but diminishing conversions over consecutive runs. L-proline-supported materials however, can be used at least nine times without loss of either conversion or selectivity.

Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity.

Positively charged halloysite nanotubes functionalized with triazolium salts (f-HNT) were employed as a carrier for curcumin molecules delivery. The synthesis of these f-HNT new materials is described. Their interaction with curcumin was evaluated by means dynamic light scattering (DLS) and UV-vis spectroscopy in comparison with pristine unmodified HNT (p-HNT). The curcumin load into HNT was estimated by thermogravimetric analysis (TGA) measurements, while the morphology was investigated by scanning electron microscopy (SEM) techniques. Release of curcumin from f-HNT, at three different pH values, by means of UV-vis spectroscopy was also studied. Furthermore, different cancer cell lines were used to evaluate the potential cytotoxic effect of HNT at different concentrations and culture times. The results indicated that the f-HNT drug carrier system improves the solubility of curcumin in water, and that the drug-loaded f-HNT exerted cytotoxic effects against different cell lines.

Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.

Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiffs base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage.

“Release and catch” catalytic systems

In this perspective article the “release and catch” catalytic system concept is discussed. A “release and catch” catalytic system is prepared by non-covalent immobilization of the catalytic moiety on a suitable support, but differently from the usual non-covalently supported catalyst, the catalytic moiety is released in solution over the course of the reaction and it is recaptured at the end of the reaction. Such a “catalyst-sponge like” or “boomerang” system allows one to combine the benefits of homogeneous and heterogeneous catalysis and can be applied to organometallic-based catalysts, organocatalysts and metal-based catalysts.

Ionic Liquids/[bmim][N3] Mixtures: Promising Media for the Synthesis of Aryl Azides by SNAr

The nucleophilic aromatic substitution of some activated aryl or heteroaryl halides has been performed in ionic liquid solution, using the 1-butyl-3-methylimidazolium azide as a nucleophile. The reaction course was studied varying the structures of both substrates and ionic liquids. In particular, in the latter case, the reaction of 2-bromo-5-nitrothiophene was carried out in five different ionic liquids ([bmim][BF 4], [bmim][PF 6], [bmim][NTf 2], [bm 2im][NTf 2], and [bmpyrr][NTf 2]). Finally, for all the substrates considered, a comparison with data obtained in MeOH solution in the presence of NaN 3 was also performed. Data collected indicate that in some cases it is possible to obtain aromatic or heteroaromatic azide derivatives in satisfactory yield by means of a S NAr reaction using [bmim][N 3] as the nucleophile.

Functionalized halloysite multivalent glycocluster as a new drug delivery system

A new design for halloysite nanotube materials was obtained by grafting chemically modified cyclodextrin units onto the nanotube surface. In particular, grafted cyclodextrins were decorated with thiosaccharide pendants, in order to mimic the well-known binding of sugars to proteins and the glyco-cluster effect occurring during cellular recognition events. The obtained materials were characterized by using a combination of varied techniques (FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy, dynamic light scattering, turbidimetry), and their potential drug-delivery abilities were tested by studying their interactions with the common naturally occurring anticancer agent curcumin. A suitable model describing the interaction between our materials and curcumin is proposed.

Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications

Halloysite (HNT) is a promising natural nanosized tubular clay mineral that has many important uses in different industrial fields. It is naturally occurring, biocompatible, and available in thousands of tons at low cost. As a consequence of a hollow cavity, HNT is mainly used as nanocontainer for the controlled release of several chemicals. Chemical modification of both surfaces (inner lumen and outer surface) is a strategy to tune the nanotubes properties. Specifically, chemical modification of HNT surfaces generates a nanoarchitecture with targeted affinity through outer surface functionalization and drug transport ability from functionalization of the nanotube lumen. The primary focus of this review is the research of modified halloysite nanotubes and their applications in biological and medical fields.

Multicavity halloysite–amphiphilic cyclodextrin hybrids for co-delivery of natural drugs into thyroid cancer cells

Multicavity halloysite nanotube materials were employed as simultaneous carriers for two different natural drugs, silibinin and quercetin, at 6.1% and 2.2% drug loadings, respectively. The materials were obtained by grafting functionalized amphiphilic cyclodextrin onto the HNT external surface. The new materials were characterized by FT-IR spectroscopy, SEM, thermogravimetry, turbidimetry, dynamic light scattering and ζ-potential techniques. The interaction of the two molecules with the carrier was studied by HPLC measurements and fluorescence spectroscopy, respectively. The release of the drugs from HNT-amphiphilic cyclodextrin, at two different pH values, was also investigated by means of UV-vis spectroscopy. Biological assays showed that the new complex exhibits anti-proliferative activity against human anaplastic thyroid cancer cell lines 8505C. Furthermore, fluorescence microscopy was used to evaluate whether the carrier was uptaken into 8505C thyroid cancer cell lines. The successful results revealed that the synthesized multicavity system is a material of suitable size to transport drugs into living cells.

Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems.

Halloysite nanotubes were explored as drug carrier for cardanol, which is considered as a promising natural anticancer active species. To this aim, besides the pristine nanoclay, a chemical modification of the nanocarrier was performed by attaching triazolium salts with different hydrophobicity at the outer surface of the hollow nanotubes. The interaction between cardanol and nanotubes was highlighted in solution by HPLC. This method proved the loading of the drug into the nanotubes. The solid dried complexes formed by pristine and modified halloysite with the cardanol were characterized by IR spectroscopy, thermogravimetric analysis as well as water contact angle to evidence the structure, thermal properties and wettability of the obtained materials. The kinetics of cardanol release as well as cell viability experiments provided promising results that put forward a new strategy for potential applications of cardanol as active antiproliferative molecule and clay nanotubes as drug carrier.

Spectrophotometric study on the thermodynamics of binding of α- and β-cyclodextrin towards some p-nitrobenzene derivatives

Binding properties of native α- and β-cyclodextrin towards some nitrobenzene derivatives have been studied by means of UV-vis spectrophotometry. The former host is able to form complexes having 1 : 1 and 1 : 2 stoichiometric ratios with these guests, while only 1 : 1 complexes are detected with the latter host. A careful analysis of the thermodynamic parameters for complexation equilibria, under the perspective of the enthalpy–entropy compensation effect, reveals that binding abilities of the two different hosts are subject to different features.