Influence of Pore Size in Benzoin Condensation of Furfural Using Heterogenized Benzimidazole Organocatalysts.

A designed N-heterocyclic carbene (NHC) catalyst was covalently anchored on a range of mesoporous and hierarchical supports, to study the influence of pore size in the benzoin condensation of furfural. The structural and spectroscopic characteristics of the anchored catalysts were investigated, also with the help of molecular dynamics simulations, in order to rationalize the degree of stability and recyclability of the heterogenized organocatalysts. Quantitative yields (99 %) and complete recyclability were maintained after several cycles, vindicating the design rationale.

Red Upconverter Nanocrystals Functionalized with Verteporfin for Photodynamic Therapy Triggered by Upconversion.

Upconversion (UC) nanoparticles characterized by red upconversion emission, particularly interesting for biological applications, have been prepared and subsequently modified by the covalent anchoring of Verteporfin (Ver), an FDA approved photosensitizer (PS) which usually exerts its photodynamic activity upon excitation with red light. ZrO2 was chosen as the platform where Yb3+ and Er3+ were inserted as the sensitizer and activator ions, respectively. Careful control of the doping ratio, along with a detailed physico-chemical characterization, was carried out. Upon functionalization with a silica shell to covalently anchor the photosensitizer, a theranostic nanoparticle was obtained whose architecture, thanks to a favorable energy level match and a uniform distribution of the PS, allowed us to trigger the photodynamic activity of Ver by upconversion, thus paving the way to the use of Photodynamic Therapy (PDT) in deep tissues, thanks to the higher penetrating power of NIR light.

Verteporfin-Loaded Mesoporous Silica Nanoparticles' Topical Applications Inhibit Mouse Melanoma Lymphangiogenesis and Micrometastasis In Vivo.

Photodynamic therapy (PDT) has been pointed out as a candidate for improving melanoma treatment. Nanotechnology application in PDT has increased its efficacy by reducing side effects. Herein, mesoporous silica nanoparticles (MSNs) conjugated with verteporfin (Ver-MSNs), in use with PDT, were administered in mice to evaluate their efficacy on lymphoangiogenesis and micrometastasis in melanoma. Melanoma was induced in mice by the subcutaneous injection of B16-F10 cells. The mice were transcutaneously treated with MSNs, Ver-MSNs, or glycerol and exposed to red light. The treatment was carried out four times until day 20. Lymphangiogenesis and micrometastasis were identified by the immunohistochemical method. Lymphoangiogenesis was halved by MSN treatment compared with the control animals, whereas the Ver-MSN treatment almost abolished it. A similar reduction was also observed in lung micrometastasis. PDT with topically administrated Ver-MSNs reduced melanoma lymphoangiogenesis and lung micrometastasis, as well as tumor mass and angiogenesis, and therefore their use could be an innovative and useful tool in melanoma clinical therapy.

The Significance of Metal Coordination in Imidazole-Functionalized Metal-Organic Frameworks for Carbon Dioxide Utilization.

The grafting of imidazole species onto coordinatively unsaturated sites within metal-organic framework MIL-101(Cr) enables enhanced CO2 capture in close proximity to catalytic sites. The subsequent combination of CO2 and epoxide binding sites, as shown through theoretical findings, significantly improves the rate of cyclic carbonate formation, producing a highly active CO2 utilization catalyst. An array of spectroscopic investigations, in combination with theoretical calculations reveal the nature of the active sites and associated catalytic mechanism which validates the careful design of the hybrid MIL-101(Cr).

Probing the Design Rationale of a High-Performing Faujasitic Zeotype Engineered to have Hierarchical Porosity and Moderated Acidity.

Porosity and acidity are influential properties in the rational design of solid-acid catalysts. Probing the physicochemical characteristics of an acidic zeotype framework at the molecular level can provide valuable insights in understanding intrinsic reaction pathways, for affording structure-activity relationships. Herein, we employ a variety of probe-based techniques (including positron annihilation lifetime spectroscopy (PALS), FTIR and solid-state NMR spectroscopy) to demonstrate how a hierarchical design strategy for a faujasitic (FAU) zeotype (synthesized for the first time, via a soft-templating approach, with high phase-purity) can be used to simultaneously modify the porosity and modulate the acidity for an industrially significant catalytic process (Beckmann rearrangement). Detailed characterization of hierarchically porous (HP) SAPO-37 reveals enhanced mass-transport characteristics and moderated acidity, which leads to superior catalytic performance and increased resistance to deactivation by coking, compared to its microporous counterpart, further vindicating the interplay between porosity and moderated acidity.

Integrated Theoretical and Empirical Studies for Probing Substrate-Framework Interactions in Hierarchical Catalysts.

Soft templating with siliceous surfactant is an established protocol for the synthesis of hierarchically porous silicoaluminophosphates (HP SAPOs) with improved mass transport properties. Motivated by the enhanced performance of HP SAPOs in the Beckmann rearrangement of cyclohexanone oxime to the nylon 6 precursor ϵ-caprolactam, an integrated theoretical and empirical study was carried out to investigate the catalytic potential of the siliceous mesopore network. Inelastic neutron scattering (INS) studies, in particular, provided unique insight into the substrate-framework interactions in HP (Si)AlPOs and allowed reactive species to be studied independent of the catalyst matrix. The spectroscopic (INS, FTIR spectroscopy, MAS NMR spectroscopy) and computational analyses revealed that in the organosilane-templated SAPO, the interconnectivity of micro- and mesopores permits cooperativity between their respective silanol and Brønsted acid sites that facilitates the protonation of cyclohexanone oxime in a physical mixture at ambient temperature.

Influence of Silicodactyly in the Preparation of Hybrid Materials.

The organic⁻inorganic hybrid materials have attracted great attention due to their improved or unusual properties that open promising applications in different areas such as optics, electronics, energy, environment, biology, medicine and heterogeneous catalysis. Different types of silicodactyl platforms grafted on silica inorganic supports can be used to synthesize hybrid materials. A careful evaluation of the dactyly of the organic precursors, normally alkoxysilanes, and of the type of interaction with the inorganic supports is presented. In fact, depending on the hydrophilicity of the silica surface (e.g., number and density of surface silanols) as well as on the grafting conditions, the hydrolysis and condensation reaction of the silylated moieties can involve only one or two out of three alkoxysilane groups. The influence of silicodactyly in the preparation of organic-inorganic silica-based hybrids is studied by TGA, 29Si, ¹H and 13C solid-state NMR and FTIR spectroscopies, with the support of Molecular Dynamics calculations. Computational studies are used to forecast the influence of the different grafting configurations on the tendency of the silane to stick on the inorganic surface.

Mesoporous Silica Scaffolds as Precursor to Drive the Formation of Hierarchical SAPO-34 with Tunable Acid Properties.

Using a distinctive bottom-up approach, a hierarchical silicoaluminophosphate, SAPO-34, has been synthesized using cetyl trimethylammonium bromide (CTAB) encapsulated within ordered mesoporous silica (MCM-41) that serves as both the silicon source and mesoporogen. The structural and textural properties of the hierarchical SAPO-34 were contrasted against its microporous analogue, and the nature, strength, and accessibility of the Brønsted acid sites were studied using a range of physicochemical characterization tools; notably probe-based FTIR and solid-state magic angle spinning (SS MAS) NMR spectroscopies. Whilst CO was used to study the acid properties of hierarchical SAPO-34, bulkier molecular probes (including pyridine, 2,4,6-trimethylpyridine and 2,6-di-tert-butylpyridine) allowed particular insight into the enhanced accessibility of the acid sites. The activity of the hierarchical SAPO-34 catalyst was evaluated in the industrially-relevant, acid-catalyzed Beckmann rearrangement of cyclohexanone oxime to ϵ-caprolactam, under vapor-phase conditions. These catalytic investigations revealed a significant enhancement in the yield of ϵ-caprolactam using our hierarchical SAPO-34 catalyst compared to SAPO-34, MCM-41, or a mechanical mixture of these two phases. The results highlight the merits of our design strategy for facilitating enhanced mass transfer, whilst retaining favorable acid site characteristics.

Unraveling the Decomposition Process of Lead(II) Acetate: Anhydrous Polymorphs, Hydrates, and Byproducts and Room Temperature Phosphorescence.

Lead(II) acetate [Pb(Ac)2, where Ac = acetate group (CH3-COO(-))2] is a very common salt with many and varied uses throughout history. However, only lead(II) acetate trihydrate [Pb(Ac)2·3H2O] has been characterized to date. In this paper, two enantiotropic polymorphs of the anhydrous salt, a novel hydrate [lead(II) acetate hemihydrate: Pb(Ac)2·(1)/2H2O], and two decomposition products [corresponding to two different basic lead(II) acetates: Pb4O(Ac)6 and Pb2O(Ac)2] are reported, with their structures being solved for the first time. The compounds present a variety of molecular arrangements, being 2D or 1D coordination polymers. A thorough thermal analysis, by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), was also carried out to study the behavior and thermal data of the salt and its decomposition process, in inert and oxygenated atmospheres, identifying the phases and byproducts that appear. The complex thermal behavior of lead(II) acetate is now solved, finding the existence of another hydrate, two anhydrous enantiotropic polymorphs, and some byproducts. Moreover, some of them are phosphorescent at room temperature. The compounds were studied by TGA, DSC, X-ray diffraction, and UV-vis spectroscopy.

Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles.

In this paper, mesoporous silica nanoparticles (MSNs) were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM) and of its 4-(N)-acyl derivatives, (4-(N)-valeroyl-(C5GEM), 4-(N)-lauroyl-(C12GEM) and 4-(N)-stearoyl-gemcitabine (C18GEM)). The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs' surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.

The protective effect of the mesoporous host on the photo oxidation of fluorescent guests: a UV-Vis spectroscopy study.

The inclusion of fluorescent molecules within the pores of an inorganic host system is one of the most common ways used for the preparation of highly fluorescent nanosystems. The confinement of labile molecules usually leads to better performances mainly due to their protection against environmental parameters which can concur with the deactivation of the fluorescent ones. In this work the protective effect of the siliceous mesoporous host on photo oxidation of fluorescent guest molecules has been investigated under different experimental conditions, highlighting an outstanding photostability if compared to the performances exerted by the fluorescent dye in solution.

Hierarchical SAPO-34 Catalysts as Host for Cu Active Sites.

Cu-containing hierarchical SAPO-34 catalysts were synthesized by the bottom-up method using different mesoporogen templates: CTAB encapsulated within ordered mesoporous silica nanoparticles (MSNs) and sucrose. A high fraction of the Cu centers exchanged in the hierarchical SAPO-34 architecture with high mesopore surface area and volume was achieved when CTAB was embedded within ordered mesoporous silica nanoparticles. Physicochemical characterization was performed by using structural and spectroscopic techniques to elucidate the properties of hierarchical SAPO-34 before and after Cu introduction. The speciation of the Cu sites, investigated by DR UV-Vis, and the results of the catalytic tests indicated that the synergy between the textural properties of the hierarchical SAPO-34 framework, the high Cu loading, and the coordination and localization of the Cu sites in the hierarchical architecture is the key point to obtaining good preliminary results in the NO selective catalytic reduction with hydrocarbons (HC-SCR).

Spray-Dried Powder Containing Cannabigerol: A New Extemporaneous Emulgel for Topical Administration.

Cannabigerol (CBG), a cannabinoid from Cannabis sativa L., recently attracted noteworthy attention for its dermatological applications, mainly due to its anti-inflammatory, antioxidant, and antimicrobial effectiveness similar to those of cannabidiol (CBD). In this work, based on results from studies of in vitro permeation through biomimetic membranes performed with CBG and CBD in the presence and in the absence of a randomly substituted methyl-ß-cyclodextrin (MßCD), a new CBG extemporaneous emulgel (oil-in-gel emulsion) formulation was developed by spray-drying. The powder (SDE) can be easily reconstituted with purified water, leading to a product with chemical-physical and technological characteristics that are comparable to those of the starting emulgels (E). Thermogravimetric analysis (TGA), attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR), x-ray powder diffraction (XRPD), and high-performance liquid chromatography (HPLC) analyses demonstrated that the spray-drying treatment did not alter the chemical properties of CBG. This product can represent a metered-dosage form for the localized treatment of cutaneous afflictions such as acne and psoriasis.

Bright photoluminescent hybrid mesostructured silica nanoparticles.

Bright photoluminescent mesostructured silica nanoparticles were synthesized by the incorporation of fluorescent cyanine dyes into the channels of MCM-41 mesoporous silica. Cyanine molecules were introduced into MCM-41 nanoparticles by physical adsorption and covalent grafting. Several photoluminescent nanoparticles with different organic loadings have been synthesized and characterized by X-ray powder diffraction, high resolution transmission electron microscopy and nitrogen physisorption porosimetry. A detailed photoluminescence study with the analysis of fluorescence lifetimes was carried out to elucidate the cyanine molecules distribution within the pores of MCM-41 nanoparticles and the influence of the encapsulation on the photoemission properties of the guests. The results show that highly stable photoluminescent hybrid materials with interesting potential applications as photoluminescent probes for diagnostics and imaging can be prepared by both methods.

A novel route to enhance the dissolution of apatite: Structural incorporation of hydrogen phosphate.

Potential use of hydroxyapatite nanoparticles (HANPs) [Ca10(PO4)6(OH)2] as slow P-release fertilizer (SRF) has recently attracted wider attention. However, commercially available HANP (with Ca/P ratio = 1.667) is the least soluble calcium phosphate and thus limits its full potential as an SRF in agronomic applications. In this research, we sought to enhance the dissolution rate of HANPs by enriching hydrogen phosphate (HPO42-) species in the phosphate (PO43-) structural sites. Seven different types of pure crystalline HANPs were synthesized at a range of Ca/P ratio from 1.46 (at pH 6.0) to 2.10 (at pH 12.0). Complementary results from FTIR and solid-state 31P MAS NMR spectroscopies showed that HPO42- species is most abundant in HANPs crystallized at pH 6.0 and gradually depleted at higher pH products. The rate of depletion of HPO42- species is proportional to the increase in carbonate incorporation into the HANP lattice, which preferentially forms B-type carbonated HANPs. The enhanced dissolution rate of HANPs due to hydrogen phosphate incorporation was tested using a flow-through macro-dialysis system that limits the partial transition of HANPs to other solid phases, which otherwise interfere with dissolution. The results show that the dissolution rate of HANPs increased with decreasing pH of synthesis and was highest in HANPs at pH 6.0. The dissolution rate differed by ten times between HANPs synthesized at pH 7.0 and 10.0. Overall, the atom-efficient synthetic route developed and the ability to tune the dissolution rate of HANPs are significant steps forward in improving the P-release efficiency of a potent SRF and is expected to contribute to efforts toward enhancing agricultural sustainability.

Fluorescence Studies: A9 Peptide, Functionalized with a Fluorogenic Probe, Interacts with Its Receptor Model HER2-DIVMP.

A recently developed synthetic protocol allowed for the functionalization of the active peptide A9 with a fluorogenic probe, which is useful for studying biomolecular interactions. Essentially, a nucleophilic attack on a halo-substituted benzofurazan is selectively performed by a cysteine sulfhydryl group. The process is assisted by the basic catalysis of activated zeolites (4 Å molecular sieves) and promoted by microwave irradiation. Fluorescence studies revealed that a donor-acceptor pair within the peptide sequence was introduced, thus allowing a deeper investigation on the interaction process between the peptide ligand and its receptor fragment. The obtained results allowed us to come full circle for all the currently understood structural determinants that were found to be involved in the binding process.

Silica Nanoparticle Internalization Improves Chemotactic Behaviour of Human Mesenchymal Stem Cells Acting on the SDF1α/CXCR4 Axis.

Human mesenchymal stem cell (hMSC)-based therapy is an emerging resource in regenerative medicine. Despite the innate ability of hMSCs to migrate to sites of injury, homing of infused hMSCs to the target tissue is inefficient. It was shown that silica nanoparticles (SiO2-NPs), previously developed to track the stem cells after transplantation, accumulated in lysosomes leading to a transient blockage of the autophagic flux. Since CXCR4 turnover is mainly regulated by autophagy, we tested the effect of SiO2-NPs on chemotactic migration of hMSCs along the SDF1α/CXCR4 axis that plays a pivotal role in directing MSC homing to sites of injury. Our results showed that SiO2-NP internalization augmented CXCR4 surface levels. We demonstrated that SiO2-NP-dependent CXCR4 increase was transient, and it reversed at the same time as lysosomal compartment normalization. Furthermore, the autophagy inhibitor Bafilomycin-A1 reproduced CXCR4 overexpression in control hMSCs confirming the direct effect of the autophagic degradation blockage on CXCR4 expression. Chemotaxis assays showed that SiO2-NPs increased hMSC migration toward SDF1α. In contrast, migration improvement was not observed in TNFα/TNFR axis, due to the proteasome-dependent TNFR regulation. Overall, our findings demonstrated that SiO2-NP internalization increases the chemotactic behaviour of hMSCs acting on the SDF1α/CXCR4 axis, unmasking a high potential to improve hMSC migration to sites of injury and therapeutic efficacy upon cell injection in vivo.

Eu3+ and Tb3+ @ PSQ: Dual Luminescent Polyhedral Oligomeric Polysilsesquioxanes.

The synthesis and characterization of novel luminescent amorphous POSS-based polysilsesquioxanes (PSQs) with Tb3+ and Eu3+ ions directly integrated in the polysilsesquioxane matrix is presented. Two different Tb3+/Eu3+ molar ratios were applied, with the aim of disclosing the relationships between the nature and loading of the ions and the luminescence properties. Particular attention was given to the investigation of site geometry and hydration state of the metal centers in the inorganic framework, and of the effect of the Tb3+ → Eu3+ energy transfer on the overall optical properties of the co-doped materials. The obtained materials were characterized by high photostability and colors of the emitted light ranging from orange to deep red, as a function of both the Tb3+/Eu3+ molar ratio and the chosen excitation wavelength. A good energy transfer was observed, with higher efficiency displayed when donor/sensitizer concentration was lower than the acceptor/activator concentration. The easiness of preparation and the possibility to finely tune the photoluminescence properties make these materials valid candidates for several applications, including bioimaging, sensors, ratiometric luminescence-based thermometers, and optical components in inorganic or hybrid light-emitting devices.

Grafting Going Green: Toward a Sustainable Preparation of Organic-Inorganic Hybrid Materials.

Organic-inorganic hybrid materials find many applications in catalysis, nanotechnology, electronics, and many others. Grafting organic functionalities on inorganic supports is one of the most used methods for their preparation. Toluene is the solvent of choice for the grafting reaction, but it is fossil fuel-derived and not devoid of toxic effects. In this work, we explore the use of sustainable alternatives, i.e., (+)-α-pinene, (-)-ß-pinene, dimethyl carbonate (DMC), (+)-limonene, and 2-methyl-tetrahydrofuran (MeTHF), as solvents for grafting. The grafting reaction between 3-aminopropyltriethoxysilane (APTS) and mesoporous ordered silica (MCM-41) was selected as a model for this study. A comparison of the rate of the grafting reaction in different solvents is reported. The resulting hybrid materials were analyzed by Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA) and compared to the reference material prepared in toluene. MeTHF proved to be the best sustainable alternative to toluene for model grafting, providing a comparable product in a significantly shorter reaction time.

Behaviour of fluorescence emission of cyanine dyes, cyanine based fluorescent nanoparticles and CdSe/ZnS quantum dots in water solution upon specific thermal treatments.

Fluorescence techniques are widely used as detection methods in a wide range of biological imaging and analytical applications. The purpose of this work is to determine a measurement method which leads to a comparison between different classes of fluorophores in term of stability of the fluorescence signal upon thermal treatment cycles. This kind of investigation can determine whether the fluorophore performance is affected by heating/cooling cycles and to what extent. The fluorophores considered in this work were organic fluorophores belonging to the family of indocyanine dyes (IRIS3 by Cyanine Technologies S.p.A.) in their molecular form or encapsulated within silica nanoparticles, and CdSe/ZnS carboxyl quantum dots (Qdots 565 ITK by Invitrogen). The NIST Standard Reference Material® SRM 1932 fluorescein solution was used in the certified concentration as reference material in order to evaluate the repeatability of the used spectrofluorimeter. The proposed measurement protocol allows to characterize all kind of fluorophores upon thermal treatments. This allows direct comparison of their performance under temperature changes, giving useful guidelines for the selection of the most suitable fluorophore for the envisaged application. Moreover the method appears to be a promising tool for the characterisation of reference fluorescent materials. The experimental results demonstrate that each fluorophore class shows a specific behaviour. The experimental data analysis points out an important hysteresis effect for quantum dots that was not detected for cyanine molecules and was only slightly detected for cyanine doped silica nanoparticles.