Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading.

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.

Sono- and mechanochemical technologies in the catalytic conversion of biomass.

This tutorial review focuses on the valorisation of biomass by sonochemical and mechanochemical activation. Although several of the examples reported herein rely on the use of model compounds rather than native feedstocks, the conversion of lignocellulosic fractions into valuable compounds is a great opportunity with which to more sustainably exploit natural resources, from environmental, economic and social points of view. The use of non-conventional technologies that generate high-energy microenvironments can improve biomass deconstruction and the accessibility of catalysts, granting higher conversion and selectivity. The critical parameters in sonochemical and mechanochemical conversions have been analysed together with the most common devices and reactors, and the potential of sonocatalysis and mechanocatalysis as emerging tools for both catalytic and biocatalytic biomass conversion will be discussed. A SWOT (strengths, weaknesses, opportunities and threats) analysis will provide an overview of the effective feasibility of these approaches in a biorefinery context. Although these technologies offer indisputable advantages (mild reaction conditions, enhanced reaction rates and mass transfer), their mechanisms and the systematic adjustment of parameters to give optimal outcomes still require further investigation, which will pave the way for reproducible and scalable experiments. Indeed, process scale-up can be accomplished both in batch and flow mode. However, results are not particularly predictable, despite the accurate control of instrumental variables, because of the variability found in biomass sources and the complexity inherent in structures.

Mechanochemical Applications of Reactive Extrusion from Organic Synthesis to Catalytic and Active Materials.

In the past, the use of mechanochemical methods in organic synthesis was reported as somewhat of a curiosity. However, perceptions have changed over the last two decades, and this technology is now being appreciated as a greener and more efficient synthetic method. The qualified "offer" of ball mills that make use of different set-ups, materials, and dimensions has allowed this technology to mature. Nevertheless, the intrinsic batch nature of mechanochemical methods hinders industrial scale-ups. New studies have found, in reactive extrusion, a powerful technique with which to activate chemical reactions with mechanical forces in a continuous flow. This new environmentally friendly mechanochemical synthetic method may be able to miniaturize production plants with outstanding process intensifications by removing organic solvents and working in a flow mode. Compared to conventional processes, reactive extrusions display high simplicity, safety, and cleanliness, which can be exploited in a variety of applications. This paper presents perspective examples in the better-known areas of reactive extrusions, including oxidation reactions, polymer processing, and biomass conversion. This work should stimulate further developments, as it highlights the versatility of reactive extrusion and the huge potential of solid-phase flow chemistry.

Structural and mechanistic insights into low-temperature CO oxidation over a prototypical high entropy oxide by Cu L-edge operando soft X-ray absorption spectroscopy.

High entropy oxides (HEOs) are an emerging class of materials constituted by multicomponent systems that are receiving special interest as candidates for obtaining novel and desirable properties. In this study we present a detailed investigation of the relevant intermediates arising at the surface of the prototypical HEO Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O during low-temperature CO oxidation. By combining Cu L2,3-edge operando soft X-ray absorption spectroscopy (soft-XAS) with density functional theory simulations and in situ FT-IR spectroscopy, we propose that upon HEO exposure to CO at 235 °C reduced Cu(I) sites arise mostly coordinated to activated CO molecules and partly to bidentate carbonate species. When the HEO surface is then exposed to a stoichiometric mixture of CO + 1/2O2 at 250 °C, CO2 is produced while bidentate carbonate moieties remain interacting with the Cu(I) sites. We structurally characterize the carbonate and CO preferential adsorption geometries on the Cu(I) surface metal centers, and find that CO adopts a bent conformation that may energetically favor its subsequent oxidation. The unique surface, structural and electronic sensitivity of soft-XAS coupled with the developed data analysis work-flow and supported by FT-IR spectroscopy may be beneficial to characterize often elusive surface properties of systems of catalytic interest.

Hydrogenation of CO2 to Methanol by Pt Nanoparticles Encapsulated in UiO-67: Deciphering the Role of the Metal-Organic Framework.

Metal-organic frameworks (MOFs) show great prospect as catalysts and catalyst support materials. Yet, studies that address their dynamic, kinetic, and mechanistic role in target reactions are scarce. In this study, an exceptionally stable MOF catalyst consisting of Pt nanoparticles (NPs) embedded in a Zr-based UiO-67 MOF was subject to steady-state and transient kinetic studies involving H/D and 13C/12C exchange, coupled with operando infrared spectroscopy and density functional theory (DFT) modeling, targeting methanol formation from CO2/H2 feeds at 170 °C and 1-8 bar pressure. The study revealed that methanol is formed at the interface between the Pt NPs and defect Zr nodes via formate species attached to the Zr nodes. Methanol formation is mechanistically separated from the formation of coproducts CO and methane, except for hydrogen activation on the Pt NPs. Careful analysis of transient data revealed that the number of intermediates was higher than the number of open Zr sites in the MOF lattice around each Pt NP. Hence, additional Zr sites must be available for formate formation. DFT modeling revealed that Pt NP growth is sufficiently energetically favored to enable displacement of linkers and creation of open Zr sites during pretreatment. However, linker displacement during formate formation is energetically disfavored, in line with the excellent catalyst stability observed experimentally. Overall, the study provides firm evidence that methanol is formed at the interface of Pt NPs and linker-deficient Zr6O8 nodes resting on the Pt NP surface.

Cross-Linked Cyclodextrins Bimetallic Nanocatalysts: Applications in Microwave-Assisted Reductive Aminations.

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H2 or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a ß-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H2. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H2 pressure. The formation of a CuxPdy alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields.

Microwave-Assisted Dehydrogenative Cross Coupling Reactions in γ-valerolactone with a Reusable Pd/ß-cyclodextrin Crosslinked Catalyst.

Transition-metal mediated C⁻H bond activation and functionalization is one of the most straightforward and powerful tools in modern organic synthetic chemistry. Oxidative C⁻H/C⁻H coupling reactions between two (hetero)arenes under heterogeneous catalysis may be a valuable means for the production of a plethora of bi(hetero)aryls, and one that adheres to the increasing demand for atom-economic and sustainable chemistry. We have therefore developed a reusable heterogeneous catalytic system, which is based on Pd cross-linked ß-cyclodextrin, to perform an efficient microwave-assisted oxidative C⁻H/C⁻H cross coupling process between benzothiazoles and methyl thiophene in the presence of green solvents.

Multifunctional and Environmentally Friendly TiO2-SiO2 Mesoporous Materials for Sustainable Green Buildings.

This work deals with the formulation of environmentally friendly, cheap, and readily-available materials for green building applications, providing the function of air purificator by improving the safety and the comfort of an indoor environment. High surface area TiO2-SiO2 samples, prepared by a simple, cost effective, and scalable synthetic approach, proved to be effective in maximizing the properties of each component, i.e., the photocatalytic properties of titania and the high surface area of silica. TiO2 was introduced onto an ordered mesoporous silica Santa Barbara Amorphous-15 (SBA-15), that is featured by interesting insulating features, by using an incipient wetness impregnation method. The photocatalytic activity was evaluated in gas phase oxidation of ethylbenzene, which was selected as model volatile organic compound (VOC) molecule. The morphological, textural and structural features along with the electronic properties, the hydrophilicity and heat capacity of the materials were investigated in depth by scanning electron microscopy, powder X-ray diffraction, N2 physisorption, diffuse reflectance UV-Vis, FT-IR spectroscopies, and modulated DSC (MDSC) dynamic scan. Outstanding performances in the ethylbenzene abatement results are promising for further application in the green building sector.

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions.

This work presents a proof of concept for a green cyclodextrin derivatisation method that uses low-boiling epoxide reagents in a high-energy ball mill (HEBM). The simplified preparation and purification of low substitution-degree common (2-hydroxy)propylated ß- and γ-cyclodextrins (ß/γ-CDs) has been realised. The intelligent use of propylene oxide has also facilitated the more effective synthesis of highly substituted γ-CD. Epichlorohydrin-crosslinked CD-polymers (CDPs) have also been effectively prepared in the ball mill. The unoptimised preparations of soluble and insoluble CDPs displayed very small particle size distributions, while the prepared polymers currently have different complexation properties to those of their classically prepared analogues.

Operando study of palladium nanoparticles inside UiO-67 MOF for catalytic hydrogenation of hydrocarbons.

Functionalization of metal-organic frameworks with metal nanoparticles (NPs) is a promising way for producing advanced materials for catalytic applications. We present the synthesis and in situ characterization of palladium NPs encapsulated inside a functionalized UiO-67 metal-organic framework. The initial structure was synthesized with 10% of PdCl2bpydc moieties with grafted Pd ions replacing standard 4,4'-biphenyldicarboxylate linkers. This material exhibits the same high crystallinity and thermal stability of standard UiO-67. Formation of palladium NPs was initiated by sample activation in hydrogen and monitored by in situ X-ray powder diffraction and X-ray absorption spectroscopy (XAS). The reduction of PdII ions to Pd0 occurs above 200 °C in 6% H2/He flow. The formed palladium NPs have an average size of 2.1 nm as limited by the cavities of UiO-67 structure. The resulting material showed high activity towards ethylene hydrogenation. Under reaction conditions, palladium was found to form a carbide structure indicated by operando XAS, while formation of ethane was monitored by mass spectroscopy and infra-red spectroscopy.

Characterisation of gold catalysts.

Au-based catalysts have established a new important field of catalysis, revealing specific properties in terms of both high activity and selectivity for many reactions. However, the correlation between the morphology and the activity of the catalyst is not always clear although much effort has been addressed to this task. To some extent the problem relates to the complexity of the characterisation techniques that can be applied to Au catalyst and the broad range of ways in which they can be prepared. Indeed, in many reports only a few characterization techniques have been used to investigate the potential nature of the active sites. The aim of this review is to provide a critical description of the techniques that are most commonly used as well as the more advanced characterization techniques available for this task. The techniques that we discuss are (i) transmission electron microscopy methods, (ii) X-ray spectroscopy techniques, (iii) vibrational spectroscopy techniques and (iv) chemisorption methods. The description is coupled with developing an understanding of a number of preparation methods. In the final section the example of the supported AuPd alloy catalyst is discussed to show how the techniques can gain an understanding of an active oxidation catalyst.

New insights into UTSA-16.

Among the metal organic framework materials proposed for CO2 separation, UTSA-16 possesses the highest CO2 volumetric density explained on the basis of favourable interactions between CO2 and structural water molecules in the material, as revealed by neutron diffraction. In this study, UTSA-16 was synthesised and extensively characterised by XRD, TEM combined with EDX analysis and DR-UV-Vis, Raman and FTIR spectroscopies, as well as by TGA measurements. The synthesised material shows XRD patterns, surface area, CO2 capacity and isosteric heat coincident to the ones reported for UTSA-16 in the original papers but a higher thermal stability and a complete removal of water upon activation under mild conditions (363 K). On the basis of EDX and IR measurements, the formula of UTSA-16 used in the present study is proposed to be K2Co3(cit)2. Infrared spectroscopy clearly shows that UTSA-16 described in this work reversibly interacts with water vapor, CO and CO2. The interaction is attributed to K(+) species, which are present as counterions in the pores. At 1 bar and 298 K a fraction of K(+) sites adsorbs 2 CO2 molecules.

Ultrasound-Driven Deposition of Au and Ag Nanoparticles on Citrus Pectin: Preparation and Characterisation of Antimicrobial Composites.

Pectin is a renewable, non-toxic and biodegradable polymer made of galacturonic acid units. Its polar groups make it suitable for complexing and supporting metallic nanoparticles (NPs). This work aimed to produce antibacterial nanocomposites using pectin and acoustic cavitation. The metal NPs (Au or Ag) were deposited using ultrasound (US, 21 kHz, 50 W) and compared with those achieved with mechanical stirring. The impact of the reducing agents (NaBH4, ascorbic acid) on the dispersion and morphology of the resulting NPs was also assessed. Characterization by diffuse reflectance (DR) UV-Vis-NIR spectroscopy and field emission scanning electron microscopy (FESEM) showed that the use of US improves the dispersion and decreases the size of both Au and Ag NPs. Moreover, with Au NPs, avoiding external reductants led to smaller NPs and more uniform in size. The prepared NPs were functionalized with oxytetracycline in water and tested against Escherichia coli (gram negative) and Staphylococcus epidermidis (gram positive) via the Kirby-Bauer test. The results show a better antibacterial activity of the functionalized nanoparticles compared to antibiotic-free NPs and pure oxytetracycline, advising the potential of the nanoparticles as drug carriers. These findings underscore the significance of US-assisted synthesis, paving the way to new environmentally friendly antimicrobial materials.

Copper-Catalyzed Continuous-Flow Transfer Hydrogenation of Nitroarenes to Anilines: A Scalable and Reliable Protocol.

A robust supported catalyst that is made up of copper nanoparticles on Celite has been successfully prepared for the selective transfer hydrogenation of aromatic nitrobenzenes to anilines under continuous flow. The method is efficient and environmentally benign thanks to the absence of hydrogen gas and precious metals. Long-term stability studies show that the catalytic system is able to achieve very high nitrobenzene conversion (>99%) when working for up to 145 h. The versatility of the transfer hydrogenation system has been tested using representative examples of nitroarenes, with moderate-to-excellent yields being obtained. The packed bed reactor (PBR) permits the use of a setup that can provide products via simple isolation by SPE without the need for further purification. The recovery and reuse of either EG or the ion-exchange resin leads to consistent waste reduction; therefore, E-factor distribution analysis has highlighted the environmental efficiency of this synthetic protocol.

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150 nm, a negative zeta potential of -35 mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Investigating site-specific interactions and probing their role in modifying the acid-strength in framework architectures.

The ability to adroitly tailor acid-strength using specifically-engineered bimetallic nanoporous materials has been investigated with a view to exploiting their potential in solid-acid catalysed transformations. Further, it has been demonstrated that through site-specific interactions, extra-framework zinc ions can suitably modify the acidity of Brønsted acid sites, to stimulate diverse catalytic responses, when combined with isomorphously-substituted framework metal cations within porous architectures, for the Beckmann rearrangement of cyclohexanone oxime and in the isopropylation of benzene.

Microwave-Assisted Reductive Amination of Aldehydes and Ketones Over Rhodium-Based Heterogeneous Catalysts.

Microwave (MW)-assisted reductive aminations of aldehydes and ketones were carried out in the presence of commercial and homemade heterogeneous Rh-based catalysts. Ultrasound (US) was used to improve dispersion and stability of metal nanoparticles, while commercial activated carbon and carbon nanofibers were used as supports. Moreover, various bio-derived molecules were selected as substrates, and aqueous ammonia was used as a cheap and non-toxic reagent. MW combined with heterogeneous Rh catalysts gave a 98.2 % yield in benzylamine at 80 °C with 10 bar H2 for 1 h; and a 43.3 % yield in phenylethylamine at 80 °C and 5 bar H2 for 2 h. Carbon nanofibers proved to be a better support for the metal active phase than simple activated carbon, since a limited yield in benzylamine (10.6 %) but a high selectivity for the reductive amination of ketones was obtained. Thus, raspberry ketone was converted to raspberry amine in a 63.0 % yield.

Freeze Drying of Polymer Nanoparticles and Liposomes Exploiting Different Saccharide-Based Approaches.

Biodegradable nanocarriers represent promising tools for controlled drug delivery. However, one major drawback related to their use is the long-term stability, which is largely influenced by the presence of water in the formulations, so to solve this problem, freeze-drying with cryoprotectants has been proposed. In the present study, the influence of the freeze-drying procedure on the storage stability of poly(lactide-co-glycolide) (PLGA) nanoparticles and liposomes was evaluated. In particular, conventional cryoprotectants were added to PLGA nanoparticle and liposome formulations in various conditions. Additionally, hyaluronic acid (HA), known for its ability to target the CD44 receptor, was assessed as a cryoprotective excipient: it was added to the nanocarriers as either a free molecule or conjugated to a phospholipid to increase the interaction with the polymer or lipid matrix while exposing HA on the nanocarrier surface. The formulations were resuspended and characterized for size, polydispersity index, zeta potential and morphology. It was demonstrated that only the highest percentages of cryoprotectants allowed the resuspension of stable nanocarriers. Moreover, unlike free HA, HA-phospholipid conjugates were able to maintain the particle mean size after the reconstitution of lyophilized nanoparticles and liposomes. This study paves the way for the use of HA-phospholipids to achieve, at the same time, nanocarrier cryoprotection and active targeting.

Batch and Flow Green Microwave-Assisted Catalytic Conversion Of Levulinic Acid to Pyrrolidones.

This paper reports a new sustainable protocol for the microwave-assisted catalytic conversion of levulinic acid into N-substituted pyrrolidones over tailor-made mono (Pd, Au) or bimetallic (PdAu) catalysts supported on either highly mesoporous silica (HMS) or titania-doped HMS, exploiting the advantages of dielectric heating. MW-assisted reductive aminations of levulinic acid with several amines were first optimized in batch mode under hydrogen pressure (5 bar) in solvent-free conditions. Good-to-excellent yields were recorded at 150 °C in 90 min over the PdTiHMS and PdAuTiHMS, that proved recyclable and almost completely stable after six reaction cycles. Aiming to scale-up this protocol, a MW-assisted flow reactor was used in combination with different green solvents. Cyclopentyl methyl ether (CPME) provided a 99 % yield of N-(4-methoxyphenyl) pyrrolidin-2-one at 150 °C over PdTiHMS. The described MW-assisted flow synthesis proves to be a safe procedure suitable for further industrial applications, while averting the use of toxic organic solvents.

CeO2 Frustrated Lewis Pairs Improving CO2 and CH3OH Conversion to Monomethylcarbonate.

Frustrated Lewis pairs (FLPs), discovered in the last few decades for homogeneous catalysts and in the last few years also for heterogeneous catalysts, are stimulating the scientific community's interest for their potential in small-molecule activation. Nevertheless, how an FLP activates stable molecules such as CO2 is still undefined. Through a careful spectroscopic study, we here report the formation of FLPs over a highly defective CeO2 sample prepared by microwave-assisted synthesis. Carbon dioxide activation over FLP is shown to occur through a bidentate carbonate bridging the FLP and implying a Ce3+-to-CO2 charge transfer, thus enhancing its activation. Carbon dioxide reaction with methanol to form monomethylcarbonate is here employed to demonstrate active roles of FLP and, eventually, to propose a reaction mechanism clarifying the role of Ce3+ and oxygen vacancies.