Hydroxytrifluoroethylation and Trifluoroacetylation Reactions via SET Processes.

Hydroxytrifluoroethyl and trifluoroacetyl groups are of utmost importance in biologically active compounds, but methods to tether these motifs to organic architectures have been limited. Typically, the preparation of these compounds relied on the use of strong bases or multistep routes. The renaissance of radical chemistry in photocatalytic, transition metal mediated, and hydrogen atom transfer (HAT) processes have allowed the installation of these medicinally relevant fluorinated motifs. This review provides an overview of the methods available for the direct synthesis of hydroxytrifluoroethyl- and trifluoroacetyl-derived compounds governed by single-electron transfer processes.

Difluoroalkylation of Anilines via Photoinduced Methods.

The development of sustainable and mild protocols for the fluoroalkylation of organic backbones is of current interest in chemical organic synthesis. Herein, we present operationally simple and practical transition-metal-free methods for the preparation of difluoroalkyl anilines. First, a visible-light organophotocatalytic system working via oxidative quenching is described, providing access to a wide range of difluoroalkyl anilines under mild conditions. In addition, the formation of an unprecedented electron donor-acceptor (EDA) complex between anilines and ethyl difluoroiodoacetate is reported and exploited as an alternative, efficient, and straightforward strategy to prepare difluoroalkyl derivatives.

Recent Advances on Antimicrobial and Anti-Inflammatory Cotton Fabrics Containing Nanostructures.

Hydrophilic cotton textiles, used in hospitals and sportswear, are prone to the growth of microorganisms (bacteria, fungi) resulting in hygiene and health risks. Thus, healthcare concerns have motivated the interest for the development of multifunctional antimicrobial cotton fabrics. Moreover, cotton textiles are also used in medical applications such as wound dressings. Their functionalization with anti-inflammatory agents is desirable in order to accelerate cicatrisation in the treatment of chronic wounds. This review summarizes recent advances (from January 2016 to January 2021) on the modification and coating of cotton fabrics with nanostructures (mainly metal and metal oxide nanoparticles, functionalized silica nanoparticles) to provide them antimicrobial (antibacterial and antifungal) and anti-inflammatory properties.

Periodic Mesoporous Organosilica Nanoparticles with BOC Group, towards HIFU Responsive Agents.

Periodic Mesoporous Organosilica Nanoparticles (PMONPs) are nanoparticles of high interest for nanomedicine applications. These nanoparticles are not composed of silica (SiO2). They belong to hybrid organic-inorganic systems. We considered using these nanoparticles for CO2 release as a contrast agent for High Intensity Focused Ultrasounds (HIFU). Three molecules (P1-P3) possessing two to four triethoxysilyl groups were synthesized through click chemistry. These molecules possess a tert-butoxycarbonyl (BOC) group whose cleavage in water at 90-100 °C releases CO2. Bis(triethoxysilyl)ethylene E was mixed with the molecules Pn (or not for P3) at a proportion of 90/10 to 75/25, and the polymerization triggered by the sol-gel procedure led to PMONPs. PMONPs were characterized by different techniques, and nanorods of 200-300 nm were obtained. These nanorods were porous at a proportion of 90/10, but non-porous at 75/25. Alternatively, molecules P3 alone led to mesoporous nanoparticles of 100 nm diameter. The BOC group was stable, but it was cleaved at pH 1 in boiling water. Molecules possessing a BOC group were successfully used for the preparation of nanoparticles for CO2 release. The BOC group was stable and we did not observe release of CO2 under HIFU at lysosomal pH of 5.5. The pH needed to be adjusted to 1 in boiling water to cleave the BOC group. Nevertheless, the concept is interesting for HIFU theranostic agents.

Acid Activation in Phenyliodine Dicarboxylates: Direct Observation, Structures, and Implications.

The use of the hypervalent iodine reagents in oxidative processes has become a staple in modern organic synthesis. Frequently, the reactivity of λ3 iodanes is further enhanced by acids (Lewis or Brønsted). The origin of such activation, however, has remained elusive. Here, we use the common combination of PhI(OAc)2 with BF3·Et2O as a model to fully explore this activation phenomenon. In addition to the spectroscopic assessment of the dynamic acid-base interaction, for the first time the putative PIDA·BF3 complex has been isolated and its structure determined by X-ray diffraction. Consequences of such activation are discussed from a structural and electronic (DFT) points of views, including the origins of the enhanced reactivity.

An alternative to the classical α-arylation: the transfer of an intact 2-iodoaryl from ArI(O2CCF3)2.

The α-arylation of carbonyl compounds is generally accomplished under basic conditions, both under metal catalysis and via aryl transfer from the diaryl λ(3)-iodanes. Here, we describe an alternative metal-free α-arylation using ArI(O2CCF3)2 as the source of a 2-iodoaryl group. The reaction is applicable to activated ketones, such as α-cyanoketones, and works with substituted aryliodanes. This formal C-H functionalization reaction is thought to proceed through a [3,3] rearrangement of an iodonium enolate. The final α-(2-iodoaryl)ketones are versatile synthetic building blocks.

Coated Cotton Fabrics with Antibacterial and Anti-Inflammatory Silica Nanoparticles for Improving Wound Healing.

Herein, we report the preparation of bifunctional silica nanoparticles by covalent attachment of both an anti-inflammatory drug (ibuprofen) and an antibiotic (levofloxacin or norfloxacin) through amide groups. We also describe the coating of cotton fabrics with silica nanoparticles containing both ibuprofen and norfloxacin moieties linked by amide groups by using a one-step coating procedure under ultrasonic conditions. The functionalized nanoparticles and cotton fabrics have been characterized using spectroscopic and microscopic techniques. The functionalized nanoparticles and textiles have been treated with model proteases for the in situ release of the drugs by the amide bond enzymatic cleavage. Topical dermal applications in medical bandages are expected, which favor wound healing.

DFT study on the recovery of Hoveyda-grubbs-type catalyst precursors in enyne and diene ring-closing metathesis.

DFT (B3LYP-D) calculations have been used to better understand the origin of the recovered Hoveyda-Grubbs derivative catalysts after ring-closing diene or enyne metathesis reactions. For that, we have considered the activation process of five different Hoveyda-Grubbs precursors in the reaction with models of usual diene and enyne reactants as well as the potential precursor regeneration through the release/return mechanism. The results show that, regardless of the nature of the initial precursor, the activation process needs to overcome relatively high energy barriers, which is in agreement with a relatively slow process. The precursor regeneration process is in all cases exergonic and it presents low energy barriers, particularly when compared to those of the activation process. This indicates that the precursor regeneration should always be feasible, unlike the moderate recoveries sometimes observed experimentally, which suggests that other competitive processes that hinder recovery should take place. Indeed, calculations presented in this work show that the reactions between the more abundant olefinic products and the active carbenes usually require lower energy barriers than those that regenerate the initial precatalyst, which could prevent precursor regeneration. On the other hand, varying the precursor concentration with time obtained from the computed energy barriers shows that, under the reaction conditions, the precursor activation is incomplete, thereby suggesting that the origin of the recovered catalyst probably arises from incomplete precursor activation.

Direct arylation of oligonaphthalenes using PIFA/BF3·Et2O: from double arylation to larger oligoarene products.

Direct dehydrogenative coupling between the linear ter- and quaternaphthalenes and substituted benzenes was achieved under the Kita conditions using the hypervalent PIFA/BF3 reagent. Products resulting from either the double arylation of the naphthalenic substrate or the formal dimerizative arylation have been prepared. For example, in the latter mode, ternaphthalene was converted into a series of linear octiarenes (counting the capping Ar). The process represents an alternative to the cross-coupling methodologies employed in related syntheses and proceeds via a selective functionalization of six relatively inert aromatic CH bonds.

Site-selective and metal-free C-H phosphonation of arenes via photoactivation of thianthrenium salts.

Aryl phosphonates are prevalent moieties in medicinal chemistry and agrochemicals. Their chemical synthesis normally relies on the use of precious metals, harsh conditions or aryl halides as substrates. Herein, we describe a sustainable light-promoted and site-selective C-H phosphonation of arenes via thianthrenation and the formation of an electron donor-acceptor complex (EDA) as key steps. The method tolerates a wide range of functional groups including biomolecules. The use of sunlight also promotes this transformation and our mechanistic investigations support a radical chain mechanism.

Mechanistic insights into ring-closing enyne metathesis with the second-generation Grubbs-Hoveyda catalyst: a DFT study.

The full catalytic process (precatalyst activation, propagating cycle and active-species interconversion) of the ring-closing enyne metathesis (RCEYM) reaction of 1-allyloxy-2-propyne with the Grubbs-Hoveyda complex as catalyst was studied by B3LYP density functional theory. Both the ene-then-yne and yne-then-ene pathways are considered and, for the productive catalytic cycle, the feasibility of the endo-yne-then-ene route is also explored. Calculations predict that the ene-then-yne and yne-then-ene pathways proceed through equivalent steps, the only major difference being the order in which they take place. In this way, all alkene metathesis processes studied here involve four steps: olefin coordination, cycloaddition, cycloreversion and olefin decoordination. Among them, the two more energetically demanding ones are the olefin coordination and decoordination steps. The reaction of the alkyne fragment consists of two steps: alkyne coordination and alkyne skeletal reorganization, the latter of which has the highest Gibbs energy barrier. Comparison between the ene-then-yne and yne-then-ene pathways shows that there is no clear energetic preference for either of the two processes, and thus both should be operative when unsubstituted enynes are involved. In addition, although the endo orientation is computed to be slightly disfavored, it is not ruled out for 1-allyloxy-2-propyne, and thus calculations seem to indicate that the exo versus endo selectivity is strongly influenced by the presence of substituents in the reagent.

Functionalized silica nanoparticles: classification, synthetic approaches and recent advances in adsorption applications.

Nanotechnology is rapidly sweeping through all the vital fields of science and technology such as electronics, aerospace, defense, medicine, and catalysis. It involves the design, synthesis, characterization, and applications of materials and devices on the nanometer scale. At the nanoscale, physical and chemical properties differ from the properties of the individual atoms and molecules of bulk matter. In particular, the design and development of silica nanomaterials have captivated the attention of several researchers worldwide. The applications of hybrid silicas are still limited by the lack of control on the morphology and particle size. The ability to control both the size and morphology of the materials and to obtain nano-sized silica particles has broadened the spectrum of applications of mesoporous organosilicas and/or has improved their performances. On the other hand, adsorption is a widely used technique for the separation and removal of pollutants (metal ions, dyes, organics,...) from wastewater. Silica nanoparticles have specific advantages over other materials for adsorption applications due to their unique structural characteristics: a stable structure, a high specific surface area, an adjustable pore structure, the presence of silanol groups on the surface which allow easy modification, less environmental harm, simple synthesis, low cost, etc. Silica nanoparticles are potential adsorbents for pollutants. We present herein an overview of the different types of silica nanoparticles going from the definitions to properties, synthetic approaches and the mention of potential applications. We focus mainly on the recent advances in the adsorption of different target substances (metal ions, dyes and other organics).

Synthesis of triethoxysilylated cyclen derivatives, grafting on magnetic mesoporous silica nanoparticles and application to metal ion adsorption.

The synthesis through click chemistry of triethoxysilylated cyclen derivative-based ligands is described. Different methods were used such as the copper catalyzed Huisgen's reaction, or thiol-ene reaction for the functionalization of the cyclen scaffold with azidopropyltriethoxysilane or mercaptopropyltriethoxysilane, respectively. These ligands were then grafted on magnetic mesoporous silica nanoparticles (MMSN) for extraction and separation of Ni(ii) and Co(ii) metal ions from model solutions. The bare and ligand-modified MMSN materials revealed high adsorption capacity (1.0-2.13 mmol g-1) and quick adsorption kinetics, achieving over 80% of the total capacity in 1-2 hours.

Direct assembly of polyarenes via C-C coupling Using PIFA/BF3·Et2O.

Direct oxidative Kita-type coupling between naphthalene and substituted benzenes was found to proceed via four-component coupling, leading to a linear tetraarene with a binaphthalene core. The methodology was extendable to the coupling of unfunctionalized 1,1'-binaphthalene with mesitylene to give a linear hexaarene product in a remarkably chemoselective manner in 87% yield. The method represents an attractive alternative to the traditional syntheses of related oligonaphthalene products via a sequence of metal-catalyzed cross-coupling steps.

DFT mechanistic study on diene metathesis catalyzed by Ru-based Grubbs-Hoveyda-type carbenes: the key role of pi-electron density delocalization in the Hoveyda ligand.

The catalytic activity and catalyst recovery of two heterogenized ruthenium-based precatalysts (H and NO(2)(4)) in diene ring-closing metathesis have been studied by means of density functional calculations at the B3LYP level of theory. For comparison and rationalization of the key factors that lead to higher activities and higher catalyst recoveries, four other Grubbs-Hoveyda complexes have also been investigated. The full catalytic cycle (catalyst formation, propagation, and precatalyst regeneration) has been considered. DFT calculations suggest that either for the homogeneous and heterogenized systems the activity of the catalysts mainly depends on the ability of the precursor to generate the propagating carbene. This ability does not correlate with the traditionally identified key factor, the Ru...O interaction strength. In contrast, precatalysts with lower alkoxy-dissociation energy barriers and lower stabilities compared with the propagating carbene also present larger C1-C2 bond length (i.e., lower pi character of the C-C bond that exists between the metal-carbene (Ru=C) and the phenyl ring of the Hoveyda ligand). Catalyst recovery, regardless of whether a release-return mechanism occurs or not, is also mainly determined by the pi delocalization. Therefore, future Grubbs-Hoveyda-type catalyst development should be based on fine-tuning the pi-electron density of the phenyl moiety, with the subsequent effect on the metalloaromaticity of the ruthenafurane ring, rather than considering the modification of the Ru...O interaction.

Organic-inorganic hybrid silica material derived from a monosilylated Grubbs-Hoveyda ruthenium carbene as a recyclable metathesis catalyst.

The synthesis of a monosilylated Grubbs-Hoveyda ruthenium alkylidene complex is described, as well as the preparation and characterization of the corresponding material by sol-gel cogelification with tetraethoxysilane (TEOS) and the assay of this recyclable supported catalyst in ring-closing diene and enyne metathesis reactions under thermal and microwave conditions.

Anti-inflammatory Cotton Fabrics and Silica Nanoparticles with Potential Topical Medical Applications.

The preparation of functional cotton fabrics and silica nanoparticles by direct covalent linking of nonsteroidal anti-inflammatory drugs (salicylic acid, ibuprofen, and diclofenac) through an amide group is reported. Moreover, the coating of cotton fabrics with silica nanoparticles functionalized with such antiinflamatory agents is found to increase the roughness of the surface, providing hydrophobicity to the modified fabrics. This property is enhanced by the addition of fluorinated alkyl silane in the co-condensation process to form the coating solution. Characterization of the functionalized nanoparticles and cotton textiles is accomplished by microscopic and spectroscopic techniques. The treatment of functionalized nanoparticles and cotton fabrics with model proteases and leukocytes from animal origin results in the in situ release of the drug by the selective enzymatic cleavage of the amide bond. Topical cutaneous applications in wound dressings and cream formulations for the acceleration of wound healing are envisaged.

Preparation and Characterization of Novel Mixed Periodic Mesoporous Organosilica Nanoparticles.

We report herein the preparation of mixed periodic mesoporous organosilica nanoparticles (E-Pn 75/25 and 90/10 PMO NPs) by sol-gel co-condensation of E-1,2-bis(triethoxysilyl)ethylene ((E)-BTSE or E) with previously synthesized disilylated tert-butyl 3,5-dialkoxybenzoates bearing either sulfide (precursor P1) or carbamate (precursor P2) functionalities in the linker. The syntheses were performed with cetyltrimethylammonium bromide (CTAB) as template in the presence of sodium hydroxide in water at 80 °C. The nanomaterials have been characterized by Transmission Electron Microscopy (TEM), nitrogen-sorption measurements (BET), Dynamic Light Scattering (DLS), zeta-potential, Thermogravimetric Analysis (TGA), FTIR, 13C CP MAS NMR and small angle X-ray diffraction (p-XRD). All the nanomaterials were obtained as mesoporous rodlike-shape nanoparticles. Remarkably, E-Pn 90/10 PMO NPs presented high specific surface areas ranging from 700 to 970 m2g-1, comparable or even higher than pure E PMO nanorods. Moreover, XRD analyses showed an organized porosity for E-P1 90/10 PMO NPs typical for a hexagonal 2D symmetry. The other materials showed a worm-like mesoporosity.

Phosphine-free perfluoro-tagged palladium nanoparticles supported on fluorous silica gel: application to the Heck reaction.

The immobilization of phosphine-free perfluoro-tagged palladium nanoparticles Pd-1 on fluorous silica gel (FSG) and their utilization in the Heck reaction have been investigated. High yields of vinylic substitution products have been obtained. Recycling studies have shown that the solid-supported palladium catalyst can be readily recovered and reused several times without significant loss of activity. Reactions and recovery of the solid-supported palladium catalyst system can be carried out in the presence of air, without any particular precaution.

Water-Soluble Gold Nanoparticles: From Catalytic Selective Nitroarene Reduction in Water to Refractive Index Sensing.

Water-soluble gold nanoparticles (Au NPs) stabilized by a nitrogen-rich poly(ethylene glycol) (PEG)-tagged substrate have been prepared by reduction of HAuCl4 with NaBH4 in water at room temperature. The morphology and size of the nanoparticles can be controlled by simply varying the gold/stabilizer ratio. The nanoparticles have been fully characterized by TEM, high-resolution (HR) TEM, electron diffraction (ED), energy-dispersive X-ray spectroscopy (EDS), UV/Vis, powder XRD, and elemental analysis. The material is efficient as a recyclable catalyst for the selective reduction of nitroarenes with NaBH4 to yield the corresponding anilines in water at room temperature. Furthermore, the potential ability of the Au NPs as a refractive index sensor owing to their localized surface plasmon resonance (LSPR) effect has also been assessed.