Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Bombyx mori Fibers.

High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers.

Diastereoselective, Catalytic Access to Cross-Aldol Products Directly from Esters and Lactones.

High oxidation-state carbonyl coupling partners including esters and lactones were reacted with enones to give aldol-type products directly using two-fold organoborane catalysis. This new retrosynthetic disconnection to aldol-type products is compatible with enolisable coupling partners, without self-condensation, and couples the high reactivity of secondary dialkylboranes with the stability of pinacolboronic esters. Excellent chemoselectivity, substrate scope (including those containing reducible functionalities and free alcohols) and diastereocontrol were achieved to access both the syn- and anti-aldol-type products. Mechanistic studies confirmed the two-fold catalytic role of the single secondary borane catalyst for boron enolate formation and formation of an aldehyde surrogate from the ester or lactone coupling partner.

Oxidation of Electron-Rich Arenes Using HFIP-UHP System.

The straightforward oxidation of electron-rich arenes, namely, phenols, naphthols, and anisole derivatives, under mild reaction conditions, is described by means of the use of an environmentally benign HFIP-UHP system. The corresponding quinones or hydroxylated arenes were obtained in moderate to good yields.

Direct Synthesis of N,N-Disubstituted Formamides by Oxidation of Imines Using an HFIP/UHP System.

The straightforward synthesis of N,N-disubstituted formamides using a combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and H2O2 is described. The unique features of HFIP allowed the utilization of a green oxidant such as H2O2, and the products, arising from an oxidation-rearrangement sequence, were obtained in good to high yields under smooth reaction conditions.

Tumor Targeted Nanocarriers for Immunotherapy.

The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market. The reasons for this disappointing outcome are varied, from the high tumor-type dependence of enhanced permeation and retention (EPR) effect to the poor penetration capacity of nanocarriers within the cancerous tissue, among others. The rapid nanoparticle clearance by immune cells, considered another important barrier, which compromises the efficacy of nanomedicines, would become an important ally in the fight against cancer. In the last years, the fine-tuned ability of immune cells to recognize and engulf nanoparticles have been exploited to deliver immunoregulating agents to specific immune cell populations selectively. In this work, the recent advances carried out in the development of nanocarriers capable of operating with immune and tumoral cells in order to orchestrate an efficient antitumoral response will be presented. The combination of nanoparticles and immunotherapy would deliver powerful weapons to the clinicians that offer safer and more efficient antitumoral treatments for the patients.

HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes.

In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of this fluorinated alcohol, which is very different from their non-fluorinated analogs, allows carrying out this new straightforward protocol under smooth reaction conditions affording the corresponding adducts in moderate yields in the majority of cases. Remarkably, this methodology has allowed the synthesis of new tetrahydrofuran-based spiro compounds as well as tetrahydrofurobenzofuran derivatives. The scope and limitations of the process are also discussed. Mechanistic studies were also performed pointing towards a purely ionic or a SN2-type process depending on the nucleophilicity of the alkene employed.

Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.

Nanomotors for Nucleic Acid, Proteins, Pollutants and Cells Detection.

The development of nanomachines able to operate at the nanoscale, performing complex tasks such as drug delivery, precision surgery, or cell detection, constitutes one of the most important challenges in nanotechnology. The principles that rule the nanoscale are completely different from the ones which govern the macroscopic world and, therefore, the collaboration of scientists with expertise in different fields is required for the effective fabrication of these tiny machines. In this review, the most recent advances carried out in the synthesis and application of nanomachines for diagnosis applications will be presented in order to provide a picture of their potential in the detection of important biomolecules or pathogens in a selective and controlled manner.

Stereogenic Centers.

The demand for chiral organic entities for different industrial purposes has grown exponentially in the last decades. [...].

Chiral 2-Aminobenzimidazole as Bifunctional Catalyst in the Asymmetric Electrophilic Amination of Unprotected 3-Substituted Oxindoles.

The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5). With this catalyst under optimized conditions, different oxindoles containing a wide variety of substituents at the 3-position were aminated in good yields and with good to excellent enantioselectivities using di-tert-butylazodicarboxylate as the aminating agent. The procedure proved to be also efficient for the amination of 3-substituted benzofuranones, although with moderate results. A bifunctional role of the catalyst, acting as Brønsted base and hydrogen bond donor, is proposed according to the experimental results observed.

Nanotechnological Strategies for Protein Delivery.

The use of therapeutic proteins plays a fundamental role in the treatment of numerous diseases. The low physico-chemical stability of proteins in physiological conditions put their function at risk in the human body until they reach their target. Moreover, several proteins are unable to cross the cell membrane. All these facts strongly hinder their therapeutic effect. Nanomedicine has emerged as a powerful tool which can provide solutions to solve these limitations and improve the efficacy of treatments based on protein administration. This review discusses the advantages and limitations of different types of strategies employed for protein delivery, such as PEGylation, transport within liposomes or inorganic nanoparticles or their in situ encapsulation.

Double Sequential Encrypted Targeting Sequence: A New Concept for Bone Cancer Treatment.

The selective transportation of therapeutic agents to tumoral cells is usually achieved by their conjugation with targeting moieties able to recognize these cells. Unfortunately, simple and static targeting systems usually show a lack in selectivity. Herein, a double sequential encrypted targeting system is proposed as a stimuli-responsive targeting analogue for selectivity enhancement. The system is able to recognize diseased bone tissue in the first place, and once there, a hidden secondary targeting group is activated by the presence of an enzyme overproduced in the malignant tissue (cathepsin K), thereby triggering the recognition of diseased cells. Transporting the cell targeting agent in a hidden conformation that contains a high selective tissular primary targeting, could avoid not only its binding to similar cell receptors but also the apparition of the binding-site barrier effect, which can enhance the penetration of the therapeutic agent within the affected zone. This strategy could be applied not only to conjugate drugs but also to drug-loaded nanocarriers to improve the efficiency for bone cancer treatments.

Synthesis of Polydopamine-Like Nanocapsules via Removal of a Sacrificial Mesoporous Silica Template with Water.

Hollow polymeric polydopamine (PDA) micro-/nanocapsules have been obtained through a very simple, mild, and straightforward method that involves coating of silica mesoporous nanoparticles through an ammonia-triggered polymerization of PDA and the posterior removal of the sacrificial template simply by dispersion in water, without the need of any harsh chemical reagent, either in the presence or absence of active principles, from doxorubicin to iron oxide nanoparticles. To demonstrate the potential of the nanocapsules obtained with this new approach, they have been successfully used as nanocarriers for drug delivery.

Readily Available Chiral Benzimidazoles-Derived Guanidines as Organocatalysts in the Asymmetric α-Amination of 1,3-Dicarbonyl Compounds.

The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di-t-butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a chiral amine in moderate-to-good yields. Among all of them, those derived from (R)-1-phenylethan-1-amine (1) and (S)-1-(2-naphthyl)ethan-1-amine (3) turned out to be the most efficient for such asymmetric transformation, rendering good-to-high yields and moderate-to-good enantioselectivities for the amination products.

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes.

The asymmetric conjugate addition of carbon and heteroatom nucleophiles to nitroalkenes is a very interesting tool for the construction of highly functionalized synthetic building blocks. Thanks to the rapid development of asymmetric organocatalysis, significant progress has been made during the last years in achieving efficiently this process, concerning chiral organocatalysts, substrates and reaction conditions. This review surveys the advances in asymmetric organocatalytic conjugate addition reactions to α,ß-unsaturated nitroalkenes developed between 2013 and early 2017.

Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non-viral Oligonucleotide Delivery Carriers.

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability.

Magnetic-Responsive Release Controlled by Hot Spot Effect.

Magnetically triggered drug delivery nanodevices have attracted great attention in nanomedicine, as they can feature as smart carriers releasing their payload at clinician's will. The key principle of these devices is based on the properties of magnetic cores to generate thermal energy in the presence of an alternating magnetic field. Then, the temperature increase triggers the drug release. Despite this potential, the rapid heat dissipation in living tissues is a serious hindrance for their clinical application. It is hypothesized that magnetic cores could act as hot spots, this is, produce enough heat to trigger the release without the necessity to increase the global temperature. Herein, a nanocarrier has been designed to respond when the temperature reaches 43 °C. This material has been able to release its payload under an alternating magnetic field without the need of increasing the global temperature of the environment, proving the efficacy of the hot spot mechanism in magnetic-responsive drug delivery devices.

Towards the Development of Smart 3D "gated scaffolds" for on-command delivery.

A new approach towards the design of "gated scaffolds" based on the combination of capped mesoporous silica nanoparticles (MSNs) with porous biomaterials is reported. Using this approach, a 3D gelatin-based scaffold able to selectively deliver cargo in the presence of an APase enzyme is prepared and tested. This new design opens up the possibility of developing new smart biomaterials with advanced drug-delivery features.

Recent Advances on the Catalytic Asymmetric Allylic α-Alkylation of Carbonyl Derivatives Using Free Allylic Alcohols.

During the last years, the development of more sustainable and straightforward methodologies to minimize the generation of waste organic substances has acquired high importance within synthetic organic chemistry. Therefore, it is not surprising that many efforts are devoted to ameliorating already well-known successful methodologies, that is, the case of the asymmetric allylic allylation reaction of carbonyl compounds. The use of free alcohols as alkylating agents in this transformation represents a step forward in this sense since it minimizes waste production and the substrate manipulation. In this review, we aim to gather the most recent methodologies describing this strategy by paying special attention to the reaction mechanisms, as well as their synthetic applications.

Asymmetric hybrid silica nanomotors for capture and cargo transport: towards a novel motion-based DNA sensor.

An innovative self-propelled nanodevice able to perform motion, cargo transport, and target recognition is presented. The system is based on a mesoporous motor particle, which is asymmetrically functionalized by the attachment of single-stranded DNA onto one of its faces, while catalase is immobilized on the other face. This enzyme allows catalytic decomposition of hydrogen peroxide to oxygen and water, giving rise to the driving force for the motion of the whole system. Moreover the motor particles are able to capture and transport cargo particles functionalized with a noncomplementary single-stranded DNA molecule, only if a specific oligonucleotide sequence is present in the media. Functionalization with characteristic oligonucleotide sequences in the system implies a potential for further developments for lab-on-chip devices with applications in biomedical applications.