Effect of thienyl units in cyanoacrylic acid derivatives toward dye-sensitized solar cells.

A series of heterocyclic donor-acceptor systems were synthesized and well characterized by using 1H, 13C NMR, FT-IR, and elemental analysis. They were designed to investigate the effect of thiophene and cyanoacrylic acid number units on the thermal, optical, electrochemical and finally photovoltaic properties of dye-sensitized solar cells prepared with the selected compounds. The effect of chemical structure on their properties was demonstrated. They showed the beginning of thermal decomposition between 230 and 270 °C. The compounds absorbed the radiation in the range of 300-500 nm or 200-400 nm. They were electrochemically active and varied in energy band gap from 3.40 to 1.58 eV. Additionally, their optimized geometry, HOMO-LUMO levels, ionization potential, and electron affinity were evaluated using density functional theory. The photovoltaic devices based on TiO2 sensitized with the obtained molecules exhibited low power conversion efficiency, which was the highest for the device containing the symmetrical molecule with bithiophene structure. Under co-sensitization, the cell made of the same compound gave significant enhancement of efficiency of 6.3% being higher to that of the individual device prepared from dye N719 (5.75%). Moreover, the effects of immersion time of TiO2 electrode in the dye solution and co-sensitization methods were tested. The surface morphology of photoanode was investigated using atomic force microscopy.

Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease.

Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they have potential advantages in terms of efficacy, selectivity, and safety. TCIs have recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish the risk of haptenization and help optimize the drug-target residence time as needed. The enteroviral 3C protease (3Cpro) is a valuable therapeutic target, but the development of 3Cpro inhibitors is far from satisfactory. Therefore, we aimed to apply a reversible TCI approach to the design of novel 3Cpro inhibitors. The introduction of various substituents onto the α-carbon of classical Michael acceptors yielded inhibitors bearing several classes of warheads. Using steady-state kinetics and biomolecular mass spectrometry, we confirmed the mode of reversible covalent inhibition and elucidated the mechanism by which the potency and reversibility were affected by electronic and steric factors. This research produced several potent inhibitors with good selectivity and suitable reversibility; moreover, it validated the reversible TCI approach in the field of viral infection, suggesting broader applications in the design of reversible covalent inhibitors for other proteases.

Poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) as possible agents in tumor treatment.

Tumor eradication has many challenges due to the difficulty of selectively delivering anticancer drugs to malignant cells avoiding contact with healthy tissues/organs. The improvement of antitumor efficacy and the reduction of systemic side effects can be achieved using drug loaded nanoparticles. In this study, poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) were prepared using an emulsion polymerization method and their potential for cancer treatment was investigated. The size, polydispersity index and zeta potential of prepared nanoparticles are about 80 nm, 0.08 and -39.7 mV, respectively. The stability test shows that the formulation is stable for 15 days, while an increase in particle size occurs after 30 days. TEM reveals the spherical morphology of nanoparticles; furthermore, FTIR and 1H NMR analyses confirm the structure of PECA-NPs and the complete polymerization. The nanoparticles demonstrate an in vitro concentration-dependent cytotoxicity against human epithelial colorectal adenocarcinoma cell lines (Caco-2), as assessed by MTT assay. The anticancer activity of PECA-NPs was studied on 3D tumor spheroids models of hepatocellular carcinoma (HepG2) and kidney adenocarcinoma cells (A498) to better understand how the nanoparticles could interact with a complex structure such as a tumor. The results confirm the antitumor activity of PECA-NPs. Therefore, these systems can be considered good candidates in tumor treatment.

Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway.

A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 µM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.

Solvation-Guided Design of Fluorescent Probes for Discrimination of Amyloids.

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer's-related ß-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment.

Biocompatible alkyl cyanoacrylates and their derivatives as bio-adhesives.

Cyanoacrylate adhesives and their homologues have elicited interest over the past few decades owing to their applications in the biomedical sector, extending from tissue adhesives to scaffolds to implants to dental material and adhesives, because of their inherent biocompatibility and ability to polymerize solely with moisture, thanks to which they adhere to any substrate containing moisture such as the skin. The ability to tailor formulations of alkyl cyanoacrylate to form derivative compounds to meet application requirements along with their biodegradability in conjunction with their inherent biocompatibility make them highly sought after candidates in the biomedical sector. There has been extensive exploration of cyanoacrylate adhesives and their homologue systems in biomedical applications, but no consolidated literature of the vast data is available. The ability of cyanoacrylate adhesives to cure at low temperatures and without the need for any hardener, which is attributed to the high-strength bonding interaction between two non-amalgamating substrates, with their ease of dispersion and self-curing, avoids the curtailing of the effective utilization of such adhesives in biomedical engineering applications as bio glues for amalgamating tissues, implants, scaffolds etc. This article consolidates copious work on cyanoacrylate adhesives and their derived systems which are functional in versatile biomedical engineering applications such as bio glues, dental material and adhesives and other potential applications.

Comparative evaluation of polycyanoacrylates.

Cyanoacrylate esters (CA) and their corresponding polymers (PolyCA) are used as general and medical adhesives, biodegradable carriers for controlled drug delivery, and as agents for fingerprint development in forensic science. Most reports of cyanoacrylate are on ethyl or 2-octyl cyanoacrylate ester with little attention to other esters. It is the objective of this study to determine the differences amongst cyanoacrylate esters regarding their synthesis, chemical characterization, hydrolytic degradation, and thermal and mechanical properties. Cyanoacrylate polymers of short and long alkyls or oxy-alkyls, cyclic, and aromatic esters have been synthesized and evaluated. All monomers form polymers when exposed to triethylamine vapours possessing molecular weights in the range of 15,000-150,000Da, where the alkyl esters form high MW polymers. A wide range of hydrolytic degradation rates has been found, as monitored by the release of formaldehyde over time. Alkoxy CAs show faster hydrolytic degradation compared to alkyl CAs. Regarding mechanical properties, CAs are classified into primarily viscous (G'>G″) and primarily elastic (G″>G'). Alkoxy CA polymers have a higher loss modulus (G') than storage modulus (G″). Octyl CA polymer possess a G'≈G″ (phase angle ∼45°) providing appropriate balance between mechanical strength and plasticity. Most alkyl CAs are compact and brittle. Alkoxy CAs show enhanced plasticity, but they lack mechanical strength. In general, the Tg for alkoxy CAs is less than alkyl CAs. Alkoxy CAs depolymerise rapidly at temperatures >200°C. Overall, ester sidechains of CA esters strongly affect the polymer property. STATEMENT OF SIGNIFICANCE: Polycyanoacrylates are an important class of biodegradable polymers mainly used as bioadhesives. The study describes comparative evaluation of different cyanoacrylate polymers with respect to their chemistry, degradation, safety, mechanical, and thermal properties. The study forms the basis for choosing appropriate combination of cyanoacrylate esters for various biomedical uses. Moreover, this study reveals properties of a few new polycyanoacrylates for the first time.

Cyanoacrylate Burn Injuries: Two Unusual Cases and a Review of the Literature.

The authors present 2 cases of cyanoacrylate glue ("Super Glue") burns, with a review of the literature and a discussion on the mechanism of action. The authors found all reported cases were with domestic - not medical-grade - cyanoacrylate glue in the presence of cotton fabric. Often erroneously designated as chemical burns, they are thermal burns caused by an intensive exothermic reaction. Cotton acts as a highly potent catalyst, speeding up the polymerization reaction leading to high-peak temperatures capable of causing burns and spontaneous ignition of the fabric. The authors identify factors that explain the different risk profiles of domestic and medical cyanoacrylate glues and could be addressed to improve safety with nonmedical applications.

PEG-Biscyanoacrylate Crosslinker for Octyl Cyanoacrylate Bioadhesive.

PEG400 (polyethylene glycol, MW 400) biscyanoacrylate is synthesized and copolymerized with 2-octyl cyanoacrylate for potential use as bioadhesive. PEG400 biscyanoacrylate is synthesized from the esterification of anthracenyl cyanoacrylic acid where the anthracene unit serves as vinyl-protecting group. Copolymerization increases the plasticity, mechanical strength, and resilience of the resulted polymer as determined by dynamic mechanical analysis. Peeling test confirms its superior bioadhesive properties. Surface morphology is characterized by SEM imaging. The formulations are cytocompatible and safe. This cyanoacrylate composition may provide improved bioadhesive cyanoacrylates.

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo.

Synthesis of Dynole 34-2, Dynole 2-24 and Dyngo 4a for investigating dynamin GTPase.

Dynamin is a large GTPase with roles in membrane fission during clathrin-mediated endocytosis, in actin dynamics and in cytokinesis. Defects in dynamin have been linked to human diseases. The synthesis of a dynamin modulator toolkit comprising two different inhibitor classes is described. The first series comprises Dynole 34-2, Dynole 2-24 and the inactive control Dynole 31-2. The Dynole compounds act on the dynamin G domain, are not GTP competitive and can be synthesized in 2-3 d. Knoevenagel condensation of 1-(3-(dimethylamino)propyl)-1H-indole-3-carbaldehyde (1) with cyanoamides (2 and 3) affords Dynole 31-2 and Dynole 34-2, respectively. Reductive amination of 1 with decylamine gives Dynole 2-24. The second series acts at an allosteric site in the G domain of dynamin and comprises Dyngo 4a and Dyngo Ø (inactive control). Both are synthesized in an overnight reaction via condensation of 3-hydroxy-2-naphthoic hydrazide with 2,4,5-trihydroxybenzaldehyde to afford Dyngo 4a, or with benzaldehyde to afford Dyngo Ø.

Biocompatibility of wollastonite-poly(N-butyl-2-cyanoacrylate) composites.

Wollastonite-poly(n-butyl-2-cyanoacrylate) composite (W-BCA) has been proposed to immobilize anatomically bone fragments in order to achieve an optimal healing process. The present study evaluated the in vitro and in vivo behavior of three types of fillers: powdered natural wollastonite (Wn), synthetic pseudowollastonite powder (Ws), and synthetic pseudowollastonite powder coated with 5% acetyl tributyl citrate (Wst). The Wst-BCA composite underwent a higher degradability in the real-time degradation test and a superior cytotoxic effect; whereas the Wn-BCA composite showed a higher degradability in the accelerated test with no cytotoxicity. The formation of an extracellular collagenous matrix deposit on its surface and the most favorable new bone formation on Wn-BCA indicate its potential for bone adhesive use in unstable orthopedic traumas.

Production of BSA-poly(ethyl cyanoacrylate) nanoparticles as a coating material that improves wetting property.

Alkyl cyanoacrylates have long been used for the synthesis of colloidal nanoparticles. In the involved polymerization reaction, hydroxyl ions derived from dissociation of water have been used as an initiator. In the current research, an animal protein, bovine serum albumin (BSA) molecules were utilized as initiator for the polymerization. Following this reaction scheme, hydrophobic poly(ethyl cyanoacrylate)s were covalently bound to BSA, which is hydrophilic. Therefore, the resultant copolymer was amphiphilic in nature, and formed nanoparticles in the reaction medium. The suspension containing these nanoparticles showed an excellent coating capability on the surface of hydrophobic materials. A simple spray coating changed the wetting property of the material instantly and dramatically.

Synthesis of a biodegradable magnetic nanomedicine based on the antitumor molecule tegafur.

The introduction of magnetic nanocarriers in chemotherapy aims to enhance the anticancer activity of antitumor molecules whereas keeping their toxicity to a very minimum. Magnetite/poly(hexylcyanoacrylate) (core/shell) nanoplatforms were synthesized by an emulsion/polymerization procedure. An exhaustive physicochemical characterization (including infrared spectrometry, electrophoresis, and thermodynamic analysis) suggested that the magnetite nuclei were embedded into a polymeric nanomatrix. The very good magnetic responsiveness of such core/shell nanoparticles was defined by the hysteresis cycle. To improve the intravenous delivery of tegafur to cancer, we investigated its incorporation into the nanoplatform. Compared to surface adsorption, drug entrapment into the polymeric shell yielded higher tegafur loading values, and a much slower release profile. A high frequency alternating magnetic gradient was used to elucidate the heating characteristics of the nanoparticles: a stable maximum temperature of 46 °C was successfully achieved within 32 min. Thus, we put forward that such kind of multifunctional nanomedicine hold very important characteristics (i.e., high drug loading, little burst release, hyperthermia, and magnetically targeted tegafur delivery), suggestive of its potential for combined antitumor therapy against cancer.

Facile preparation of carbon nanotube/poly(ethyl 2-cyanoacrylate) composite electrode by water-vapor-initiated polymerization for enhanced amperometric detection.

A carbon nanotube/poly(ethyl 2-cyanoacrylate) (CNT/PECA) composite electrode was developed for enhanced amperometric detection. The composite electrode was fabricated on the basis of water-vapor-initiated polymerization of a mixture of CNTs and ethyl 2-cyanoacrylate in the bore of a piece of fused silica capillary. The morphology and structure of the composite were investigated by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The results indicate that the CNTs were well dispersed and embedded throughout the PECA matrix to form an interconnected CNT network. The analytical performance of this unique CNT-based detector has been demonstrated by separating and detecting six flavones in combination with capillary electrophoresis. The advantages of the CNT/PECA composite detector include lower operating potential, higher sensitivity, low expense of fabrication, satisfactory resistance to surface fouling, and enhanced stability; these properties indicate great promise for a wide range of applications.

Elasticity and safety of alkoxyethyl cyanoacrylate tissue adhesives.

Cyanoacrylate glues are easily applied to wounds with good cosmetic results. However, they tend to be brittle and can induce local tissue toxicity. A series of cyanoacrylate monomers with a flexible ether linkage and varying side-chain lengths was synthesized and characterized for potential use as tissue adhesives. The effect of side-chain length on synthesis yield, physical and mechanical properties, formaldehyde generation, cytotoxicity in vitro and biocompatibility in vivo were examined. The incorporation of etheric oxygen allowed the production of flexible monomers with good adhesive strength. Monomers with longer side-chains were found to have less toxicity both in vitro and in vivo. Polymerized hexoxyethyl cyanoacrylate was more elastic than its commercially available and widely used alkyl analog 2-octyl cyanoacrylate, without compromising biocompatibility.

Preparation of poly(MePEGCA-co-HDCA) nanoparticles with confined impinging jets reactor: experimental and modeling study.

In this work, the biodegradable copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) is used to prepare nanoparticles via solvent displacement in a confined impinging jets reactor (CIJR). For comparison, nanoparticles constituted by the homopolymer counterpart are also investigated. The CIJR is a small passive mixer in which very fast turbulent mixing of the solvent (i.e., acetone and tetrahydrofuran) and of the antisolvent (i.e., water) solutions occurs under controlled conditions. The effect of the initial copolymer concentration, solvent type, antisolvent-to-solvent ratio, and mixing rate inside the mixer on the final nanoparticle size distribution, surface properties, and morphology is investigated from the experimental point of view. The effect of some of these parameters is studied by means of a computational fluid dynamics (CFD) model, capable of quantifying the mixing conditions inside the CIJR. Results show that the CIJR can be profitably used for producing nanoparticles with controlled characteristics, that there is a clear correlation between the mixing rate calculated by CFD and the mean nanoparticle size, and therefore that CFD can be used to design, optimize, and scale-up these processes.

Design, synthesis, and herbicidal activities of novel 2-cyanoacrylates containing isoxazole moieties.

A series of novel 2-cyanoacrylates containing an isoxazole moiety were designed and synthesized. Their structures were characterized by (1)H NMR and elemental analysis (or high-resolution mass spectrometry). Their herbicidal activities against four species were evaluated, and the results indicated that some of the title compounds showed excellent herbicidal activities against rape and amaranth pigweed in postemergence treatment even at a dose of 75 g/ha.

Facile preparation of poly(ethyl alpha-cyanoacrylate) superhydrophobic and gradient wetting surfaces.

Hollow microspheres of poly(ethyl alpha-cyanoacrylate) were prepared via vapor phase polymerization using micro-waterdroplets as template and initiator. Depending on the ratio of the shell thickness to the radius, the hollow microspheres would crimple to form either microballoons or microcups during drying. These two types of microparticles were used as building blocks to construct surfaces with diverse wettability. The microballoons linked up to form a porous-netlike surface which was rough enough to render the surface superhydrophobic, while the microcups-built surface showed less hydrophobicity. In addition, surfaces consisting of both microparticles with gradual decrease of roughness along the length direction were obtained, which presented gradient wetting property varied from superhydrophobic to hydrophobic. The as-formed superhydrophobic or gradient wetting surfaces may find potential applications in biomedical field because of the biocompatibility of poly(ethyl alpha-cyanoacrylate).

Synthesis and biological evaluation of arylhydrazinocyanoacrylates and N-aryl pyrazolecarboxylates.

A series of arylhydrazino-substituted cyanoacrylates 3 and N-aryl pyrazolecarboxylates 6 were synthesized and their bioactivities were evaluated. Though compounds 3 were designed as herbicide, some of them showed fungicidal activity and anti-tumor activity. Some of the compounds 6 exhibited plant growth regulatory activity.