Synthesis,photophysical and NMR evaluations of thiourea-based anion receptors possessing an acetamide moiety

The synthesis and photophysical evaluation of three diaryl thiourea-based anion receptors (4–6) for comparison with their urea counterparts (1–3) is outlined. These anion receptors posses an acetamide functionality on one of the aryl groups and an electron-withdrawing CF₃ group on the other. By varying the position of the acetamide group, in the o-, m- and p-positions of 4–6, respectively, the anion binding ability was both tuneable and found to be, in some cases, significantly different from that seen for the urea analogues 1–3. The binding affinities of the receptors 4–6, as well as the binding stoichiometries, were evaluated using UV–vis absorption spectroscopy in MeCN. However, these receptors were not sufficiently emissive to quantify the anion recognition using fluorescence. The results confirmed strong binding of these receptors to anions such as fluoride, acetate, phosphate, pyrophosphate and chloride. Nevertheless, the overall results obtained did not conform to the anticipated trends seen for 1–3, which is most likely due to the enhanced binding affinity of the thiourea analogues 4–6. The binding interactions were also investigated by using ¹H NMR which confirmed that these receptors interacted with the anions in a stepwise manner, where the primary anion binding interaction occurred at the thiourea side, which led to an activation of the acetamide moiety towards the second anion binding interaction, an example of an allosteric activation mode.     

Electrochemical DNA biosensor for human papillomavirus 16 detection in real samples

An electrochemical DNA biosensor for human papillomavirus (HPV) 16 detection has been developed. For this proposed biosensor, l-cysteine was first electrodeposited on the gold electrode surface to form l-cysteine film (CYSFILM). Subsequently, HPV16-specific probe was immobilized on the electrode surface with CYSFILM. Electrochemistry measurement was studied by differential pulse voltammetry method (DPV). The measurement was based on the reduction signals of methylene blue (MB) before and after hybridization either between probe and synthetic target or extracted DNA from clinical samples. The effect of probe concentration was analyzed and the best results were seen at 1000 nM. The hybridization detection presented high sensitivity and broad linear response to the synthetic-target concentration comprised between 18.75 nM and 250 nM as well as to a detection limit of 18.13 nM. The performance of this biosensor was also investigated by checking probe-modified electrode hybridization with extracted DNA from samples. The results showed that the biosensor was successfully developed and exhibited high sensitivity and satisfactory selectivity to HPV16. These results allow for the possibility of developing a new portable detection system for HPVs and for providing help in making an effective diagnosis in the early stages of infection.     

Selective Sulfenylative Desulfonylation or Decarbalkoxylation of α-Sulfonyl Malonates with DABCO or Bu3N: Reactivity and Conformational Analysis

The study on reactivity of several α-substituted α-sulfonyl malonates toward 1,4-diazabicyclo[2.2.2]octane (DABCO) and Bu₃N is described. The reactivity with DABCO revealed the possible competition between decarbalkoxylation and unexpected desulfonylation, depending on the α-substituent, because of sterical hindrance around the electrophilic centers (SO₂ and CO₂R). The derivatives with crowded α-substituents suffer selective desulfonylation, and a novel and efficient desulfonylation method can be proposed. The dependence of the reactivity of α-sulfonyl malonates on the sterical hindrance around the electrophilic centers is confirmed by conformational analysis (Macromodel/MM2? and Mopac/MP3). The carbanionic mechanism is proved because the corresponding protonated, deuterated, and sulfenylated products were obtained by addition of the corresponding electrophilic agents. Bu₃N showed itself to be a novel selective decarbalkoxylation agent for any α-substituted α-sulfonyl malonate.     

DOT2: Macromolecular docking with improved biophysical models

Computational docking is a useful tool for predicting macromolecular complexes, which are often difficult to determine experimentally. Here, we present the DOT2 software suite, an updated version of the DOT intermolecular docking program. DOT2 provides straightforward, automated construction of improved biophysical models based on molecular coordinates, offering checkpoints that guide the user to include critical features. DOT has been updated to run more quickly, allow flexibility in grid size and spacing, and generate an infinitive complete list of favorable candidate configurations. Output can be filtered by experimental data and rescored by the sum of electrostatic and atomic desolvation energies. We show that this rescoring method improves the ranking of correct complexes for a wide range of macromolecular interactions and demonstrate that biologically relevant models are essential for biologically relevant results. The flexibility and versatility of DOT2 accommodate realistic models of complex biological systems, improving the likelihood of a successful docking outcome. © 2013 Wiley Periodicals, Inc.     

Diffusiophoresis in suspensions of highly charged soft particles

Diffusiophoresis phenomenon of aoft particles suspended in binary electrolyte solutions is explored theoretically in this study based on the spherical cell model, focusing on the chemiphoresis component in absence of diffusion potential. Both the electrostatic and hydrodynamic aspects of the boundary confinement, or steric effect, due to the presence of neighboring particles are examined extensively under various electrokinetic conditions. Significant local extrema are found in mobility profiles expressed as functions of the Debye length in general, synchronized with the strength of the motion-inducing double layer polarization. Moreover, a seemingly peculiar phenomenon is observed that the soft particles may move faster in more concentrated suspensions. The competition between the simultaneous enhancement of the motion-inducing electric driving force and the motion-retarding hydrodynamic drag force from the boundary confinement effect of the neighboring particles is found to be responsible for it. The above findings are also demonstrated experimentally in a very recent study on the diffusiophoretic motion of soft particles through porous collagen hydrogels. The results presented here are useful in various practical applications of soft particles like drug delivery.     

UV assisted photo reactive polyether-polyesteramide resin for future applications in 3D printing

Among additive manufacturing, photocuring 3D printing technologies are very relevant because of its high printing speed and high precision. However, the limited performance of photosensitive thermoset polymers is the bottleneck for the application of photocuring 3D printing in some fields, particularly in the biomedical sector. Thus, the development of biodegradable and biocompatible materials is highly desirable and of utmost importance. In this work, a biodegradable and non-cytotoxic thermoset polymer for photocuring 3D printing is reported. It consists of an unsaturated polyesteramide bearing phenylalanine, 2-butene-1,4-diol and fumarate building blocks, which is photocured under UV irradiation using a low molecular weight poly(ethylene glycol) diacrylate as crosslinker. The main characteristics of the new thermoset are: (1) very high volumetric and mechanical integrity stabilities, comparable to that of photocured epoxides; (2) very high degradation temperature; (3) very low water absorption capacity; (4) relatively fast enzymatic degradation, reaching 16.5% after 3 months; and (5) non-cytotoxic response in presence of epithelial cells, even when soluble molecular fragments coming from biodegradation are considered. These properties favor the future utilization of the new polyether-polyesteramide resin in the manufacturing of more sustainable products via 3D printing methods, such as stereolithography, that uses UV sources.     

Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.