N–H⋯X interactions stabilize intra-residue C5 hydrogen bonded conformations in heterocyclic α-amino acid derivatives

Nature makes extensive and elaborate use of hydrogen bonding to assemble and stabilize biomolecular structures. The shapes of peptides and proteins rely significantly on N–H⋯O C interactions, which are the linchpins of turns, sheets and helices. The C5 H-bond, in which a single residue provides both donor and acceptor, is generally considered too weak to force the backbone to adopt extended structures. Exploiting the synergy between gas phase (experimental and quantum chemistry) and solution spectroscopies to decipher IR spectroscopic data, this work demonstrates that the extended C5-based conformation in 4-membered ring heterocyclic α-amino acid derivatives is significantly stabilized by the formation of an N–H⋯X H-bond. In this synergic system the strength of the C5 interaction remains constant while the N–H⋯X H-bond strength, and thereby the support provided by it, varies with the heteroatom.

In 4-membered ring heterocyclic α-amino acid derivatives, extended conformations based on intraresidue C5 H-bonds can be stabilized by N–H⋯X H-bonds, making the combined C5–C6γ structures prominent in both gas phase and in weakly polar solutions.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Method development and validation for optimised separation of salicylic, acetyl salicylic and ascorbic acid in pharmaceutical formulations by hydrophilic interaction chromatography and response surface methodology

This paper introduces a design of experiments (DOE) approach for method optimisation in hydrophilic interaction chromatography (HILIC). An optimisation strategy for the separation of acetylsalicylic acid, its major impurity salicylic acid and ascorbic acid in pharmaceutical formulations by HILIC is presented, with the aid of response surface methodology (RSM) and Derringer's desirability function. A Box-Behnken experimental design was used to build the mathematical models and then to choose the significant parameters for the optimisation by simultaneously taking both resolution and retention time as the responses. The refined model had a satisfactory coefficient (R2>0.92, n=27). The four independent variables studied simultaneously were: acetonitrile content of the mobile phase, pH and concentration of buffer and column temperature each at three levels. Of these, the concentration of buffer and its cross-product with pH had a significant, positive influence on all studied responses. For the test compounds, the best separation conditions were: acetonitrile/22 mM ammonium acetate, pH 4.4 (82:18, v/v) as the mobile phase and column temperature of 28°C. The methodology also captured the interaction between variables which enabled exploration of the retention mechanism involved. It would be inferred that the retention is governed by a compromise between hydrophilic partitioning and ionic interaction. The optimised method was further validated according to the ICH guidelines with respect to linearity and range, precision, accuracy, specificity and sensitivity. The robustness of the method was also determined and confirmed by overlying counter plots of responses which were derived from the experimental design utilised for method optimisation.     

A Review on Bioengineering Approaches to Insulin Delivery: A Pharmaceutical and Engineering Perspective

Diabetes mellitus (DM) is the most prevalent non‐contagious disease, which has affected a large number of people all over the world. Among all treatments known to have a positive influence in the control of DM, insulin therapy is the most common and effective one. Nowadays, various methods of insulin delivery are under investigation, which are able to reach a plausible bioavailability with ignorable side effects instead of insulin injection. This article presents a comprehensive review of the insulin therapy approach with a focus on modified methods in insulin delivery strategies and current advances in engineered insulin delivery systems.     

Fe3O4@NCs/BF0.2: A magnetic bio‐based nanocatalyst for the synthesis of 2,3‐dihydro‐1H‐perimidines

Nanocellulose (NC) materials have some unique properties, which make them attractive as organic or inorganic supports for catalytic applications. Nanocatalysts with diameters of less than 100 nm are difficult to separate from the reaction mixture, therefore, magnetic nanoparticles (MNPs) were used as catalysts to overcome this problem. Fe₃O₄@NCs/BF_0.2 as a green, bio‐based, eco‐friendly, and recyclable catalyst was synthesized and characterized using fourier‐transform infrared spectroscopy (FT‐IR), vibrating sample magnetometer (VSM), X‐ray diffraction (XRD), X‐ray fluorescence (XRF), Brunauer–Emmett–Teller (BET), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and thermal gravimetric analysis (TGA) techniques. Fe₃O₄@NCs/BF_0.2 was employed for the synthesis of 2,3‐dihydro‐1H‐perimidine derivatives via a reaction of 1,8‐diaminonaphthalene with various aldehydes at room temperature under solvent‐free conditions. The present procedure offers several advantages including a short reaction time, excellent yields, easy separation of catalyst, and environmental friendliness.     

Genipin‐crosslinked gelatin hydrogel incorporated with PLLA‐nanocylinders as a bone scaffold: Synthesis,characterization, and mechanical properties evaluation

Nowadays, despite remarkable progress in developing bone tissue engineering products, the fabrication of an ideal scaffold that could meet the main criteria, such as providing mechanical properties and suitable biostability as well as mimicking the bone extracellular matrix, still seems challenging. In this regard, utilizing combinatorial approaches seems more beneficial. Here, we aim to reinforce the mechanical characteristics of gelatin hydrogel via a combination of Genipin‐based chemical cross‐linking and incorporation of the poly l ‐lactic acid (PLLA) nanocylinders for application as bone scaffolds. Amine‐functionalized nanocylinders are prepared via the aminolysis procedure and incorporated in gelatin hydrogel. The nanocylinder content (0, 1, 2, 3, and 4 wt%) and cross‐linking density (0.1, 0.5, and 1 wt/vol%) are optimized to achieve suitable morphology, swelling ratio, degradation rate, and mechanical behaviors. The results indicate that hydrogel scaffold cross‐linking by 0.5 wt% of Genipin shows optimized morphological feathers with a pore size of around 300 to 500 μm as well as an average degradation rate (40.09% ± 3.08%) during 32 days. Besides, the incorporation of 3 wt% PLLA nanocylinders into the cross‐linked gelatin scaffold provides an optimized mechanical reinforcement as compressive modulus, and compressive strength show a 4‐ and 2.6‐fold increase, respectively. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay indicates that the scaffold does not have any cytotoxicity effect. In conclusion, gelatin composite reinforced with 3 wt% PLLA nanocylinders cross‐linked via 0.5 wt/vol% Genipin is suggested as a potential scaffold for bone tissue engineering applications.     

A three‐component,one‐pot synthesis of oxazinoquinolin‐3‐one derivatives

Oxazino[5,6‐f]quinolin‐3‐one derivatives have been synthesized in a one‐pot, and efficient process by condensation of 6‐quinolinol, aromatic aldehydes and urea under microwave‐assisted and thermal solvent‐free conditions.     

Synthesis and preparation of biodegradable and visible light crosslinkable unsaturated fumarate‐based networks for biomedical applications

Biodegradable polymers have currently attracted high interest as ideal carriers in drug delivery and tissue engineering applications. In situ forming devices based on these materials will synergistically provide the advantages of the customary prefabricated devices as well as ease of administration. To acheive these objectives, optically transparent and biodegradable macromers based on poly(ethylene glycol) and fumaric acid copolymers were synthesized using propylene oxide as a different proton scavenger to enhance in situ photocrosslinking capability. The macromers in different compositions were then photocured for 300 sec in the presence of a visible light initiator/accelerator couple and also a reactive diluent. Characterization of the macromers and the resulting networks were performed using different spectroscopic, chromatographic, physical, and thermal analysis techniques. The resulted shrinkage strain of the macromers upon photocuring was studied using the bounded disk technique, and initial shrinkage strain rates were obtained by numerical differentiation. Our results suggest that the compositions based on these unsaturated aliphatic polyesters are potentially useful to develop injectable, in situ photocrosslinkable carriers for drug and cell delivery applications. Copyright © 2008 John Wiley & Sons, Ltd.     

Pore-Scale Numerical Experiment on the Effect of the Pertinent Parameters on Heat Flux Splitting at the Boundary of a Porous Medium

Pore-scale heat and fluid flow simulation through reconstructed porous media is presented with the aim of investigating the physics of heat flux splitting at the boundary of porous media. As such, the effects of the solid to fluid thermal conductivity ratio, porosity, pore-scale Reynolds number, Prandtl number and heat conduction within the solid matrix are investigated. The results of the present study for heat transfer coefficient and pressure drop are compared with available experimental data and good agreement was observed. The validated results are then used to investigate the validity of the existing volume-averaged models. It was observed that while results based on the volume-averaged models are reasonably close to current predictions for $\varepsilon \le 0.7$ , the discrepancy between the two becomes notable for higher porosities. While existing models rely exclusively on porosity and thermal conductivity ratio, our newly proposed correlations show the effects of Reynolds number on the heat split mechanism for high porosities. On the other hand, the Prandtl number, at least for the range of parameters studies here, is found to be less influential on the boundary heat split mechanism.