Influence of Tween 80 Surfactant on the Binding of Roxatidine Acetate and Roxatidine Acetate–loaded Chitosan Nanoparticles to Lysozyme

The drug binding to protein is an attractive research topic. In order to assess the release of RxAc-CsNPs and their binding with lysozyme under physiological conditions, nanocomposite materials based on chitosan (Cs) and Roxatidine acetate (RxAc) in the presence Tween 80 (Tw80) surfactant were developed. The addition of Tw80 to CsNPs increased RxAc release in vitro. In this work, Stern–Volmer plot and thermodynamic results indicated that the mechanism of Lyz with RxAc and Lyz with RxAc-CsNPs was static mechanism and the main forces in both systems were hydrogen bonding and Van der Waals forces, which indicated that the binding reaction in both systems is spontaneous, exothermic and enthalpically driven. Synchronous fluorescence and CD results indicated that the RxAc and RxAc-CsNPs cause change in the secondary construction of Lyz. It was also found that the addition of Tw80 affects the binding constant of drug with protein. Finally, the molecular docking results have also been in accordance with the results of other techniques. Hence, the developed RxAc loaded Chitosan nanoparticles could be used as an effective strategy for designing and application of the antiulcer drugs. Altogether, the present study can provide an important insight for the future designing of antiulcer drugs.

On the Futility of Dynamics in Robust Mechanism Design

We consider a principal who repeatedly interacts with a strategic agent holding private information. In each round, the agent observes an idiosyncratic shock drawn independently and identically from a distribution known to the agent but not to the principal. The utilities of the principal and the agent are determined by the values of the shock and outcomes that are chosen by the principal based on reports made by the agent. When the principal commits to a dynamic mechanism, the agent best-responds to maximize his aggregate utility over the whole time horizon. The principal’s goal is to design a dynamic mechanism to minimize his worst-case regret, that is, the largest difference possible between the aggregate utility he could obtain if he knew the agent’s distribution and the actual aggregate utility he obtains. We identify a broad class of games in which the principal’s optimal mechanism is static without any meaningful dynamics. The optimal dynamic mechanism, if it exists, simply repeats an optimal mechanism for a single-round problem in each round. The minimax regret is the number of rounds times the minimax regret in the single-round problem. The class of games includes repeated selling of identical copies of a single good or multiple goods, repeated principal-agent relationships with hidden information, and repeated allocation of a resource without money. Outside this class of games, we construct examples in which a dynamic mechanism provably outperforms any static mechanism.

Structural and Spectral Investigation of a Series of Flavanone Derivatives

Four flavanone Schiff bases (E)-1-(2-phenylchroman-4-ylidene)thiosemicarbazide (FTSC) (1), N′,2-bis((E)-2-phenylchroman-4-ylidene)hydrazine-1-carbothiohydrazide (FTCH) (2), (E)-N’-(2-phenylchroman-4-ylidene)benzohydrazide (FHSB) (3) and (E)-N′-(2-phenylchroman-4-ylidene)isonicotinohydrazide (FIN) (4) were synthesized and evaluated for their electronic and physicochemical properties using experimental and theoretical methods. One of them, (2), consists of two flavanone moieties and one substituent, the rest of the compounds (1, 3, 4) comprises of a flavanone-substituent system in relation to 1:1. To uncover the structural and electronic properties of flavanone Schiff bases, computational simulations and absorption spectroscopy were applied. Additionally, binding efficiencies of the studied compounds to serum albumins were evaluated using fluorescence spectroscopy. Spectral profiles of flavanone Schiff bases showed differences related to the presence of substituent groups in system B of the Schiff base molecules. Based on the theoretically predicted chemical descriptors, FTSC is the most chemically reactive among the studied compounds. Binding regions within human and bovine serum albumins of the ligands studied are in the vicinity of the Trp residue and a static mechanism dominates in fluorescence quenching.

Fluorescent Imprinted Nanoparticles for the Effective Monitoring of Irinotecan in Human Plasma

Fluorescent, imprinted nanosized polymers for the detection of irinotecan have been synthesised using a napthalimide polymerisable derivative (2-allyl-6-[2-(aminoethyl)-amino] napthalimide) as functional monomer. The imprinted polymers contain ethylene glycol dimethacrylate (EGDMA) as a cross-linker and were prepared by high dilution radical polymerisation in dimethylsulphoxide (DMSO). The material was able to rebind irinotecan up to 18 nmol/mg with good specificity. Fluorescence emission at 525 nm (excitation at 448 nm) was quenched by increasing concentrations of irinotecan via a static mechanism and also in analytically useful environments as mixtures of human plasma and organic solvents. This allowed the direct detection of irinotecan (in the 10–30 μM range) in human plasma treated with acetonitrile; the limit of detection (LOD) was 9.4 nM, with within-run variability of 10% and day-to-day variability of 13%.

Spectroscopic and Molecular Modeling Investigation on the Interaction between Folic Acid and Bovine Lactoferrin from Encapsulation Perspectives

The impact of thermal treatment on the ability of lactoferrin (FL) to bind folic acid (FA) was investigated by employing fluorescence spectroscopy, molecular dynamics and docking tests. The structural and conformational particularities of LF upon heating at 80 °C and 100 °C were first estimated based on the intrinsic fluorescence changes in respect to the native protein. The emission spectra indicated gradual unfolding events accompanied by Trp exposure with increasing temperature. In agreement with the experimental results, molecular modeling investigations showed that the secondary and tertiary structure of LF are slightly affected by the thermal treatment. Some minor unfolding events related particularly to the α-helical regions of LF were observed when the temperature increased to 100 °C. The LF fluorescence quenching upon FA addition indicated that a static mechanism stands behind LF-FA complex formation. Regardless of the simulated temperature, the hydrogen bonds played an important role in regulating the interaction between the protein and ligand. FA binding to LF equilibrated at different temperatures occurred spontaneously, and all complexes displayed good thermodynamic stability. The obtained results support the suitability of LF as biocompatible material, for obtaining micro- and nanoparticles for delivery of dietary supplements or for enhancing the functionality of target delivery systems.

Credible Auctions: A Trilemma

Consider an extensive‐form mechanism, run by an auctioneer who communicates sequentially and privately with bidders. Suppose the auctioneer can deviate from the rules provided that no single bidder detects the deviation. A mechanism is credible if it is incentive‐compatible for the auctioneer to follow the rules. We study the optimal auctions in which only winners pay, under symmetric independent private values. The first‐price auction is the unique credible static mechanism. The ascending auction is the unique credible strategy‐proof mechanism.

Study of the character and causes of destruction of the cardan shaft of the propeller engine

The results of studying operational destruction of a high-loaded cardan shaft of the propeller engine made of steel 38KhN3MFA are presented to elucidate the cause of damage and develop a set of recommendations and measures aimed at elimination of adverse factors. Methods of scanning electron and optical microscopy, as well as X-ray spectral microanalysis are used to determine the mechanical properties, chemical composition, microstructure, and fracture pattern of cardan shaft fragments. It is shown that the mechanical properties and chemical composition of the material correspond to the requirements of the regulatory documentation, defects of metallurgical origin both in the shaft metal and in the fractures are absent. The microstructure of the studied shaft fragments is tempered martensite. Fractographic analysis revealed that the destruction of cardan shaft occurred by a static mechanism. The fracture surface is coated with corrosion products. The revealed cracks developed by the mechanism of corrosion cracking due to violation of the protective coating on the shaft. The results of the study showed that the destruction of the cardan shaft of a propeller engine made of steel 38Kh3MFA occurred due to formation and development of spiral cracks by the mechanism of stress corrosion cracking under loads below the yield point of steel. The reason for «neck» formation upon destruction of the shaft fragment is attributed to the yield point of steel attained during operation. Regular preventive inspections are recommended to assess the safety of the protective coating on the shaft surface to exclude formation and development of corrosion cracks.

Ketoprofen-Based Ionic Liquids: Synthesis and Interactions with Bovine Serum Albumin

The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol−1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages.

Inhibition of CpLIP2 Lipase Hydrolytic Activity by Four Flavonols (Galangin, Kaempferol, Quercetin, Myricetin) Compared to Orlistat and Their Binding Mechanisms Studied by Quenching of Fluorescence

The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested.

Aggregation-Induced Emission (AIE)-Labeled Cellulose Nanocrystals for the Detection of Nitrophenolic Explosives in Aqueous Solutions

Aggregation-induced emission (AIE) active cellulose nanocrystals (TPE-CNCs) were synthesized by attaching tetraphenylethylene (TPE) to cellulose nanocrystals (CNCs). The structure and morphology of TPE-CNCs were characterized by FT-IR, XRD, ζ-potential measurements, elemental analysis, TEM, atomic force microscopy (AFM), and dynamic laser light scattering (DLS). Fluorescent properties of TPE-CNCs were also further studied. Unlike aggregation-caused quenching (ACQ), TPE-CNCs emitted weak fluorescence in the dilute suspensions, while emitting efficiently in the aggregated states. The AIE mechanism of TPE-CNCs was attributed to the restriction of an intramolecular rotation (RIR) process in the aggregated states. TPE-CNCs displayed good dispersity in water and stable fluorescence, which was reported through the specific detection of nitrophenolic explosives in aqueous solutions by a fluorescence quenching assay. The fluorescence emissions of TPE-CNCs showed quantitative and sensitive responses to picric acid (PA), 2,4-dinitro-phenol (DNP), and 4-nitrophenol (NP), and the detection limits were 220, 250, and 520 nM, respectively. Fluorescence quenching occurred through a static mechanism via the formation of a nonfluorescent complex between TPE-CNCs and nitrophenolic analytes. A fluorescence lifetime measurement revealed that the quenching was a static process. The results demonstrated that TPE-CNCs were excellent sensors for the detection of nitrophenolic explosives in aqueous systems, which has great potential applications in chemosensing and bioimaging.