Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins,calixarenes and cucurbiturils

Abstract

The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (α-, β-, and γ-), p-sulfonatocalix[n]arenes (n = 4–6) as well as cucurbit[n]urils (n = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by β-cyclodextrin and p-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (ΔH° < 0), accompanied by slightly unfavourable entropy changes (ΔS° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.     

Toward the computer-aided discovery of FabH inhibitors. Do predictive QSAR models ensure high quality virtual screening performance?

Antibiotic resistance has increased over the past two decades. New approaches for the discovery of novel antibacterials are required and innovative strategies will be necessary to identify novel and effective candidates. Related to this problem, the exploration of bacterial targets that remain unexploited by the current antibiotics in clinical use is required. One of such targets is the \(\beta \) -ketoacyl-acyl carrier protein synthase III (FabH). Here, we report a ligand-based modeling methodology for the virtual-screening of large collections of chemical compounds in the search of potential FabH inhibitors. QSAR models are developed for a diverse dataset of 296 FabH inhibitors using an in-house modeling framework. All models showed high fitting, robustness, and generalization capabilities. We further investigated the performance of the developed models in a virtual screening scenario. To carry out this investigation, we implemented a desirability-based algorithm for decoys selection that was shown effective in the selection of high quality decoys sets. Once the QSAR models were validated in the context of a virtual screening experiment their limitations arise. For this reason, we explored the potential of ensemble modeling to overcome the limitations associated to the use of single classifiers. Through a detailed evaluation of the virtual screening performance of ensemble models it was evidenced, for the first time to our knowledge, the benefits of this approach in a virtual screening scenario. From all the obtained results, we could arrive to a significant main conclusion: at least for FabH inhibitors, virtual screening performance is not guaranteed by predictive QSAR models.     

Non-singular dislocation loops in gradient elasticity

Using gradient elasticity, we give in this Letter the non-singular fields produced by arbitrary dislocation loops in isotropic media. We present the ‘modified’ Mura, Peach–Koehler and Burgers formulae in the framework of gradient elasticity theory.     

Modelling of sorbic acid diffusion through bacterial cellulose-based antimicrobial films

Antimicrobial packaging protects the product from the external environment and microbial contamination, conferring numerous advantages on human health. Interest in biopolymers as packaging materials has considerably increased recently. Bacterial cellulose is an interesting biomaterial produced as nanofibrils by Acetobacter xylinium and is a promising candidate due to its remarkable properties. New composite materials with antimicrobial properties were developed in this work, containing poly(vinyl alcohol) (PVA) as polymer matrix and ground bacterial cellulose (BC) as reinforcing fibres. Sorbic acid was used as an antimicrobial agent because it is a preservative recognised in the food industry. The materials obtained were studied using Fourier-transformed infrared spectroscopy (FTIR). The swelling rate of the composites was also measured. Release experiments of sorbic acid from the composite films into water were performed and the mass transfer phenomena were investigated using Fick’s law of diffusion. The antimicrobial effect was tested against Escherichia coli K12-MG1655. The results obtained indicated that the new biocomposite films could be promising antimicrobial food packaging materials.     

The Effect of UV-Irradiation on Poly(vinyl alcohol) Composites with Bacterial Cellulose

The development of biodegradable packaging materials, especially from renewable resources is a constant preoccupation of nowadays, because of the environmental problems caused by synthetic polymers. The combination of cellulose with other polymeric materials could be an ecologic alternative and a way to use renewable resources for food packaging. Bacterial cellulose which is produced by microbial fermentation is also a promising material which can be used not only in biomedical application, but also as food packaging material. In this research different composite films between poly(vinyl alcohol)-bacterial cellulose (PVA-BC) were obtained by casting method. The obtained films were UV irradiated for different periods of times from 1 to 10 hours, using a mercury lamp, Philips TUV-30, emitting light mainly at 254 nm. Changes in FT-IR spectra before and after UV irradiation and the modification of transparency and of the swelling characteristics of the films were observed. As it was expected the composites materials are sensitive at UV exposure.     

Silicone composites containing stabilized silver clusters or nanoparticles

Silver nanoparticles are of high importance due to their electrical, magnetic, and optical properties, as well as catalytic and biocidal activity that are superior to the bulk silver and other metals. To prepare certain devices, generally, silver is incorporated into a matrix either as preformed or in situ‐generated particles. Silver nanoparticles were generated in situ into a silicone matrix formed by cohydrolysis of the mixture of silanes, each of them having a certain role: dimethyldiethoxysilane (DMDES) as a precursor for highly flexible polydimethylsiloxane, methyltriethoxysilane (MTES) as a cross‐linker highly compatible with polydimethylsiloxane, and 3‐aminopropyltriethoxysilane as a stabilizer, since it can readily complex to silver atoms through its amine functionality. Dimethylformamide (DMF) was used as a solvent for the silver nitrate and reducing agent. The samples were investigated both in sol state and as aged coating films deposited on glass substrate. The complexation of the silver and the matrix formation were emphasized by FTIR. The size of the formed silicone particles encapsulating silver was estimated by dynamic light scattering (DLS) (about 100 nm) in sol and by AFM in film (about 90 nm). The formation of the clusters or nanoparticles depending on the ratio between the reducing and complexing agents was evidenced by UV–Vis absorption spectra. Thus, it would create conditions to stop and isolate clusters at the desired size by precise control of the experimental conditions. The composites could be used alone as antibacterial‐coating materials but also, porous silica having incorporated silver clusters with potential applicability in catalysis may result after their calcination. Copyright © 2010 John Wiley & Sons, Ltd.     

A convenient synthesis of pyrazolo[3,4‐d]pyrimidine‐4,6‐dione and pyrazolo[4,3‐d]pyrimidine‐5,7‐dione derivatives

Pyrazolo‐[3,4‐d]pyrimidine‐4,6‐diones 5 and pyrazolo[4,3‐d]pyrimidine‐5,7‐diones 7 were synthesized by Curtius rearrangement of pyrazolic mono‐esters 2 and 3 followed by hetero‐cyclization via the ureas derivatives 4 and 6 under alkaline conditions.     

Process Intensification of Emulsion Polymerization in the Continuous Taylor Reactor

Summary: Process intensification is investigated by the emulsion polymerization of styrene in the continuous Taylor reactor. The result is an increase in space time yield up to a factor 200 in comparison to a semi-batch polymerization process. This is obtained by a fast emulsion polymerization with a mean residence time, which is reduced to 60 seconds. The article presented the results of the process and the economical aspects of the Taylor reactor plant.