Computational study of radicals derived from hydroxyurea and its methylated analogues.

Structural and electronic properties and chemical fate of free radicals generated from hydroxyurea (HU) and its methylated analogues N-methylhydroxyurea (NMHU) and O-methylhydroxyurea (OMHU) are of utmost importance for their biological and pharmacological effects. In this work the cis/trans conformational processes, tautomerizations, and intramolecular hydrogen and methyl migrations in hydroxyurea-derived radicals have been considered. Potential energy profiles for these reactions have been calculated using two DFT functionals (BP86 and B3LYP) and two composite models (G3(MP2)RAD and G3B3). Solvation effects have been included both implicitly (CPCM) and explicitly. It has been shown that calculated energy barriers for free radical rearrangements are significantly reduced when a single water molecule is included in calculations. In the case of HU-derived open-shell species, a number of oxygen-, nitrogen-, and carbon-centered radicals have been located, but only the O-centered radicals (e1 and z1) fit to experimental isomeric hyperfine coupling constants (hfccs) from EPR spectra. The reduction of NMHU and OMHU produces O-centered and N-centered radicals, respectively, with the former being more stable by ca. 60 kJ mol−1. The NMHU-derived radical e4 undergoes rearrangements, which can result in formation of several conceivable products. The calculated hfccs have been successfully used to interpret the experimental EPR spectra of the most probable rearranged product 10. Reduction potentials of hydroxyureas, radical stabilization energy (RSE) and bond disocciation energy (BDE) values have been calculated to compare stabilities and reactivities of different subclasses of free radicals. It has been concluded, in agreement with experiment, that reductions of biologically relevant tyrosyl radicals by HU and NMHU are thermochemically favorable processes, and that the order of reactivity of hydroxyureas follows the experimentally observed trend NMHU > HU > OMHU

Base-catalyzed reactions of environmentally relevant N-chloro-piperidines. A quantum-chemical study

Electronic structure methods have been applied to calculate the gas and aqueous phase reaction energies for base-induced rearrangements of N-chloropiperidine, N-chloro-3-(hydroxymethyl)piperidine, and N-chloro-4-4-fluorophenyl)-3-(hydroxymethyl)piperidine. These derivatives have been selected as representative models for studying the chemical fate of environmentally relevant chloramines. The performance of different computational methods (MP2, MP4, QCISD, B3LYP and B2PLYP) for calculating the thermochemistry of rearrangement reactions was assessed. The latter method produces energies similar to those obtained at G3B3(+) level, which themselves have been tested against experimental results. Experimental energy barriers and enthalpies for ring inversion, nitrogen inversion and dehydrochlorination reactions in -chloropiperidine have been accurately reproduced when solvent effects have been included. It was also found that the combined use of continuum solvation models (e.g. CPCM) and explicit consideration of a single water molecule is sufficient to properly describe the water-assisted rearrangement of N-chlorinated compounds in basic media. In the case of N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine, which represents the chlorinated metabolite of the antidepressant paroxetine, several different reactions (intramolecular addition, substitution, and elimination reactions) have been investigated. Transition state structures for these processes have been located together with minimum energy structures of conceivable products. Imine 4A is predicted to be the most stable reaction product, closely followed by imine 4B and oxazinane 8, while formation of isoxazolidine 7 is much less favourable. Calculated reaction barriers in aqueous solution are quite similar for all four processes, the lowest barrier being predicted for the formation of imine 4A

An Extended Model for Multi-Criteria Software Component Allocation on a Heterogeneous Embedded Platform

A recent development of heterogeneous platforms (i.e. those containing different types of computational units such as multicore CPUs, GPUs, and FPGAs) has enabled significant improvements in performance for real-time data processing. This potential, however, is still not fully utilized due to the lack of methods for optimal configuration of software; the allocation of different software components to different computational unit types is crucial for getting the maximal utilization of the platform, but for more complex systems it is difficult to find ad-hoc a good enough or the best configuration. With respect to system and user defined constraints, in this paper we are applying analytical hierarchical process and a genetic algorithm to find feasible, locally optimal solution for allocating software components to computational units

Fate and transformation of silver nanoparticles in different biological conditions

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Colloidal stability, biochemical transformation, dissolution, and degradation behaviour of different types of AgNPs were evaluated in systems modelled to represent biological environments relevant for oral administration, as well as in cell culture media and tissue compartments obtained from animal models. A multimethod approach was employed by implementing light scattering (dynamic and electrophoretic) techniques, spectroscopy (UV-vis, atomic absorption, nuclear magnetic resonance) and transmission electron microscopy. The obtained results demonstrated that AgNPs may transform very quickly during their journey through different biological conditions. They are able to degrade to an ionic form and again reconstruct to a nanoparticulate form, depending on the biological environment determined by specific body compartments. As suggested for other inorganic nanoparticles by other research groups, AgNPs fail to preserve their specific integrity in in vivo settings

The chemical fate of paroxetine metabolites. Dehydration of radicals derived from 4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine

Quantum chemical calculations have been used to model reactions which are important for understanding the chemical fate of paroxetine-derived radicals in the environment. In order to explain the experimental observation that the loss of water occurs along the (photo)degradation pathway, four different mechanisms of radical-induced dehydrations have been considered. The elimination of water from the N-centered radical cation, which results in the formation of an imine intermediate, has been calculated as the most feasible process. The predicted energy barrier (Delta G(298)(#) = 98.5 kJ mol(-1)) is within the barrier limits set by experimental measurements. All reaction intermediates and transition state structures have been calculated using the G3(MP2)-RAD composite procedure, and solvent effects have been determined using a mixed (cluster/continuum) solvation model. Several new products, which comply with the available experimental data, have been proposed. These structures could be relevant for the chemical fate of antidepressant paroxetine, but also for biologically and environmentally related substrates

The chemical fate of paroxetine metabolites. Dehydration of radicals derived from 4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine

Quantum chemical calculations have been used to model reactions which are important for understanding the chemical fate of paroxetine-derived radicals in the environment. In order to explain the experimental observation that the loss of water occurs along the (photo)degradation pathway, four different mechanisms of radical-induced dehydrations have been considered. The elimination of water from the N-centered radical cation, which results in the formation of an imine intermediate, has been calculated as the most feasible process. The predicted energy barrier (Delta G(298)(#) = 98.5 kJ mol(-1)) is within the barrier limits set by experimental measurements. All reaction intermediates and transition state structures have been calculated using the G3(MP2)-RAD composite procedure, and solvent effects have been determined using a mixed (cluster/continuum) solvation model. Several new products, which comply with the available experimental data, have been proposed. These structures could be relevant for the chemical fate of antidepressant paroxetine, but also for biologically and environmentally related substrates

Efecto del injerto en las propiedades antioxidantes del tomate (Solanum lycopersicum L.)

The use of grafted plants in vegetable crop production is now being expanded greatly. However, few data are available on the nutritional composition of grafted vegetables with emphasis on antioxidant properties. Therefore, the major objective of this study was to evaluate antioxidant components of tomatoes influenced by grafting technique. The tomato plants were grown in a greenhouse located at Kriz˘evci, Croatia. The cultivars ‘Efialto’, ‘Heman’, and ‘Maxifort’ were used as rootstocks, while ‘Tamaris’ was used as scion. Grafting resulted in increase of number of marketable fruits per plant by 30%. Content of total vitamin C and total phenolics significantly decreased after grafting. The concentration of total extractable phenolics in tomatoes ranged from 287.1 to 977.4 mg gallic acid equivalents (GAE) kg–1 fresh weight, whereas lycopene content ranged from 11.44 to 60.99 mg kg–1 fresh weight. Antioxidant activities determined by 1,1-diphenyl-2 picrylhydrazyl (DPPH) method of grafts were significantly different compared to their respective rootstocks. The overall results showed that tomato grafting on suitable rootstocks has positive effects on the cultivation performance, but decreases nutritional quality of tomatoes. En la producción de cultivos hortícolas se está expandiendo actualmente de forma considerable el uso de plantas injertadas. Sin embargo, hay pocos datos disponibles sobre la composición nutricional de las hortícolas injertadas, especialmente sobre sus propiedades antioxidantes. El principal objetivo de este estudio fue evaluar los componentes antioxidantes de tomates influenciados por la técnica de injerto. Se cultivaron plantas de tomate en un invernadero de Kriz˘evcii, Croacia. Se utilizaron como portainjertos los cultivares ‘Efialto’, ‘Heman’, y ‘Maxifort’, mientras que ‘Tamaris’ fue utilizado como injerto. El resultado del injerto fue un aumento del 30% en el número de frutos comerciales por planta, mientras que el contenido de vitamina C y de fenoles totales disminuyó significativamente. La concentración del total de fenoles extraíbles en los tomates varió entre 287,1 y 977,4 mg de equivalentes de ácido gálico (GAE) por kilo sobre la base de peso fresco, mientras que el contenido de licopeno varió desde 11,44 hasta 60,99 mg kg–1 de peso fresco. Las actividades antioxidantes determinadas por el método DPPH (2,2-difenil-1-picrilhidrazilo) de los injertos fueron significativamente diferentes respecto de sus respectivos patrones. Los resultados globales muestran que el injerto de tomate sobre patrones adecuados tiene efectos positivos sobre el rendimiento de cultivo, pero la calidad nutricional de los frutos disminuye

Host-Catalyzed Cyclodehydration–Rearrangement Cascade Reaction of Unsaturated Tertiary Alcohols

The Brønsted acidic resorcin[4]arene hexamer can be applied as an effective catalyst in the dehydrative cyclization and subsequent rearrangement of unsaturated tertiary alcohols. This is the first report on catalyzing such a reaction with a Brønsted acid. Scope and limitations of this cyclopentene-forming reaction sequence are presented. Furthermore, substrate-selective conversion as well as competitive inhibition are described and provide evidence that the reactions proceed within the cavity of the self-assembled structure. Additionally, a cyclobutanone-forming intramolecular hydride transfer of an encapsulated cyclopropyl acetate is reported

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally