Mixtures of polymers and cholinium-based ionic liquids to tailor the phase diagrams and extraction efficiency of aqueous biphasic systems

Aqueous biphasic systems (ABS) are outstanding alternatives over conventional liquid-liquid extraction processes since it is avoided the use of volatile and hazardous organic solvents (VOCs). ABS are more biocompatible systems formed by two aqueous-rich phases that can be designed by combining different pairs of solutes (polymer-polymer, polymer-salt or salt-salt) above specific concentrations. In the past years, ABS have been studied as powerful techniques for purification, separation and extraction purposes. Ionic liquids (ILs) have been described as interesting fluids towards the development of more sustainable processes. Due to the ILs unique properties, their introduction in ABS led to systems with higher selectivity and extraction performance for a wide plethora of compounds. In fact, it was already shown that ILs allow to overcome the low hydrophilic-hydrophobic range of ABS composed of two polymers or one polymer and one inorganic salt. IL-based ABS formed with polyethylene glycol (PEG) polymers were recently introduced and a successful control of the phase polarities, through the manipulation of the IL chemical structure, was demonstrated. Lately, it was also demonstrated that a new class of natural-derived cholinium-based ILs are capable of undergoing two phase separation by the addition of PEGs with different molecular weights. In the present work, mixtures of PEGs with different molecular weights (400 and 2000 g/mol) were used to ascertain on the formation ability of ABS composed of water and cholinium-based ILs or salts. The results obtained indicate that the formation ability of these ABS increase with the content of PEG2000 over PEG400 (and follow a continuous increase), meaning that a close-fitting control on their phases polarity can be attained. These systems were then evaluated on their performance for extracting a series of alkaloids with different polarities, namely caffeine, theophylline, theobromine and nicotine. In general, the alkaloids partition extent to the most hydrophobic phase (PEG-rich) follows their polarity/hydrophobicity. In summary, it is here demonstrated that mixtures of polymers as phase-forming components of ABS allow to tailor the partition coefficients of different alkaloids and their use in the purification of added-value compounds from biomass extracts is straightforwardly foreseen.publishe

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.B.L.C., C.H., and A.M. were funded by the Cambridge Conservation Initiative’s Collaborative Fund sponsored by the Prince Albert II of Monaco Foundation. E.J.P. was supported by the Natural Environment Research Council C-CLEAR doctoral training programme (Grant no. NE/S007164/1). We are grateful to all those who assisted with the collection and curation of tracking data. Further details are provided in the Supplementary Acknowledgements. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewe

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors

Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors

Biochemical and computational insights into the anti-aromatase activity of natural catechol estrogens

High levels of endogenous estrogens are associated with increased risks of breast cancer. Estrogen levels are mainly increased by the activity of the aromatase enzyme and reduced by oxidative/conjugative metabolic pathways. In this paper, we demonstrate for the first time that catechol estrogen metabolites are potent aromatase inhibitors, thus establishing a link between aromatase activity and the processes involved in estrogen metabolism. In particular, the anti-aromatase activity of a set of natural hydroxyl and methoxyl estrogen metabolites was investigated using biochemical methods and subsequently compared with the anti-aromatase potency of estradiol and two reference aromatase inhibitors. Catechol estrogens proved to be strong inhibitors with an anti-aromatase potency two orders of magnitude higher than estradiol. A competitive inhibition mechanism was found for the most potent molecule, 2-hydroxyestradiol (2-OHE2) and a rational model identifying the interaction determinants of the metabolites with the enzyme is proposed based on ab initio quantum-mechanical calculations. A strong relationship between activity and electrostatic properties was found for catechol estrogens. Moreover, our results suggest that natural catechol estrogens may be involved in the control mechanisms of estrogen production.http://www.sciencedirect.com/science/article/B6T8X-4RW435B-1/1/e10135327f6ef1e2c98b343e9e9b8f2

An efficient steroid pharmacophore-based strategy to identify new aromatase inhibitors

Aromatase, an enzyme involved in the conversion of androgens into estrogens, is an important target for the endocrine treatment of breast cancer. Aromatase inhibition is usually achieved with steroids structurally related to the substrate of catalysis or, alternatively, with azole non-steroid compounds. Substituted androstenedione derivatives with Delta(1), Delta(6) and Delta(1,6) unsaturations and 6-alkyl/6-phenyl aliphatic substitutions, are among the most potent steroid aromatase inhibitors known to date. In this paper we have combined the common pharmacophoric and shape features of these molecules into a new pharmacophore model, useful for virtual screening of large compound databases. Small subsets of the best fitting anti-aromatase candidates were extracted from the NCI database and experimentally tested on an in vitro assay with human placental aromatase. New potent aromatase inhibitors were identified such as compounds 8 and 14. Considering the lack of a crystal structure for the aromatase enzyme, this ligand-based method is a valuable tool for the virtual screening of new aromatase inhibitors. (C) 2009 Elsevier Masson SAS. All rights reserved

Aqueous biphasic systems formed by cholinium-based ionic liquids and mixtures of polymers

In the past years, the relevance of introducing ionic liquids (ILs) has been shown as phase-forming components of aqueous biphasic systems (ABS), which allow the tailoring of polarity differences between the coexisting phases. Although investigations on the IL chemical structure and polymermolecularweight have been carried out, the use of mixtures of polymers can also be seen as a way of tailoring their two-phase formation ability and separation performance, which was not attempted earlier. In this work, we investigate novel ABS composed of cholinium-based ILs and mixtures of polymers, namely polyethylene glycol (PEG) of 400 and 2,000 g·mol-1, at differentmole fractions, as a way of tailoring the formation of ABS and their separation performance. The respective liquid-liquid phase diagrams were determined, and their ability to separate a set of alkaloids (caffeine, theophylline and theobromine) appraised. An increase on the PEG 2000mole fraction favors the formation of ABS. However, this does not follow a monotonous trend, where mole fractions of PEG 400 up to 0.3 do not display significant impact on the two-phase separation capability. Among the studied alkaloids, nicotine preferentially partitions to the IL-rich phase, while the remaining alkaloids majorly partition to the polymer-rich phase. Different selectivity patterns were verified, depending on the cholinium-based IL used and water content at the IL-rich phase. Overall, by using mixtures of polymers it is possible to decrease the viscosity of the coexisting phases and their toxicity impact, without losing their formation and separation capacities, by the addition of PEGs of lower molecular weight.publishe