Terpenes solubility in water and their environmental distribution

Terpenes and terpenoids belong to the largest and most diverse class of natural products. Due to the increasing importance of their applications and the emerging perception of their impact on the environment, the available physico-chemical characterization is insufficient. In this work the water solubility of geraniol, linalool, DL-citronellol, thymol, eugenol, carvacrol and p-cymene, in the temperature range from (298.15 to 323.15) K, and at atmospheric pressure, is studied. Due to the low solubility of these compounds a novel technique was adopted for their measurements and validated using the aqueous solubility data for sparingly soluble aromatic compounds. The thermodynamic properties of solution were derived from the experimental data at infinite dilution. It is shown that the solubility of terpenes in water is an endothermic process confirming the existence of UCST phase diagrams, and only for carvacrol and eugenol is entropically driven. The experimental information is shown in a two-dimensional chemical space diagram providing indications to their probable distribution in the environment once released.Thisworkwas developed in the scope of the project CICECO - Aveiro Institute ofMaterials, POCI-01-0145-FEDER-007679, and Associate Laboratory LSRE-LCM, POCI-01-0145-FEDER-006984, both funded by FEDER under the PT2020 Partnership Agreement - Programa Operacional Competitividade e Internacionalização (POCI) - and by national funds through FCT - Fundação para a Ciência e a Tecnologia. M.A.R.M acknowledges FCT for her PhD grant (SFRH/BD/87084/2012).info:eu-repo/semantics/publishedVersio

Salt effects on the solubility of aromatic and dicarboxylic amino acids in water

The salt effect on the solubility of the amino acids l-aspartic acid, l-glutamic acid, l-tryptophan, and l-tyrosine, seldomly found in the literature, was studied at 298.2 K, in aqueous solutions of KCl and (NH4)2SO4, for salt concentrations up to 2.0 mol·kg−1. In this concentration range, both salts are salting-in agents for glutamic acid and aspartic acid, with a stronger effect induced by (NH4)2SO4. Regarding the two aromatic amino acids, a slight increase in the solubility was obtained at low salt concentrations, followed by a stronger salting-out effect, more pronounced by (NH4)2SO4 than by KCl. The relative solubility data obtained in this work were compared to literature data for other amino acids in the same electrolyte solutions to establish a relative solubility ranking connected to their structure. Finally, the solubility data were modeled using the electrolyte Perturbed-Chain Statistical Association Theory (ePC-SAFT). The modeling requires parameters for the amino acids and ions as well as melting properties of the amino acids. All these parameters and properties were obtained from previous works. To quantitatively describe the solubility of amino acids upon salt addition, binary interaction parameters (kij) between any amino acid and anions were determined, while between any amino acid and the cations were fixed to kij = 0.08. The kij parameters between amino acid and the inorganic anions show very similar values for amino acids of the same chemical class (e.g. kij between anion and amino acid with apolar side chains), which may be used to systematically reduce the number of adjustable parameters in future work.publishe

Experimental solubility and density studies on aqueous solutions ofquaternary ammonium halides, and thermodynamic modelling formelting enthalpy estimations

Aiming to extend the yet limited knowledge on phase equilibria and physical-chemical properties of quaternaryalkylammonium halides and their aqueous binary systems, the solubilities of ten salts in water were measured inthis work in the temperature range between 293.2 K and 348.2 K along with their densities. The PC-SAFT equa-tion of state was thenapplied in the description of density as well as water activity coefficients data. The model-ling results describe very satisfactorily the experimental data, and the non-associating parameters follow well-defined trends with the molecular weight of the alkylammonium halides. These parameters were applied inthe prediction of the solubility data with unsatisfactory results, with mole fraction average absolute deviation(AAD= 0.018), deteriorating with increasing alkyl chain length.However, refitting thebinaryinteraction param-eter a much better description is obtained (AAD = 0.0045). COSMO-RS was also applied for the solubility predic-tion (AAD = 0.025), with poorer results for the chloride salts. After, the melting enthalpies of the quaternaryalkylammonium halides were estimated using the PC-SAFT equation, which in spite of their uncertainty, are pos-sibly the best option to perform solid-liquid equilibrium analysis of utmost importance when designing andscreening new deep eutectic mixtures based on these compounds.publishe

Indirect assessment of the fusion properties of choline chloride from solid-liquid equilibria data

The temperature and enthalpy of fusion of choline chloride -[Ch]Cl- are not directly measurable since this compound decomposes upon melting. Yet, given the wide use of this compound in the preparation of deep eutectic solvents (DES), its thermophysical fusion properties are very important for a better understanding of these mixtures and the thermodynamic description of their solid-liquid phase diagrams. In this work, the fusion properties of choline chloride were estimated using the solubility curves of choline chloride in ten different ionic compounds, forming simple binary eutectic mixtures with quasi-ideal liquid phases. Experimental solid-liquid equilibria data for these systems -[Ch] Cl + ionic compounds- were measured, and the ideality of the systems assessed through the quantification of the activity coefficients and their comparison in each pair of binary solutions. The values estimated for the fusion properties of choline chloride are T fus,[Ch]Cl = 597 ± 7 K and Δ fus H [Ch]Cl = 4300 ± 600 J mol −1 . These were additionally checked by thermodynamic consistency tests and by the prediction of the solid-liquid curves with COSMO-RS model. The results obtained with both procedures allow us to guarantee the usefulness and robustness of the estimated data.This work was developed in the scope of the project CICECOAveiro Institute of Materials, POCI-01-0145-FEDER-007679 (Ref. FCT UID/CTM/50011/2013) and Project POCI-01-0145-FEDER- 006984 e Associate Laboratory LSRE-LCM, both funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalizaç~ao (POCI) e and by national funds through FCT - Fundaç~ao para a Ci^encia e a Tecnologia. M.A.R.M acknowledges FCT for her PhD grant (SFRH/BD/87084/2012). J.O. and L.F. thank the financing provided by the Spanish Government, Ministerio de Economia y Competitividad (MINECO), under the project CTQ2012- 37114 and the short-stay grant EEBB-I-16-11792.info:eu-repo/semantics/publishedVersio

The Role of Polyfunctionality in the Formation of [Ch]Cl-Carboxylic Acid-Based Deep Eutectic Solvents

Aiming at providing an extensive characterization of the solid−liquid equilibria (SLE) of deep eutectic solvents (DESs), the phase diagrams of nine eutectic mixtures composed of choline chloride ([Ch]Cl) and (poly)carboxylic acids, commonly reported in the literature as DESs, were measured experimentally. Contrarily to the behavior reported for eutectic mixtures composed of [Ch]Cl (hydrogen-bond acceptor, HBA) and monofunctional hydrogen-bond donors (HBD) such as fatty acids and fatty alcohols, which have recently been shown to be almost ideal mixtures, a significant decrease of the melting temperature, at the eutectic point, was observed for most of the systems studied. This melting temperature depression was attributed to a pronounced nonideality of the liquid phase induced by the strong hydrogen-bond interactions between the two mixture components. Perturbed-chain statistical associating fluid theory (PC-SAFT) was used to describe these interactions physically. PC-SAFT allowed accurately modeling the experimental phase diagrams over the entire concentration and temperature ranges. Depending on the kind of mixture, up to two temperature-independent binary interaction parameters between HBA and HBD were applied. The PC-SAFT approach was used to provide trustworthy information on the nonideality of the liquid phase (expressed as the activity coefficients of HBA and HBD) as well as to estimate the eutectic points coordinates. The experimental data along with the modeling results allowed us to infer about the importance of the HBD’s chemical structure on the formation of [Ch]Cl-based DESs.This work was developed in the scope of the project CICECO − Aveiro Institute of Materials, POCI-01-0145-FEDER- 007679 (ref. FCT UID/CTM/50011/2013) and Associate Laboratory LSRE-LCM, POCI-01-0145-FEDER-006984 (ref. FCT UID/EQU/50020/2013), both financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement. This work is also a result of project “AlProc- Mat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, with the reference NORTE-01-0145-FEDER-000006, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). M.A.R.M and E.A.C acknowledge FCT for the Ph.D. grants SFRH/BD/87084/2012 and SFRH/BD/130870/2017, respectively. FCT is also acknowledged for funding the project DeepBiorefinery (PTDC/AGRTEC/1191/2014). C.H. gratefully acknowledges financial support from the Max-Buchner Research Foundation and from German Science Foundation (DFG), grant HE 7165/7-1.info:eu-repo/semantics/publishedVersio

Characterization and Modeling of the Liquid Phase of Deep Eutectic Solvents Based on Fatty Acids/Alcohols and Choline Chloride

The solid-liquid equilibria phase diagrams of eight eutectic systems formed by choline chloride and fatty acids, or fatty alcohols, were measured to characterize the nonideality of the liquid phase of these systems, commonly reported in the literature as examples of type III deep eutectic solvents (DESs), and to evaluate the best modeling approaches to their description. Most of these systems are shown to present only slight deviations from ideal behavior, resulting from a fine balance of the hydrogen bonding between the hydroxyl/carboxylic groups with the chloride anion and the interactions present in the pure compounds. The phase diagrams measured were modeled with an associative equation of state (EoS) and a g E model. As an EoS, the perturbed-chain statistical associating fluid theory (PC-SAFT) was used, and this model was able to accurately describe the experimental data and to provide reliable estimates of the eutectic points using just a single binary temperature-dependent interaction parameter that often correlates with the acid/alcohol chain length. The performance of PC-SAFT was further compared with the g E model, a non-random two-liquid model (NRTL), and was found to provide a better description of the experimental data, especially for the more nonideal systems. Ultimately, the data gathered, and the molecular modeling, allowed the discussion of the behavior of fatty acids or fatty alcohols as hydrogen bond donors in choline chloride-based DESs.This work was developed in the scope of Projects POCI-01- 0145-FEDER-007679 - CICECO - Aveiro Institute of Materials (ref. FCT UID/CTM/50011/2013), POCI-01-0145-FEDER- 006984 - Associate Laboratory LSRE-LCM both funded by European Regional Development Fund (ERDF) through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI), and by national funds through FCT - Fundação para a Ciência e a Tecnologia. This work is also a result of project “AIProcMat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, with the reference NORTE-01-0145- FEDER-000006, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through ERDF. M.A.R.M acknowledges FCT for her Ph.D. grant (SFRH/BD/87084/2012). C.H. gratefully acknowledges financial support of Max- Buchner Research Foundation.info:eu-repo/semantics/publishedVersio

Application of PEG400 in the one-pot synthesis of 7-[4-alkyl- or (hetero) aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines via SNAr and Cu(I)- Catalyzed Azide-Alkyne Cycloaddition and preliminary evaluation of their anti-tumour activity

Several novel 7-[4-alkyl- or (hetero)aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines were prepared in good to high yields, using the environmentally friendly solvent PEG400 in a one-pot procedure from 7- chlorothieno[3,2-b]pyridine to form the corresponding azide via SNAr with NaN3, followed by Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) using different types of alkynes. This one-pot reaction in PEG400 starting from a halogenated heteroaromatic system is reported for the first time and demonstrated a wide scope of application for alkynes. Preliminary anti-tumour activity on human tumour cell lines using the prepared 1,4-di(hetero)aryl-1,2,3-triazoles was evaluated, together with their toxicity in non-tumour cells. Among the tested compounds the most promising one was a 2-ethynylpyridine derivative.Fundação para a Ciência e Tecnologia (FCT)–Portugal financially supports CQUM (UID/QUI/686/2019), CIMO-IPBragança (UID/ AGR/690/2019), the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020) also financed by European Regional Development Fund (ERDF), COMPETE2020 and Portugal2020, the PTNMR network also supported by Portugal2020 and the PhD grant of J.M.R. (SFRH/BD/115844/2016) also financed by ESF (European Social Fund) and HCOP (Human Capital Operational Programme).info:eu-repo/semantics/publishedVersio

Magnetoliposomes containing calcium ferrite nanoparticles for applications in breast cancer therapy

Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy.This research was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013; UID/FIS/04650/2019), CQUM (UID/QUI/00686/2016; UID/QUI/00686/2019) and LA-26 (PEst-C/SAU/LA0026/2013), and through the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020), financed by FCT, European Fund of Regional Development (FEDER), COMPETE2020 and Portugal2020. The magnetic measurements were supported by projects UTAP-EXPL/NTec/0046/2017, NORTE-01-0145-FEDER-028538 e PTDC/FIS-MAC/29454/2017. The APC was also funded by FCT. B.D.C. acknowledges FCT for a PhD grant (SFRH/BD/141936/2018)

Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant <it>E. coli </it>that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant <it>E. coli</it>.</p> <p>Methods</p> <p>The susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (<it>Capparis spinosa </it>L., <it>Artemisia herba-alba Asso, Echinops polyceras </it>Boiss., <it>Gundelia tournefortii </it>L, <it>Varthemia iphionoides </it>Boiss. & Blanche, <it>Eruca sativa Mill</it>., <it>Euphorbia macroclada </it>L., <it>Hypericum trequetrifolium </it>Turra, <it>Achillea santolina </it>L., <it>Mentha longifolia </it>Host, <it>Origanum syriacum </it>L., <it>Phlomis brachydo</it>(Boiss.) Zohary, <it>Teucrium polium </it>L., <it>Anagyris foetida </it>L., <it>Trigonella foenum-graecum </it>L., <it>Thea sinensis </it>L., <it>Hibiscus sabdariffa </it>L., <it>Lepidium sativum </it>L., <it>Pimpinella anisum </it>L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.</p> <p>Results</p> <p>Methanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of <it>E. coli</it>. Two edible plant extracts (<it>Gundelia tournefortii L</it>. and <it>Pimpinella anisum L</it>.) generally enhanced activity against resistant strain. Some of the plant extracts like <it>Origanum syriacum </it>L.(Labiateae), <it>Trigonella foenum- graecum </it>L.(Leguminosae), <it>Euphorbia macroclada </it>(Euphorbiaceae) and <it>Hibiscus sabdariffa </it>(Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant <it>E. coli</it>. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like <it>Anagyris foetida </it>(Leguminosae) and <it>Lepidium sativum </it>(Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia <it>tournefortii </it>L. (Compositae) <it>Eruca sativa </it>Mill. (Cruciferae), and <it>Origanum syriacum </it>L. (Labiateae), enhanced activity of clarithromycin against the resistant <it>E. coli </it>strain.</p> <p>Conclusion</p> <p>This study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by <it>E. coli </it>or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.</p