Insights into the Limitations of Parameter Transferability in Heteronuclear SAFT-type Equations of State

The use of heteronuclear models are often viewed as ways to improve the predictive ability and parameter transferability of advanced association models, such as those derived from the Statistical Associating Fluid Theory (SAFT). Indeed, several results in the literature have suggested that this approach can be useful to accurately describe a given family/series of homologous compounds and their mixtures, with accuracies competitive (and in some cases better) than those obtained using the more traditional SAFT variants. However, the parameter transferability of the different groups, i.e. between different families of compounds, without the introduction of new groups or refitting existing ones, is seldom reported, and often overlooked, making an accurate evaluation of the heteronuclear models difficult. This work analyzes whether the increased complexity of a heteronuclear treatment of a SAFT-type EoS, namely the SAFT-{\gamma}-Mie EoS, results in a significant increase on both the predictive ability and parameter transferability of the model, across different families of compounds. This is done by using a case study involving some different (yet related) families of compounds, containing a small number of common functional groups. The results obtained show that the transferability of group parameters, across different families of compounds, in a heteronuclear SAFT-type EoS does not allow an adequate description of the phase equilibria of these systems. Therefore, to achieve a reasonable accuracy in the description of these systems, a specific refitting of group parameters is required for a given family, or even for a particular system, destroying the predictive capability of these models. Moreover, this increases the number of adjustable parameters to numbers similar to those used in homonuclear approaches, further reducing the advantages of using heteronuclear models

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

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

Thermodynamic characterization of deep eutectic solvents at high pressures

Despite the large spectrum of applications being reported for DESs over the last decade, their thermodynamic characterization is often neglected, hindering a better understanding of their nature, and the development of accurate and robust thermodynamic models to describe them, essential for the conceptual and design stages of new industrial processes. This work aims at decreasing such a gap in literature by reporting new experimental density and viscosity data in wide temperature and pressure ranges for the three archetypal DESs of cholinium chloride, as hydrogen bond acceptor, combined with either ethylene glycol, glycerol, or urea, as hydrogen bond donor. The experimental data measured in this work were then correlated using the Perturbed Chain - Statistical Associating Fluid Theory equation of state coupled with the Free Volume Theory to assess the performance of existing coarse-grained models when applied to the description of DESs. The modelling results obtained highlight the limitation of the existing models, since a correct prediction of DES density could not be achieved, reinforcing the need for viable alternative approaches for the development of coarse-grained models that are appropriate for the thermodynamic modelling of DESs.publishe

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

Measurement and PC-SAFT modeling of solid-liquid equilibrium of deep eutectic solvents of quaternary ammonium chlorides and carboxylic acids

In this study the solid-liquid equilibria (SLE) of 15 binary mixtures composed of one of three different symmetrical quaternary ammonium chlorides and one of five different fatty acids were measured. The experimental data obtained showed extreme negative deviations to ideality causing large melting-temperature depressions (up to 300 K) that are characteristic for deep eutectic systems. The experimental data revealed that cross-interactions between quaternary ammonium salt and fatty acid increase with increasing alkyl chain length of the quaternary ammonium chloride and with increasing chain length of the carboxylic acid. The pronounced decrease of melting temperatures in these deep eutectic systems is mainly caused by strong hydrogen-bonding interactions, and thermodynamic modeling required an approach that takes hydrogen bonding into account. Thus, the measured phase diagrams were modeled with perturbed-chain statistical associating fluid theory based on the classical molecular homonuclear approach. The model showed very good agreement with the experimental data using a semi-predictive modeling approach, in which binary interaction parameters between quaternary ammonium chloride and carboxylic acid correlated with chain length of the components. This supports the experimental findings on the phase behavior and interactions present in these systems and it allows estimating eutectic points of such highly non-ideal mixtures.This work was developed in the scope of the project CICECO e Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (Ref. FCT UID/CTM/50011/2013) and LSRE-LCM, POCI-01-0145- FEDER-006984jUID/EQU/50020/2013, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. M.A.R.M acknowledges FCT for her PhD grant (SFRH/BD/87084/2012). FCT is also acknowledged for funding the project DeepBiorefinery (PTDC/AGRTEC/ 1191/2014). P.V.A.P., G.J.M., M.D.H. and E.A.C.B thank the national funding agencies CNPq (National Council for Scientific and Technological Development) (305870/2014-9, 309780/2014, 406856/2013-3), FAPESP (Research Support Foundation of the State of S~ao Paulo) (2014/21252-0, 2016/08566-1), FAEPEX/UNICAMP (Fund for Research, Teaching, and Extension) (0125/16) and CAPES (Coordination of Improvement of Higher Level Personnel) for financial support and scholarships. E.A.C thanks Erasmusþ program of the European Union for co-funding.info:eu-repo/semantics/publishedVersio

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article