Solvent Dynamics and Thermodynamics at the Crystal-Solution Interface of Ibuprofen

The choice of solvent is key in the manufacturing of solution-grown crystals due to the critical effect it can exert on their morphology. Here we set out to investigate the dynamics and thermodynamics of solvent molecules at the crystal-solution interface for the morphologically dominant crystal faces of ibuprofen. In particular, we evaluate how thermodynamically favourable the desorption of a solvent molecule is and estimate the rate of exchange of adsorbed solvent molecules with molecules from the bulk solution. This analysis is carried out for all four morphologically dominant crystal faces of ibuprofen {100}, {002}, {011} and {110}, and ten solvents, i.e. water, 1-butanol, toluene, cyclohexanone, cyclohexane, acetonitrile, trichloromethane, methanol, ethyl acetate and ethanol. Our work reveals that the structure of the solution and the exchange dynamics can be strongly dependent on both the crystal face and the solvent, i.e. the same solvent can show radically different structure when in contact with different faces, alternatively the same face can induce different structuring in different solvents. Moreover, we find particularly strong surface-solvent interactions for the {002} and {100} crystal faces in several of the solvents examined. We conclude that the role of desolvation in the growth process is solvent- and face-specific, and therefore it has the potential of impacting the crystal shape anisotropy. We provide a framework to rationalise this effect based on molecular simulations of the crystal/solution interface

Carbonatite Melts and Electrical Conductivity in the Asthenosphere

Electrically conductive regions in the Earth mantle have been interpreted to reflect the presence of either silicate melt or water dissolved in olivine. On the basis of laboratory measurements we show that molten carbonates have electrical conductivities that are 3 orders of magnitude higher than those of molten silicate and 5 orders of magnitude higher than those of hydrated olivine. High conductivities in the asthenosphere probably indicate the presence of small amounts of carbonate melt in peridotite and can therefore be interpreted in terms of carbon concentration in the upper mantle. We show that the conductivity of the Oceanic asthenosphere can be explained by 0.1 volume % of carbonatite melts on average, which agrees with the CO2 content of Mid Ocean Ridge Basalts

Role of non-mantle CO2 in the dynamics of volcano degassing: The Mount Vesuvius example

International audienceMount Vesuvius, Italy, quiescent since A. D. 1944, is a dangerous volcano currently characterized by elevated CO2 emissions of debated origin. We show that such emissions are most likely the surface manifestation of the deep intrusion of alkalic-basaltic magma into the sedimentary carbonate basement, accompanied by sidewall assimilation and CO2 volatilization. During the last eruptive period (1631-1944), the carbonate-sourced CO2 made up 4.7-5.3 wt% of the vented magma. On a yearly basis, the resulting CO2 production rate is comparable to CO2 emissions currently measured in the volcanic area. The chemical and isotopic composition of the fumaroles supports the predominance of this crust-derived CO2 in volatile emissions at Mount Vesuvius

Melt inclusions track changes in chemistry and oxidation state of Etnean magmas

Mount Etna (Italy) is a stratovolcano, located near the convergent boundary between African and European plates. Since its appearance, it was characterized by continuous variability of eruptive style and magma composition, though more subtle. Currently, its volcanic activity consists of effusive and explosive eruptions marked by high gas fluxes. Olivine hosted melt inclusions (MIs), belonging to products of the last 15 ky, were analysed for their chemical composition, volatiles contents and Fe speciation, in order to interpret the chemical variability and to evaluate the oxidation state of Etnean magmas and its eventual evolution. Olivine phenocrysts were selected from the most primitive Fall Stratified (FS) eruption of picritic composition (Fo91), from the oldest Mt. Spagnolo and from more recent eruptions: 2002-2003, 2006, 2008-2009, and 2013; the MIs of some of these eruptions (Mt Spagnolo, 2008-2009 and 2013) are here investigated for the first time. The variability of the major elements contents in the MIs designates a continuous differentiation trend, marked by the decrease of MgO and CaO/Al2O3 ratio and the increase of alkalis. The volatiles content in etnean magmas is extremely variable. The highest H2O (5-6 wt.%) and CO2 (~0.5 wt.%) contents are found in FS magma entrapped at depth of 16-18 km (below crater level). S content achieves 4150 ppm in the older Mt. Spagnolo inclusions, completely H2O and CO2\u2013free. Fe3+/\u3a3Fe ratios obtained from XANES spectra for some melt inclusions, generally decrease from the most primitive and volatile-rich FS to the most evolved and degassed melts, suggesting changing in the oxidation state of etnean magmas. Petrological arguments coupled to modelling of fractional crystallization and degassing processes concur to suggest that the magmas of Mt. Spagnolo and of the recent eruptions may be produced by differentiation from the most oxidized and hydrous pristine FS magma along highly variable P-T paths, occasionally accompanied by mixing processes

A structured approach to cope with impurities during industrial crystallization development

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development

Investigating the role of solvent in the formation of vacancies on ibuprofen crystal facets

Surface defects play a crucial role in the process of crystal growth, as incorporation of growth units generally takes place on undercoordinated sites on the growing crystal facet. In this work, we use molecular simulations to obtain information on the role of the solvent in the roughening of three morphologically relevant crystal faces of form I of racemic ibuprofen. To this aim, we devise a computational strategy to evaluate the energetic cost associated with the formation of a surface vacancy for a set of ten solvents, covering a range of polarities and hydrogen bonding propensities. We find that the mechanism as well as the work of defect formation are markedly solvent and facet dependent. Based on Mean Force Integration and Well Tempered Metadynamics, the methodology developed in this work has been designed with the aim of capturing solvent effects at the atomistic scale while maintaining the computational efficiency necessary for implementation in high-throughput in-silico screenings of crystallization solvents

Organocatalyzed Beckmann rearrangement of cyclohexanone oxime by trifluoroacetic acid in aprotic solvent

The Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam catalyzed by trifluoroacetic acid in aprotic solvents such as toluene, 1,2-dichloroethane, acetonitrile, benzonitrile, nitromethane and their mixtures is described. High yield and selectivity in ε-caprolactam have been observed. Data relative to cyclohexanone oxime protonation equilibrium, interaction of ε-caprolactam with the acid, solvent effect on reaction kinetics and apparent activation energy are given together with some thoughts on the reaction mechanism

Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway

γ-Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2O2-) induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h. ORY pretreatment also enhanced the activity of antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). Interestingly, ORY induced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and upregulation of Nrf2-dependent defensive genes such as NAD(P)H quinone reductase (NQO1), heme oxygenase-1 (HO-1), and glutathione synthetase (GSS) at mRNA and protein levels in both basal condition and after H2O2 insult. Thus, this study suggested an intriguing effect of ORY in modulating the Nrf2 pathway, which is also involved in regulating longevity as well as age-related diseases

Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021

Background. Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.Methods. We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.Results. The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.Conclusion. We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility