Excess Thermodynamics of Mixtures Involving Xenon and Light Linear Alkanes by Computer Simulation

Excess molar enthalpies and excess molar volumes as a function of composition for liquid mixtures of xenon + ethane (at 161.40 K), xenon + propane (at 161.40 K) and xenon + n-butane (at 182.34 K) have been obtained by Monte Carlo computer simulations and compared with available experimental data. Simulation conditions were chosen to closely match those of the corresponding experimental results. The TraPPE-UA force field was selected among other force fields to model all the alkanes studied, whereas the one-center Lennard−Jones potential from Bohn et al. was used for xenon. The calculated and for all systems are negative, increasing in magnitude as the alkane chain length increases. The results for these systems were compared with experimental data and with other theoretical calculations using the SAFT approach. An excellent agreement between simulation and experimental results was found for xenon + ethane system, whereas for the remaining two systems, some deviations that become progressively more significant as the alkane chain length increases were observed

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

Following a recent experimental investigation of the effect of the length of the alkyl side chain in a series of cholesterol analogues (Angew. Chem., Int. Ed., 2013, 52, 12848–12851), we report here an atomistic molecular dynamics characterization of the behaviour of methyl-branched side chain sterols (iso series) in POPC bilayers. The studied sterols included androstenol (i-C0-sterol) and cholesterol (i-C8-sterol), as well as four other derivatives (i-C5, i-C10, i-C12 and i-C14-sterol). For each sterol, both subtle local effects and more substantial differential alterations of membrane properties along the iso series were investigated. The location and orientation of the tetracyclic ring system is almost identical in all compounds. Among all the studied sterols, cholesterol is the sterol that presents the best matching with the hydrophobic length of POPC acyl chains, whereas longer-chained sterols interdigitate into the opposing membrane leaflet. In accordance with the experimental observations, a maximal ordering effect is observed for intermediate sterol chain length (i-C5, cholesterol, i-C10). Only for these sterols a preferential interaction with the saturated sn-1 chain of POPC (compared to the unsaturated sn-2 chain) was observed, but not for either shorter or longer-chained derivatives. This work highlights the importance of the sterol alkyl chain in the modulation of membrane properties and lateral organization in biological membranes

Conformational landscape and low lying excited states of imatinib

Abstract The conformational changes of imatinib (IMT) are crucial for understanding the ligand–receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848–853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8 kcal mol−1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMTand in the c- Abl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine–pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket. The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann populationaveraged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers

Acetonitrile adducts of tranexamic acid as sensitive ions for quantification at residue levels in human plasma by UHPLC-MS/MS

The quantitative analysis of pharmaceuticals in biomatrices by liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is often hampered by adduct formation. The use of the molecular ion resulting from solvent adducts for quantification is uncommon, even if formed in high abundance. In this work, we propose the use of a protonated acetonitrile adduct for the quantitative analysis of tranexamic acid (TXA) by LC-MS/MS. The high abundance of the protonated acetonitrile adduct [M + ACN + H]+ was found to be independent of source-dependent parameters and mobile phase composition. The results obtained for TXA analysis in clinical samples were comparable for both [M + ACN + H]+ and [M + H]+ , and no statistically significant differences were observed. The relative stability and structure of the [M + ACN + H]+ ions were also studied by analyzing probable structures from an energetic point of view and by quantum chemical calculations. These findings, and the studied fragmentation pathways, allowed the definition of an acetimidium structure as the best ion to describe the observed acetonitrile protonated adduct of TXA.info:eu-repo/semantics/publishedVersio

Gaining insight into the photophysical properties of a coumarin STP ester with potential for bioconjugation.

The photophysical properties of coumarin 392 4-sulfotetrafluorophenyl ester, C392STP (sodium (E/Z)-4-(4-(2-(6,7-dimethoxycoumarin-3-yl)vinyl)-benzoyl)-2,3,5,6-tetrafluoro-benzenesulfonate) an amine reactive coumarine with potential for bioconjungation, have been studied in different solvents. Strong red shifts (31 to 56 nm on going from dioxane to DMSO and PBS, respectively) were observed in the emission spectra by increasing the solvent polarity while the absorption spectra remain slightly changed. It was found that in addition to non specific solute-solvent interactions, in protic solvents specific interactions such as hydrogen-bonding occur. The photophysical behaviour of coumarin also pointed out to an increase of the polarity of the molecule upon excitation. The molar absorption coefficient, ε385 = 1.03 ˑ 104 M-1cm-1 and brigtness, ε x Φ = 1.18 ˑ 103 M-1cm-1, of the coumarin ester were found to be moderate in PBS even if the fluorescence quantum yield (Φ = 0.115) was found to be relatively low. The large stokes shifts (Δλ = λem-λ abs were found to increase from 74 nm in dioxane to 136 nm in PBS), the photostability and pH insensitivity are characteristics that turn C392STP, into a promising fluorescent dye with potential applications in different fields.This work was co-financed by FCT – Fundação para a Ciência e a Tecnologia through the project "MICROTECH-ART- Microorganisms Thriving on and Endamaging Cultural Heritage -an Analytical Rapid Tool-" (PTDC/BBB-IMG/0046/2014) and by European Union, European Regional Development Fund ALENTEJO 2020 through the project “MEDUSA-Microrganisms Monitoring and Mitigation–Developing and Unlocking novel Sustainable Approaches-“(ALT20-03-0145-FEDER-000015). Marina González-Pérez and Sérgio Martins acknowledge FCT for the economic support through the post-doctoral and doctoral grants SFRH/BPD/100754/2014 and SFRH/BD/128807/2017, respectively

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study

A complete homologous series of fluorescent phosphatidylethanolamines (diCnPE), labelled at the head group with a 7-nitrobenz-2-oxa-1,3-diazo-4-yl(NBD) fluorophore and inserted in 1-palmitoyl, 2-oleoyl-snglycero- 3-phosphocholine (POPC) bilayers, was studied using atomistic molecular dynamics simulations. The longer-chained derivatives of NBD-diCnPE, with n = 14, 16, and 18, are commercially available, and widely used as fluorescent membrane probes. Properties such as location of atomic groups and acyl chain order parameters of both POPC and NBD-diCnPE, fluorophore orientation and hydrogen bonding, membrane electrostatic potential and lateral diffusion were calculated for all derivatives in the series. Most of these probes induce local disordering of POPC acyl chains, which is on the whole counterbalanced by ordering resulting from binding of sodium ions to lipid carbonyl/glycerol oxygen atoms. An exception is found for NBD-diC16PE, which displays optimal matching with POPC acyl chain length and induces a slight local ordering of phospholipid acyl chains. Compared to previously studied fatty amines, acyl chain-labelled phosphatidylcholines, and sterols bearing the same fluorescent tag, the chromophore in NBD-diCnPE locates in a similar region of the membrane (near the glycerol backbone/carbonyl region) but adopts a different orientation (with the NO2 group facing the interior of the bilayer). This modification leads to an inverted orientation of the P–N axis in the labelled lipid, which affects the interface properties, such as the membrane electrostatic potential and hydrogen bonding to lipid head group atoms. The implications of this study for the interpretation of the photophysical properties of NBD-diCnPE (complex fluorescence emission kinetics, differences with other NBD lipid probes) are discussed

Prediction of diffusion coefficients of chlorophenols in water by computer simulation

Intra-diffusion coefficients of seven chlorophenols (2-chlorophenol, 3-chlorophenol, 4-chlorophenol, 2,4-dichlorophenol, 2,6-dichlorophenol, 2,4,6-dichlorophenol and pentachlorophenol) in water were determined by computer simulation (molecular dynamics) for dilute solutions at three different temperatures and the corresponding mutual diffusion coefficients estimated. The mutual diffusion coefficients of 2-chlorophenol in water agree with the available experimental results from the literature for all the temperatures studied. From the dependence of the diffusion coefficients on temperature, diffusion activation energies were estimated for all the solutes inwater. Analyzing the radial distribution functions and spatial distribution functions of water around chlorophenols sites enable a discussion about intermolecular interactions (dominated by hydrogen bonding) between solute and solvent and its importance on the relative magnitude of diffusion coefficients. Finally the mutual diffusion coefficients obtained by simulation were correlated by the well-known Wilke–Chang equation

Fluorinated surfactants in solution: Diffusion coefficients of fluorinated alcohols in water

Intra-diffusion coefficients of three fluorinated alcohols, 2,2,3,3,3-pentafluoropropan-1-ol (PFP), 2,2,3,3,4,4,4-heptafluorobutan-1-ol (HFB) and 2,2,3,3,4,4,5,5,5-nonafluoropentan-1-ol (NFP) in water have been measured by the PFG–NMR spin-echo technique as a function of temperature and composition, focusing on the alcohol dilute region. For comparison, intra-diffusion coefficients of 2,2,2- trifluoroethanol (TFE) and HFB have also been measured in heavy water using the same method and conditions. As far as we know, these are the first experimental measurements of this property for these binary systems. Intra-diffusion coefficients for NFP in water and for TFE and HFB in heavy water have also been obtained by molecular dynamics simulation, complementing those for TFE, PFP and HFB reported in a previous work. The agreement between experimental and simulated results for PFP, HFB and NFP in water is reasonable, although presenting higher deviations than for the TFE/water system. From the dependence of the intra-diffusion coefficients on temperature, diffusion activation energies were estimated for all the solutes in water and heavy water

Avaliação de propriedades estruturais de membranas lipídicas após substituição do colesterol por análogos fluorescentes

A espectroscopia e a microscopia de fluorescência têm sido usadas em biofísica de membranas há décadas. Como a unidade estrutural básica das membranas biológicas é a bicamada de lípidos e estes não fluorescem, o uso de sondas extrínsecas de membrana é uma necessidade. Contudo, duas questões preocupantes se levantam quanto ao uso de sondas extrínsecas de fluorescência em estudos de membranas. Em primeiro lugar, o comportamento das moléculas de sonda na bicamada (que região da bicamada elas reportam, as suas dinâmicas translacional e rotacional) é frequentemente mal conhecido. Em segundo lugar, na interpretação de resultados de experiências de fluorescência, pode ser difícil distinguir entre propriedades legítimas da membrana e efeitos de perturbação resultantes da incorporação da sonda. Para este efeito, as simulações por dinâmica molecular (MD), ao providenciarem informação detalhada à escala atómica, representam um meio valioso para caracterizar a localização e dinâmica de sondas na bicamada, assim como a magnitude de perturbação que elas induzem na estrutura lipídica [1]. Neste contexto, optimizaram-se, com recurso ao programa Firefly, as estruturas do colesterol e de dois análogos fluorescentes (desidroergoesterol e colestatrienol) ao nível de teoria DFT/R-B3LYP/6-31G(d) e submeteram-se em seguida ao servidor de topologias ATB, inscrevendo simultaneamente as cargas parciais calculadas na topologia molecular. Estas topologias foram utilizadas na construção de modelos de membranas lipídicas constituídas por POPC, colesterol e uma das sondas fluorescentes acima identificadas. Os modelos assim obtidos foram hidratados e sujeitos a simulações de MD, donde se calculou a área por lípido, a espessura e densidade da bicamada, os coeficientes de difusão lateral para as espécies presentes e os parâmetros de ordem das cadeias acilo. As simulações foram efectuadas em ensemble NPT através do pacote de software GROMACS. Análises preliminares permitiram a comparação dos comportamentos na bicamada dos esteróis fluorescentes com o do colesterol, informação vital para validar o uso dos primeiros como análogos fluorescentes do segundo. REFERÊNCIAS [1] Loura, L.M.S.; Prates Ramalho, J.P. Biophys. Rev. 1 (2009), 141

Ambipolar Pentacyclic Diamides with Interesting Electrochemical and Optoelectronic Properties

Developing organic semiconductors (OSCs) for organic thin film transistors (OTFT) and optoelectronic applications is a challenge. We developed highly crystalline pentacyclic diamides (3) and (4) which showed good OTFT and OLED potential and energy gaps of 2.60 eV and 2.54 eV. They exhibited interesting photo and eletroluminescence activity. Both compounds showed good quantum yields (0.56 for (3) and 0.6 for (4))