In situ dsDNA-bevacizumab anticancer monoclonal antibody interaction electrochemical evaluation.

The interaction of the anticancer monoclonal antibody bevacizumab (BEVA) with double-stranded DNA (dsDNA) was studied by voltammetry and gel-electrophoresis in incubated samples and using the dsDNA-electrochemical biosensor. The voltammetric results revealed a decrease and disappearance of the dsDNA oxidation peaks with increasing incubation time, showing that BEVA binds to the dsDNA but no DNA oxidative damage was detected electrochemically. Non denaturing agarose gel-electrophoresis experiments were in agreement with the voltammetric results showing the formation of compact BEVA-dsDNA adduct. The dsDNA-electrochemical biosensor in incubated solutions showed that BEVA also undergoes structural modification upon binding dsDNA, and BEVA electroactive amino acid residues oxidation peaks were detected.

Evidence for the interactions occurring between ionic liquids and tetraethylene glycol in binary mixtures and aqueous biphasic systems.

The well-recognized advantageous properties of poly(ethylene glycol)s (PEGs) and ionic liquids (ILs) in the context of an increasing demand for safe and efficient biotechnological processes has led to a growing interest in the study of their combinations for a wide range of procedures within the framework of green chemistry. Recently, one of the most promising and attractive applications has been the novel IL/polymer-based aqueous biphasic systems (ABS) for the extraction and purification of biomolecules. There still lacks, however, a comprehensive picture of the molecular phenomena that control the phase behavior of these systems. In order to further delve into the interactions that govern the mutual solubilities between ILs and PEGs and the formation of PEG/IL-based ABS, (1)H NMR spectroscopy in combination with classical molecular dynamics (MD) simulations performed for binary mixtures of tetraethylene glycol (TEG) and 1-alkyl-3-methylimidazolium-chloride-based ILs and for the corresponding ternary TEG/IL/water solutions, at T = 298.15 K, were employed in this work. The results of the simulations show that the mutual solubilities of the ILs and TEG are mainly governed by the hydrogen bonds established between the chloride anion and the -OH group of the polymer in the binary systems. Additionally, the formation of IL/PEG-based ABS is shown to be controlled by a competition between water and chloride for the interactions with the hydroxyl group of TEG.

"Washing-out" ionic liquids from polyethylene glycol to form aqueous biphasic systems.

The molecular-level mechanisms behind the formation of aqueous biphasic systems (ABS) composed of ionic liquids (ILs) and polymers are hitherto not completely understood. For the first time, it is herein shown that polymer-IL-based ABS are a result of a "washing-out" phenomenon, and not of a salting-out effect of the IL over the polymer as assumed in the past few years. Novel evidence is herein provided by experimental results combined with molecular dynamics (MD) simulations and density functional theory (DFT) calculations.

Salting-in with a salting-out agent: explaining the cation specific effects on the aqueous solubility of amino acids.

Although the understanding of ion specific effects on the aqueous solubilities of biomolecules is crucial for the development of many areas of biochemistry and life sciences, a consensual and well-supported molecular picture of the phenomena has not yet been established. Mostly, the influence of cations and the nature of the molecular interactions responsible for the reversal of the Hofmeister trend in aqueous solutions of amino acids and proteins are still defectively understood. Aiming at contributing to the understanding of the molecular-level mechanisms governing the cation specific effects on the aqueous solubilities of biocompounds, experimental solubility measurements and classical molecular dynamics simulations were performed for aqueous solutions of three amino acids (alanine, valine, and isoleucine), in the presence of a series of inorganic salts. The evidence gathered suggests that the mechanism by which salting-in inducing cations operate in aqueous solutions of amino acids is different from that of anions, and allows for a novel and consistent molecular description of the effect of the cation on the solubility based on specific interactions of the cations with the negatively charged moieties of the biomolecules.

The origin of the LCST on the liquid-liquid equilibrium of thiophene with ionic liquids.

Mixtures of thiophene with two ionic liquids, namely, [C(4)C(1)im][SCN] and [C(4)C(1)im][NTf(2)], were chosen as prototypes of systems presenting lower critical solution temperature (LCST) and upper critical solution temperature (UCST) behavior, respectively. This distinct behavior is due to different interactions between the constituting species which are investigated here by means of experimental and computational studies. Experimentally, density measurements were conducted to assess the excess molar volumes and (1)H and (13)C NMR spectroscopies were used to obtain the corresponding nuclear chemical shifts with respect to those measured for the pure ionic liquids. Computationally, molecular dynamics simulations were performed to analyze the radial distribution neighborhoods of each species. Negative values of excess molar volumes and strong positive chemical shift deviations for [C(4)C(1)im][SCN] systems, along with results obtained from MD simulations, allowed the identification of specific interactions between [SCN](-) anion and the molecular solvent (thiophene), which are not observed for [NTf(2)](-). It is suggested that these specific [SCN](-)-thiophene interactions are responsible for the LCST behavior observed for mixtures of thiophene with ionic liquids.

Molecular dynamics simulation studies of the interactions between ionic liquids and amino acids in aqueous solution.

Although the understanding of the influence of ionic liquids (ILs) on the solubility behavior of biomolecules in aqueous solutions is relevant for the design and optimization of novel biotechnological processes, the underlying molecular-level mechanisms are not yet consensual or clearly elucidated. In order to contribute to the understanding of the molecular interactions established between amino acids and ILs in aqueous media, classical molecular dynamics (MD) simulations were performed for aqueous solutions of five amino acids with different structural characteristics (glycine, alanine, valine, isoleucine, and glutamic acid) in the presence of 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide. The results from MD simulations enable to relate the properties of the amino acids, namely their hydrophobicity, to the type and strength of their interactions with ILs in aqueous solutions and provide an explanation for the direction and magnitude of the solubility phenomena observed in [IL + amino acid + water] systems by a mechanism governed by a balance between competitive interactions of the IL cation, IL anion, and water with the amino acids.

Toward an understanding of the aqueous solubility of amino acids in the presence of salts: a molecular dynamics simulation study.

Ion-specific effects on the aqueous solubilities of biomolecules are relevant in many areas of biochemistry and life sciences. However, a general and well-supported molecular picture of the phenomena has not yet been established. In order to contribute to the understanding of the molecular-level interactions governing the behavior of biocompounds in aqueous saline environments, classical molecular dynamics simulations were performed for aqueous solutions of four amino acids (alanine, valine, isoleucine, and 2-aminodecanoic acid), taken as model systems, in the presence of a series of inorganic salts. The MD results reported here provide support for a molecular picture of the salting-in/salting-out mechanism based on the presence/absence of interactions between the anions and the nonpolar moieties of the amino acids. These results are in good qualitative agreement with experimental solubilities and allow for a theoretical interpretation of the available data.

On the interactions between amino acids and ionic liquids in aqueous media.

The understanding of the molecular-level interactions between biomolecules and ionic liquids (ILs) in aqueous media is crucial for the optimization of a number of relevant biotechnological processes. In this work, the influence of a series of amino acids on the liquid-liquid equilibria between 1-butyl-3-methylimidazolium tricyanomethane and water was studied to evaluate the preferential interactions between these three compounds. The solubility effects observed are dependent on the polarity, size, and charge distribution of the amino acid side chains and are explained in terms of a refined version of the model proposed earlier (Freire et al. J. Phys. Chem. B 2009, 113, 202; Tome et al. J. Phys. Chem. B 2009, 113, 2815) for ion specific effects on aqueous solutions of imidazolium-based ILs. Although acting through different mechanisms, salting-in and salting-out phenomena possess a common basis which is the competition between water-amino acid side chain, IL-amino acid side chain, and water-IL interactions. The delicate balance between these interactions is dependent on the relative affinities of the biomolecules to water molecules or to IL cation and anion and determines the trend and magnitude of the solubility effect observed.

Towards an understanding of the mutual solubilities of water and hydrophobic ionic liquids in the presence of salts: the anion effect.

The understanding of the specific interactions between salt ions and ionic liquids (ILs) in aqueous solutions is relevant in multiple applications. The influence of a series of anions on the solubility of 1-butyl-3-methylimidazolium tricyanomethane in aqueous environment was here studied. This study aims at gathering further information to evaluate the recently proposed mechanisms of salting-in- and salting-out-inducing ions in aqueous solutions of ILs and to provide insights at the molecular-level on the phenomena occurring in these systems. The observed effect of the inorganic species on the aqueous solubility of the ionic liquid qualitatively follows the Hofmeister series, and it is dependent on the nature and concentration of the anions. The liquid-liquid equilibrium data and 1H NMR results here reported support a model according to which salting-in- and salting-out-inducing ions operate by essentially different mechanisms. While salting-out is an entropically driven effect resulting from the formation of hydration complexes and the increase of the surface tension of cavity formation, the salting-in phenomena is a consequence of the direct binding of the ions to the hydrophobic moieties of the IL. Further evidence here obtained suggests that the interactions of the inorganic ions are not only established with the cation of the IL, but also with the anion, with the observed solubility effect the result of a balance between those two types of interactions.

Hydration of cyclohexylamines: CPCM calculation of hydration Gibbs energy of the conformers.

This work presents a theoretical study on the hydration of cyclohexylamine and isomers of cyclohexyldiamine. All possible conformers were fully optimized in solution using the conductor-like polarizable continuum model (CPCM) and density functional theory. Values of the Gibbs energy of solvation, its respective contributions (electrostatic, nonelectrostatic and conformational change), and the relative Gibbs energy of the conformers in aqueous solution and gas phase are reported. From these values and the Boltzmann populations of the conformers in both phases, the weighted mean values of DeltaG(solv) for the compounds are calculated. Three structural features were found to be important for the hydration of these compounds: the distance between the two NH2 groups (proximity disfavors hydration), their position relative to the ring (equatorial is preferred over axial), and the orientation of the nitrogen lone-pairs (gauche is more favorable to hydration than trans). In the particular case of vicinal cyclohexyldiamines, in addition to these two factors, the relative orientation of one group to the other should also be taken into account.

Determination of the enthalpy of solute-solvent interaction from the enthalpy of solution: aqueous solutions of erythritol and L-threitol.

In this work the enthalpy of the solute-solvent interaction of erythritol and L-threitol in aqueous solution was determined from the values obtained for the enthalpy of solvation. The values for this property were calculated from those determined for the enthalpies of solution and sublimation. To determine the values of the enthalpy of solute-solvent interaction, the solvation process is considered as taking place in three steps: opening a cavity in the solvent to hold the solute molecule, changing the solute conformation when it passes from the gas phase into solution, and interaction between the solute and the solvent molecules. The cavity enthalpy was calculated by the scaled particle theory and the conformational enthalpy change was estimated from the value of this function in the gas phase and in solution. Both terms were determined by DFT calculations. The solvent effect on the solute conformation in solution was estimated using the CPCM solvation model. The importance of the cavity and conformational terms in the interpretation of the enthalpy of solvation is noted. While the cavity term has been used by some authors, the conformational term is considered for the first time. The structural features in aqueous solution of erythritol and L-threitol are discussed.

Conformational study of erythritol and threitol in the gas state by density functional theory calculations.

Density functional theory calculations using the B3LYP functional and the 6-311++G(d,p) basis set were carried out on the isolated molecules of erythritol and L-threitol. For the meso isomer, a relatively large number of conformers have to be considered to describe the gas state structure. The lowest energy conformer is characterized by the establishment of a strong intramolecular H-bond between the two terminal hydroxyl groups, giving rise to a seven-membered ring and two additional weaker H-bonds between vicinal OH groups. In the case of L-threitol, two conformers are predominant in the gas state, and both are stabilized by the formation of a cyclic system of four intramolecular hydrogen bonds involving all OH groups. The conformational stability in both diastereomers is discussed in terms of the electronic energy and of the Gibbs energy. The weighted mean enthalpy of both diastereomers in the gas state at 298.15 K was obtained from the thermodynamic data and Boltzmann populations of the low-energy conformers.

Enthalpy of sublimation in the study of the solid state of organic compounds. Application to erythritol and threitol.

The enthalpies of sublimation of erythritol and L-threitol have been determined at 298.15 K by calorimetry. The values obtained for the two diastereomers differ from one another by 17 kJ mol(-1). An interpretation of these results is based on the decomposition of this thermodynamic property in a term coming from the intermolecular interactions of the molecules in the crystal (delta(int)H degrees) and another one related with the conformational change of the molecules on going from the crystal lattice to the most stable forms in the gas phase (delta(conf)H degrees). This last term was calculated from the values of the enthalpy of the molecules in the gas state and of the enthalpy of the isolated molecules with the crystal conformation. Both quantities were obtained by density functional theory (DFT) calculations at the B3LYP/6-311G++(d,p) level of theory. The results obtained in this study show that the most important contribution to the differences observed in the enthalpy of sublimation are the differences in the enthalpy of conformational change (13 kJ mol(-1)) rather than different intermolecular forces exhibited in the solid phase. This is explained by the lower enthalpy of threitol in the gas phase relative to erythritol, which is attributed to the higher strength of the intramolecular hydrogen bonds in the former. The comparison of the calculated infrared spectra obtained for the two compounds in the gas phase supports this interpretation.