Enthalpy Of Interaction Research Articles

Immersion Enthalpy of Activated Carbon–Cyclohexane and Activated Carbon–Hexane. Difference in the Solid–Liquid Interaction Enthalpy Due to the Structure of the Solvent

The enthalpy of immersion for five activated carbons (with different surface chemistry) in cyclohexane and hexane was determined in order to observe the intensity of the solid–liquid interaction. The enthalpy of immersion was related to the properties of activated carbons, such as micropore volume, total basic groups content, and the EoWo product, that characterized each solid-liquid system. The values for the immersion enthalpy were between −21.2 and −91.7 J g−1 for cyclohexane and between −16.4 and −66.1 J g−1 for hexane. It showed greater interaction between the cyclohexane and the activated carbons and it was related to the properties of this adsorbate, such as molecular size and molecular arrangement. The difference in the enthalpy of immersion between the solvents per unit of micropore volume for the set of activated carbons was calculated obtaining a value of −487 J cm−3.

The vapor pressure and vaporization enthalpy of squalene and squalane by correlation gas chromatography

Vapor pressures and vaporization enthalpies of both squalane and squalene are evaluated by correlation gas chromatography using n-alkanes as standards. Vapor pressures as a function of temperature from T = (298.15–600) K are fit to a second order polynomial. Vaporization enthalpies of (134.4 ± 2.4 and 139.8 ± 2.4) kJ mol−1 and vapor pressures of p = ((15 ± 5.4) and (3.7 ± 1.3))·10−7 Pa at T = 298.15 K are evaluated for squalane and squalene, respectively. Vapor pressures are compared with existing literature data. Enthalpies of interaction with the column are evaluated for all analytes and are found to be endothermic at the mean temperatures of the chromatography.

Investigations into the interaction thermodynamics of TRAP-related peptides with a temperature-responsive polymer-bonded porous silica stationary phase

The interaction thermodynamics of the thrombin receptor agonistic peptide (TRAP-1), H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-OH, and a set of alanine scan substitution peptides, have been investigated with an n-octadecylacrylic polymer-bonded porous silica (Sil-ODA18) and water-acetonitrile mobile phases at temperatures ranging from 5 to 80 °C in 5 °C increments. The retention of these peptides on the Sil-ODA18 stationary phase decreased as the water content in the mobile phase was lowered from 80% (v/v) to ca. 45% (v/v) and reached a minimum value for each peptide at a specific water-acetonitrile composition. Further decreases in the water content of the mobile phase led to increased retention. The magnitude of the changes in enthalpy of interaction, ΔHassoc0, changes in entropy of interaction, ΔSassoc0, and changes in heat capacity, ΔCp0, were found to be dependent on the molecular properties of the mobile phase, the temperature, the structure/mobility of the stationary phase, and the conformation and solvation state of the peptides. With water-rich mobile phases, the retention behaviour of the TRAP analogues was dominated by enthalpic processes, consistent with the participation of strong hydrogen bonding effects, but became dominated by entropic effects with acetonitrile-rich mobile phases as the temperature was increased. These changes in the retention behaviour of these TRAP peptides are consistent with the generation of water or acetonitrile clusters in the mobile phase depending on the volume fractions of the organic solvent as the Sil-ODA18 stationary phase transitions from its crystalline to its isotropic state.

Enthalpy-Entropy Interplay in π-Stacking Interaction of Benzene Dimer in Water.

Aromatic groups can engage in an interesting class of noncovalent interactions termed π-π interactions, which play a pivotal role in stabilizing a variety of molecular architectures, including nucleic acids, proteins, and supramolecular assemblies. When the aromatic compounds interact with each other in an aqueous environment, their association is facilitated by the hydrophobic effect-the trend of nonpolar solutes to aggregate in a polar solution. To develop an in-depth understanding of hydrophobic association, we investigate in the present work π-π interactions in water, employing as a paradigm the benzene dimer. Using DFT-CES, a mean-field QM/MM method recently developed by our group, we describe the benzene solute at a quantum-mechanical level. Full consideration of detailed solute-electron density enables an optimal description of the solute-solvent interactions, leading to an accurate prediction of hydration free energies. In π-stacking of benzene, we find an entropic stabilization associated with the shrinkage of the solvent-excluded volume, which agrees with the theory of hydrophobic effect at subnanoscales. However, at the equilibrium binding distance of the benzene dimer, we find that the entropic stabilization nearly cancels out due to the enthalpic cost required for dewetting the internal space. Such an enthalpy-entropy compensation leads the association free energy to be predominantly dictated by the solute-solute interaction enthalpy. The present work offers new insight into the mechanistic role of water and the primary thermodynamic driving force of hydrophobic association.

Genome-wide analysis of LXXLL-mediated DAX1/SHP-nuclear receptor interaction network and rational design of stapled LXXLL-based peptides to target the specific network profile.

The atypical orphan receptors DAX1 and SHP constitute the NR0B subgroup of human nuclear receptor (hNR) family; they play key roles in metabolism, reproduction, nutrition and steroidogenesis, and are involved in the pathogenesis of a variety of diseases such as cancer and adrenal hypoplasia. The two receptors lack the classical DNA-binding domain and act as the corepressors of other hNRs. The DAX1 and SHP contains three and two conserved LXXLL motifs, respectively, which can be recognized and bound by the activation function-2 (AF-2) domain of hNR proteins in agonist conformation. Here, we attempt to explore the systematic interaction profile between the five DAX1/SHP LXXLL motifs and all the 48 hNR AF-2 domains found in the human genome, to analyze the binding affinity and specificity of these motifs towards the complete domain array, and to design LXXLL-based, hydrocarbon-stapled peptides that can target the specific interaction profile for each motif. A weighted source-target network from motifs to domains is created based on the modeled domain-motif complex structures and calculated binding potencies, from which the specific interaction profile of each motif against the whole hNR array is depicted and clustered to measure the binding similarity and relationship among these motifs. Dynamics simulations reveal that the LXXLL-based peptides are highly flexible in free unbound state, thus unfavorable to be recognized and bound by AF-2 domains. Hydrocarbon-stapling technique is employed to help the constraint of these unstructured peptides to active helical conformation, thus largely improving their binding affinity to the hNR array. The hydrocarbon bridge is designed to point out of the domain's active pocket, which would not disrupt the direct interaction between the domain and peptide. Energetic decomposition imparts that the stapling has only a very modest influence on the interaction enthalpy and desolvation effect of domain-peptide binding, but can substantially reduce entropy penalty upon the binding. For a peptide ligand, the entropic reduction can be roughly regarded as a constant, which only improves (absolute) peptide binding affinity towards the whole domain array, but does not alter (relative) peptide binding specificity over different domains in the array. Overall, the stapled peptides can be considered as potent competitors to selectively target the specific interaction networks mediated by their parent LXXLL motifs in DAX1 and SHP proteins.

Mechanisms of Methylparaben Adsorption onto Activated Carbons: Removal Tests Supported by a Calorimetric Study of the Adsorbent⁻Adsorbate Interactions.

In this study, the mechanisms of methylparaben adsorption onto activated carbon (AC) are elucidated starting from equilibrium and thermodynamic data. Adsorption tests are carried out on three ACs with different surface chemistry, in different pH and ionic strength aqueous solutions. Experimental results show that the methylparaben adsorption capacity is slightly affected by pH changes, while it is significantly reduced in the presence of high ionic strength. In particular, methylparaben adsorption is directly dependent on the micropore volume of the ACs and the π- stacking interactions, the latter representing the main interaction mechanism of methylparaben adsorption from liquid phase. The equilibrium adsorption data are complemented with novel calorimetric data that allow calculation of the enthalpy change associated with the interactions between solvent-adsorbent, adsorbent-adsorbate and the contribution of the ester functional group (in the methylparaben structure) to the adsorbate–adsorbent interactions, in different pH and ionic strength conditions. It was determined that the interaction enthalpy of methylparaben-AC in water increases (absolute value) slightly with the basicity of the activated carbons, due to the formation of interactions with π- electrons and basic functional groups of ACs. The contribution of the ester group to the adsorbate-adsorbent interactions occurs only in the presence of phenol groups on AC by the formation of Brønsted–Lowry acid–base interactions.

Quantitative characterization of temperature-independent polymer-polymer interaction and temperature-dependent protein-protein and protein-polymer interactions in concentrated polymer solutions.

To study the effect of non-specific interactions arising from proteins being in a crowded environment on physiological processes, the self-interaction of concentrated Dextran T70 and Ficoll 70 and the interactions between a dilute protein and these polymeric macromolecules were quantified using non-ideal tracer sedimentation equilibrium. Sedimentation equilibria of each polymer were measured between 5 and 37°C, and sedimentation equilibria of 2mgcm-3 superoxide dismutase (SOD) in 0-0.1gcm-3 of each polymer was also measured. Results were analyzed using a model-free thermodynamic virial expression of activity coefficients in terms of the concentration of polymer and a structural model using a statistical thermodynamics approximation. The equilibrium gradients of each of the polymers suggest repulsive interaction, which is independent of temperature. However, the net repulsive interaction between superoxide dismutase (SOD) species and the polymers is dependent on temperature. The ratio of the solvation energy of SOD in Dextran T70 to that in Ficoll 70, lnγSOD(Dex)/lnγSOD(Fic) at the same w/v concentration was about 1.8 at 37°C, 1.6 at the intermediate temperature, and ranges from 1.2 to 1.6 at 5°C over the entire concentration range. The enthalpy and entropy of interaction of SOD with dilute Dextran T70 are - 14kJmol-1 and - 5.6JK-1 mol-1, respectively. For SOD in dilute Ficoll 70, the enthalpy and entropy are - 8.1kJmol-1 and 12.9JK-1mol-1, respectively. Thus, Dextran T70 contributes more to the attractive protein-polymer interaction and to self-association of protein than Ficoll 70 and reasons for this are discussed.

Thermodynamics of adsorption on nanocellulose surfaces

Understanding the thermodynamic interactions of cellulose nanomaterials with their environment is important to understand the forces behind their self-organization and co-organisation with other compounds, and to be able to use self-assembly to form new functional multicomponent materials. This review analyzes published studies that determined the thermodynamic parameters of the surface interactions of and adsorption of various compounds (proteins, polymers, and small molecules/ions) onto cellulose nanomaterials. We compiled the data reported and performed a meta-analysis for better comparison and to find trends in the published data. We first introduce the methods employed and describe the adsorption isotherm models typically used to describe the adsorption thermodynamics on nanocellulose surfaces. We then discuss and analyze the published results for the interaction of the various compounds with nanocellulose surfaces. The systems that have been reported on most were adsorption of natural binding proteins and various pollutants from water, such as heavy metal ions, dyes, and drugs. Interactions between cellulose surfaces and the cellulose binding module were generally both enthalpy- and entropy-driven, where the negative binding enthalpy indicates the formation of specific interactions between peptides and the carbohydrate backbone. On the other hand, interactions with charged molecules were mostly endothermic and purely entropy-driven, indicating that the adsorption on nanocellulose surfaces can be described as an interaction between opposite charges, where the entropy increase that arises from the release of surface-structured water molecules and counterions from the electronic double layer supplies the major contribution to the free energy of adsorption. We performed a meta-analysis on all published data, and found a linear relationship between ∆H and ∆S with the slope equal to the reference temperature, irrespective of whether the interacting compound is a specific cellulose binding protein, a non-specific binding protein, a polymer, or a small molecule/ion. This indicates that the process of adsorption is the same for all compounds and takes place with a constant change in Gibbs free energy of interaction, ∆G, where a change in interaction enthalpy is offset by change in entropy change upon binding and vice versa.

Nanothermometry Reveals Calcium-Induced Remodeling of Myosin.

Ions greatly influence protein structure-function and are critical to health and disease. A 10, 000-fold higher calcium in the sarcoplasmic reticulum (SR) of muscle suggests elevated calcium levels near active calcium channels at the SR membrane and the impact of localized high calcium on the structure-function of the motor protein myosin. In the current study, combined quantum dot (QD)-based nanothermometry and circular dichroism (CD) spectroscopy enabled detection of previously unknown enthalpy changes and associated structural remodeling of myosin, impacting its function following exposure to elevated calcium. Cadmium telluride QDs adhere tomyosin, function as thermal sensors, and reveal that exposure of myosin to calcium is exothermic, resulting in lowering of enthalpy, a decrease in alpha helical content measured using CD spectroscopy, and the consequent increase in motor efficiency. Isolated muscle fibers subjected to elevated levels of calcium further demonstrate fiber lengthening and decreased motility of actin filaments on myosin-functionalized substrates. Our results, in addition to providing new insights into our understanding of muscle structure-function, establish a novel approach to understand the enthalpy of protein-ion interactions and the accompanying structural changes that may occur within the protein molecule.

Preparation, characterization, dielectric properties and solvent-imbibing behavior of styrene–butadiene rubber/zinc sulfide nanocomposites

This work focuses on the preparation of styrene–butadiene rubber (SBR)/zinc sulfide (ZnS) nanocomposites using a simple and inexpensive two-roll mill mixing technique. The structural, morphological and thermal properties of the nanocomposites were analyzed by FT-IR, UV–visible spectroscopy, XRD, SEM and DSC measurements. The results of the spectroscopic studies revealed the interaction of ZnS nanoparticles with SBR through the shift in the peaks of UV and FT-IR spectra. The XRD and SEM studies showed that the nanoparticles were well inserted into the macromolecular structure of SBR. The glass transition temperature of the composites increased with the addition of nanoparticles. The dielectric constant of nanocomposite with different loading of nanoparticles was carried out in the frequency range 100–106 Hz. The dielectric properties of nanocomposites were higher than that of pure SBR. In addition, the diffusion and transport properties of organic solvents through SBR/ZnS nanocomposites were studied in detail as a function of ZnS content. The polymer–solvent interaction parameter, enthalpy and entropy of sorption data were estimated from the transport properties. The high dielectric constant of these nanocomposites infers that ZnS is one of the ideal nanofiller for the development of high-k materials for flexible energy storage applications.

The effect of polyethylene glycols on the interaction and stability of AOT/water/isooctane microemulsions

The influence of water-soluble polyethylene glycols PEG200 on the properties of sodium bis(2-ethylhexyl)-sulfosuccinate (AOT) water-in-isooctane microemulsions has been investigated by conductivity measurement and isothermal titration microcalorimetry (ITC). The percolation temperatures (Tp), the thermodynamic properties of droplet aggregation and the interaction enthalpy (−ΔHφ) between droplets for AOT/water/PEG200/isooctane with different PEG concentrations and a fixed molar ratio of water to surfactant ω = 22.2 were determined. Based on a two-stage thermodynamic approach of the percolation, we obtained the fusion enthalpy (ΔHf0) of the close contact droplets by a combination of the droplet aggregation enthalpy (ΔHag0) and −ΔHφ. It was found that both (−ΔHφ) and (ΔHf0) varied with the concentration of PEG200 (cPEG) and had the extreme value at cPEG = 25 g L−1. This phenomenon was interpreted by the variation of interface rigidity due to the varied distributions of added PEG200 between the water pool and the surfactant interface.

The hydrogen bonding enthalpies of water and methanol in ionic liquids

The thermochemical study of hydrogen bonding of water with different proton acceptor ionic liquids was carried out. Along with the available experimental data, the solution enthalpies of water in [BMIM][TfO], [BMIM][BF4] and [BMIM][PF6] were measured. The hydrogen bonding enthalpies of water with various ionic liquids were determined by using previously developed method of solvation enthalpy separation into the nonspecific solvation enthalpy and the specific solute-solvent interaction enthalpy (hydrogen bonding). The findings indicate the formation of a complex, where one molecule of water is bound to two molecules of ionic liquids. Similarly, hydrogen bonding enthalpies of methanol with the same proton acceptor ionic liquids were determined.

Cocrystal Ternary Phase Diagrams from Density Functional Theory and Solvation Thermodynamics

Several solid–liquid ternary phase diagrams consisting of an active ingredient, an excipient (coformer), and a solvent have been computed by means of density functional theory and COSMO-RS solvation thermodynamics. In all these ternary systems, cocrystal formation occurs; furthermore, the active ingredient and coformer are capable of forming strong, concerted hydrogen bonds in solution. The formation of such exceptionally strong bonds in solution has been taken into account by the introduction of an additional binary interaction parameter. This approach leads to a good agreement with experimental data using a minimum set of fit parameters. Quantum-chemically computed interaction enthalpies between solutes are of similar magnitude as the optimized interaction parameters and computed free energies in solution corroborate the existence of a significant population of aggregated drug–coformer complexes. The outlined procedure provides detailed insights into solvation and solubility enhancement effects at the m...

Study of the temperature effect on the acid-base properties of cellulose acrylate by inverse gas chromatography at infinite dilution

Inverse gas chromatography (IGC) at infinite dilution was used to characterize the surface and interfacial properties of polymers, oxides or polymers adsorbed on oxides. In this paper, the dispersive component of the surface energy of CA was calculated following the molecular models of the surface areas of n-alkanes proving the presence of two linear zones with two different slopes in the temperature intervals and indicating a change in the structure of CA groups. The acid-base properties in the Lewis terms of cellulose acrylate were determined. One proved that the specific enthalpy and entropy of interaction of polar probes are functions of the temperature The application of Hamieh’s model allows to the determination of the acid-base constants KA and KD and the amphoteric constant K of cellulose acrylate surface. It was proved that the constants KA, KD and K of cellulose acrylate strongly depend on the temperature. This study allowed us to determine the probability w of the specific adsorption of polar probes on the cellulose acrylate surface. This probability parameter also depends on the temperature.

ENTHALPY OF INTERACTION OF ION-EXCHANGE HETEROGENEOUS MEMBRANES AND THEIR GRANULAR ANALOGUES WITH AMMONIUM NITRATE SOLUTION

Ion-exchange membranes are widely used for extraction, separation and concentration of aqueous nitrogen-containing solutions. In the study the heterogeneous ion-exchange membranes of cationic type- MK-40, Ralex CM (H) -PP, MK-41 – and anionic type - MA-41, Ralex AM (H) -PP and also their granular analogues – cation exchanger KУ-2·8 and anion exchanger AB-17·8 were used. Sorption of nitrate ions and ammonium ions was conducted from the ammonium nitrate solution with concentration of 0.012 mole / dm³. To determine sorption thermochemical characteristics of the studied ions the calorimetric method was used. It was found that for all the studied types of membranes and ion exchangers the processes were accompanied by heat evolution. From the calorimetric measurements the thermokinetic interaction curves of cation-exchange membranes and KУ-2×8 with the ammonium nitrate solution and anion-exchange membranes and AB-17×8 with the solution of the same salt were obtained. According to the curves the power of heat evolution and time of the process were determined. It was shown that the ion exchangers KУ-2·8 and AB-17·8 are characterized by a longer time to achieve the maximum of heat evolution and process time than for the similar membranes. This fact is explained by the different number and accessibility of the functional groups in the membranes and ion exchangers. From the thermo-kinetic curves the enthalpies of interaction were calculated. The process of the interaction between the granular ion exchangers and ions is characterized by higher values of the enthalpy than for the membranes which large steric effects are common for. Saline concentration, nature of exchangeable ions and type of functional groups of the ion exchanger and also its moisture content influence the enthalpy value. Experimental calorimetric data indicated that the energy costs connected with the effects of dehydration and conformational changes in the sorbent polymer chains do not overlap the exothermic sorption effect. The calorimetric method is informative to determine the nature and mechanism of sorption.

Drug partitioning in individual and mixed micelles and interaction with protein upon delivery form micellar media

Poor solubility of drugs has led to the use of drug delivery vehicles to solubilize and to increase the bioavailability of drugs at the target site. Micelles can encapsulate the hydrophobic drugs in their hydrophobic core and thus increase the bioavailability in vivo. Mixed micelles have complementary properties of its individual micelles and can be used as efficient drug delivery vehicles. In the present investigation, we report the partitioning of naproxen (anti-inflammatory) and methimazole (anti-thyroid) drugs in hexadecyltrimethylammonium bromide (HTAB), triton X-100 (TX-100) and their mixed micelles and detailed comparison of partitioning of diclofenac sodium (anti-inflammatory) with these micelles. The interaction of these drugs with transporter protein BSA upon delivery from micellar media was also studied in order to use these micelles as drug delivery vehicles. Quantitative aspects of interactions have been reported in terms of binding constant, standard molar enthalpy and standard molar entropy of interaction obtained from isothermal titration calorimetry (ITC) in combination with pyrene emission fluorescence, dynamic light scattering, and circular dichroism measurements. Diclofenac sodium and naproxen showed better partitioning in mixed micelles than in individual micelles. Binding of diclofenac sodium with BSA was also enhanced upon delivery from HTAB or mixed micelles whereas the binding of naproxen was reduced upon delivery from micellar media than direct delivery. No effect on the binding of methimazole with BSA was observed even upon the delivery from mixed micelles. Detailed analysis on the energetics of interaction of drugs with micelles and further with BSA upon delivery from micellar media can assist in developing effective drug delivery vehicles and also provide guidelines for rational drug design.

Molecularly Imprinted Polymers for Compound-Specific Isotope Analysis of Polar Organic Micropollutants in Aquatic Environments.

Compound-specific isotope analysis (CSIA) of polar organic micropollutants in environmental waters requires a processing of large sample volumes to obtain the required analyte masses for analysis by gas chromatography/isotope-ratio mass spectrometry (GC/IRMS). However, the accumulation of organic matter of unknown isotopic composition in standard enrichment procedures currently compromises the accurate determination of isotope ratios. We explored the use of molecularly imprinted polymers (MIPs) for selective analyte enrichment for 13C/12C and 15N/14N ratio measurements by GC/IRMS using 1 H-benzotriazole, a typical corrosion inhibitor in dishwashing detergents, as example of a widely detected polar organic micropollutant. We developed procedures for the treatment of >10 L of water samples, in which custom-made MIPs enabled the selective cleanup of enriched analytes in organic solvents obtained through conventional solid-phase extractions. Hydrogen bonding interactions between the triazole moiety of 1 H-benzotriazole, and the MIP were responsible for selective interactions through an assessment of interaction enthalpies and 15N isotope effects. The procedure was applied successfully without causing isotope fractionation to river water samples, as well as in- and effluents of wastewater treatment plants containing μg/L concentrations of 1 H-benzotriazole and dissolved organic carbon (DOC) loads of up to 28 mg C/L. MIP-based treatments offer new perspectives for CSIA of organic micropollutants through the reduction of the DOC-to-micropollutant ratios.

Thermal properties and CT-DNA/BSA binding behavior of a binuclear Cu(II) complex with acylhydrazone containing naphthalene ring

A novel Cu(II) complex [Cu2L2(NO3)2] with 2-hydroxy-1-naphthaldehyde-(4’hydroxy)phenylacetyl hydrazone (C19H14N2O2·H2O, HL) was synthesized. The structure of [Cu2L2(NO3)2] was characterized by X-ray single-crystal diffraction and can be described as a distorted rectangular pyramid with binuclear coordination. IR, UV–vis and EPR spectra are used to discuss the structure of Cu(II) complex in different conditions. Magnetic properties were determined by EPR spectra and magnetic susceptibility studies, showing magnetic exchange interaction and weak antiferromagnetic exchange between two Cu(II) ions. The apparent activation energy (Ea) of thermal decomposition of compounds indicated that the thermal stability of [Cu2L2(NO3)2] is better than HL. The CT-DNA binding behavior of compounds was determined by UV–vis absorption and viscosity measurements and the results confirmed an intercalative binding mode with CT-DNA. Kb obtained was 6.24(±0.12) × 106 M−1 and 3.09(±0.006) × 106 M−1 for [Cu2L2(NO3)2] and HL, respectively, revealing that the binding ability of [Cu2L2(NO3)2] with CT-DNA was stronger. The thermogenic curves of compounds interacting with CT-DNA were monitored by microcalorimetry, showing they were all endothermic reactions with reaction within 27–42 min; interaction enthalpies (ΔH) of [Cu2L2(NO3)2] and HL were 30.3 and 4.31 kJ mol−1. Binding studies with BSA were evaluated by fluorescence spectroscopy and the same relative interactions were found comparing with the above CT-DNA experiments.

Interaction Enthalpy of Side Chain and Backbone Amides in Polyglutamine Solution Monomers and Fibrils.

We determined an empirical correlation that relates the amide I vibrational band frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding, van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We used this correlation to determine the Q side chain carbonyl interaction enthalpy (Δ Hint) in monomeric and amyloid-like fibril conformations of D2Q10K2 (Q10). We independently verified these Δ Hint values through molecular dynamics simulations that showed excellent agreement with experiments. We found that side chain-side chain and side chain-peptide backbone interactions in fibrils and monomers are more enthalpically favorable than are Q side chain-water interactions. Q10 fibrils also showed a more favorable Δ Hint for side chain-side chain interactions compared to backbone-backbone interactions. This work experimentally demonstrates that interamide side chain interactions are important in the formation and stabilization of polyQ fibrils.

Crystal Nucleation of Tolbutamide in Solution: Relationship to Solvent, Solute Conformation, and Solution Structure.

The influence of the solvent in nucleation of tolbutamide, a medium-sized, flexible and polymorphic organic molecule, has been explored by measuring nucleation induction times, estimating solvent-solute interaction enthalpies using molecular modelling and calorimetric data, probing interactions and clustering with spectroscopy, and modelling solvent-dependence of molecular conformation in solution. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: acetonitrile<ethyl acetate<n-propanol<toluene. The combined DFT and MD modelling results show that in acetonitrile, ethyl acetate and n-propanol the nucleation difficulty is a function of the strength of solvent-solute interaction, with emphasis on the interaction with specific H-bonding polar sites of importance in the crystal structure. A clear exception from this rule is the most difficult nucleation in toluene despite the weakest solvent-solute interactions. However molecular dynamics modelling predicts that tolbutamide assumes an intramolecularly H-bonded conformation in toluene, substantially different from and more stable than the conformation in the crystal structure, and thus presenting an additional barrier to nucleation. This explains why nucleation in toluene is the most difficult and why the relatively higher propensity for aggregation of tolbutamide molecules in toluene solution, as observed with FTIR spectroscopy, does not translate into easier nucleation. Thus, our combined experimental and molecular modelling study suggests that the solvent can influence on the nucleation not only via differences in the desolvation but also through the influence on molecular conformation.