Enthalpy Contributions Research Articles

Spatially Resolved Hydration Thermodynamics in Biomolecular Systems.

Water is essential for the structure, dynamics, energetics, and thus the function of biomolecules. It is a formidable challenge to elicit, in microscopic detail, the role of the solvation-related driving forces of biomolecular processes, such as the enthalpy and entropy contributions to the underlying free-energy landscape. In this Perspective, we discuss recent developments and applications of computational methods that provide a spatially resolved map of hydration thermodynamics in biomolecular systems and thus yield atomic-level insights to guide the interpretation of experimental observations. An emphasis is on the challenge of quantifying the hydration entropy, which requires characterization of both the motions of the biomolecules and of the water molecules in their surrounding.

Computational studies suggest compounds restoring function of p53 cancer mutants can bind SARS-CoV-2 spike protein

It is reasonable to think that cancer patients undergoing chemotherapy or immunotherapy may have a more aggressive course if they are positive for the novel coronavirus disease. Their compulsive condition requires investigation into effective drugs. We applied computational techniques to a series of compounds known for restoring the function of p53 cancer mutant p53R175H and p53G245S. Two potent inhibitors, 1-(3-chlorophenyl)-3-(1, 3 -thiazol-2-yl) urea (CTU, PubChem NSC321792) with the highest binding affinity −6.92 kcal/mol followed by a thiosemicarbazone compound N’-(1-(Pyridin-2-yl)ethylidene) azetidine − 1 -carbothiohydrazide (NPC, PubChem NSC319726) with −6.75 kcal/mol were subjected to Molecular Dynamics simulation with receptor binding domain (RBD) and compared with control ligand dexamethasone. In particular, CTU adheres to pocket 1 with an average free energy of binding −21.65 2.89 kcal/mol at the RBD - angiotensin-converting enzyme 2 binding region with the highest frequency of amino acid residues after reaching a local equilibrium in 100 ns MD simulation trajectory. A significant enthalpy contribution from the independent simulations unfolds the possibility of dual binding sites for NPC as shifted pocket 1 (−15.59 5.98 kcal/mol) and pocket 2 (−18.90 5.02 kcal/mol). The obtained results for these two compounds are in good agreement with dexamethasone (−18.45 2.42 kcal/mol). Taken together our findings could facilitate the discovery of small molecules that restore the function of p53 cancer mutants newly against COVID-19 in cancer patients.

Analytical modelling of flame transfer functions for technically premixed flames

The linear response to harmonic acoustic excitation of the total heat release rate in technically premixed flames (Flame Transfer Function, FTF) is studied in case of an ideal swirl burner. The analysis is based on the linearization of the production rate for the mean reaction progress variable modelled with a turbulent flame speed closure. Three main components of the FTF are identified which are generated by: I) direct fluctuations in the fuel mixture fraction (formation enthalpy contribution), II) direct fluctuations in the turbulent flame speed and III) flame surface area fluctuations driven by velocity and turbulent flame speed fluctuations. The velocity fluctuation is separated into an irrotational acoustic displacement and a rotational convective component. The effect of the rotational velocity component on the FTF is modelled here in a semi-empirical way, related to swirl number fluctuations at the flame base due to the phase shift between convected tangential velocity fluctuations and acoustically propagating axial velocity fluctuations. It is finally shown that fuel mixture fraction fluctuations can be generated not only by air mass flow rate fluctuations but also by fuel flow rate fluctuations which depend upon the air side impedance at the fuel injection location. It is shown that this impedance changes with the geometry of the plenum placed upstream the burner affecting in this way also the FTF.

A microcalorimetric and microscopic strategy to assess the interaction between dietary fibers and small molecules

The interaction between small molecules and neutral soluble dietary fiber is one of the proposed mechanisms determining the bioavailability of these components in the small intestine. However, the weak nature of these interactions makes it difficult to find an analytical method sensitive enough to detect them. Here, we probed the molecular interaction between galactomannan, arabinoxylan, and β-glucan with gallic acid, cinnamic acid, acetylsalicylic acid, and acetaminophen, using advanced analytical methods, namely isothermal titration calorimetry (ITC) and in the form of gold-nanoparticles, transmission electron microscopy (TEM). The results obtained from ITC analysis were fully consistent with the results obtained from TEM. In short, the interaction of these fibers and small molecules was mainly entropically driven, hence involving hydrophobic type association and possible conformational changes of the polysaccharide. However, the enthalpy contribution (hydrogen interaction) is also significant, especially regarding interactions with the acetylsalicylic acid molecule.

Potentiometric entropy and operando calorimetric measurements reveal fast charging mechanisms in PNb9O25

The Wadsley–Roth compound PNb9O25 is a promising fast charging lithium ion battery anode material with high operating voltage to prevent solid electrolyte interface formation. Here, we present potentiometric entropy measurements featuring signatures of semiconductor-to-metal transition and intralayer ordering upon lithiation in the anode material PNb9O25 that could not be observed with in situ X-ray diffraction. In addition, the instantaneous heat generation rates at the PNb9O25 working electrode and at the lithium metal counter electrode during galvanostatic cycling were measured individually for the first time by operando isothermal calorimetry. The heat generation rate decreased at the PNb9O25 electrode upon lithiation due to the decrease in electrical resistivity caused by the semiconductor-to-metal transition observed in potentiometric entropy measurements. Furthermore, the heat generation rate at the lithium metal electrode was positive during delithiation due to the exothermic plating of Li+ ions on the lithium metal counter electrode associated with dendrite formation. Furthermore, calorimetric measurements established that the entropy change dominated the reversible heat generation rate at each electrode. Finally, the contribution of enthalpy of mixing was relatively small even at high C-rates thanks to the high Li+ ion mobility in Pnb9O25 confirming its promises as a fast charging anode material.

Influence of ionization and position of substituents on the solubility, solvation and transfer processes: A thermodynamic study of hydroxybenzamide and acetamidobenzoic acid isomers

Solubility of i-hydroxybenzamides and i-acetamidobenzoic acids (i = 2, 3, 4) in buffer solutions (pH 2.0 and 7.4), 1-octanol and n-hexane were measured by the isothermal saturation method in the temperature range (293.15–315.15 K). The following order of the solubility was revealed (in mole fraction): 1-octanol > buffer pH 7.4 > buffer pH 2.0 > n-hexane. The solubility was correlated by the van’t Hoff and Apelblat equations. The best result was achieved with the van’t Hoff model. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor–acceptor capacity of the molecules on drug solubility has been studied. The thermodynamic parameters of solubility, solvation and transfer processes were calculated and discussed in view of solute–solvent interactions. A diagram approach was used to analyze the enthalpy and entropy contributions to the Gibbs energy of transfer processes from n-hexane to solvents and from buffer solutions to 1-octanol for the substances studied.

Temperature Dependence of Hydrophobic and Hydrophilic Forces and Interactions.

Molecular dynamics simulations are used to compare the forces and Gibbs free energies associated with bringing small hydrophobic and hydrophilic solutes together in an aqueous solution at different temperatures between 280 and 360 °K. For the hydrophilic solutes, different relative orientations are used to distinguish between direct, intersolute hydrogen bonds (Hbond) and solutes simultaneously hydrogen bonding to a solvent water bridge. Interestingly, the temperature dependence of the hydrophobic and directly hydrogen bonding solutes turns out to be opposite to that of the bridged hydrophilic solutes, with the ΔG becoming more negative for the former and less negative for the latter with increasing temperature. Dissection of the free energy curves into enthalpy and entropy contributions, and further separation of the enthalpy term into solute-solute, solute-solvent, and solvent-solvent components provides insight into the physical molecular causes for the distinctive thermodynamic results. Finally, it is reasoned how the opposite temperature dependencies of the two types of hydrophilic interactions provide a rationale for the cold denaturation of proteins.

What is the Enthalpy Contribution to the Stabilization of the Co–Cr–Fe–Mn–Ni Faced-centered Cubic Solid Solution?

The aim of this paper is to investigate the contribution of the mixing enthalpy to the stability of the faced-centered cubic (fcc) phase of the Co–Cr–Fe–Mn–Ni system. For this purpose, systematic first principles calculations on Special Quasirandom Structures (SQS) were performed in a comprehensive manner on the fcc solution in every \(\left( {\begin{array}{c}5\\ 2\end{array}}\right) =10\) binary, \(\left( {\begin{array}{c}5\\ 3\end{array}}\right) =10\) ternary, \(\left( {\begin{array}{c}5\\ 4\end{array}}\right) =5\) quaternary and the quinary systems. The magnetic contributions have been considered carefully i.e. including non-collinear spin polarization. An analysis of the different system order interactions to the enthalpy of mixing is detailed. This concludes that, at equiatomic composition, there is no special “cocktail” effect with an increase of components and that the thermodynamic properties can be well anticipated from the lower order systems, essentially binary and ternary systems.

Application of a Fluorescent Biosensor in Determining the Binding of 5-HT to Calmodulin

Here, we show the utility of the fluorescent biosensor hCaM-M124C-mBBr in detecting and determining the affinity of serotonin (5-HT). We obtained a Kd of 5-HT (0.71 μm) for the first time, the same order of magnitude as most anti-CaM drugs. This data can contribute to understanding the direct and indirect modulation of CaM on its binding proteins when the 5-HT concentration varies in different tissues or explain some of the side effects of anti-CaM drugs. On the other hand, molecular modeling tools help the rational design of biosensors and adequately complement the experimental results. For example, the docking study indicates that 5-HT binds at the same site as chlorpromazine (site 1) with a theoretical Ki of 2.84 μM; while the molecular dynamics simulations indicate a stability of the CaM–5-HT complex with a theoretical ΔG of −4.85 kcal mol−1, where the enthalpy contribution is greater. Thus, the combination of biotechnology and bioinformatics helps in the design and construction of more robust biosensors.

Numerical modelling of a three-zone combustion for heavy fuel oil in inert porous media reactor

Numerical model for heavy fuel oil and air mixtures combustion is presented to simulate the behavior of the fuel in an inert porous medium reactor for hydrogen production. Three-zone combustion of oil and petroleum cokes separated by temperature ranges starting from ambient temperature to 560 K, from 560 K to 673 K, and above 673 K, is presented. Hydrogen production is achieved using water gas shift equilibrium reaction on the combustion products at different temperatures. Results show a high enthalpy contribution due to coke combustion formed in the low temperature oxidation reaction, being the most important reaction in relation to its zone size. Simulations increasing filtration velocity (from 0.05 to 0.9 m/s) has a favorable effect on the maximum temperature and the combustion front velocity. The effect of the simplified combustion model lowers computational time, with acceptable results for temperature as well as hydrogen production in contrast to laboratory tests and other software simulation such as COMSOL Multiphysics.

Thermochemical investigation of glycyl-L-alanine dissolution in aqueous solution of some acetamides and formamides at T = 298.15 K (Similarities and differences)

The paper presents data on the glycyl-L-alanine dissolution enthalpies in aqueous solutions of formamide (FA), N-methyl-formamide (MFA), N,N-dimethylformamide (DMF), acetamide (AM), N-methyl-acetamide (NMA), and N,N-dimethylacetamide (DMA) at an organic co-solvent concentration x2 = 0 ÷ 0.25 - mole fraction and T = 298.15 K, obtained by calorimetry. The standard values of dissolution enthalpies (ΔsolHo), transfer enthalpies (ΔtrHo), and enthalpic coefficients of pairwise interaction (hxy) were calculated from these data. The dependences of the enthalpic characteristics of glycyl-L-alanine dissolution on the mixture composition and the interaction energy between the mixture components have been established. A comparative analysis of the values of the enthalpic coefficients of pairwise interactions of glycyl-L-alanine, glycyl-glycine, and glycyl-L-tyrosine in similarly mixed solvents has been carried out. A quantitative assessment of the enthalpy contributions of the side-chains of glycyl-L-alanine and glycyl-L-tyrosine to the energetics of interaction with amide molecules in an aqueous solution is given.

Per|Mut: Spatially Resolved Hydration Entropies from Atomistic Simulations.

The hydrophobic effect is essential for many biophysical phenomena and processes. It is governed by a fine-tuned balance between enthalpy and entropy contributions from the hydration shell. Whereas enthalpies can in principle be calculated from an atomistic simulation trajectory, calculating solvation entropies by sampling the extremely large configuration space is challenging and often impossible. Furthermore, to qualitatively understand how the balance is affected by individual side chains, chemical groups, or the protein topology, a local description of the hydration entropy is required. In this study, we present and assess the new method “Per|Mut”, which uses a permutation reduction to alleviate the sampling problem by a factor of N! and employs a mutual information expansion to the third order to obtain spatially resolved hydration entropies. We tested the method on an argon system, a series of solvated n-alkanes, and solvated octanol.

A micromechanics-based model for deformation-induced damage and failure in elastomeric media

In order to predict damage and failure in elastomeric media, a new physically-based model based upon a multiscale approach is proposed. The behavior of polymer chains is described by means of statistic mechanics, in which the stretchability and detachability of the internal bonds are introduced to account for the enthalpy contribution to chain elasticity and the time-dependent stochastic process of chain scission, respectively. The complex but inevitable coupling effect between the chain conformation change and the bond length change is addressed in a rigorous approach, and the bond rupture is treated as an energy activation process that is related to the thermal oscillation and stimulated by the chain stretch. The micro-macro transition is realized with a non-affine microsphere-based strategy where the length variability of polymer chains is considered statistically, as well as its evolution with the loading histories. The model is firstly used to discuss some history-dependent features (Mullins effect and monotonic biaxial failure) of rubbers in relation to damage accumulation due to progressive chain scission events. The efficiency of the model is then critically discussed by comparisons with a few illustrative experiments of different rubbery media under high thermal environmental and thermal aging effects. To illustrate further the predictive capability of the model, the failure of rubbers is finally treated under a wide range of biaxial loading conditions.

Determination of the critical micelle concentration and thermodynamic parameters of phenylcarbamic acid derivatives using a fluorescence method

Critical micelle concentration (CMC) values of 1-[3-(2-alkoxyphenylcarbamoyloxy)-2-hydroxypropyl]-4-(4-fluorophenyl)piperazin-1-ium-chlorides (alkoxy = methoxy to propoxy; 6a–c) were determined by a fluorescence method using pyrene as a probe over a temperature interval T = 293.15–313.15 K. The dependence of CMC on T turned out forming the U-shape. The curve was drawn by fitting of observed values using a second-degree polynomial function and so-called power-law equation, minimum of the curve was observed at T = 298.15 K. Thermodynamic parameters of micellization, i.e., molar Gibbs energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°), respectively, were calculated according to a phase separation model. Following the observations, the enthalpy (ΔH°) and entropy contributions (−TΔS°) to the molar Gibbs energy (ΔG°) were calculated. It was found that contribution of enthalpy increased with the increase in temperature, and entropy contribution decreased within chosen range of the temperature. Finally, the enthalpy–entropy compensation and the compensation temperature (Tc) were determined.

Evodiamine in several binary aqueous co-solvents: Solubility measurement and modeling, Hansen solubility parameter, preferential solvation and apparent dissolution and transfer properties

Equilibrium solubilities of evodiamine were determined in four aqueous mixtures of methanol, isopropanol, acetone and ethanol over their full mass fraction range via the shake-flask approach covering from 283.15 to 323.15 K. The solubility profiles showed maxima in the neat cosolvents. The temperature and the mixture composition dependence of evodiamine solubility in mole fraction scale was well described by using five well-known models involving NRTL, Jouyban-Acree, van't Hoff-Jouyban-Acree, UNIQUAC and Wilson. The means of the relative deviations were recorded as 5.40%, 0.98% and 0.48% for the Wilson, UNIQUAC and NRTL models, respectively. The Jouyban-Acree and van't Hoff-Jouyban-Acree models resulted in the calculated relative average and root-mean-square deviations lower than 6.83% and 9.19 × 10−6, respectively. Hansen solubility parameter was utilized to disclose the solubility behavior of evodiamine. We also employed the linear solvation energy relationships to detect which intermolecular interactions were mainly responsible for the observed solvent effect upon solubility behavior. This analysis revealed the highlighted role of cavity term and dipolarity-polarizability of solvent in solubility variation of evodiamine. Solubility data was further examined by using the inverse Kirkwood-Buff integrals method in order to analysis the preferential solvation of evodiamine in the mixtures. Results showed the selective solvation of evodiamine by organic solvent in intermediate and organic solvent-rich compositions, and by water in water-rich compositions. The thermodynamic quantities including the apparent molar dissolution enthalpy, molar dissolution entropy and molar Gibbs energy, and the relative contribution of dissolution enthalpy and dissolution entropy to the dissolution Gibbs energy change for dissolution of evodiamine were calculated in each binary mixture. Moreover, the transfer properties were derived and discussed.

Thermodynamic modeling and phase diagram prediction of salt lake brine systems II. Aqueous Li+-Na+-K+-SO42− and its subsystems

Predicted result of complete structure phase diagram of Li 2 SO 4 -Na 2 SO 4 -H 2 O system at temperature ranging from eutectic point 251.19–373.15 K: P1, P2, P3, P4, P5 are Transition points of three solid co-saturated in the ternary system. • Thermodynamic model of aqueous Li+-Na+-K+-SO 4 2− systems across entire temperature range. • Predicting the polythermal full structure phase diagram of ternary and quaternary aqueous system.. • The multi-objective optimization method to obtain solid constants and liquid parameters. It is still a challenging task to accurately and temperature-continuously express the thermodynamic properties and phase equilibrium behaviors of the salt-lake brine with multi-component, multi-temperature and high concentration. The essential subsystem of sulfate type brine, aqueous Li + -Na + -K + -SO 4 2− and its subsystems across a temperature range from 250 K to 643 K are investigated with the improved comprehensive thermodynamic model. Liquid parameters ( Δ g IJ , Δ h IJ , and Δ C p , I J ) associated with the contributions of Gibbs energy, enthalpy, and heat capacity to the binary interaction parameters, i . e . the temperature coefficients of eNRTL parameters formulated with a Gibbs Helmholtz expression, are determined via multi-objective optimization method. The solid constants Δ f G k ° ( 298.15 ) and Δ f H k ° ( 298.15 ) of 11 solid species occurred in the quaternary system are rebuilt from multi-temperature solubilities. The modeling results show the accurate representation of (1) solution properties and binary phase diagram at temperature ranges from eutectic points to 643 K; (2) isothermal phase diagrams for Li 2 SO 4 -Na 2 SO 4 -H 2 O, Li 2 SO 4 -K 2 SO 4 -H 2 O and Na 2 SO 4 -K 2 SO 4 -H 2 O ternary systems. The predicted results of complete structure and polythermal phase diagram of ternary systems and the isothermal phase diagrams of quaternary system excellently match with the experimental data.

Permut - Spatially Resolved Hydration Entropies from Atomistic Simulations

The thermodynamics of the first few surface water layers profoundly affects the overall free energy change in protein folding and unfolding, bilayer self-assembly, and ligand binding, and many other biomolecular processes. Whereas the enthalpy contribution can, in principle, be directly calculated from atomistic molecular dynamics simulations, the solvation shell entropy calculation suffers particularly from the poor sampling of the high dimensional configuration space. To furthermore understand, e.g., the effects of water molecules inside a binding pocket or the contribution of individual side chains to the hydration entropy, spatial resolution is required. To address these problems, we developed Per|Mut, a new method to calculate spatially resolved hydration entropies. In Per|Mut, we first employ a permutation reduction, which exploits the permutation symmetry of the identical water molecules to alleviate the sampling problem by the Gibbs factor N! without changing the physics. Next, we use a third-order mutual information expansion to obtain the hydration shell entropy. The spatial resolution and the decomposition into one- two- and three-body correlations of the translational and rotational entropies, as well as of the translation-rotation correlation, allows for an easy physical interpretation and characterization of the resolved entropy changes. In test-simulations, Per|Mut yielded accurate entropies for an argon gas test system and solvated alkanes. Applied to the solvation statistical mechanics of hydrated octanol and the protein Crambin, Per|Mut revealed the local effects of individual chemical groups or side chains on the solvation entropy.

Temperature Studies Reveal the Roles of Entropy and Enthalpy in Polymer-Nanopore Interactions

Detecting and characterizing polymers with a nanopore sensor requires a significant interaction between the polymer and nanopore in order for the polymer to yield measurable current blockades. To design a selective nanopore sensor, quantitative measurement of the free energy profile including the contributions of both entropy and enthalpy is essential. We have developed a laser-based tool to rapidly control the solution temperature of an alpha-hemolysin nanopore sensor, resulting in nearly continuous Arrhenius plots in less than 2 min.

Unfolding Thermodynamics of an RNA Pseudoknot and its DNA Analog

There is considerable interest in the stability and physical properties of nucleic acid pseudoknots because of their significant role in the folding of the secondary/tertiary structures of RNA. We have investigated the unfolding thermodynamics of an intramolecular RNA pseudoknot (U-PsKn) and its DNA analog (dU-PsKn) with sequence: UCUCUU11AAAAAAAAGAGAU5UUUUUUU, where U11 and U5 are loops of 11 and 5 uridines, respectively. We used a combination of temperature-dependent UV spectroscopy and differential scanning calorimetric techniques to determine the unfolding thermodynamics of each pseudoknot. Additional UV melting experiments were done as a function of oligomer, salt and osmolyte concentrations to determine the transition molecularity, ion and water binding, respectively. In the 16-116 mM NaCl range, U-PsKn has a higher TMs and is thermodynamically more stable (by 12.3 kcal/mol) than dU-PsKn. This large differential free energy contribution is driven by a differential favorable enthalpy contribution of 34.3 kcal/mol. In addition, U-PsKn immobilizes more counterions (by 0.3 per mol,) and water molecules (by 16 per mol), and unfolds with a higher heat capacity contribution (by 1.0 kcal/oC-mol) than its DNA analog. Furthermore, the overall enthalpy is higher than the corresponding enthalpy of its double helical stem (estimated from nearest-neighbors contributions), suggesting the longer U11loop could potentially form local UAU base-triplets with the adjacent A7/U7 stem. We estimate U-PsKn forms ∼7 base-triplet stacks while dU-PsKn forms 4 base-triplet stacks. The overall results imply U-PsKn forms a more compact structure. Supported by Grant MCB-1912587 from the National Science Foundation.

Accelerated curing of G-FRP rods glued into timber by means of inductive heating – Influences of curing kinetics

ABSTRACT Glued-in Rods (GiR) are nowadays widely established as an adhesively bonded connection type in timber engineering. The assemblies consist of rods, e.g. threaded rods or rebars, made of steel, or Fibre-Reinforced Polymers (FRP), which are bonded into wooden construction elements. In contrast to mechanical fastening, adhesive bonding often results in a better load transfer between the adherends, and consequently a reduction of local stress peaks in comparison to mechanical fasteners. Bonding of GiR is typically performed with 2 K polyurethanes (2 K-PUR) or 2 K epoxies (2 K-EPX), for which full curing can last up to several days. Consequently, before the connection can be stressed, or moved for further processing, components have to be maintained in fixed position. This process can be very time, and cost, consuming for contractors. In order to create a speedier, thus more efficient, bonding process, the present study investigated accelerated curing of large-scale GiR specimens with the help of inductively heated Curie particles (CP). The CP are added to the adhesives, and exposed to a high frequency (HF) electromagnetic field (EMF). The EMF heats the mix up until the Curie temperature (T C) is reached, at which point the heating automatically stops. Due to the generated heat, polymerisation is significantly accelerated in a process independent of external monitoring techniques that prevents adhesive overheating. In order to design this practitioner-friendly and controllable manufacturing process, kinetic models were developed, allowing the prediction of the degree of cure, α, in dependency of CP content. The kinetic models were applied to experimentally determined temperature profiles during inductive heating of large-scale GiR specimens, considering three commercially available 2 K-EPX, and one 2 K-PUR, all of which are widely used. The kinetic modelling allowed for a much better interpretation of the heating behaviour, highlighting, in particular, the contribution of enthalpy for adhesive curing, and by extension of the whole induction process.