Enthalpy-entropy Compensation Research Articles

Thermodynamic analysis of water vapor adsorption onto freeze-dried ora-pro-nobis (Pereskia aculeata Miller) mucilage

The mucilage of Pereskia aculeata Miller is a hydrocolloid with the potential to be used as a food additive. Thus, data on its physical, chemical and microbiological stability are necessary to evaluate the storage stability of the product. This study aimed to determine the thermodynamic properties of water vapor adsorption onto freeze-dried ora-pro-nobis mucilage (OPNM) and to interpret the mechanisms that govern water adsorption onto powder particles through the study of enthalpy-entropy compensation. In addition, OPNM was characterized in terms of moisture, ash, ether extract, protein, fiber and carbohydrates beyond the functional chemical groups by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Thermodynamic analysis showed that water adsorption onto OPNM powder was characterized as a spontaneous process with strong attractive forces in the water and OPNM mixture. The water sorption mechanism for OPNM at the studied adsorption range was regulated by energy interactions related to the chemical composition of the product.

Isokinetic and Compensation Temperature in the Analysis of Thermal Dissociation of the Solid Phase under Dynamic Conditions

Sets of Arrhenius parameters, determined according to known different equations for dynamic conditions, in the vast majority form the Kinetic Compensation Effect (KCE). Converting these data to the simplified components of the Eyring equation comes down to Enthalpy–Entropy Compensation (EEC), which is consistent with the second law of thermodynamics. It has been proved that the impact of the generally known Coats−Redfern solution on the equation in differential form results in an isokinetic form of the equations and a very important coordinate T0;α0 (initial temperature and conversion degree), depending on the heating rate. This makes it possible to determine the parameters of Arrhenius’ law for both in silico and experimental data. An analytical method for determining this coordinate has been proposed. These considerations have given rise to an analysis of the relationship between two temperatures: initial and isokinetic. The sense of isokinetic temperature has been verified by the parameters CQF and K. Going further, it was found that the effects of EEC can be transformed into KCE and vice versa, which means that the two temperatures should be identical, i.e., Tiso=Tc. However, the experimental data indicate that the analyzed temperatures form a sequence T0↔Tiso↔Tc≤Teq, where Teq is the equilibrium temperature.

Equilibrium solubility, solvation and dissolution thermodynamics, and density functional theory study of albendazole in solutions of acetone/methanol/isopropanol + water

In this work, albendazole was dissolved in mixtures of acetone/methanol/isopropanol + water to examine its solubility, dissolution thermodynamics, solvation behavior, and intermolecular interactions. The shake-flask method was used to conduct solubility tests at a pressure of 101.0 kPa and temperatures from 278.15 to 323.15 K. In water and pure organic solvents, respectively, the lowest and greatest levels of albendazole solubility were found. XRD analysis-based experiments found no evidence of crystal solvation or transition. Jouyban-Acree, modified Wilson, QSPR and modified van't Hoff-Jouyban-Acree models correlated the solubility to solvent composition and temperature with the relative average deviations (RAD) of no more than 8.99 %. The equilibrium solubility at 298.15 K was examined using the approach of extended Hildebrand solubility parameter, which produced an average relative deviation of 3.63 %. The dipolarity-polarizability and solubility parameter of solutions have a considerable impact on the solubility fluctuation, according to the analysis of linear solvation energy relationship. The preferred solvation of albendazole by water and different organic solvents was quantitatively examined with the help of the inverse Kirkwood-Buff integrals. Albendazole was preferentially solvated by the organic solvents in moderate and rich organic solvent compositions in blends, where albendazole served as a Lewis acid. An enthalpy-driven mechanism and an endothermic process were identified by thermodynamic analysis of the entropy-enthalpy compensation and dissolution properties for albendazole dissolving in blends. The electrostatic characteristics of albendazole acidity/basicity were highlighted using analysis of Hirshfeld surface and molecular surface. The primary targets of nucleophilic and electrophilic assault are the –NH and -S-groups. An independent gradient model based on Hirshfeld partition analysis was used to visual the weak interactions between albendazole and different solvents.

Using Implicit-Solvent Potentials to Extract Water Contributions to Enthalpy-Entropy Compensation in Biomolecular Associations.

Biomolecular assembly typically exhibits enthalpy-entropy compensation (EEC) behavior whose molecular origin remains a long-standing puzzle. While water restructuring is believed to play an important role in EEC, its contribution to the entropy and enthalpy changes, and how these changes relate to EEC, remains poorly understood. Here, we show that water reorganization entropy/enthalpy can be obtained by exploiting the temperature dependence in effective, implicit-solvent potentials. We find that the different temperature dependencies in the hydrophobic interaction, rooted in water reorganization, result in substantial variations in the entropy/enthalpy change, which are responsible for EEC. For lower-critical-solution-temperature association, water reorganization entropy dominates the free-energy change at the expense of enthalpy; for upper-critical-solution-temperature association, water reorganization enthalpy drives the process at the cost of entropy. Other effects, such as electrostatic interaction and conformation change of the macromolecules, contribute much less to the variations in entropy/enthalpy.

Enhancing the equilibrium solubility of salicylic acid in aqueous media by using polyethylene glycols 200, 400 and 600 as cosolvents: Correlation and dissolution thermodynamics

The solubility of salicylic acid in three mixtures of polyethylene glycol (PEG) with different molar masses of 200 to 600 g/mole were experimentally determined by a shake flask method at temperature range of (293.15 to 313.15) K under ambient pressure (≈85 kPa). The experimental results indicated that the solubility of salicylic acid enhanced by the introduction of PEGs to the water, and that could be explained with Hansen’s parameters and like-dissolves-like rule. Based on the results, PEG 600 had the best solubilization power, whereas PEG 200 displayed the lowest solubilization power, and generally the solubility decreased with decreasing molar mass of PEG and also decreasing temperature. Moreover, the equilibrium solid phase crystal of salicylic acid is characterized with X-ray powder diffraction analysis to identify no polymorphic transformation, solvate formation or crystal transition during the whole solvent crystallization process. A number of linear and nonlinear cosolvency models including the Jouyban-Acree based models along with the equations of van’t Hoff, the mixture response surface, the combined nearly ideal binary solvent/Redlich-Kister, λh and the modified Wilson-van’t Hoff were challenged to correlate/predict the solubility of salicylic acid in these mixtures. The computed values of the Jouyban-Acree based models presented a good agreement with the experiment data than the others, as a consequent of a low mean percentage deviation (MPD ≤ 15.7%). According to the enthalpy–entropy compensation analysis, there observed slope changes indicating that two mechanisms, enthalpy or entropy controlled the solubility increment depending on the PEG mass fraction in each solution.

Solubility of Salicylic Acid in Some (Ethanol + Water) Mixtures at Different Temperatures: Determination, Correlation, Thermodynamics and Preferential Solvation

Equilibrium mole fraction solubility of salicylic acid in nine aqueous-ethanolic mixtures, as well as in neat water and neat ethanol, was determined at seven temperatures from T = (293.15 to 323.15) K. Salicylic acid solubility in these mixtures was adequately correlated with well-known correlation/prediction methods based on Jouyban-Acree model. Apparent thermodynamic quantities, i.e. Gibbs energy, enthalpy, and entropy, for the dissolution and mixing processes, were computed by means of the van’t Hoff and Gibbs equations. The enthalpy–entropy compensation plot of enthalpy vs. Gibbs energy of dissolution was not linear exhibiting positive slopes from neat water to the mixture of w1 = 0.30 and from the mixture of w1 = 0.50 to neat ethanol indicating enthalpy-driven drug transfer processes but negative in the interval of 0.30 < w1 < 0.50 indicating entropy-driven drug transfer processes from more polar to less polar solvent systems. Moreover, by using the inverse Kirkwood–Buff integrals it is observed that salicylic acid is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in those mixtures of 0.24 < x1 < 1.00.

The Nature of the Enthalpy–Entropy Compensation and “Exotic” Arrhenius Parameters in the Denaturation Kinetics of Proteins

Protein unfolding is a ubiquitous process responsible for the loss of protein functionality (denaturation), which, in turn, can be accompanied by the death of cells and organisms. The nature of enthalpy–entropy compensation (EEC) in the kinetics of protein unfolding is a subject of debate. In order to investigate the nature of EEC, the “completely loose” transition state (TS) model has been applied to calculate the Arrhenius parameters for the unfolding of polyglycine dimers as a model process. The calculated Arrhenius parameters increase with increasing dimer length and demonstrate enthalpy–entropy compensation. It is shown that EEC results from the linear correlations of enthalpy and entropy of activation with dimer length, which are derived directly from the properties of the transition state. It is shown that EEC in solvated (hydrated, etc.) proteins is a direct consequence of EEC in proteins themselves. The suggested model allows us also to reproduce and explain “exotic” very high values of the pre-exponential factor measured for the proteins unfolding, which are drastically higher than those known for unimolecular reactions of organic molecules. A similar approach can be applied to analyzing the nature of EEC phenomena observed in other areas of chemistry.

Comparative Effect of Physiological Salts upon Micellization of T1304 and T1307.

We present a comprehensive investigation on the interaction of tetronics (T1304 and T1307) with some important physiological salts (NaH2PO4, KH2PO4, Na2CO3, NaCl, and KI). Thermodynamic and microstructural aspects of these interactions were studied as a function of the solution temperature, pH and salt concentration. Characterizations were performed using turbidimetric, calorimetric, and scattering techniques. We show that, at ambient temperature, T1304 molecules aggregated to form spherical core-shell aggregates displaying a unimodal distribution pattern. On the other hand, unimers and large clusters dominated in the case of highly hydrophilic T1307. Its micellization was promoted in the presence of salts as per the following trend: NaCl < KH2PO4 < NaH2PO4 ≪ Na2CO3. Aggregation was found to be endothermic, and hydrophobic interactions (TΔSmic > ΔHmic) prevailed. The enthalpy-entropy compensation plot was found to be linear for both copolymers. Demicellization occurred in the presence of KI as it facilitated the buildup of water structures around the copolymer chains. This could be verified from the increase in the cloud point, critical micelle concentration, and free energy. Overall, the temperature and salts inflicted a stronger hydrophobic effect upon T1304 in comparison to T1307.

Equilibrium solubility, solvation and dissolution thermodynamics, and DFT study of 18β-glycyrrhetinic acid in solutions of 1,4-dioxane/N,N-dimethylformamide/ethanol/isopropanol + water

This study investigated the solubility, solvation behavior, dissolution thermodynamics, and intermolecular interactions of 18β-glycyrrhetinic acid (GA) in binary aqueous blends of 1,4-dioxane, N,N-dimethylformamide (DMF), ethanol and isopropanol. The solubility experiments were performed using the shake-flask technique at 101.0 kPa and temperatures ranging from 278.15 to 323.15 K. The lowest and highest GA solubility was observed in water and neat organic solvent, respectively. Experiments based on XRD analysis revealed no crystal transition or solvation. Modified van't Hoff–Jouyban–Acree and Jouyban–Acree models connected the solubility with relative average deviations (RAD) not exceeding 3.63 %. The extended Hildebrand solubility parameter method was utilized here to examine the equilibrium solubility at 298.15 K, yielding a RAD of 3.95 %. According to the linear solvation energy relationship examination, the dipolarity-polarizability and solubility parameter of solutions significantly influence the solubility variation. Using the inverse Kirkwood–Buff integrals, the preferential solvation of GA by organic solvents and water was investigated quantitatively. Positive preferential solvation parameter for organic solvents in rich and moderate organic solvent blends indicated that GA was preferentially solvated by the organic solvents. GA is a Lewis acid with respect to the cosolvent molecules. Thermodynamic investigation of dissolution characteristics and enthalpy–entropy compensation revealed an endothermic process and enthalpy-driven mechanism for dissolving GA in various blends. Finally, microscopic quantitative examination of molecular surface was used to highlight the electrostatic properties of acidity/basicity of GA. The –C = O, OH, and > COOH groups are the main targets of electrophilic and nucleophilic attack. The weak interactions between GA and solvent were visually examined using an independent gradient model based on Hirshfeld partition analysis.

Impacts of hydrotropes on clouding phenomena and physico-chemical parameters coupled with the triton X 100 & promethazine hydrochloride mixture

ABSTRACT Phase separation behaviour of non-ionic surfactants (NISs)-drug in aq. hydrotropes (HDTs) has appealed interest to researcher over the decades. Herein, we have investigated clouding phenomenon and physico-chemical variables of TX 100 and promethazine hydrochloride (PMH) drug mixture in presence of different HDTs. Study reveals that cloud point (CP) is dependent on the concentration of HDTs in aqueous media. CP values increase with the augmentation of HDTs concentrations while CP values at nearly 100 mmol kg−1 HDTs follow the trend: . The positive standard Gibbs free energy () values signify the non-spontaneity of phase separation in all experimental cases. The positive values of decrease with the augmentation of HDTs concentration. The observed and values are positive at low concentration of HDTs which demonstrates that hydrophobic interactions are the key forces of interaction among the studied ingredients. At high concentration of HDTs, the observed and values are found to be negative which demonstrates the enthalpy control process and the presence of exothermic interactions amongst TX 100, HDTs, and promethazine hydrochloride (PMH) drug in aqueous media. The thermodynamic properties of transfer, as well as enthalpy entropy compensation entities, were calculated and presented with proper clarification.

Linear hydrophobic congeneric groups of bile acid anion derivatives based on the self-association (micellization) process and the phenomenon of enthalpy–entropy compensation

If anions of bile acids form primary micelles by means of hydrophobic effect and interaction, then these anions of bile acids in the lnk - lnCMC plane (k = RP-HPLC capacity factor and CMC = Critical Micellization Concentration) form linear hydrophobic congeneric groups (LCG). Bile salts that form H-bonds in the primary micelles hydrophobic domain are outliers concerning LCG from the plane lnk - lnCMC. In the manuscript, LCG is described using a thermodynamic approach (analytical theory). LCG resulting from enthalpy-entropy compensation (EEC) in the plane of enthalpy and entropy of bile salts micellization is connected with an LCG in the plane of lnk - lnCMC. Bile acid anion, an outliner in the plane of lnk – lnCMC, in the plane of enthalpy and entropy of micellization is included in LCG. This means that in the EEC phenomenon, the formation of LCG is not determined solely by the hydrophobic effect and interaction but also by the energy and the entropy changes of the hydrogen bonds in primary micelles.

Investigation on florasulam in aqueous blends including solubility, preferential solvation, thermodynamic properties and enthalpy–entropy compensation

The equilibrium solubility of florasulam in solvent mixtures (methanol/ethanol /n-propanol/propylene glycol (PG) + water) was determined experimentally by isothermal saturation method at 278.15 K to 323.15 K under 101.2 kPa. Both high temperature and low water content of solvent promoted the dissolution of florasulam. Under given conditions, the mole fraction of florasulam was greater in (n-propanol + water) than other three solvent mixtures. Besides, the solubility of florasulam was correlated with the Jouyban-Acree (J-A) model and van’t Hoff-Jouyban-Acree (V-J-A) model. The obtained average relative deviations (RAD) and root mean square deviations (RMSD) were no >4.04 % and 1.73 × 10-4. The calculated preferential solvation parameter δx1,3 was used to analyze the preferential dissolution of florasulam between water and alcohols from the molecular perspective. The result is that in the intervals 1 > xmethanol > 0.32, 1 > xethanol > 0.23 and 1 > xn-propanol > 0.19, the florasulam was preferentially dissolved by methanol/ethanol/n-propanol. In other concentration ranges, the florasulam was preferentially dissolved by water. The reason for the special existence of PG + water is that |δx1,3| < 1 × 10-2 and the dissolution of florasulam in it conformed to the uncertainty propagation rather than preferential solvation theory. The parameters (ΔsolHo, ΔsolGo, ΔsolSo, ΔtrGo, ΔtrHo and ΔtrSo) that could reflect the apparent and transfer thermodynamic properties were obtained. It was concluded that the solubility change of florasulam was dominated by entropy and the transfer of florasulam from pure water to mixtures was an exothermic process. Finally, the enthalpy–entropy compensation analysis further studied the mechanism of enthalpy and entropy in the dissolution process.

Multiple Modes of Zinc Binding to Histatin 5 Revealed by Buffer-Independent Thermodynamics.

Histatin 5 (Hist5) is an antimicrobial peptide found in human saliva as part of the innate immune system. Hist5 can bind several metal ions in vitro, and Zn2+ has been shown to function as an inhibitory switch to regulate the peptide's biological activity against the opportunistic fungal pathogen Candida albicans in cell culture. Here, we studied Zn2+ binding to Hist5 at four temperatures from 15 to 37 °C using isothermal titration calorimetry to obtain thermodynamic parameters that were corrected for competing buffer effects. Hist5 bound Zn2+ with a buffer-dependent association constant of ∼105 M-1 and a buffer-independent association constant of ∼6 × 106 M-1 at pH 7.4 and at all temperatures tested. Zn2+ binding was both enthalpically and entropically favorable, with larger entropic contributions at 15 °C and larger enthalpic contributions at 37 °C. Additionally, the Zn:Hist5 binding stoichiometry increased from 1:1 to 2:1 as temperature increased. The enthalpy-entropy compensation and the variable stoichiometry lead us to propose a model in which the Zn-Hist5 complex exists in an equilibrium between two distinct binding modes with different Zn:Hist5 stoichiometries. The in-depth thermodynamic analysis presented herein may help illuminate the biophysical basis for Zn-dependent changes in the antifungal activity of Hist5.

Micelle formation and physico-chemical variables for the sodium dodecyl sulfate/cetylpyridinium chloride and their mixture in aqueous propranolol hydrochloride drug solvent: Conductivity and theoretical analysis

Herein, study of both single and mixed micelle development of an anionic surfactant sodium dodecyl sulfate (SDS) and a cationic surfactant cetylpyridinium chloride (CPC) in propranolol hydrochloride (PPH) drug medium has been performed using a conductometric technique at different temperatures and compositions. The critical micelle concentration (CMC) along with degree of ionization (g) were assessed from the specific conductivity (κ) versus [surfactant] plots. Within the concentration of surfactant studied, a single CMC was achieved in the situations of pure and mixed surfactant micellization. The CMC and g values have been noticed reliant on the employed drug concentrations, variations of mole fractions of the mixture of surfactants and experimental temperature. For the micellization of single SDS/ CPC surfactants in aq. PPH drug medium, PPH drug causes delayed micelle development which has been detected as the upsurge of CMC values of SDS/CPC in PPH drug media. For the association of SDS/ CPC surfactants in aq. PPH drug medium, the CMC values experienced a lessening with the growth of study temperature. At a fixed temperature, the experimental CMC values, of the SDS + CPC mixture, endure a decline through the upsurge of mole fractions of CPC (α1), attain a minimum value and the CMC values tend to enhance at and above α1= 16.2 × 10-5. The ideal critical micelle concentrations (CMCid) are detected always as higher values than experimental CMC up to the α1= 10.8 × 10-5. The -β values and |β| > |ln(CMC1/ CMC2)| for the present study reveal that the interaction among the amphiphiles under analysis is synergistic. The negative free energy (-ΔGmO) of micellization were obtained throughout the study. The enthalpy (ΔHmO) and entropy (ΔSmO) of micellization reveal the presence of hydrophobic interaction as the principal type of interaction among the studied constituents. The negative excess free energy (ΔGex) values inferred that stable mixed micelles are formed for the mixture of SDS + CPC in aq. PPH drug medium. The micellar mole fractions (both experimental and ideal values), activity coefficients of components in mixed micelles as well as enthalpy–entropy compensation parameters were also measured and illustrated. It is possible that the knowledge gained from the current analysis may be used to enhance pharmaceutical formulations, drug delivery carriers, along with drug act proficiency.

Associated Water Dynamics Might Be a Key Factor Affecting Protein Stability in the Crowded Milieu.

Over the past 20 years, the most studied and debated aspect of macromolecular crowding is how it affects protein stability. Traditionally, it is explained by a delicate balance between the stabilizing entropic effect and the stabilizing or destabilizing enthalpic effect. However, this traditional crowding theory cannot explain experimental observations like (i) negative entropic effect and (ii) entropy-enthalpy compensation. Herein, we provide experimental evidence that associated water dynamics plays a crucial role in controlling protein stability in the crowded milieu for the first time. We have correlated the modulation of associated water dynamics with the overall stability and its individual components. We showed that rigid associated water would stabilize the protein through entropy but destabilize it through enthalpy. In contrast, flexible associated water destabilizes the protein through entropy but stabilizes through enthalpy. Consideration of entropic and enthalpic modulation through crowder-induced distortion of associated water successfully explains the negative entropic part and entropy-enthalpy compensation. Furthermore, we argued that the relationship between the associated water structure and protein stability should be better understood by individual entropic and enthalpic components instead of the overall stability. Although a huge effort is necessary to generalize the mechanism, this report provides a unique way of understanding the relationship between protein stability and associated water dynamics, which might be a generic phenomenon and should trigger much research in this area.

Characterization of polar surface groups on siliceous materials by inverse gas chromatography and the enthalpy-entropy compensation effect.

Surface-modified porous silica is a well-established composite material. To improve its embedding and application behavior, adsorption studies of various probe molecules have been performed using the technique of inverse gas chromatography (IGC). For this purpose, IGC experiments were carried out in the infinite dilution mode on macro-porous micro glass spheres before and after surface modification with (3-mercaptopropyl)trimethoxysilane. To provide information about the polar interactions between probe molecules and the silica surface, in particular, eleven polar molecules have been injected. In summary, the free surface energy for pristine silica ( = 229mJ/m2) and for (3-mercaptopropyl)trimethoxysilane-modified silica ( = 135mJ/m2) indicates a reduced wettability after surface modification. This is due to the reduction of the polar component of the free surface energy ( ) from 191mJ/m2 to 105mJ/m2. Simultaneously, with the reduction of surface silanol groups caused by surface modification of silica and, therefore, the decrease in polar interactions, a substantial loss of Lewis acidity was observed by various IGC approaches. Experiments with all silica materials have been conducted at temperatures in the range from 90°C to 120°C to determine the thermodynamic parameters, such as adsorption enthalpy ( ) and adsorption entropy ( ), using the Arrhenius regression procedure evaluating the IGC data. With the help of the enthalpy-entropy compensation, two types of adsorption complexes are assumed between polar probe molecules and the silica surface because of different isokinetic temperatures. Identical adsorption complexes with an isokinetic temperature of 370°C have been assigned to alkanes and weakly interacting polar probes such as benzene, toluene, dichloromethane, and chloroform. Polar probe molecules with typical functional groups such as OH, CO, and CN, having the ability to form hydrogen bonds to the silica surface, exhibit a lower isokinetic temperature of 60°C. Quantum chemical calculations of the probe molecules on a non-hydroxylated and hydroxylated silica cluster supported the formation of hydrogen bonds in the case of a strong polar adsorption complex with a bonding distance of 1.7nm-1.9nm to the silica surface.

Effects of alcohols and temperature on association, micellar parameters, and energetics of mixture of cetylpyridinium bromide and polyvinyl alcohol

The mixture of polymer and surfactant is extensively employed in numerous daily used products such as detergents, perfumes, cleaning agents, foodstuffs, oil recovery procedures, paints, as well as pharmaceutical formulations. Interaction of cetylpyridinium bromide (CPB) with polyvinyl alcohol (PVA) has been investigated in water and aqueous solution of different alcohols using the conductivity technique. The type and strength of interaction between CPB and PVA during assembly process have been assessed from different micellar parameters i.e., critical micelle concentration (CMC), extent of counterion dissociation (α), Gibbs free energy (ΔGm0), enthalpy (ΔHm0), entropy (ΔSm0) of micellization etc. The CMC and α were determined from the specific conductivity vs [CPB] plots. The micellization of CPB was attained to be augmented in occurrence of PVA. The CMC values of CPB + PVA system were experienced to be increased through the elongation of chain length of carbon as well as increase of concentration of certain alcohol. The sharp increase of CMC values was also observed with the increase of temperature in a certain alcoholic medium. The values of degree of dissociation were undergone to be augmented by the increase of concentration of certain alcohol as well as the elongation of carbon chain length. The negative free energy of micellization (-ΔGm0) values reveal that the CPB + PVA system undergoes aggregation spontaneously and spontaneity of micellization experienced a reduction with the elongation of carbon chain length. Values of enthalpy (ΔHm0) of micellization were negative i.e., aggregation of CPB + PVA system is an exothermic phenomenon. The ΔHmoandΔSmo values disclose that the main interaction forces between CPB and PVA are electrostatic, hydrophobic, and ion–dipole interactions. The stability of the micelle formed was assessed from enthalpy-entropy compensation parameters.

Phase separation and aggregation phenomena of TX-100 and promethazine hydrochloride mixture: Influences of monohydroxy organic compounds

Clouding nature and thermodynamic characteristics of surfactant-drug systems are novel approaches to chemists, industrialists, and researchers due to the enormous applications of the such mixture in pharmaceutical as well as technological sectors. In this study, the phase separation, assembly formation, and thermodynamic properties of triton X-100 (TX-100) + promethazine hydrochloride (PMH) drug mixed system were investigated by means of cloud point (CP) measurement and UV–visible spectroscopic techniques. The influences of the monohydroxy alcohols (ethanol (EtOH), 1-propanol (1-PrOH), 2-propanol (2-PrOH), along with 2-methyl-1-propanol (iso-BuOH) on the clouding development of TX-100 + drug mixed system have also been demonstrated. At lower concentrations of aqueous alcoholic media, the variation of CP with the enhancement of concentrations of alcohol were observed and increased CP values follow the trend: CPH2O+2-PrOH>CPH2O+EtOH>CPH2O+iso-BuOH>CPH2O+1-PrOH. The critical micelle concentration (CMC) of TX-100 + PMH mixture was found to be experienced an augmentation with the boost of the temperature. The obtained free energy values revealed the non-spontaneity of clouding and spontaneous aggregation of TX-100 + PMH mixture. The non-spontaneity of clouding of TX-100 + PMH mixture reduces with enhancement of concentrations of alcohols. The ΔHc0 and ΔSc0 values were found to be positive in almost all cases except at higher concentration of aq. 2-PrOH and iso-BuOH which disclosed the existence of hydrophobic as well as electrostatic interactions. The micellization of TX-100 + PMH mixed system in an aqueous medium was also accompanied by the hydrophobic interaction. The entropy-enthalpy compensation parameters of the clouding and micellization phenomenon were also elucidated through appropriate explanations.

Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design.

Single-stranded DNA-binding protein (SSB) is a bacterial interaction hub and an appealing target for antimicrobial therapy. Understanding the structural adaptation of the disordered SSB C-terminus (SSB-Ct) to DNA metabolizing enzymes (e.g., ExoI and RecO) is essential for designing high-affinity SSB mimetic inhibitors. Molecular dynamics simulations revealed the transient interactions of SSB-Ct with two hot spots on ExoI and RecO. The residual flexibility of the peptide-protein complexes allows adaptive molecular recognition. Scanning with non-canonical amino acids revealed that modifications at both termini of SSB-Ct could increase the affinity, supporting the two-hot-spot binding model. Combining unnatural amino acid substitutions on both segments of the peptide resulted in enthalpy-enhanced affinity, accompanied by enthalpy-entropy compensation, as determined by isothermal calorimetry. NMR data and molecular modeling confirmed the reduced flexibility of the improved affinity complexes. Our results highlight that the SSB-Ct mimetics bind to the DNA metabolizing targets through the hot spots, interacting with both of segments of the ligands.

Physico-chemical study of the effects of electrolytes and hydrotropes on the clouding development of TX-100 and ceftriaxone sodium drug mixture

The potential interactions between third-generation broad-spectrum cephalosporin antibiotic ceftriaxone sodium (CTS) and nonionic surfactant triton X-100 (TX-100) in the absence and existence of various sodium based electrolytes (sodium chloride (NaCl), sodium acetate (NaAc), sodium sulphate (Na2SO4)) /hydrotropic salts (sodium benzoate (NaBenz) and sodium salicylate (NaSal)) were investigated. The CTS drug is widely used to treat bacterial infections and it showed remarkable reactivity towards Gram-positive and Gram-negative bacteria. The assessments of CP in the TX-100 + CTS system with NaSal demonstrated the hydrophilic interaction which was not found significant when NaBenz solutions were used. The CP values observed for TX-100 + CTS system in aq. electrolytes and hydrotropic salts media demonstrated the order: CPaq.NaSal>CPaq.NaBenz>CPaq.NaCl>CPaq.NaAc>CPaq.Na2SO4. Different thermodynamic variables such as Gibbs free energy (ΔGco), enthalpy (ΔHco), and entropy (ΔSco) changes of clouding were computed to evaluate the nature of interactions between CTS and TX-100 in various electrolytes and hydrotropes medium. The ΔGco was found to be positive in every case indicating the non-spontaneity of the phase separation process. The enthalpy–entropy compensation was analyzed in the respective mixtures and the plot of ΔHc0 vs ΔSc0 showed a linear relationship between them. The findings of this study may be highly useful in different pharmaceutical formulations. These interesting results can also be utilized as significant tools to understand the behaviors of drugs-surfactants interactions in various systems used in different pharmaceutical industries as well as in medical science.