Search Results (73)

This short review describes the expansion of the solvatochromic approach utilizing water-soluble solvatochromic dyes to the analysis of solvent features of aqueous media in solutions of various compounds. These solvent features (polarity/dipolarity, hydrogen bond donor ability (HBD acidity), and hydrogen bond acceptor ability (HBA basicity)) vary depending on the nature and concentration of a solute. Furthermore, the solvent features of water (the solvent dipolarity/polarizability and hydrogen bond donor ability) in solutions of various compounds describe multiple physicochemical properties of these solutions (such as the solubility of various compounds in aqueous solutions, salting-out and salting-in constants for polar organic compounds in the presence of different inorganic salts, as well as water activity, osmotic coefficients, surface tension, viscosity, and the relative permittivity of aqueous solutions of different individual compounds) and are likely related to changes in the arrangement of hydrogen bonds of water in these solutions. Full article

Molecular dynamics simulations have been used to investigate the structural changes in confined liquids. The density distribution functions for weakly and strongly interacting liquids were determined and compared to those of a non-interacting system in order to assess the impact of the entropic forces on the equilibrium state of the systems. The effect of the entropic forces was assessed by quantifying the layering on the liquid structure upon confinement. The more pronounced layering obtained for weakly interacting and non-interacting systems indicated that entropic forces are more effective in these systems where an increase in the multiplicity of states does not require a prohibitively high cost in energy. Full article

Many reactions are carried out in solvent mixtures, mainly because of practical reasons. For example, E2 eliminations are favored over S_N2 substitutions in aqueous organic solvents because the bases are desolvated. This example raises the question: how do we chose binary solvents to favor reaction outcomes? This important question is deceptively simple because it requires that we understand the details of all interactions within the system. Solvatochromism (solvent-dependent color change of a substance) has contributed a great deal to answer this difficult question, because it gives information on the interactions between solvents, solute-solvent, and presumably transition state-solvent. This wealth of information is achieved by simple spectroscopic measurements of selected (solvatochromic) substances, or probes. An important outcome of solvatochromism is that the probe solvation layer composition is almost always different from that of bulk mixed solvent. In principle, this difference can be exploited to “tune” the composition of solvent mixture to favor the reaction outcome. This minireview addresses the use of solvatochromic probes to quantify solute-solvent interactions, leading to a better understanding of the complex effects of solvent mixtures on chemical phenomena. Because of their extensive use in chemistry, we focus on binary mixtures containing protic-, and protic-dipolar aprotic solvents. Full article

This review article is devoted to the colloidal properties of fullerene solutions. According to generally accepted understandings, all solvents in relations to fullerenes are divided into “good”, “poor”, and “reactive”. We have consistently considered the state of fullerenes in these systems. In “good”, predominantly non-polar aromatic solvents and CS₂, non-equilibrium dissolution methods lead to the formation of colloidal aggregates, whereas the utilization of equilibrium methods results in the formation of molecular solutions. The latter, however, have some unusual properties; new results considered in this review confirm previously expressed ideas about colloidal properties of these solutions. In “poor” (polar) solvents, lyophobic colloidal systems appear. Both “bottom-up” and “top-down” methods of preparation are well documented in the literature. However, N-methylpyrrolidine-2-one, DMSO, and DMF dissolve fullerenes quite easily and with less energy consumption. These solvents can be considered a subset of “poor” solvents that have some features of being “reactive” at the expense of basic properties. New data confirm that hydrosols of fullerenes are typical hydrophobic colloids that obey the Schulze–Hardy rule and other regularities in the presence of electrolytes. Organosols in acetonitrile and methanol are much less stable with respect to the effects of electrolytes. This allows us to assume a non-DLVO stabilizing factor in the hydrosols. Accordingly, a new estimate of the Hamaker constant of fullerene–fullerene interaction is proposed. In DMSO and DMF, the coagulation of fullerene sols is hindered due to strong solvation with these basic solvents. Full article

The pivotal role of proteins in pharmaceuticals is challenged by stability issues, making the study of inclusion bodies—a source of insoluble protein aggregates—increasingly relevant. This review outlines the critical procedures in inclusion body processing, focusing on ’mild solubilization concepts’ and refolding methodologies. Attention is afforded to the emerging role of ionic liquids with unique and tunable physicochemical properties in optimizing protein unfolding and refolding processes. The review critically assesses the existing literature at the intersection of inclusion bodies and ionic liquids, identifying recent advancements, potential applications, and avenues for future research. This comprehensive analysis aims to elucidate the complexities in efficient protein processing from inclusion bodies. Full article

The objective of this research is to propose a general model utilizing the solvatochromic polarity of electronic transition energy (ET) of the Reichardt indicator to predict paracetamol solubility in the solvent mixtures. In order to model validation, the available ET (30) values of nine aqueous mixtures obtained from existing literature sources were utilized. The trained model yielded a relatively accurate estimation of paracetamol solubility in the investigated systems. Full article

Intermolecular interactions form the basis of the properties of solvents, such as their polarity, and are of central importance for chemistry; such interactions are widely discussed. Solvent effects were reported on the basis of various polarity probes with the E_T(30) polarity scale of Dimroth and Reichardt being of special interest because of its sensitivity, precise measurability and other advantages, and has been used for the investigation of solvent interactions. A two-parameter equation for the concentration dependence of medium effects has been developed, providing insights into structural changes in liquid phases. Moving from condensed gases to binary solvent mixtures, where the property of one solvent can be continuously transformed to the other, it was shown how the polarity of a solvent can be composed from the effect of polar functional groups and other structural elements that form the matrix. Thermochromism was discussed as well as the effect of very long-range interactions. Practical applications were demonstrated. Full article

The reported total Hildebrand solubility parameter (δ₂) value of meloxicam, as calculated based on the group contribution method proposed by Fedors, was compared with those estimated based on the maximum solubility peaks observed in different aqueous cosolvent systems at T = 298.15 K. Thus, the observed δ₂ values varied from (19.8 to 29.1) MPa^1/2, respectively. Moreover, the Hansen solubility parameters (HSPs) and the total Hildebrand solubility parameter were also determined by using the Bustamante regression method with the reported experimental solubility values of meloxicam in 31 neat solvents (30 organic solvents and water), obtaining the values: δ_d = 19.9 MPa^1/2, δ_p = 16.9 MPa^1/2, δ_h = 5.7 MPa^1/2, and δ_T = 26.7 MPa^1/2. Furthermore, the HSPs of meloxicam were also estimated based on the Hoftyzer–van Krevelen group contribution method, obtaining the values: δ_d = 17.9 MPa^1/2, δ_p = 20.3 MPa^1/2, and δ_h = 9.2 MPa^1/2, and the total solubility parameter as: δ_T = 28.6 MPa^1/2. In addition, the Kamlet–Abboud–Taft linear solvation energy relationship (KAT-LSER) model was also employed to evaluate the role of different intermolecular interactions on the dissolution of meloxicam in different solvents that varied in terms of polarity and hydrogen bonding capability. Full article

Lyotropic liquid crystals (LLCs) are liquids that have crystalline structures. LLCs as drug delivery systems that can deliver hydrophobic, hydrophilic, and amphiphilic agents. Due to their unique phases and structures, LLCs can protect both small molecules and biologics from the gastrointestinal tract’s harsh environment, thus making LLCs attractive as carriers for oral drug delivery. In this review, we discuss the advantages of LLCs and LLCs as oral formulations targeting intestinal lymphatic transport. In oral LLC formulations, the relationship between the micelle compositions and the resulting LLC structures as well as intestinal transport and absorption were determined. In addition, we further demonstrated approaches for the enhancement of intestinal lymphatic transport: (1) lipid-based LLCs promoting chylomicron secretion and (2) the design of LLC nanoparticles with M cell-triggered ligands for targeting the M cell pathway. In this review, we introduce LLC drug delivery systems and their characteristics. Our review focuses on recent approaches using oral LLC drug delivery strategies targeting the intestinal lymphatic system to enhance drug bioavailability. Full article

Materials that generate structural color may be promising alternatives to dyes and pigments due to their relative long-term stability and environmentally benign properties. Liquid crystal (LC) mixtures of cholesteryl esters demonstrate structural color due to light reflected from the helical structure of the self-assembled molecules. The apparent color depends on the pitch length of the liquid crystal. While a wide range of colors have been achieved with such LC formulations, the nature of the pitch–concentration relationship has been difficult to define. In this work, various machine learning approaches to predict the reflected wavelength, i.e., the position of the selective reflection band, based on LC composition are compared to a Scheffe cubic model. The neural network regression model had a higher root mean squared error (RMSE) than the Scheffe cubic model with improved predictions for formulations not included in the dataset. Decision tree regression provided the best overall performance with the lowest RMSE and predicted position of the selective reflection band within 0.8% of the measured values for LC formulations not included in the dataset. The predicted values using the decision tree were over two-fold more accurate than the Scheffe cubic model. These results demonstrate the utility of machine learning models for predicting physical properties of LC formulations. Full article

Due to the similarity of host–guest complexes and protein–ligand and protein–protein assemblies, computational tools for protein–drug complexes are commonly applied in host–guest binding. One of the methods with the highest popularity is the end-point free energy technique, which estimates the binding affinity with gas-phase and solvation contributions extracted from simplified end-point sampling. Our series papers on a set of carboxylated-pillararene host–guest complexes have proven with solid numerical evidence that standard end-point techniques are practically useless in host–guest binding, but alterations, such as slightly increasing interior dielectric constant in post-processing calculation and shifting to the multi-trajectory realization in conformational sampling, could better the situation and pull the end-point method back to the pool of usable tools. Also, the force-field selection plays a critical role, as it determines the sampled region in the conformational space. In the current work, we continue the efforts to explore potentially promising end-point modifications in host–guest binding and further extend the sampling time to an unprecedent length. Specifically, we comprehensively benchmarked the shift from the original MM description to QM Hamiltonians in post-processing the popular single-trajectory sampling. Two critical settings in the multi-scale QM/GBSA regime are the selections of the QM Hamiltonian and the implicit-solvent model, and a scan of combinations of popular semi-empirical QM Hamiltonians and GB models is performed. The multi-scale QM/GBSA treatment is further combined with the three-trajectory sampling protocol, introducing a further advanced modification. The sampling lengths in the host–guest complex, solvated guest and solvated host ensembles are extended to 500 ns, 500 ns and 12,000 ns. As a result, the sampling quality in end-point calculations is unprecedently high, enabling us to draw conclusive pictures of investigated forms of modified end-point free energy methods. Numerical results suggest that the shift to the QM Hamiltonian does not better the situation in the popular single-trajectory regime, but noticeable improvements are observed in the three-trajectory sampling regime, especially for the DFTB/GBSA parameter combination (either DFTB2 or its third-order extension), the quality metrics of which reach an unprecedently high level and surpass existing predictions (including costly alchemical transformations) on this dataset, hinting on the applicability of the advanced three-trajectory QM/GBSA end-point modification for host–guest complexes. Full article

Diffusiophoresis is the migration of a macromolecule in response to a concentration gradient of a cosolute in liquids. Diffusiophoresis of polyethylene glycol (PEG) in water occurs from high to low concentration of trimethylamine-N-oxide (TMAO). This is consistent with the preferential hydration of PEG observed in the presence of TMAO. In other words, PEG migrates in the direction in which it lowers its chemical potential. On the other hand, although PEG is found to preferentially bind urea in water, PEG diffusiophoresis still occurs from high to low urea concentration. Thus, PEG migrates in the direction that increases its chemical potential in the urea case. Here, a ligand-binding model for polymer diffusiophoresis in the presence of a cosolute that preferentially binds to polymer is developed. It includes both actual polymer–ligand binding and the effect of the polymer on cosolute thermodynamic activity. This model shows that polymer–cosolute binding has a marginal effect on polymer diffusiophoresis and indicates that weak repulsive interactions, such as hard-core exclusion forces, are the main factor responsible for the observed PEG diffusiophoresis from high to low urea concentration. This work contributes to a better understanding of diffusiophoresis of macromolecules in response to gradients of nonelectrolytes. Full article

Spectrophotometric measurements were used to determine the mole fraction solubilities of vitamin K4 dissolved in cyclohexane, methylcyclohexane, 1-heptanol, 2-butanol, 2-pentanol, 2-methyl-1-butanol, 4-methyl-2-pentanol, and cyclopentanol at 298.15 K. Results from our experimental measurements, combined with the published solubility data, are used to calculate the solute descriptors of the vitamin K4 solute. The calculated solute descriptors describe the observed solubility data to within an overall standard deviation of 0.110 log units. The calculated solute descriptors were also used to estimate the several blood-to-rat tissue partition coefficients of vitamin K4, as well as the equilibrium vapor pressure above the solid vitamin at 298 K, and the vitamin’s enthalpy of solvation in both water and in 1,4-dioxane organic mono-solvent. Full article

Deep eutectic solvents (DESs) have emerged as novel alternatives to common solvents and VOCs. Their employment as electrolytes in batteries has been an area of intense research. In this context, understanding changes in the physicochemical properties of DESs in the presence of Li salts becomes of utmost importance. Solvatochromic probes have the potential to gauge such changes. It is reported herein that one such UV–vis molecular absorbance probe, Reichardt’s betaine dye 33, effectively manifests changes taking place in a DES Glyceline composed of H-bond accepting salt choline chloride and H-bond donor glycerol in a 1:2 molar ratio, as salt LiCl is added. The lowest energy intramolecular charge–transfer absorbance band of this dye exhibits a 17 nm hypsochromic shift as up to 3.0 molal LiCl is added to Glyceline. The estimated $E_T^N$ parameter shows a linear increase with the LiCl mole fraction. Spectroscopic responses of betaine dye 33, N,N-diethyl-4-nitroaniline and 4-nitroaniline are used to assess empirical Kamlet–Taft parameters of dipolarity/polarizability (${\pi }^{*}$), H-bond-donating acidity (α) and H-bond-accepting basicity ($\beta$) as a function of LiCl concentration in Glyceline. LiCl addition to Glyceline results in an increase in α and no change in ${\pi }^{*}$ and $\beta$. It is proposed that the added lithium interacts with the oxygen of the –OH functionalities on the glycerol rendering of the solvent with increased H-bond-donating acidity. It is observed that pyrene, a popular fluorescence probe of solvent polarity, does respond to the addition of LiCl to Glyceline, however, the change in pyrene response starts to become noticeable only at higher LiCl concentrations ($m_{\mathrm{L}\mathrm{i}\mathrm{C}\mathrm{l}}$ ≥ 1.5 m). Reichardt’s betaine dye is found to be highly sensitive and versatile in gauging the physicochemical properties of DESs in the presence of LiCl. Full article

The self-organization properties of C₇₀ fullerene molecules in a xylene/tetrahydrofuran binary mixture were studied for the first time by optical absorption, refractometry, and dynamic light scattering. A correlation has been established between the change in the refractive index of the C₇₀/xylene/tetrahydrofuran solution and the degree of self-organization of C₇₀ molecules in the medium at various concentrations and storage periods of the solution. It is shown that the features of the optical absorption spectrum of C₇₀/xylene/tetrahydrofuran at a fixed low concentration of fullerene are sensitive to its storage time. It was determined that the beginning time of the formation of C₇₀ nanoclusters and their final size depend on the degree of concentration of fullerene and the time spent keeping the solution. The observed nature of the C₇₀ fullerene solution in a binary mixture may help to elucidate its mechanism of self-organization in the future. Full article