Solvent Parameters Research Articles

Equilibrium solubility, preferential solvation and solvent effect study of clotrimazole in several aqueous co-solvent solutions

The equilibrium solubility of clotrimazole in co-solvent mixtures of n-propanol/isopropanol/acetonitrile/1,4-dioxane + water was attained by the saturation shake-flask technique at temperatures between 278.15 K and 323.15 K under ambient pressure of 101.2 kPa. The solubility of clotrimazole in mole fraction scale increased with increasing temperature and mass fractions of n-propanol/isopropanol/acetonitrile/1,4-dioxane. The maximum value was recorded in the neat co-solvent for each mixture studied. The Jouyban-Acree model and van’t Hoff-Jouyban-Acree model were applied to mathematically describe the dependence of clotrimazole solubility upon the co-solvent content and temperature, obtaining the values of relative average deviations and root-mean-square deviations no more than 8.02 × 10−2 and 8.17 × 10−4, individually. KAT-LSER model was implemented to quantitatively acquire evidence about solvent effect upon the variation of clotrimazole solubility magnitudes. The variation in clotrimazole solubility mainly depended upon the Hildebrand solubility parameter and dipolarity-polarizability of solutions in the four aqueous systems studied. Quantitative investigation was carried out for the local mole fractions of n-propanol/isopropanol/acetonitrile/1,4-dioxane and water around solute clotrimazole by using the Inverse Kirkwood–Buff integrals way utilized to the solubility data determined. Clotrimazole was preferentially solvated by n-propanol/isopropanol/acetonitrile/1,4-dioxane for these aqueous co-solvent mixtures in intermediate and n-propanol/isopropanol/acetonitrile/1,4-dioxane-rich proportions.

Determination of physicochemical properties of small molecules by reversed-phase liquid chromatography.

The physicochemical properties of small molecules that can be determined by retention measurements in reversed-phase liquid chromatography include solvent-based properties inferred from equilibrium processes occurring predominantly in the mobile phase and sorption properties for materials which can be used as stationary phases inferred from solute-stationary phase interactions. In addition, physicochemical properties can be estimated from correlation models based on surrogate chromatographic systems with a similar capability for intermolecular interactions to the chemical or biological system. Examples of properties determined by direct methods include molecular descriptors (solvation parameter model), acid dissociation constants, formation constants, and surface properties of solids determined by inverse liquid chromatography. Examples of properties estimated by indirect methods include hydrophobicity, lipophilicity, n-octanol-water partition constant, soil-water sorption constant, non-specific toxicity to fish and microorganisms, and permeation coefficients for the blood-brain and skin-water barriers. Since all approaches depend on an accurate measurement of chromatographic retention parameters typical operational and mechanistic problems are discussed from the perspective of data quality. Fundamentally the accuracy of direct methods is limited by stationary phase heterogeneity and indirect methods by the limited number of suitable surrogate chromatographic models.

Rutaecarpine dissolved in binary aqueous solutions of methanol, ethanol, isopropanol and acetone: Solubility determination, solute-solvent and solvent-solvent interactions and preferential solvation study

The main objective of this work was to report the mole fraction solubility of rutaecarpine in four binary solutions of methanol (1) + water (2), isopropanol (1) + water (2), acetone (1) + water (2) and ethanol (1) + water (2) acquired through the saturation shake-flask technique. All experiments were conducted at temperatures from 283.15 K to 323.15 K. The maximum solubility was observed in the pure solvent of methanol/ethanol/isopropanol/acetone for each solution. The achieved rutaecarpine solubility in mole fraction was mathematically described by two common co-solvency models, namely Jouyban-Acree model and van’t Hoff-Jouyban-Acree model. The calculated relative average deviations were no more than 6.78%; and root-mean-square deviations, no more than 23.69 × 10−6. The linear solvation energy relationships suggested by Kamlet and Taft was used to examine the effect of solvent descriptors on the behaviour of rutaecarpine solubility. The Hildebrand solubility parameter and dipolarity-polarizability were predominant contributors to solvent effect for the four mixtures studied. The local mole fractions of methanol (acetone, isopropanol or ethanol) and water nearby the solute rutaecarpine were quantitatively analyzed through an Inverse Kirkwood–Buff integrals method. For these mixtures within intermediate and methanol/ethanol/isopropanol/acetone-rich compositions, rutaecarpine was preferentially solvated by the methanol/ethanol/isopropanol/acetone; while within water-rich compositions, by the water.

Machine Learning for Polymer Swelling in Liquids

Swelling in liquids is of paramount importance for polymers used in many liquid-phase applications. This critical property has motivated numerous analytical theories and empirical experiments as well as recent atomistic simulations; however, a data-driven approach for polymer swelling is currently not available. In this study, we develop a machine learning (ML) methodology to investigate polymer swelling in liquids. This methodology is illustrated for the swelling of organic solvent nanofiltration (OSN) membranes and polydimethylsiloxane (PDMS) in various solvents. First, chemically intuitive descriptors such as solubility parameters and solvent properties are proposed to construct ML models. Using kernel ridge regression, the model based on the solubility parameters of the solvent and polymer is found to offer the best quantitative prediction and reveal multimodal swelling behavior for OSN membranes. For PDMS swelling, the solubility parameter and geometry of solvent are identified to be key properties. Then, a molecular representation via the sum-of-fragments approach is proposed and demonstrated remarkable predictive capability. Through appropriate data augmentation, reasonable out-of-sample prediction is achieved for polyetherimide swelling in nine solvents and PDMS swelling in substituted aromatic solvents. Finally, principal component analysis is applied to the proposed sum-of-fragments to explore its suitability as a molecular representation and the chemical space of polymer swelling. The relationships between molecular fragments and swelling degrees are quantitatively determined by Pearson correlations. This ML study demonstrates the development and utilization of physically meaningful chemical descriptors to construct models capable of superior prediction and unraveling fundamental insight into polymer swelling. Such a methodology can also be extended to other physical properties for polymers in liquids, thereby expanding its scope of potential applications.

Prediction of the Oral Bioavailability Correlation Between Humans and Preclinical Animals.

Experimental determination of a drug's oral bioavailability in humans is cost and time consuming; therefore,isusually performed on preclinical animals. It is believed that animal data are predictive of human data; however, there are some doubts regarding the reliability of this concept. The aim of this study is to clarify whether it is possible to predict a correlation between human and animal bioavailability data based on structural parameters. Oral bioavailability data of drugs for humans and preclinical animals (rats and dogs) were collected from the literature. Structural descriptors [Abraham solvation parameters, topological polar surface area (TPSA), logarithm of partition coefficient (logP) and logarithm of distribution coefficient at pH = 6.8 (logD6.8)] were calculated by ACD/Labs software. Data were divided into two classes by percentage deviation (PD) of oral bioavailability between humans and preclinical animals (PD < 40%: class I and PD > 40%: class II). Classification-based models were used to predict the class of each drug using structural parameters. The results of this study revealed that logD6.8 is the main parameter for evaluation of the correlation between oral bioavailability in humans and animals. Moreover, the developed models using logistic regression based on logP, TPSA and Abraham solvation parameters are able to predict the class of a drug with 75% accuracy. The structural parameters and developed models in this study can be used to find compounds that have an acceptable correlation between oral bioavailabilities in animals, i.e., rats and dogs, and humans.

Activity Coefficient at Infinite Dilution Study of Molecular Interaction-Selectivity in Separation Processes

The activity coefficient at infinite dilution for 47 selected organic solutes in 1-allyl-3-methylimidazolium chloride ([AMIM]Cl) ionic liquid (IL) was determined at 303.15 K to 343.15 K through inverse gas chromatography (IGC). The partial molar excess enthalpy, entropy, Gibbs free energy at infinite dilution, and Hildebrand solubility parameters were obtained from the values of activity coefficient at infinite dilution. The selectivity and capacity of heptane/thiophene, heptane/benzene and benzene/thiophene separation problems were also calculated based on the activity coefficient at infinite dilution values. The selectivity of three separation problems of [AMIM]Cl was 85.36, 30.65 and 2.79, which indicated that [AMIM]Cl is an ideal solvent for the separation of heptane/thiophene.

Insight into the hydrophilic interaction liquid chromatographic retention behaviors of hydrophilic compounds on different stationary phases

In this work, the correlations between retention behavior and lipophilicity of a large set of hydrophilic neutral and ionic analytes were studied based on three hydrophilic interaction liquid chromatography (HILIC) stationary phases, including zwitterionic, crosslinked diol and triazole stationary phases. It was found that HILIC, due to the diversity of retention mechanism, is a more complex chromatography separation mode than reversed-phase liquid chromatography (RPLC) which has been widely accepted for lipophilicity assessment. Because electrostatic interactions contributed to the overall retention of the charged solutes on all three stationary phases, ion-strength of the mobile phase kept the same during the whole experiment. After the correlations between retention factor log k and water volume fraction Φ were investigated, the mixed retention model was revealed to be more suitable for HILIC retention behavior than other single models including partitioning and adsorption model. Moreover, in order to bridge the relationship between HILIC log k and lipophilicity parameter log D, net charge ne and Abraham solvation parameter were introduced in the quantitative structure-retention relationship (QSRR) model. Although the correlation coefficients between log D and log k were still moderate, the significant improvement in correlation has made HILIC a potential choice as the complement of RPLC for log D measurement.

The Solvent Effect on Weak Interactions in Supramolecular Polymers: Differences between Small Molecular Probes and Supramolecular Polymers.

In this minireview, weak interactions that occur in supramolecular polymers are discussed. Combination of weak and strong interactions plays an important role in the construction of supramolecular polymers. It is beneficial to separate the contributions of the weak interactions, as well as each solvent effect on the weak interactions. However, it is generally difficult to observe each solvent effect separately at work in each interaction. Small molecular probes are useful to estimate the contributions of the weak interaction. But, the results should be treated with caution when applied to supramolecular polymer systems. To overcome the problems, a new solvent parameter, solvation ability (SA), is introduced, which was determined on the balance point of extended and stacked forms of porphyrin-based interconvertible supramolecular polymers.

Quaternary‐Ammonium‐Based Gels with Varied Alkyl Chains for the Efficient Removal of Toxic Acid Orange 7

AbstractWe report the design and synthesis of thiol‐norbornene based ingenious gels with pendent quaternary ammonium substituents on the norbornene backbone that are conducive to remove toxic anionic azo dye acid orange 7 (AO7) from wastewater. Three different alkyl side chains on the dangling quaternary ammonium moiety were chosen prudently and their performance towards removal of azo dye was scrutinised. The characterisation of all the precursor monomers and the ensuing gels were accomplished by 1H, 13C NMR and Mass spectrometry. The influence of extent of crosslinking on the solvent uptake ability was investigated and the swelling nature of the gels were correlated with the solubility parameter of different solvents. The surface morphology of the gels as visualised by FE‐SEM analysis, revealed macropores in the range 4–12 μm. The relationship between the composition of quaternary ammonium moiety on the gels and their viscoelastic properties was realised. The dye removal kinetics as observed from UV‐Vis spectra were best correlated with the pseudo‐second‐order model and the adsorption isotherm of dye removal process was best fitted with the Langmuir isotherm model with high correlation coefficient. The material was found to be fairly recyclable up to 10th cycles with loss of only 8% efficiency. To the best of our knowledge, this is the first ever report on the removal of anionic dye based on thiol‐norbornene photo crosslinked network. We believe that this design and composition‐property relationship will enthuse the researchers to develop efficient chemical adsorbents based on environmentally benign systems.

Thermodynamic properties and contact angles of CTAB and SDS in acetone–water mixtures at different temperatures

The thermodynamic properties of sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) in neat water and acetone–water mixtures were studied by measuring the conductivity at 298.15, 308.15, 318.15 and 323.15 K. The critical micelle concentration (CMC), degree of ionization (α), standard Gibbs free energy of micellization (\(\Delta G_{\text{m}}^{\text{o}}\)), standard entropy of micellization (\(\Delta S_{\text{m}}^{\text{o}}\)), standard heat of micellization (\(\Delta H_{\text{m}}^{\text{o}}\)), the heat capacity of micellization (\(\Delta _{\text{m}} C_{\text{P}}^{\text{o}} )\) and free energy of transfer (\(\Delta G_{\text{trans}}^{\text{o}}\)) were evaluated from conductivity data. The contact angles (CAs) were measured using a drop shape analyzer (DSA-25E). The correlation of \(\Delta G_{\text{m}}^{\text{o}}\)with solvent parameters and the solvophobic parameter was explored.

Electronic Properties of Artificial Metal‐DNA Base Pair Complexes Formed from Hydroxypyridone Base

AbstractThe metal‐mediated hydroxypyridone base pairs containing Ni2+, Cu2+, Zn2+, Pd2+, Cd2+, Pt2+, and Hg2+ ions were designed theoretically using by density functional theory (DFT) method in Gaussian 09 program. The calculations which were performed in the gas phase, methanol, water, and formamide were done at B3LYP functional with LANL2DZ and 6–311++G (d, p) basis sets which were used metals and rest atoms, respectively. The Gibbs free energies of the complexes were calculated and their relative stabilities were determined in the mentioned fields. Furthermore, geometric parameters, HOMO, LUMO, energy gap energies of the compounds were computed in all media and effect on these parameters of solvents were determined. Based on these parameters, the relative conductivities of the investigated molecules were predicted. On the other hand, using Atomistix ToolKit (ATK‐VNL) 2016 program, nonequilibrium Green's function (NEGF) calculations based on the combination DFT of the mentioned complexes were carried out. The transport properties of the molecules were found in detailed via NEGF‐DFT method.

Characterization of the thermodynamic properties of ionic liquid 1-allyl-3-vinylimidazolium bis((trifluorompropyl)sulfonyl)imide by inverse gas chromatography

The thermodynamic parameters at infinite dilution for twenty-six organic solutes in 1-allyl-3-vinylimidazolium bis((trifluorompropyl)sulfonyl)imide ([AVIM][NTf2]) ionic liquid were determined by the inverse gas chromatography (IGC). The parameters encompassed the Flory-Huggins interaction parameter (γ12∞), the activity coefficient at infinite dilution (γ12∞), the thermodynamic functions (ΔH1E,∞,ΔS1E,∞) and the Hildebrand solubility parameter (δ2) in the temperature range of 313.15 K − 343.15 K. The values of selectivity and capacity for four separation problems as heptane (1)/benzene (2), cyclohexane (1)/benzene(2), benzene(1)/ methanol(2) , hexane(1) /1-hexene(2) were calculated from γ12∞ and compared to literature values for bis((trifluorompropyl)sulfonyl)imide-based ionic liquids (ILs) for the same separation problems. The Hansen solubility parameter (δT) and its partial solubility parameters (δd, δp, δh) were also determined based on the method proposed by Voelkel and Janas. It was found that for tested solutes, the value of χ12∞was less than 4 and γ12∞value was less than 25 except for the n-alkanes. The five types of solubility parameters showed a linear decrease trend with the increase of temperature and the solubility parameters at room temperature were obtained as δ2 = 23.27, δT = 23.21, δd = 22.78, δp = 3.366, δh = 2.486 (MPa)1/2 by the extrapolation.

Thiamethoxam in aqueous co-solvent mixtures of 1,4-dioxane, N,N-dimethylacetamide, dimethyl sulfoxide and acetonitrile: Solubility solute-solvent and solvent-solvent interactions, and preferential solvation analysis

The determination of equilibrium solubilities of thiamethoxam in solutions of 1,4-dioxane (1) + water (2), N,N-dimethylacetamide (DMAC, 1) + water (2), dimethyl sulfoxide (1) + water (2) and acetonitrile (1) + water (2) was carried out through the shake-flask method from 278.15 to 323.15 K under 101.2 kPa. The relative contributions of solvent–solvent and solute–solvent interactions on the drug solubility variation were studied via the analysis of linear solvation energy relationships. The significant contributions to the solubility variation were the cavity term and dipolarity-polarizability term in aqueous solution of 1,4-dioxane; and cavity term in aqueous solutions of DMAC/DMSO/acetonitrile. The inverse Kirkwood–Buff integrals were employed to investigate the preferential solvation in light of several solution thermodynamic properties. The preferential solvation parameters for 1,4-dioxane, DMAC and acetonitrile presented positive values in the three aqueous solutions within intermediate and 1,4-dioxane/DMAC/acetonitrile-rich compositions, demonstrating that the drug thiamethoxam was solvated preferentially by 1,4-dioxane/DMAC/acetonitrile. It is conjectured that in these regions thiamethoxam serves as a Lewis acid with the 1,4-dioxane and DMAC molecules; while for the (acetonitrile + water) mixture, the preferential solvation could be attributed to polarization effects. Moreover, the solubility data in mole fraction was mathematically described by the van’t Hoff–Jouyban-Acree model and Jouyban-Acree model attaining the average relative deviations no more than 6.67%.

Characterization of retention and separation mechanisms with Pirkle-type enantioselective stationary phases in supercritical fluid chromatography.

In the present study, we characterize a famous Pirkle-type enantioselective stationary phase ((R,R)-Whelk-O1 from Regis Technologies) and an equivalent enantiomeric phase (ReproSil Chiral-NR from Dr. Maisch) in supercritical fluid chromatography (SFC) with carbon dioxide - methanol (90:10 v/v) mobile phase. First, the interactions contributing to retention are evaluated with a modified version of the solvation parameter model, comprising five Abraham descriptors (E, S, A, B, V), two additional descriptors to take account of molecular shape (flexibility F and globularity G), and two additional descriptors to take account of interactions with ionizable species (D- and D+). Linear solvation energy relationships (LSER) are established based on the retention of 212 achiral analytes. As expected, π-π interactions are the most significant to explain retention, while dipole-dipole, hydrogen bonding and ionic interactions with cationic species are of secondary importance. Secondly, the contributions of interactions to enantioseparations are discussed, based on the analysis of 79 racemates. Discriminant analyses (DA) were computed to gain some insight on retention mechanisms. The set of racemates is first divided between racemates eluted earlier than expected based on the LSER models, and those eluted later than expected. Small spherical molecules are more retained than expected, as they may better fit inside the cleft of the chiral selector. They are also most frequently resolved, probably for the same reason. Among the molecules that are less retained than expected, which are rather large and/or non-spherical, other features are favourable to enantiorecognition: π-electrons, dipoles and electron-donating properties. Contrary to the observations on other sorts of chiral selectors, flexibility was found to have no contribution on the enantiorecognition process.

Abraham Solvation Parameter Model: Prediction of Enthalpies of Vaporization and Sublimation of Mono-methyl Branched Alkanes Using Measured Gas Chromatographic Data

Abraham model L solute descriptors have been determined for 174 additional mono-methyl branched alkanes based on published linear-programmed gas chromatographic retention indices. Standard molar enthalpies of vaporization and sublimation at 298 K are calculated for the 174 mono-methylated alkanes using the reported solute descriptors and our recently published Abraham model correlations. Calculated vaporization and sublimation enthalpies derived from the Abraham model compare very favorable with values based on a popular atom-group additivity model. Unlike the additivity model the Abraham model gives different predicted values for each mono-methyl alkane having a given C n H 2n+2 molecular formula

Evaluation of the solvation parameter model as a quantitative structure-retention relationship model for gas and liquid chromatography.

The Wayne State University (WSU) experimental descriptor database is utilized to bench mark the current capability of the solvation parameter model for use as a quantitative structure-retention relationship tool for estimating retention in gas and reversed-phase liquid chromatography. The prediction error for the retention factors of varied compounds on six open-tubular columns for gas chromatography (Rtx-5 SIL MS, DB-35 ms, RtxCLPesticides, HP-88, HP-INNOWAX and SLB-IL76) and three packed columns for reversed-phase liquid chromatography (SunFire C18, XBridge Shield RP18, and XBridge Phenyl) is used to establish expectations related to current practices. Each column data set was divided into a training set for calibration and a test set for validation employing a roughly 1 to 2 split, such that each test set contained about 40 to 80 varied compounds. The average absolute error for the prediction of retention factors by gas chromatography varied from about 0.1 to 0.4 on the retention factor scale with the larger error typical of stationary phases ranked as the most polar (or cohesive). For reversed-phase liquid chromatography the average error for the prediction of retention factors was 0.3 to 0.5 and generally larger than for gas chromatography. Statistical filters where utilized to identify a group of polycyclic aromatic compounds without hydrogen-bonding functional groups with a larger prediction error on the SunFire C18 column than for other compounds of smaller size, flexible structure or containing hydrogen-bonding functional groups. The heterogeneity of the retention mechanism is speculated to be the main contribution to the prediction error for both gas and liquid chromatography using the solvation parameter model.

Structure characteristics and association behavior of coal and petroleum C7-asphaltenes

The structural characteristics and differences of coal tar and petroleum C7-asphaltenes were studied, such as chemical composition, functional groups and molecular structure, using nuclear magnetic resonance (NMR), small angle X-ray scattering (SAXS), X-ray photoelectron spectroscopy (XPS), improved B-L method and other methods. Furthermore, the association behavior and aggregation size of two different types of asphaltenes as well as the hydrogen bonds and acidic-basic interaction were analyzed by asphaltenes solubility parameters in polar solvents. The experiment results showed that the coal tar asphaltenes (CT-asp) was mainly composed of less aromatic rings with short alkyl branched chains and possessed a high aromaticity degree. The higher content oxygen heteroatoms of CT-asp were mostly presented as aromatic ether bonds and phenolic hydroxyl groups. The aromatic nucleus size and the average relative molecular weight of petroleum asphaltenes (M-asp) were larger than that of CT-asp. The M-asp consisted primarily of more aromatic rings with long alkyl branched chains and possessed a low aromaticity degree. The association and aggregation degree between CT-asp and M-asp was associated with the amount of substance ratio (nCT-asp/nM-asp) and their molecular structure characteristics. The association force of two types mainly was the hydrogen bonds and the acidic-basic interaction from heteroatomic functional groups.

Regeneration of used lubricating oil by solvent extraction and phase diagram analysis

The methodology presented in this work is developed for the removal of sludge and thus regenerate the properties of the engine lubricating synthetic oil for its reuse. This was achieved removing contaminants from waste lubricant (WL) by solvent extraction. The technique used analyze ternary phase diagrams of solvent mixtures with WL and dehydrated WL determine regions that allow maximum wet sludge removal. The pair of solvents chosen to create ternary phase diagrams with WL consists of a polar solvent and a non-polar solvent. The pairs of solvents selected were methyl isobutyl ketone (MIBK) and methanol with toluene according to their miscibility with WL and their Hildebrand solubility parameter values. The liquid systems solvent mixture with WL corresponding to the points selected in the ternary phase diagrams were centrifuged to quantify the percentage of wet sludge removal (PWSR) to evaluate the efficiency of the process. The properties of the recovered lubricants were evaluated carrying out tests of viscosity and density at different temperatures as well as flash point. The results were compared to those of the WLO and the new lubricant (NL).

Apixaban (I) in several aqueous co-solvent mixtures: Solubility, solvent effect and preferential solvation

Equilibrium apixaban (I) solubility in isopropanol (1) + water (2), ethanol (1) + water (2), acetone (1) + water (2) and methanol (1) + water (2) mixtures was acquired by a shake-flask method from 288.15 K to 328.15 K under atmospheric pressure of 101.2 kPa. At a certain temperature, the highest apixaban (I) solubility in mole fraction scale was observed in neat solvents of acetone/methanol for the acetone/methanol (1) + water (2) solutions; while for the ethanol/isopropanol (1) + water (2) solutions, the solubility data presented a maximum value with the ethanol/isopropanol mass fraction of about 0.8. The determined solubility values were treated by linear solvation energy relationships in order to explain the solvent effect and find its major descriptors. The preferential solvation was studied by the method of inverse Kirkwood–Buff integrals based on some thermodynamic solution properties. In the methanol (1) + water (2) mixture with compositions 0.31 < x1 < 1, ethanol (1) + water (2) mixture with compositions 0.25 < x1 < 0.58, isopropanol (1) + water (2) mixture with compositions 0.25 < x1 < 0.53, acetone (1) + water (2) mixture with compositions 0.20 < x1 < 1 and 1,4-dioxane (1) + water (2) mixture with compositions 0.175 < x1 < 0.570, the preferential solvation parameters for methanol/ethanol/isopropanol/acetone/1,4-dioxane were positive values, indicating that apixaban (I) was preferentially solvated by the co-solvents. It is conjecturable that in these regions apixaban (I) serves as a Lewis acid with the molecules of organic solvents. Moreover, the drug solubility was correlated through the Jouyban-Acree and van’t Hoff-Jouyban-Acree models attaining average relative deviations less than 9.64%.

Role of stable hydrogen isotope variations in water for drug dissolution managing

Abstract In the present work, we provide the results of defining by utilizing Laser diffraction spectroscopy, the kinetic isotopic effect of solvent and constant of dissolution rate κ, s−1 of аn active pharmaceutical ingredient (API) in water with a different content of a stable 2 1 H _2^1{\rm{H}} isotope on the basis of the laws of first-order kinetics. This approach is based on the analysis of the light scattering profile that occurs when the particles of the dispersion phase in the aquatic environment are covered with a collimated laser beam. For the first time, the dependence of the rate of dissolution is demonstrated not only on the properties of the pharmaceutical substance itself (water solubility mg/ml, octanol–water partition coefficient log P oct/water, topological polar surface area, Abraham solvation parameters, the lattice type), but also on the properties of the solvent, depending on the content of stable hydrogen isotope. We show that the rate constant of dissolution of a sparingly hydrophobic substance moxifloxacin hydrochloride (MF · HCl) in the Mili-Q water is: k=1.20±0.14∙10−2 s−1 at 293.15 K, while in deuterium depleted water, it is k=4.24±0.4∙10−2 s−1. Consequently, we have established the development of the normal kinetic isotopic effect (kH/kD &gt;1) of the solvent. This effect can be explained both by the positions of the difference in the vibrational energy of zero levels in the initial and transition states, and from the position of water clusters giving volumetric effects of salvation, depending on the ratio D/H. The study of kinetic isotopic effects is a method that gives an indication of the mechanism of reactions and the nature of the transition state. The effect of increasing the dissolution of the API, as a function of the D/H ratio, we have discovered, can be used in the chemical and pharmaceutical industries in the study of API properties and in the drug production through improvement in soluble and pharmacokinetic characteristics.