Prediction of the octanol-water partition constant of neutral compounds by reversed-phase liquid chromatography using alternative organic solvent modifiers.

Reversed-phase liquid chromatography (RPLC) offers significant advantages over traditional methods for estimating octanol-water partition constants, which are a critical parameter in drug discovery. In contrast to classical methods for determining the octanol-water partition constant, such as shake-flask techniques, RPLC is less time-consuming and easier to automate. In this study, we explored three alternative organic solvent modifiers: acetone, 2-propanol, and tetrahydrofuran for the indirect determination of the octanol-water partition constant for neutral compounds by RPLC using either isocratic retention factors or retention factors extrapolated to 100 % water for several stationary phases.

Predicting biophysical properties of small molecules from chromatographic measurements and the solvation parameter model.

Biopartitioning processes are challenging to study and often require the sacrifice of multiple animals. Therefore, it is more practical and cost-effective to correlate these processes with easily determined properties, such as chromatographic retention data, or to make predictions based on structural descriptors such as quantitative structure-property relationships or linear free energy relationships. Abraham's solvation parameter model uses six solute properties to characterize the interactions responsible for the transfer of neutral compounds between immiscible phases in chromatographic or biological systems.

Evaluation of the Goss-modified solvation parameter model for the characterization of biphasic systems and descriptor assignments.

The solvation parameter model uses six descriptors identified as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L to model the distribution of neutral compounds in biphasic systems. Abraham's version of this model uses all six descriptors with two separate linear free energy relationship models for the transfer of compounds from a gas phase to a condensed phase and between condensed phases. Goss proposed a modification to this model that uses a single calibration model regardless of the physical state for each phase and five of the descriptors employed in Abraham's model (E descriptor is eliminated).

Guidelines for descriptor assignments for the solvation parameter model by separation techniques.

The solvation parameter model uses six compound descriptors to model equilibrium properties in biphasic systems formally defined as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L. The V descriptor can be assigned from structure and the E descriptor for compounds liquid at 20 °C can be calculated from its refractive index and characteristic volume. The E descriptor for compounds solid at 20 °C and the S, A, B, and L descriptors are assigned from experimental properties traditionally obtained by chromatographic, liquid-liquid partition, and solubility measurements.

Assessment of liquid-liquid partition for the assignment of descriptors for the solvation parameter model.

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index.

Determination of solvation parameter model compound descriptors by gas chromatography.

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and the gas-liquid partition constant at 25 °C on n-hexadecane, L, to model transfer properties in gas-condensed phase biphasic systems. The E descriptor for compounds liquid at 20 °C is available by calculation using a refractive index value while E for solid compounds at 20 °C and the S, A, B, and L descriptors are determined by experiment. As a single-technique approach, it is shown that with up to 20 retention factor measurements on four columns comprising a poly(siloxane) containing methyloctyl or dimethyldiphenylsiloxane monomers (SPB-Octyl or HP-5), a poly(siloxane) containing methyltrifluoropropylsiloxane monomers (Rtx-OPP or DB-210), a poly(siloxane) containing bis(cyanopropylsiloxane) monomers (HP-88 or SGE BPX-90), and a poly(ethylene glycol) stationary phase (DB-WAXetr or HP-INNOWAX) are suitable for assigning the S, A, and L descriptors.

Determination of the hydrogen-bond basicity descriptor by reversed-phase liquid chromatography.

Except for alkanes, most organic compounds are hydrogen-bond bases. The B° descriptor of the solvation parameter model provides a convenient measure of the effective (or summation) hydrogen-bond basicity of organic compounds. A fast and convenient method to assign the B° descriptor is required to support studies of hydrogen-bonding in separation systems.

Determination of descriptors for the principal flavor compounds of the cinnamons of commerce by gas chromatography and liquid-liquid partition.

Descriptors for fourteen semivolatile organic compounds associated with the authenticity, botanical origin, and flavor potential of the cinnamons of commerce were determined using the Solver method and experimental retention factors determined by gas chromatography at several temperatures on a minimum of seven selectivity-selected, open-tubular columns and liquid-liquid partition constants in up to twenty totally organic biphasic systems. The six descriptors that encode the solvation properties of the compounds were used to predict water-gas, octanol-gas, and octanol-water partition constants commonly employed to assess environmental distribution properties. For octanol-water partition constants, log K, the predicted partition constants exhibited an average absolute deviation of 0.

Revised descriptors for polycyclic aromatic and related hydrocarbons for the prediction of environmental properties using the solvation parameter model.

Revised descriptors for twenty-five polycyclic aromatic and related hydrocarbons (PAHs) forming a component of the Wayne State University (WSU) descriptor database are provided for use with the solvation parameter model. The descriptors are determined by the Solver method using experimental data for calibrated gas-liquid and reversed-phase liquid chromatographic retention factors and liquid-liquid partition constants in totally organic biphasic systems. The characteristic solvation properties of the PAHs are accounted for mainly by the additional dispersion interactions (E descriptor) and dipole-type interactions (S descriptor) resulting from the availability of easily polarizable electrons that complement typical dispersion interactions for saturated hydrocarbons.

The effect of the assigned descriptors for phthalate esters on the characterization of their separation properties using the solvation parameter model.

Revised descriptors are determined for fifteen phthalate esters for use in the solvation parameter model and form part of the Wayne State University (WSU) compound descriptor database. For thirteen phthalate esters a comparison is made with the same compounds in the Abraham descriptor database. Gas chromatographic retention factors on poly(methyloctylsiloxane), SPB-Octyl, and poly(cyanopropylphenyldimethylsiloxane), DB-225, stationary phases are used to facilitate an assessment of the contribution of cavity formation and dispersion interactions, L descriptor, and dipole-type interactions, S descriptor, to the experimental retention factors (log k) for the phthalate esters with minimum interference from competing intermolecular interactions.

The effect of descriptor database selection on the physicochemical characterization and prediction of water-air, octanol-air and octanol-water partition constants using the solvation parameter model.

The distribution of neutral compounds in biphasic separation systems can be described by the solvation parameter model using six solute properties, or descriptors. These descriptors (McGowan's characteristic volume, excess molar refraction, dipolarity/polarizability, hydrogen-bond acidity and basicity, and the gas-liquid partition constant on n-hexadecane at 298.15 K) are curated in two publicly accessible databases for hundreds (WSU compound descriptor database) or thousands (Abraham compound descriptor database).

Selectivity evaluation of extraction systems.

Extraction is the most common sample preparation technique prior to chromatographic analysis for samples which are too complex, too dilute, or contain matrix components incompatible with the further use of the separation system or interfere in the detection step. The most important extraction techniques are biphasic systems involving the transfer of target compounds from the sample to a different phase ideally accompanied by no more than a tolerable burden of co-extracted matrix compounds. The solvation parameter model affords a general framework to characterize biphasic extraction systems in terms of their relative capability for solute-phase intermolecular interactions (dispersion, dipole-type, hydrogen bonding) and within phase solvent-solvent interactions for cavity formation (cohesion).

Sample preparation for planar chromatography.

High-performance thin-layer chromatography has favorable properties for high-throughput separations with a high matrix tolerance. Sample preparation, however, is sometimes required to control specific matrix interferences and to enhance the detectability of target compounds. Trends in contemporary applications have shifted from absorbance and fluorescence detection to methods employing bioassays and mass spectrometry.

The influence of descriptor database selection on the solvation parameter model for separation processes.

The distribution of neutral compounds in biphasic separation systems can be described by the solvation parameter model using six solute properties, or descriptors. These descriptors characterize the size (McGowan's characteristic volume), V, excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity and basicity, A and B, and the gas-liquid partition constant on n-hexadecane at 298.15 K, L.

Recent advances for estimating environmental properties for small molecules from chromatographic measurements and the solvation parameter model.

The transfer of neutral compounds between immiscible phases in chromatographic or environmental systems can be described by six solute properties (solute descriptors) using the solvation parameter model. The solute descriptors are size (McGowan's characteristic volume), V, excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity and basicity, A and B, and the gas-liquid partition constant on n-hexadecane at 298.15 K, L.

Planar chromatography - Current practice and future prospects.

Planar chromatography, in the form of thin-layer or high-performance thin-layer chromatography (TLC, HPTLC), continues to provide a robust and widely used separation technique. It is unrivaled as a simple and rapid qualitative method for mixture analysis, or for finding bioactive components in mixtures. The format of TLC/HPTLC also provides a unique method for preserving the separation, enabling further investigation of components of interest (including quantification/structure determination) separated in both time and space from the original analysis.

Analysis of the solvent strength parameter (linear solvent strength model) for isocratic separations in reversed-phase liquid chromatography.

The solvent strength parameter (slope) and intercept (log k) of the linear solvent strength model are determined for methanol-water (17 columns), acetonitrile-water (15 columns), acetone-water (7 columns), tetrahydrofuran-water (6 columns), and 2-propanol-water (4 columns) for varied compounds. It is shown that the linear region of the plots of the retention factor (log k) against the volume fraction of organic solvent (ϕ) is largely a system property independent of solute type for compounds with accessible retention factors. Solvent strength parameters for methanol (3.

Solvation parameter model: Tutorial on its application to separation systems for neutral compounds.

The solvation parameter model affords a useful tool to model distribution properties of neutral compounds in biphasic separation systems. Common applications include column characterization and method development in gas chromatography; reversed-phase, micellar and hydrophilic interaction liquid chromatography; supercritical fluid chromatography; and micellar electrokinetic chromatography. The characterization of the distribution properties of liquid-liquid partition systems is another major application of this model.

Determination of physicochemical properties of ionic liquids by gas chromatography.

Over the years room temperature ionic liquids have gained attention as solvents with favorable environmental and technical features. Both chromatographic and conventional methods afford suitable tools for the study of their physicochemical properties. Use of gas chromatography compared to conventional methods for the measurement of physicochemical properties of ionic liquids have several advantages; very low sample concentrations, high accuracy, faster measurements, use of wider temperature range and the possibility to determine physicochemical properties of impure samples.

Selectivity evaluation of core-shell sislica columns for reversed-phase liquid chromatography using the solvation parameter model.

For the selectivity evaluation of core-shell silica, siloxane-bonded reversed-phase columns by the solvation parameter model a minimal set of thirty-five calibration compounds were identified for applications with mobile phases containing from 20-70 % (v/v) methanol- or acetonitrile-water. The Kennard-Stone uniform mapping algorithm was employed to select the calibration compounds from a larger database of compounds with known retention properties used previously for column selectivity evaluation. The number and identity of the calibration compounds was optimized by considering the statistical quality of the calibration models, the absolute value for the standard deviation of the individual system constants, and the closeness of the estimated system constants for the calibration models to the values for the full data set on seven core-shell columns with different morphology for mobile phases containing 50 % (v/v) methanol- or acetonitrile-water.

Selection of calibration compounds for selectivity evaluation of siloxane-bonded silica columns for reversed-phase liquid chromatography by the solvation parameter model.

For the faster evaluation of selectivity in reversed-phase liquid chromatography of siloxane-bonded silica columns using the solvation parameter model a minimal set of calibration compounds is described suitable for mobile phase composition from 20-70% (v/v) methanol-, acetonitrile-, or tetrahydrofuran-water. The Kennard-Stone uniform mapping algorithm is used to select the calibration compounds from a larger database of compounds with known retention properties used earlier for column selectivity evaluation. Thirty-five compounds are shown to be necessary to minimize the standard deviation of the system constants and to minimize the difference between the system constants determined by conventional calibration and the values obtained for the reduced calibration compounds.

Selection of calibration compounds for selectivity evaluation of wall-coated, open-tubular columns for gas chromatography by the solvation parameter model.

To facilitate faster selectivity evaluation of wall-coated, open-tubular columns using the solvation parameter model a reduced set of calibration compounds is identified and validated for the temperature ranges 60-140 °C and 160-260 °C. The Kennard-Stone uniform mapping algorithm is used to identify the calibration compounds from a larger database of compounds with known retention properties previously adopted for column selectivity evaluation. Thirty-five compounds for each temperature range are required to minimize the standard deviation of the system constants used for selectivity evaluation and to minimize differences between system constants determined by conventional calibration and the reduced calibration compounds.

Recent advances in analytical methods for the determination of citrinin in food matrices.

Citrinin is a toxic small organic molecule produced as a secondary metabolite by fungi types Penicillium, Monascus and Aspergillus and is known to contaminate various food commodities during postharvest stages of food production. During the last 10 years, most reported methods for citrinin analysis employed enzyme-linked immunosorbent assays or high-performance liquid chromatography. Over this same time period, liquid extraction, solid-phase extraction, dispersive liquid-liquid microextraction and QuEChERS were the most cited sample preparation and clean-up methods.

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 C, XBridge Shield RP, 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.

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.