Chau My Du

Rapid Method for the Estimation of Octanol / Water Partition Coefficient (Log Poct) from Gradient RP-HPLC Retention and a Hydrogen Bond Acidity Term (Sigma alpha2H)

We propose a rapid method for the measurement of octanol/water partition coefficients (log P(oct)) via fast gradient reversed phase retention and the calculation of the hydrogen bond acidity of the compounds. The cycle time of the generic gradient HPLC method is 5 minutes. The general solvation equation obtained for the log Poct values and the fast gradient Chromatographic Hydrophobicity Indices with acetonitrile (CHI(ACN)) and methanol

Rapid-Gradient HPLC Method for Measuring Drug Interactions with Immobilized Artificial Membrane: Comparison with Other Lipophilicity Measures

A fast-gradient high-performance liquid chromatographic (HPLC) method has been suggested to characterize the interactions of drugs with an immobilized artificial membrane (IAM). With a set of standards, the gradient retention times can be converted to Chromatographic Hydrophobicity Index values referring to IAM chromatography (CHI(IAM)) that approximates an acetonitrile concentration with which the equal distribution of compound can be achieved between the mobile phase and IAM. The CHI(IAM) values are more suitable for interlaboratory comparison and for high throughput screening of new molecular entities than the log k(IAM) values (isocratic retention factor on IAM). The fast-gradient method has been validated against the isocratic log k(IAM) values using the linear free energy relationship solvation equations based on the data from 48 compounds. The compound set was selected to provide a wide range and the least cross-correlation between the molecular descriptors in the solvation equation: (2) where SP is a solute property (e.g., logarithm of partition coefficients, reversed-phase (RP)-HPLC retention parameters, such as log k, log k(w), etc.) and the explanatory variables are solute descriptors as follows: R(2) is an excess molar refraction that can be obtained from the measured refractive index of a compound, pi(2)(H) is the solute dipolarity/polarizability, summation operatoralpha(2)(H) and summation operatorbeta(2)(0) are the solute overall or effective hydrogen-bond acidity and basicity, respectively, and V(x) is the McGowan characteristic volume (in cm(3)/100 mol) that can be calculated for any solute simply from molecular structure using a table of atomic constants. It was found that the relative constants of the solvation equation were very similar for the CHI(IAM) and for the log k(IAM). The IAM lipophilicity scale was quite similar to the octanol/water lipophilicity scale for neutral compounds. The effect of charge on the interaction with IAM was studied by varying the mobile phase pH.

Selective vapor sorption by polymers and cavitands on acoustic wave sensors: is this molecular recognition?

Selectivity patterns for the sorption of organic vapors from the gas phase into cavitand monolayers on acoustic wave sensors are very similar to those seen for sorption of the same vapors by amorphous polymers, demonstrating that the vapor/cavitand selectivity patterns are determined primarily by solubility interactions. The amorphous polymers serve as controls demonstrating that the three-dimensional structure of a cavitand layer is not primarily responsible for the selectivity observed. Binding and selectivity in the examples cited are governed primarily by general dispersion interactions and not by specific oriented interactions that could lead to molecular recognition.

Unique selectivity of perfluorinated stationary phases with 2,2,2-trifluoroethanol as organic mobile phase modifier

The selectivity of Luna C18 Xterra C18 and Fluophase (perfluorinated C6) stationary phases has been investigated with aqueous acetonitrile, methanol and 2,2,2-trifluoroethanol mobile phases using linear solvation equations. The gradient retention times of a set of 60 compounds with known molecular descriptors have been determined. Linear solvation equations have been set up to describe the relationship between the gradient retention times and the molecular properties. The selectivity of the stationary phase/mobile phase systems was characterised by the regression coefficients of the molecular descriptors. The perfluorinated stationary phase showed very different selectivity using 2,2,2-trifluoroethanol (TFE) as co-solvent. Compounds with H-bond donor functionality were retained much less than in the other investigated high-performance liquid chromatography (HPLC) systems. This unique selectivity can be explained by the stronger adsorption of trifluoroethanol on the perfluorinated stationary phase surface, than on the hydrocarbon surface. It suggests the importance of the adsorbed organic modifiers in the separation mechanism during reversed-phase HPLC.

Rapid method for estimating octanol-water partition coefficient (log POCT) from isocratic RP-HPLC and A hydrogen bond acidity term (A)

The linear solvation equation approach has been used to describe the octanol/water lipophilicity scale (logPoct) and the isocratic retention factors (log k) obtained using reversed phase HPLC with acetonitrile. Both the octanol/water partition coefficients and the RP-HPLC retention data obtained from the literature, showed good correlation with the molecular descriptors such as size, excess molar refractivity, H-bond acidity/basicity, and polarity/dipolarity. However, the impact of the H-bond acidity term was very different on the two lipophilicity scales. The H-bond acidity term was not significant in describing the octanol/water lipophilicity, while the H-bond acidity of the molecules decreased significantly their RP-HPLC retention. As the other terms had very similar impact on the two lipophilicity scales, it made it possible to convert one scale to the other by incorporating only the H-bond acidity of the compounds as is shown by the equation below, where A is the compound H-bond acidity. Using the simpler hydrogen bond donor counts (HBC) also helped to align the two lipophilicity scales to each other. The validity of the above equations was tested using a test set of 41 drug compounds with our measured data. The log Poct values were estimated from isocratic RP-HPLC retention data with the H-bond acidity term and counts, with an error of 0.284 and 0.325 log unit, respectively.

Hydrogen bonding. Part 29. Characterization of 14 sorbent coatings for chemical microsensors using a new solvation equation

Gas-liquid partition coefficients, K, have been obtained for 20–70 solute analytes on 14 candidate phases for chemical microsensors at 298 K and on three of the phases at higher temperatures. The phases can then be characterized through the equation log K=c+rR2+sπ2H+aΣαH2+bΣβH2+llog L16 where log K relates to a series of solutes on the same phase. The explanatory variables are solute parameters, R2 an excess molar refraction, πH2 the solute dipolarity–polarizability, ΣαH2 and ΣβH2 the solute hydrogen bond acidity and basicity and L16 where L16 is the K-value on hexadecane. The coefficients in the above equation then characterize the particular phase, the most important being s the phase dipolarity–polarizability, a the phase basicity, b the phase acidity and I a constant that reflects a combination of cavity effects and general dispersion interactions and is related to the ability of the phase to distinguish between homologues. Derivation of the constants for the various phases provides a quantitative method for the analysis of the selectivity of phases for particular solute analytes and a termby-term investigation of log K values shows exactly the solubility interactions that lead to sorption of a solute by a phase and hence to the analytical determination of the solute through chemical microsensors.

Comparison of uncorrected retention data on a capillary and a packed hexadecane column with corrected retention data on a packed squalane column

Abstract Retention data obtained previously at 25°C on a hexadecane capillary column by Zhang et al. and a packed hexadecane column by Abraham et al., both uncorrected for any effects due to interfacial adsorption, were compared with retention data obtained by Poole et al. on a packed squalane column at 120°C, with the latter fully corrected for such effects. It is shown that for most solutes, the capillary and packed column data are equally compatible with the squalene corrected data, but for the solutes dimethyl sulfoxide, dimethylformamide and dimethylacetamide the packed column data are in much better accord with the corrected data than are the capillary column data. It is further shown that both sets of results at 25°C for carboxylic acids are in error, owing to dimerization. Retention volumes on Chromosorb G AW DMCS are reported at 25 and at 93°C. It is shown that at 25°C, there could be some contribution to solute retention from adsorption on the support, but that this is almost impossible at 93°C.

On the prediction of polymer-probe χ and Ω values from inverse gas-chromatographic data

Abstract The solvation equation Log V G =c+rR 2 +s π 2 H +a α 2 H +b β 2 H +1 log L 16 has been applied to the solubility of 24 probes on poly(butadiene) at 353, 363 and 373 K using VG values obtained by Romdhane and Danner by inverse gas-chromatography. In the above equation the explanatory variables are solute probe parameters as follows: R2 is an excess molar refraction, π2H is the probe dipolarity/polarizability, α2H and β2H are the probe hydrogen-bond acidity and basicity, and L16 is the probe gas-liquid partition coefficient on hexadecane at 298 K. It is shown that log VG can be predicted to ± 0.04 log units, using this equation, and that from the predicted log VG values, the weight fraction activity coefficient, Ω ∞ , can be predicted to around ± 0.04 log units, and the Flory-Huggins polymer-probe χ coefficient to within ± 0.10 units. The same general equation has also been applied to literature data on the solubility of 50 probes on poly(trifluoropropyl)methyl siloxane at 298 K, with similar results.