Sanka N. Atapattu

Determination of solute descriptors by chromatographic methods

The solvation parameter model is now well established as a useful tool for obtaining quantitative structure-property relationships for chemical, biomedical and environmental processes. The model correlates a free-energy related property of a system to six free-energy derived descriptors describing molecular properties. These molecular descriptors are defined as L (gas-liquid partition coefficient on hexadecane at 298K), V (McGowans characteristic volume), E (excess molar refraction), S (dipolarity/polarizability), A (hydrogen-bond acidity), and B (hydrogen-bond basicity). McGowans characteristic volume is trivially calculated from structure and the excess molar refraction can be calculated for liquids from their refractive index and easily estimated for solids. The remaining four descriptors are derived by experiment using (largely) two-phase partitioning, chromatography, and solubility measurements. In this article, the use of gas chromatography, reversed-phase liquid chromatography, micellar electrokinetic chromatography, and two-phase partitioning for determining solute descriptors is described. A large database of experimental retention factors and partition coefficients is constructed after first applying selection tools to remove unreliable experimental values and an optimized collection of varied compounds with descriptor values suitable for calibrating chromatographic systems is presented. These optimized descriptors are demonstrated to be robust and more suitable than other groups of descriptors characterizing the separation properties of chromatographic systems.

Solute descriptors for characterizing retention properties of open-tubular columns of different selectivity in gas chromatography at intermediate temperatures

An iteration procedure is used to optimize the solute descriptors for 94 compounds suitable for characterizing the retention properties of open-tubular columns for gas chromatography in the intermediate temperature range of 160-240 degrees C. These solute descriptors are used to calculate the system constants of the solvation parameter model for nine open-tubular columns (SPB-Octyl, HP-5, Rtx-440, Rxi-50, Rtx-OPP, DB-1701, DB-225, HP-Innowax, and HP-88) at increments of 20 degrees C from 160 to 240 degrees C. The optimized descriptors afford a two- to three-fold improvement in the fit to the retention model compared with literature values as determined by the standard deviation of the difference between the model predicted and experimental retention factors (log k). Combining literature values for the system constants at lower temperatures (60-140 degrees C) with those obtained here allowed system maps to be constructed for the nine columns over the full temperature range of 60-240 degrees C. For a wide temperature range the system maps indicate that the relationship between the system constants and temperature is non-linear and that polar interactions are likely to be important in relative and absolute terms to quite high temperatures.

Determination of descriptors for semivolatile organosilicon compounds by gas chromatography and non-aqueous liquid-liquid partition

The measurement of retention factors by gas chromatography on up to 15 stationary phases at several temperatures in the range 60-240 degrees C for each stationary phase and liquid-liquid partition coefficients in three biphasic organic solvent systems (n-hexane-acetonitrile, n-heptane-N,N-dimethylformamide, and n-heptane-2,2,2-trifluoroethanol) were used to calculate solute descriptors for 28 semivolatile linear and cyclic organosilicon compounds for use in the solvation parameter model. Regression analysis for oligomeric compounds allowed the descriptor values for the dimethylsiloxane, diethylsiloxane, methylvinylsiloxane, and methylhydrosiloxane monomer groups to be estimated. These monomer groups contribute significantly to the hydrogen-bond basicity (B descriptor) and cavity formation and dispersion interactions (L and V descriptors) of oligomeric organosilicon compounds, are non-hydrogen-bond acidic (A descriptor=0), are slightly less dipolar/polarizable than an n-alkane (S descriptors are negative and close to zero), and bind electron lone pairs more tightly than an n-alkane (E descriptor is small and negative). The semivolatile organosilicon compounds with polar functional groups in their side chain demonstrate a much wider range of selective intermolecular interactions than alkylsiloxanes and have solvation properties closer to those of polar organic compounds.

Extension of the system constants database for open-tubular columns: system maps at low and intermediate temperatures for four new columns.

The solvation parameter model is used to characterize the separation properties of four open-tubular columns for gas chromatography at low and intermediate column temperatures covering the range 60-240 degrees C. Solute descriptors for compounds suitable for characterizing columns over the intermediate temperature range are optimized using an iterative procedure. These compounds, and those previously recommended for the lower temperature range, are used to provide system constant maps for Rxi-5Sil MS, Rxi-17, Rtx-TNT and Rtx-TNT2 columns suitable for merging with a system constants database with entries for more than 50 columns. The Rxi-5Sil MS column is shown to have separation properties similar to the silphenylene-dimethylsiloxane copolymer stationary phase (DB-5ms) but these two columns are not selectivity equivalent. The Rxi-17 column has similar separation properties to the Rxi-50 column but is not selectivity equivalent to it. Rxi-17 is a poly(dimethyldiphenylsiloxane) stationary phase containing 50% diphenylsiloxane monomer and Rxi-50 a poly(methylphenylsiloxane) stationary phase with the same nominal composition but a different monomer structure. The difference in monomer structure results in only small changes in selectivity, and for all but the most demanding separations, the columns are interchangeable. The application-specific column (energetic materials) Rtx-TNT is shown to be selectivity equivalent to columns coated with the poly(dimethyldiphenylsiloxane) stationary phases containing 5% diphenylsiloxane monomer. The Rtx-TNT2 column is selectivity equivalent to the proprietary Rtx-OPPesticides column. Rtx-OPPesticides is a low bleed stationary phase, possibly based on silarylene-siloxane chemistry, with a composition designed to mimic the separation properties of the poly(dimethylmethyltrifluoropropylsiloxane) stationary phases containing 35% methyltrifluoropropylsiloxane monomer. Selectivity equivalence of columns is determined by the statistical agreement in system constants at 20 degrees C intervals over the full temperature range from 60 to 240 degrees C, and by the construction of correlation plots for the retention factors of varied compounds for the same temperature intervals.

Determination of descriptors for plasticizers by chromatography and liquid-liquid partition

Retention factors on a minimum of eight stationary phases at various temperatures by gas–liquid chromatography and in acetonitrile–water and methanol–water mobile phases by reversed-phase liquid chromatography on a Synergi Polar-RP column were combined with further values taken from the literature and liquid–liquid partition coefficients for up to eight totally organic biphasic systems to estimate descriptors for 24 esters (phthalate, oleate, stearate, arbietate, adipate, succinate, sebacate, and diethylmalonate) widely used as plasticizers and solvents in industry. The descriptors facilitated the estimation of several properties of environmental interest (octanol–water, air–octanol, and air–water partition coefficients, and soil–water distribution coefficients, vapor pressure, and water solubility). The descriptors are suitable for use in the solvation parameter model and facilitate the estimation of a wide range of physicochemical, chromatographic, biological, and environmental properties using existing models.

Selectivity equivalence of two poly(methylphenylsiloxane) open-tubular columns prepared with different deactivation techniques for gas chromatography

The solvation parameter model is used to characterize the retention properties of a poly(methylphenylsiloxane) column Rxi-50 over the temperature range 60-240 degrees C. The smooth variation of the system constants with temperature affords a general picture of how the relative importance of the different intermolecular interactions change with temperature. The system constants and retention factors for varied compounds are compared with those for Rtx-50 prepared with a similar stationary phase but using a different surface deactivation technique. The two columns are shown to be nearly selectivity equivalent. The Rtx-50 column is slightly more cohesive, dipolar/polarizable and hydrogen-bond basic than Rxi-50, while Rxi-50 is slightly more electron lone pair attractive and hydrogen-bond acidic. Only the difference in hydrogen-bond acidity can be identified with some certainty as related to the difference in deactivation processes. For compounds with a separation greater than 0.2 retention factor units on Rtx-50, it should be relatively straightforward to achieve an acceptable separation for the same compounds on Rxi-50.

The hydrogen bond acidity and other descriptors for oximes

The solvation descriptors for cyclohexanone oxime and acetone oxime have been obtained from measurements on water–solvent partitions, and gas–liquid chromatographic retention data. These yield values of 0.33 and 0.37 for the Abraham hydrogen bond acidity, A, in reasonable agreement with a value of 0.37 for cyclohexanone oxime obtained by our recent NMR method. The other descriptors E, S, B, L and V have also been obtained for cyclohexanone oxime and acetone oxime, and have been estimated for a number of other oximes as well. The value for A, the overall or effective hydrogen bond acidity of the oximes is reasonably close to the 1 : 1 hydrogen bond acidity, α2H = 0.39 to 0.46, that can be deduced from previous literature measurements on oximes, and to the 1 : 1 hydrogen bond acidity, α2H = 0.43 for another NOH compound, N,N-dibenzylhydroxylamine, that again can be deduced from literature measurements.

System maps for retention of small neutral compounds on a superficially porous particle column in reversed-phase liquid chromatography.

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral molecules on the ocadecylsiloxane-bonded silica superficially porous particle stationary phase (Kinetex C18) for aqueous-organic solvent mobile phases containing 10-70% (v/v) methanol or acetonitrile. A comparison of the system constants with eight commercially available octadecylsiloxane-bonded silica columns for the same separation conditions confirms that the general retention properties of Kinetex C-18 are similar to totally porous octadecylsiloxane-bonded silica stationary phases and that method transfer should be no more difficult than that usually observed when substituting one octadecylsiloxane-bonded silica column for another.

System Maps for Retention of Small Neutral Compounds on a Superficially Porous Ethyl-Bridged, Octadecylsiloxane-Bonded Silica Stationary Phase in Reversed-Phase Liquid Chromatography

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral compounds on an ethyl-bridged, ocatadecylsiloxane-bonded superficially porous silica stationary phase (Kinetex EVO C18) for aqueous mobile phases containing 10–70% (v/v) methanol or acetonitrile. Electrostatic interactions (cation-exchange) are important for the retention of weak bases with acetonitrile–water but not methanol–water mobile phase compositions. Compared with a superficially porous octadecylsiloxane-bonded silica stationary phase (Kinetex C18) with a similar morphology but different topology statistically significant differences in selectivity at the 95% confidence level are observed for neutral compounds that vary by size and hydrogen-bond basicity with other intermolecular interactions roughly similar. These selectivity differences are dampened with acetonitrile–water mobile phases, but are significant for methanol–water mobile phase compositions containing <30% (v/v) methanol. A comparison of a totally porous ethyl-bridged, octadecylsiloxane-bonded silica stationary phase (XBridge C18) with Kinetex EVO C18 indicated that they are effectively selectivity equivalent.

Insights into the Retention Mechanism of Small Neutral Compounds on Octylsiloxane-Bonded and Diisobutyloctadecylsiloxane-Bonded Silica Stationary Phases in Reversed-Phase Liquid Chromatography

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral compounds on an octylsiloxane-bonded (Kinetex C8) and diisobutyloctadecylsiloxane-bonded (Kinetex XB-C18) superficially porous silica stationary phases for aqueous mobile phases containing 10–70% (v/v) methanol or acetonitrile. Electrostatic interactions (cation-exchange) are important for the retention of weak bases with acetonitrile–water but not for methanol–water mobile phases. Compared with an octadecylsiloxane-bonded silica stationary phase (Kinetex C18) retention is reduced due to a less favorable phase ratio for both the octylsiloxane-bonded and diisobutyloctadecylsiloxane-bonded silica stationary phases while selectivity differences are small and solvent dependent. Selectivity differences for neutral compounds are larger for methanol–water but significantly suppressed for acetonitrile–water mobile phases. The selectivity differences arise from small changes in all system constants with solute size and hydrogen-bond basicity being the most important due to their dominant contribution to the retention mechanism. Exchanging the octadecylsiloxane-bonded silica column for either the octylsiloxane-bonded or diisobutyloctadecylsiloxane-bonded silica column affords little scope for extending the selectivity space and is restricted to fine tuning of separations, and in some cases, to obtain faster separations due to a more favorable phase ratio. For weak bases larger differences in relative retention are expected with acetonitrile–water mobile phases on account of the additional cation exchange interactions possible that are absent for the octadecylsiloxane-bonded silica stationary phase.