Structure-retention Correlations Research Articles

Quantitative structure–retention relationship of curcumin and its analogues

The natural product curcumin is widely used in Asian countries for the treatment of several diseases. However, the clinical potential of curcumins remains limited due to their relatively poor bioavailability and no experimental data about their lipophilicity for bioavailability prediction. To evaluate the retention and lipophilicity of curcumin and its 31 newly synthesized analogues, they were subjected to 3D quantitative structure-retention relationship studies by RP-HPLC. Superior than the classical four-variant quantitative structure-retention relationship model (conventional r(2) =0.734), the 3D comparative molecular similarity index analysis model with combined steric, electrostatic, and H-bond donor fields, resulted in a robust structure-retention correlation (cross-validated q(2) =0.613 and r(2) =0.979). The statistical analyses indicate that the electrostatic and H-bond donor fields have a primary influence on the chromatographic retention of analytes. The predictive power and robustness of the derived comparative molecular similarity index analysis model was further confirmed by the test-set validation (q(2) =0.702, r(2) =0.905, and the slope K=1.016) and Y-randomization examination. Statistically significant and physically meaningful 3D-quantitative structure-retention relationship provided better insight into understanding the retention behaviors of curcumin and its analogues, and their separation mechanism in a given RP-HPLC system.

Experimental and molecular statistical study of alkyladamantane adsorption on graphitized thermal carbon black

Experimental measurements and molecular statistics methods were used to calculate thermodynamic characteristics of adsorption (TCA) of alkyladamantanes of different structure on the surface of hydrogen-treated graphitized thermal carbon black (GTCB) Carbopack C HT. High selectivity of separation of isomeric alkyladamantanes on GTCB is due to specific features of their geometry and electronic structure. The influence of the spatial structure of adsorbates on the TCA was established. Special attention was given to analysis of the heat capacities of adsorption. The best agreement between the experimental TCA and those calculated by the molecular statistics methods is achieved when the “cage effect“ in the adamantane ring is taken into account. The corresponding corrections are introduced into the parameters of the atom-atomic potential function of pair intermolecular interaction of the Me groups with the carbon atoms of the basal face of graphite, which are localized in the nodal positions of the lattice. The critical parameters for a large group of alkyladamantanes were calculated in terms of the additive group Lydersen method. A set of various topological indices used further for constructing structure-retention correlations on GTCB was obtained.

Quantitative Structure-Retention Relationship of Nucleic-Acid Bases Revisited. CoMFA on Purine RPLC Retention

3D Quantitative Structure-Retention Relationship (QSRR) using comparative molecular field analysis (CoMFA) has been successfully developed for the experimental RPLC retention on a C18 column of 33 purine nucleobases for the molecular understanding of their interfacial interaction in essentially nonpolar environment as found in the inner core of phospholipid bilayer. Models based on various partial-atomic-charge formalisms resulted in robust structure-retention correlation (R2>0.938 and q2>0.693) superior to the classical QSRR in addition to the spatial information obtained as contour maps which is useful in future molecular design purposes. Further Y-randomization procedure has been performed in confirming the absence of correlation by mere chance. As long as the ab initio-optimized geometries were used, the QSRR spatial feature was rather insensitive to the particular partial charge model adopted. For readily ionizable tautomeric species at neutral pH, however, a more realistic partial charge representation was found to be critical even only for a qualitatively correct prediction. Based on the current results, CoMFA-QSRR is likely applicable to congeners of biological interests as long as the retention is governed by essentially nonpolar isotropic interactions.

Structure–Retention Correlation of Some Oxicam Drugs in Reversed‐Phase Liquid Chromatography

The main parameters related to the retention behavior of some oxicam drugs (meloxicam, piroxicam, and tenoxicam) in reversed‐phase liquid chromatography (RP‐LC) processes using a monolithic column were studied under isocratic elution conditions. The hydrophobicity parameter (octanol/water partition coefficient) obtained by extrapolation of the capacity factor—methanol content of the mobile phase relationship did not fit the well‐known dependence on pH. This fact might be assigned to the keto–enolic equilibrium that does not behave like common acids. The dissociation constants for these oxicams were estimated from the retention dependence on the organic modifier content (methanol) in the mobile phase and pH of aqueous components (interval 2–7). Two corrections were applied to the hydrophobicity parameter of analytes, taking into consideration the pH of aqueous component in the mobile phase, and hydrophobicity parameter of the stationary phase. The results were compared to other experimental data and data predicted by the fragment methodology.

Prediction of the gas chromatographic retention values of chlorobenzenes on different stationary phases by using structure–retention correlations

The retention values (capacity factors or retention indices) of the isomers of chlorobenzenes with two to six chlorine atoms were predicted by using structure–retention correlations and the calculated contributions of the ortho, meta and para positions of the substituent atoms on the aromatic ring. The method permits the prediction of the retention of every isomer by starting from the measured retention of a few compounds, and does not require the use of all of the possible isomers as standard samples for the identification in complex mixtures.

Simultaneous analysis and retention behavior of the glucuronide, glucoside, and N-acetylglucosaminide conjugates of bile acids in conventional and inclusion high-performance liquid chromatographic methods

Simultaneous analysis and structure–retention correlation were examined for various glycosidic-conjugated bile acids in reversed-phase high-performance liquid chromatography (HPLC). The substrates examined included the β-glucuronide, β-glucoside, and β-N-acetylglucosaminide conjugates of C 24 bile acids related to lithocholic, hyodeoxycholic, chenodeoxycholic, ursodeoxycholic, deoxycholic, hyocholic, and cholic acids having an O-β- d-glycosidic linkage at the position C-3, C-6, or C-7 in the 5β-steroid nucleus. The bile acids as their fluorescence-sensitive C 24 pyrenacyl ester derivatives were measured on a C 18 reversed-phase column, eluting with methanol–water mixtures in the absence and presence of methyl-β-cyclodextrin (Me-β-CD). Changes in the retentions of these compounds depended significantly not only on the Me-β-CD concentration but rather on the methanol content, implying the possible formation of solute–Me-β-CD–methanol ternary complexes by hydrogen-bonding interactions. The combined use of conventional and inclusion HPLC retention data reported herewith provided important information for characterizing the structures of bile acid glycosides as well as inclusion complexes.

Structure-retention correlation of isomeric bile acids in inclusion high-performance liquid chromatography with methyl beta-cyclodextrin.

The structure-retention correlation of various C24 bile acid isomers was studied by the addition of methyl beta-cyclodextrin (Me-beta-CD) to mobile phases in reversed-phase high-performance liquid chromatography (HPLC). The compounds examined include a series of monosubstituted bile acids related to cholanoic acids differing from one another in the position and configuration of an oxygen-containing function (hydroxyl or oxo group) at the position C-3, C-6, C-7, or C-12 and the stereochemistry of the A/B-ring fusion (trans 5 alpha-H and cis 5 beta-H) in the steroid nucleus. The inclusion HPLC with Me-beta-CD was also applied to biologically important 4 beta- and 6-hydroxylated bile acids substituted by three to four hydroxyl groups in the 5 beta-steroid nucleus. These bile acid samples were converted into their fluorescence prelabeled 24-pyrenacyl ester derivatives and chromatographed on a Capcell Pak C18 column eluted with methanol-water mixtures in the presence or absence of 5 mM Me-beta-CD. The effects of Me-beta-CD on the retentions of each compound were correlated quantitatively to the decreasing rate of capacity factors and the relative strength of host-guest interactions. On the basis of the retention data, specific and nonspecific hydrogen-bonding interactions between the bile acids and the Me-beta-CD were discussed.

Structure-retention correlations of chlorobenzenes as a method for the comparison of the behaviour of gas-liquid-solid and gas-liquid capillary columns of various polarities

The structure-retention correlations of chlorobenzenes were investigated by using retention data measured on narrow-bore capillary columns: bonded-phase gas-liquid non-polar polydimethylsiloxane, polar polyglycol, carbon and graphite layer gas-liquid-solid modified by addition of various amount of polar liquid phase (polyglycols and terephthalic acid). The retention values obtained in various isothermal runs (ranging from 60 to 200°C) were correlated with the available physical properties data: boiling point, dipole moment, vapour pressure at the analysis temperature and the effect of the reciprocal position of the chlorine atoms on the aromatic ring was evaluated.

Structure-Retention Correlation on Methyl Phenyl Polysiloxane Phases in Capillary Gas Chromatography

Abstract The selectivity of phenyl methyl polysiloxane phases was examined from the structure-retention correlations of alkanes, alkanols, alkylbenzenes, chlorobenzenes, and polycyclic aromatic hydrocarbons. Selectivity R* was obtained from plots of van der Waals volume vs. the difference of their logarithm of capacity ratios, and enthalpy of these compounds was calculated from van’t Hoff plot. The enthalpy −ΔH of polycyclic aromatic hydrocarbons was greater on phenyl methyl phases compared to those obtained on 100% methyl polysiloxane phase. The retention time of homologue series of compounds can be predicted from the selectivity or enthalpy, but not for chlorinated benzenes due to the difficulty of the estimation of electron donner effect of chloro group.

Separation and identification of all isomeric n-nonadecenes by capillary gas chromatography on a mesogenic stationary phase with Fourier transform infrared and mass spectrometric detection

High-resolution capillary gas chromatography (HRGC) with an isomeric selective liquid crystal as stationary phase permits a better separation of the seventeen possible n-nonadecene isomers n-nonadecane than a separation system with a non-mesogenic stationary phase. For the identification of the separated isomers structure-retention correlations based on extrapolation of the dependence of homomorphous factors on the number of carbon atoms for homologous series of n-alkenes and the different temperature dependences of the retention indices of geometrical isomers were used. Identification was confirmed by a combination of HRGC with Fourier transform infrared and mass spectrometric detection on the basis of infrared spectra which are distinctly different for the geometrical isomers. The rule of the alternation retention of cis- and trans-alkenes with an odd number of carbon atoms separated on a mesogenic stationary phase was reformulated.

Structure—retention correlations of isomeric alkylphenols in gas—liquid chromatography

Correlations of the chromatographic retention of alkylphenols with their boiling points, molecular refraction and ionization constants were studied. The correlations were obeyed better for the alkylphenol groups which differ in the degree of shielding of the hydroxyl group. The dependences are approximated most exactly for alkylphenols with substituents at positions 2 and 6 by a four-factor equation and for the other phenols by a eight-factor equation which include the Van der Waals volume and connectivity indices of the first five orders as independent variables.

Structure—retention correlations of alkylphenols in gas—liquid and gas—liquid chromatography

The retention behaviour of alkyl- and dialkylphenols has been investigated by gas—liquid chromatography (GLC) on glass capillary columns, coated with PS-255 and OV-1701-Vi, and by gas—solid chromatography (GSC) on a microcolumn, packed with uncoated graphitized thermal carbon black (GTCB). The dependence of the chromatographic properties of the alkyl phenols on their molecular structure is discussed. Due to electronic and steric effects, alkyl groups neighbouring the phenolic hydroxyl group decrease the retention values in GLC. In contrast, the interaction between vicinal alkyl groups leads to increased retention. GSC on GTCB is advantageous for the distinction of meta- and para-isomers, which are difficult to separate by GLC.

Structure-retention correlations of hydrocarbons in GLC and GSC alkenylbenzenes

For the study of relationships between retention behaviour and molecular structure in GLC and GSC the retention indices of alkenylbenzenes with 2–6 carbon atoms in a straight or branched side chain and of isotopological alkylbenzenes were determined on capillary columns coated with OV-1 and Ucon LB and on a micropacked column filled with graphitized thermal carbon black. From the values obtained index differences corresponding to the increments of the double bond in the side chain were derived. These differences depend significantly on the structure of the side chain and of the position of the double bond.

Structure-retention correlations of hydrocarbons in gas-liquid and gas-solid chromatography. Cycloalkenes and cycloalkadienes

The retention indices of cycloalkenes and cycloalkadienes with C6–C13 rings are determined by gas-liquid chromatography (GLC) on glass capillary columns coated with OV-1 and Ucon LB 550X and by gas-solid chromatography (GSC) on a microcolumn packed with uncoated graphitized thermal carbon black (GTCB). Structure — retention correlations are derived on using index differences such as HOV, HGTCB and ΔI values, considering the differences in the stereochemistry of these compounds. It is shown that the combined application of index increments obtained in GLC and GSC provides more detailed structure informations. The value of the retention index units agree with the most stable conformations of the alicyclic compounds. The high value for the energy equivalent to an index unit (ΔGI.U.=4.18kJ/mol) confirmes that graphitized thermal carbon black causes much stronger dispersive interactions than any nonpolar liquid phase.

Structure-retention correlation of dihydropyrazolo-trazinone derivatives in thin-layer and gas chromatrography

Relationships between logarithmic retention factors and carbon atom numbers for some homologous series of the title compounds were studied in thin-layer and gas chromatographic systems. Reversed-phase R M values and Kováts retention indices showed linear correlation with the carbon atom numbers of the homologous species. In silica gel chromatography, these correlations were non-linear in several cases. The chromatographic behaviour of the compounds investigated could be explained on the basis of their structural properties.

Retention behaviour of conjugated and isolated n-alkadienes : Identification of n-nona- and n-decadienes by capillary gas chromatography using structure-retention correlations and mass spectrometry

The isomerization products of n-C 8C 10 α,ω-alkadienes were separated on a high-efficiency squalane column (195 m × 0.25 mm I.D.) with 500,000 effective plates. Of the 102 possible n-C 8C 10 dienes with isolated and conjugated double bonds, only nine groups of isomers were not separated. All isomers, except those with cumulated double bonds, were identified (23 octadienes, 33 nonadienes and 46 decadienes). The n-octadienes were identified by matching measured and published retention data. Because of the lack of standards, retention data and mass spectra of n-nona- and decadienes, and because the previously reported identification method for n-dienes up to C 8 was succesful, the problem of the identification of C 9C 10 n-alkadienes was solved similarly by using structure-retention correlations and combined capillary gas chromatography-mass spectrometry. Based on these results, the retention behaviour of the conjugated and isolated n-alkadienes, on squalane stationary phase, is generalized.

Capillary gas chromatography of n-alkynes on squalane and a liquid crystal as stationary phases

The elution behaviour of 43 possible C 6C 14 n-alkynes was studied on squalane and 4- n-pentylacetophenone-(O-4- n-pentyloxybenzoyloxime) liquid crystal as stationary phases in glass capillary columns. The influence of factors affecting the reproducibility of the retention indices of n-alkynes was investigated. Structure—retention correlations are discussed as a means of characterization, considering fine structural effects (propyl effect, hyperconjugation, alternation). Advantages of the use of a liquid crystal as a stationary phase for the separation of n-alkyne isomers are demonstrated.

Hochleistungs-gaschromatographie an flüssigkristallglaskapillaren : III. Trennung von isomeren kohlenwassertstoffen an cholesterinischer mesophase

High-resolution gas chromatography with liquid crystal glass capillaries. III. Separation of hydrocarbon isomers on cholesteric mesophase high-performance glass capillary columns with cholesteryl butyrate as stationary phase were applied for separations of isomeric alkylbenzenes and n-alkenes in cholesteric, crystalline, isotropic and supercooled range. Structure-retention correlations, retention indices, d I/d T values and homomorphy factors are discussed. The cholesteric modification shows a higher selectivity for trans- cis-isomeric n-alkenes, than nematic and smectic mesophases or common stationary phases.

Hochleistungs-Gaschromatographie an flüssigkristallglaskapillaren: I. Trennung von isomeren kohlenwasserstoffen an nematischen mesophasen

High-performance glass capillary columns with 4- n-pentyl-acetophenone (O-4- n-octyloxybenzoyloxime) were applied for separations of isomeric alkylbenzenes and n-alkenes in the nematic liquid-crystalline also in the crystalline and isotropic range. From the calculated retention indices and their dependence on temperature structure-retention correlations were discussed. A specific selectivity of the liquid crystals for isomeric n-alkenes was found and also their influence on other effects ( e. g. hindrance of propyl effect, anomaly order of retention of trans-6- trans-5-dodecenes, alternation of the relative retention with C-number). Different orientation in the mesophase shows differences in selectivity. The applied liquid crystal capillaries permit better separation of isomers in shorter time.

Analysis of alkylated mixtures of polychlorinated biphenyls by capillary gas chromatography-mass spectrometry

Gas chromatographic separations of chlorobiphenyls, alkylbiphenyls and alkylchlorobiphenyls were carried out at 200° on glass capillary columns coated with OV-101, Carbowax 20M and Apiezon L as stationary phases. Apiezon L was the most suitable phase for this purpose, in terms of separation, reproducibility of retention indices and reliability of structure-retention correlations for the prediction of indices. Compounds in the mixtures were identified by comparison with reference materials analyzed under similar conditions, by structure-retention correlations and by combined gas chromatography-mass spectrometry. Quantitative analysis of a mixture of polychlorinated biphenyls was performed by using the internal standard method, taking into account experimentally determined flame ionization detector response factors. The results, obtained on stationary phases with different polarities, can be used as an additional tool for qualitative analysis.