Quantitative Relationships between Retention Behavior and Molecular Structure of Organic Compounds in Reversed Phase Liquid Chromatography
Sung Kwang Lee
Department of Chemistry
The Graduate School
Yonsei University
Quantitative structure-retention relationships (QSRRs) methods were applied to explain the retention behavior of solutes and to characterize intermolecular interaction of retention process in liquid chromatography. The QSRRs models used in this study contain meaningful descriptors that could explain retention behavior, calculated by molecular modeling and quantum chemical method.
The solutes investigated in this study were bioactive compounds (quinolones and peptides) and environmental pollutants (benzenes, phenols and polyaromatic hydrocarbon (PAHs)). As stationary phase, monomeric C18, polymeric C18, polystyrene-divinylbenzene copolymer, and propyl columns were used. Eluents were prepared by mixing water with organic modifier such as methanol, acetonitrile, tetrahydrofuran. For quinolones, eluents were adjusted to pH 3 and pH 11. For peptides, propyl column and water containing Na2SO4 salt were used to keep the active conformation during separation process.
Retention of quinolones is affected by π-π interaction with the stationary phase at pH 3. The HOMO orbital and energy were informative descriptors. Retention is mainly affected by polar interaction with the mobile phase at pH 11. Descriptors of entire molecular surfaces(hydrogen bond donor ability and standard deviation of negative atomic charge) were useful.
The enthalpy and entropy changes of peptides in retention process were elucidated by using nonpolar surface area and dipole moment. Hydrophobic interaction chromatographic retention model of adsorption mechanism on propyl column is proposed.
For benzenes and phenols on PRP-1 column, mean polarizability, polar surface area and electrostatic potential minimum value over molecular surfaces were useful descriptors. The retention of benzenes and phenols were affected by dispersion, electrostatic repulsion of stationary phase(PRP-1 column) and electrostatic attraction of mobile phase.
The enthalpy and entropy changes of PAHs on micro C18 column were described by mean polarizability and polar surface area. The retention of PAHs were mainly affected by enthalpy effect estabilished by dispersive interaction.
For monosubstituted phenols, nonpolar surface area, electrostatic Hbond acidity and basicity were selected for QSRRs model. Retention on monomeric C18 column was demonstrated to be a net effect of dispersion interaction by carbon chain and electrostatic interaction by silanol between stationary phase and phenols.
For polysubstituted phenols on polymeric C18 column, retention was explained by nonpolar surface area, mean polarizability and electrostatic potential minimum value over molecular surface. QSRRs model for polysubstituted phenols proved the predominance of comparative dispersion interaction between solutes and stationary phase, and electrostatic interaction of mobile phase. A descriptive model is proposed, based on the way that ACN is organized in clusters in the ACN/water mixture when mobile phase contain more than 30% (v/v) ACN.
To find the similarity between descriptors and structures, principal component analysis followed by varimax rotation and cluster analysis were used.
※ Key words : QSRRs, molecular modeling, quantum chemical descriptor, quinolones, peptides, benzenes, phenols, PAHs