The chemical interpretation and practice of linear solvation energy relationships in chromatography

Mark Vitha, Peter W. Carr

Research output: Contribution to journalReview articlepeer-review

460 Scopus citations


This review focuses on the use of linear solvation energy relationships (LSERs) to understand the types and relative strength of the chemical interactions that control retention and selectivity in the various modes of chromatography ranging from gas chromatography to reversed phase and micellar electrokinetic capillary chromatography. The most recent, widely accepted symbolic representation of the LSER model, as proposed by Abraham, is given by the equationSP = c + e E + s S + a A + b B + v Vin which, SP can be any free energy related property. In chromatography, SP is most often taken as log k′ where k′ is the retention factor. The letters E, S, A, B, and V denote solute dependent input parameters that come from scales related to a solute's polarizability, dipolarity (with some contribution from polarizability), hydrogen bond donating ability, hydrogen bond accepting ability, and molecular size, respectively. The e-, s-, a-, b-, and v-coefficients and the constant, c, are determined via multiparameter linear least squares regression analysis of a data set comprised of solutes with known E, S, A, B, and V values and which span a reasonably wide range in interaction abilities. Thus, LSERs are designed to probe the type and relative importance of the interactions that govern solute retention. In this review, we include a synopsis of the various solvent and solute scales in common use in chromatography. More importantly, we emphasize the development and physico-chemical basis of - and thus meaning of - the solute parameters. After establishing the meaning of the parameters, we discuss their use in LSERs as applied to understanding the intermolecular interactions governing various gas-liquid and liquid-liquid phase equilibria. The gas-liquid partition process is modeled as the sum of an endoergic cavity formation/solvent reorganization process and exoergic solute-solvent attractive forces, whereas the partitioning of a solute between two solvents is thermodynamically equivalent to the difference in two gas/liquid solution processes. We end with a set of recommendations and advisories for conducting LSER studies, stressing the proper chemical and statistical application of the methodology. We intend that these recommendations serve as a guide for future studies involving the execution, statistical evaluation, and chemical interpretation of LSERs.

Original languageEnglish (US)
Pages (from-to)143-194
Number of pages52
JournalJournal of Chromatography A
Issue number1-2
StatePublished - Sep 8 2006

Bibliographical note

Funding Information:
Acknowledgment is made to the Donors of the American Chemical Society Petroleum Research Fund for the support of the writing of this manuscript, to Drake University, and to the University of Sydney. We also acknowledge the National Science Foundation for support through a series of grants over nearly a decade for work in this area. The senior author wishes to acknowledge the inspiring friendship and scientific comradeship of the late Mort Kamlet and Bob Taft. As is said in Brooklyn, both were real mensch. He is also indebted to his colleagues and friends Sarah Rutan, Lloyd Snyder, Chuck Eckert and most certainly Mike Abraham for hundreds of hours of discussion of our mutual passion for solvatochromism, linear solvation energy relationships and understanding retention in chromatography. He also wishes to thank his many students who worked so hard and contributed so much to his understanding. He would be remiss to not single out Jim Brady—a brilliant scientist and his first co-worker in the field of this review. Finally our sincere thanks to John Dorsey and Steve Weber for their efforts, time, and insight in preparing this review.


  • Adsorption
  • Cavity formation
  • Dielectric constant
  • Dipole
  • Dispersion
  • Enthalpy of retention
  • Entropy of retention
  • GLC
  • Gas chromatography
  • Hydrogen bonding
  • Hydrophobic
  • Induced dipole
  • LSER
  • Linear free energy
  • Linear solvation energy relationship
  • MEKC
  • Micellar electrokinetic capillary chromatography
  • Micellar liquid chromatography
  • Microheterogeneity
  • NPLC
  • Normal phase
  • Partition
  • Partition coefficient
  • Polarizability
  • Preferential solvation
  • RPLC
  • Regular solution
  • Retention mechanism
  • Reversed phase
  • Solubility parameter
  • Solvatochromism
  • Solvent strength
  • Solvophobic
  • α
  • β
  • π


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