Liquid Chromatography in Studying Lipophylicity and Bioactivity of Pesticides

Abstract

During the past decades the interest of new bioactive compounds for applications in medicine or agriculture has increased dramatically (Gocan & Cimpan, 2005; Kaliszan, 1987; Kaliszan, 1992; Krieger et al., 2001; Lipinski et al, 2001; Nasal et al., 2003; Sangster, 1997). Physicochemical properties of new bioactive compounds like pesticides, such as solubility, lipophylicity (hydrophobicity), stability and acid-base character, should be determined in the early stages of development. These properties affect absorption, distribution and transport of xenobiotics in biological systems. The hydrophobic effect is assumed to be one of the driving forces for the passive transport of xenobiotics through bio-membranes and to a certain degree responsible for interactions with receptor. The expressions “lipophylicity” and “hydrophobicity” are frequently used as synonymous, but in scientific use their meaning should be distinguished. According to IUPAC suggestions (Pliska et al., 1996) hydrophobicity means the association of nonpolar species in aqueous environment arising from the tendency of water to exclude nonpolar molecules. Lipophylicity as a measure of relative affinity of a molecule for a lipophylic environment has a broader meaning than hydrophobicity because may be connected with polar interactions. Lipophylicity as a property determining biological activity of substance was firstly recognized by Overton, Meyer and Baum (Kaliszan, 1987; Kaliszan, 1992). During the time hundreds of articles, among them some review papers, of lipophylic properties of different bioactive compounds in medicine, agriculture or environmental chemistry have appeared (Heberger, 2007; Kah & Brown, 2008; Komsta et al., 2010; Poole & Poole, 2003; Valko, 2004; Wang et al., 1999; Sherma, 2003). Lipophylicity is commonly measured by solute distribution in biphasic liquid system and universal lipophylicity scale is formed by the logarithms of partition coefficients (log P) in the case of neutral species or distribution ratio (log D) for ionisable compounds (Kah & Brown, 2008; Pliska et al., 1996). In early seventies octanol-water was proposed as reference system for lipophylicity measurements and to this day it remains as a standard for experimental and theoretical investigations. Due to experimental limitations connected with direct measurements of log P (log D) parameters by shake-flask method, chromatographic techniques are getting more and more popular in studying lipophilic properties of organic substances. Though partition parameters produce more universal scale of lipophylicity,