Affinity of Compounds for Phosphatydylcholine-Based Immobilized Artificial Membrane—A Measure of Their Bioconcentration in Aquatic Organisms

Abstract

The BCF (bioconcentration factor) of solutes in aquatic organisms is an important parameter because many undesired chemicals enter the ecosystem and affect the wildlife. Chromatographic retention factor log kwIAM obtained from immobilized artificial membrane (IAM) HPLC chromatography with buffered, aqueous mobile phases and calculated molecular descriptors obtained for a group of 120 structurally unrelated compounds were used to generate useful models of log BCF. It was established that log kwIAM obtained in the conditions described in this study is not sufficient as a sole predictor of bioconcentration. Simple, potentially useful models based on log kwIAM and a selection of readily available, calculated descriptors and accounting for over 88% of total variability were generated using multiple linear regression (MLR), partial least squares (PLS) regression and artificial neural networks (ANN). The models proposed in the study were tested on an external group of 120 compounds and on a group of 40 compounds with known experimental log BCF values. It was established that a relatively simple MLR model containing four independent variables leads to satisfying BCF predictions and is more intuitive than PLS or ANN models.

Immobilized Keratin HPLC Stationary Phase—A Forgotten Model of Transdermal Absorption: To What Molecular and Biological Properties Is It Relevant?

“…According to our earlier research, the bioconcentration factor log BCF can be predicted using log k IAM and two additional parameters: F Csp3 and TPSA [31]. The predictive potential of Equation (10) (Figure 3) is compared to that of a model based on chromatographic retention factors obtained using immobilized keratine as a stationary phase (Equation ( 11), Figure 4).…”

“…Chromatography on immobilized protein stationary phases was originally developed to separate enantiomers [18]; apart from that, some protein-based stationary phases simulate the interaction between a molecule and main plasma proteins, such as human serum albumin (HSA) [19][20][21][22] or α 1 acid glycoprotein (AGP) [21,[23][24][25]. Retention data obtained from chromatography in biomimetic systems are used to predict ADME (absorption, distribution, metabolism, and excretion) properties of compounds in early drug discovery phases [11,26], as well as their environmental impact-mobility in soil, bioconcentration/bioaccumulation, or aquatic toxicity [27][28][29][30][31]. Elements of natural biomembranes, incorporated in chromatographic systems used in pharmacokinetic studies, include also cholesterol or amide moieties [32,33].…”

“…More recently, the bioconcentration of compounds in aquatic organisms has been investigated using chromatography on IAM stationary phases, developed initially to mimic molecule-biomembrane interactions in ADME studies [31,52]. Earlier research pointed to the importance of additional parameters, incorporated alongside log k IAM : (i) a biodegradation estimate, BioWin5, calculated using the EPISuite TM software and (to a lesser extent) topological polar surface area (TPSA) [52]; (ii) TPSA-the fraction of sp 3 carbon atoms (F Csp3 ) and hydrogen bond donor count (#HD) [31].…”