Quantitative structure-activity relationship correlation between molecular structure and the Rayleigh enantiomeric...

Area of Science:

• Environmental Chemistry
• Biocatalysis
• Computational Chemistry

Background:

• The Rayleigh equation describes enantiomeric enrichment under environmental conditions.
• The enantiomeric enrichment factor (εER) quantifies this enrichment.
• Predicting εER based on molecular structure is crucial for environmental analysis.

Purpose of the Study:

• To develop a quantitative structure-activity relationship (QSAR) model for predicting the enantiomeric enrichment factor (εER).
• To correlate εER with molecular structure for 2-(phenoxy)propionate derivatives.
• To differentiate enzyme binding site characteristics using QSAR.

Main Methods:

• Analysis of enantioselective hydrolysis of 16 2-(phenoxy)propionate (PPM) derivatives.
• Enzymatic degradation using lipases from Pseudomonas fluorescens (PFL), Pseudomonas cepacia (PCL), and Candida rugosa (CRL).
• Application of the linear Hansch model for QSAR development and validation.

Main Results:

• Significant QSAR relationships were established with R(2) values of 0.90-0.93.
• High predictive abilities were confirmed by internal (QLOO(2) 0.85-0.87) and external (QExt(2) 0.8-0.91) validations.
• The model successfully differentiated enzymes based on electronic properties (PFL, PCL) versus lipophilicity and steric factors (CRL).

Conclusions:

• A robust QSAR model accurately predicts the enantiomeric enrichment factor (εER) based on molecular structure.
• The model provides insights into enzyme-specific enantioselectivity mechanisms.
• This predictive tool can aid in environmental source tracking of chiral compounds.