Quantitative Structure–Retention Relationship Approach in Assessing the Chloroacetamides’ Biological Profile

Chloroacetamides (CAAs) are an important class of synthetic herbicides long utilized in agriculture for their strong weed-control efficacy. However, their environmental and health impacts have raised significant concerns. Therefore, both the structural modification of known active compounds and the identification and design of new compounds with desirable properties and biological activity represent a significant challenge in pesticide chemistry. The bioactivity parameters of 18 new chloroacetamide derivatives were evaluated by using both in silico and chromatographic approaches. Correlation of chromatographic parameters with software-derived log P and EC₅₀ values by linear regression analysis identified key structural factors affecting their lipophilicity and potential toxicity to non-target organisms. Multivariate analysis revealed and quantified that the total number of carbon atoms in the molecule (determines lipophilicity), along with the chemical nature of the hydrocarbon substituent (affects water solubility), plays a major role in shaping the biological profile of the tested derivatives. Moreover, it was found that the number of rotatable bonds significantly influences their toxicity. Furthermore, the results show that chromatographic parameter R_M ⁰ can serve as an alternative measure of lipophilicity, while the parameter m can indicate toxicity of the analyzed CCAs'.