Reactivity prediction in aza-Michael additions without transition state calculations: the Ames test for mutagenicity

• Published in: Chemical communications (Cambridge, England) England), 2020-11, Vol.56 (88), p.13661-13664
• Main Authors: Townsend, Piers A, Grayson, Matthew N
• Format: Article
• Language: English
• Subjects: Ames test; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Density Functional Theory; Models, Chemical; Molecular Structure; Mutagenicity; Mutagens - chemistry; Mutagens - pharmacology; Quantitative Structure-Activity Relationship; Quantum chemistry; Salmonella typhimurium - drug effects; Toxicology
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d0cc05681b

Animal testing remains a contentious ethical issue in predictive toxicology. Thus, a fast, versatile, low-cost quantum chemical model is presented for predicting the risk of Ames mutagenicity in a series of 1,4 Michael acceptor type compounds. This framework eliminates the need for transition state calculations, and uses an intermediate structure to probe the reactivity of aza-Michael acceptors. This model can be used in a variety of settings e.g. , the design of targeted covalent inhibitors and polyketide biosyntheses. This work demonstrates a novel method for aza-Michael reactivity prediction using easily calculable intermediate structures instead of time-consuming transition states.