One of the most popular herbicide classes over the past 50 years is the chloroacetanilides, which feature a highly electrophilic haloacetamide motif. These herbicides are N-alkoxy alkyl-N-chloroacetyl substituted derivatives of aniline and commonly used to minimize weed control for agricultural goods such as corn, maize, and rice . Despite increased regulation due to evidence for carcinogenicity and potential to accumulate in soil and wetlands , chloroacetanilides remain widely used throughout the world . Although the reported carcinogenicity is presumably through the formation of DNA and protein adducts , other studies have found that chloroacetanilides are not genotoxic and do not damage DNA in vivo . Little work has been performed to identify which proteins are most susceptible to chloroacetanilide conjugation, and none at all to determine how this modification impacts protein stability (Scheme 1A).