Electrophilic Toxicophores

Substituents that are electrophilic or are metabolized to electrophilic species are particularly problematic because they are capable of reacting covalently (irreversibly) with nucleophilic substituents of cellular macromolecules such as DNA, RNA, 

Handbook of Green Chemistry Volume 9 Designing Safer Chemicals, First Edition. Edited by Robert Boethling and Adelina Voutchkova. 

Neurotoxicity. When at least two of the alkyl-substituents are relatively small, all can cause a curare-like (neuromuscular blocking) effect. [1, 2]. Ammonium tends to be the most toxic, followed by sulfonium, and phosphonium (the least toxic). 

NS-bis-alkyl-onium and S,S-bis-alkyl-onium compounds also have neuromuscular blocking activity [3—6] 

Acute lethality. Rapidly decompose in body to liberate cyanide [7, 8]. Esters thereof will hydrolyze to free cyanohydrin. 

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Table 4.2 Examples of electrophilic toxicophores commonly encountered in commercial substances, the reactions they undergo with biological nucleophiles, and the resulting toxicity3. ... 

Blocking metabolism to electrophilic intermediates Eliminating known toxicophores... 

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