title: Modeling the reactivity of acrylic acid and acrylate anion with biological nucleophiles.
abstract: Based on the results of prior in-vitro reactivity experiments, the pathway for the Michael addition of two representative nucleophiles (methylamine and imidazole) to acrylate anion (AA-) was explored with the semiempirical quantum model, AM1. The results of the calculations indicate that there is no viable reaction pathway for the addition of nucleophiles to AA-. An alternative route for the formation of the Michael products via the non-ionized form of acrylic acid (AA) was explored and found to be theoretically possible. The alternative route is plausible, but is considered to be insignificant in vivo based upon the rapid metabolism and excretion of AA (excretion half-life of 1-8 h after oral dosing).
authors.affiliation: Toxicology Department, Rohm and Haas Co., Spring House, PA 19477.
authors.forename: C B
authors.initials: CB
authors.lastname: Frederick
authors.forename: C H
authors.initials: CH
authors.lastname: Reynolds
mesh_terms: D000179:Acrylates / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000838:Anions; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D007093:Imidazoles; D008744:Methylamines; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D000179:Acrylates; D000838:Anions; D007093:Imidazoles; D008744:Methylamines; C029899:imidazole; D004247:DNA; C027451:methylamine; C036658:acrylic acid