title: Theoretical determination of chromophores in the chromogenic effects of aromatic neurotoxicants.
abstract: We report the first computational study of the chromophores responsible for the chromogenic effects of aromatic neurotoxicants containing a 1,2-diacetyl moiety in their oxidation metabolites. A series of ab initio electronic structure calculations was performed on two representative aromatic compounds, 1,2-diacetylbenzene (1,2-DAB) and 1,2-diacetyl tetramethyl tetralin (1,2-DATT), the putative active metabolites of the neurotoxic aromatic hydrocarbon compounds 1,2-diethylbenzene (1,2-DEB) and acetyl ethyl tetramethyl tetralin (AETT), and on the products of their possible reactions with proteins that result in chromogenic effects. The electronic excitation energies determined by three different computational approaches were found to be consistent with each other. The calculated results are consistent with the conclusion/prediction that the chromogenic effects of 1,2-DAB (or 1,2-DEB) and 1,2-DATT (or AETT) could result from ninhydrin-like reactions, rather than the formation of pyrrole-like compounds. Our pK(a) calculations further indicate that the chromophore, i.e., the product of the ninhydrin-like reaction showing the blue color, is deprotonated in neutral aqueous solution. The corresponding protonated structure has a different color as it absorbs in the blue region of the visible spectrum, and its chromogenic contribution would be significant in solution at low pH.
authors.affiliation: Theory, Modeling & Simulation, William R. Wiley Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, MS K1-83, P.O. Box 999, Richland, WA 99352, USA.
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Zhan
authors.forename: David A
authors.initials: DA
authors.lastname: Dixon
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Sabri
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Peter S
authors.initials: PS
authors.lastname: Spencer
mesh_terms: D000098:Acetophenones / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D008958:Models, Molecular; D008968:Molecular Conformation; D009422:Nervous System Diseases / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*
chemical_list: C454814:1,2-diacetyltetramethyltetralin; D000098:Acetophenones; D013764:Tetrahydronaphthalenes; C048792:1,2-diacetylbenzene