title: A combined experimental and computational investigation on the unusual molecular mechanism of the Lossen rearrangement reaction activated by carcinogenic halogenated quinones.
abstract: The classic Lossen rearrangement is a well-known reaction describing the transformation of an O-activated hydroxamic acid into the corresponding isocyanate. In this study, we found that chlorinated benzoquinones (CnBQ) serve as a new class of agents for the activation of benzohydroxamic acid (BHA), leading to Lossen rearrangement. Compared to the classic one, this new kind of CnBQ-activated Lossen rearrangement has the following unique characteristics: (1) The stability of CnBQ-activated BHA intermediates was found to depend not only on the degree but also on the position of Cl-substitution on CnBQs, which can be divided into two subgroups. (2) It is the relative energy of the anionic CnBQ-BHA intermediates that determine the rate of this CnBQ-activated rearrangement, which is the rate-limiting step, and the Cl or H ortho to the reaction site at CnBQ is crucial for the stability of the anionic intermediates. (3) A pKa-activation energy correlation was observed, which can explain why the correlation exists between the rate of the rearrangement and the acidity of the conjugate acid of the anionic leaving group, the hydroxlated quinones. These findings may have broad implications for future research on halogenated quinoid carcinogens and hydroxamate biomedical agents.
authors.affiliation: †State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.|‡Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Shan
authors.affiliation: §Central Laboratory, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Yu
authors.affiliation: §Central Laboratory, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Chuan-Fang
authors.initials: CF
authors.lastname: Zhao
authors.affiliation: †State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Huang
authors.affiliation: ‡Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Zhu
authors.affiliation: †State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.|¶Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, United States.
authors.forename: Ben-Zhan
authors.initials: BZ
authors.lastname: Zhu
mesh_terms: D016227:Benzoquinones / Q000138:chemical synthesis / Q000737:chemistry*; D002273:Carcinogens / Q000138:chemical synthesis / Q000737:chemistry*; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D011789:Quantum Theory
chemical_list: D016227:Benzoquinones; D002273:Carcinogens; D006843:Hydrocarbons, Chlorinated