title: Enzyme catalytic nitration of aromatic compounds.
abstract: Nitroaromatic compounds are important intermediates in organic synthesis. The classic method used to synthesize them is chemical nitration, which involves the use of nitric acid diluted in water or acetic acid, both harmful to the environment. With the development of green chemistry, environmental friendly enzyme catalysis is increasingly employed in chemical processes. In this work, we adopted a non-aqueous horseradish peroxidase (HRP)/NaNO2/H2O2 reaction system to study the structural characteristics of aromatic compounds potentially nitrated by enzyme catalysis, as well as the relationship between the charges on carbon atoms in benzene ring and the nitro product distribution. Investigation of various reaction parameters showed that mild reaction conditions (ambient temperature and neutral pH), plus appropriate use of H2O2 and NaNO2 could prevent inactivation of HRP and polymerization of the substrates. Compared to aqueous-organic co-solvent reaction media, the aqueous-organic two-liquid phase system had great advantages in increasing the dissolved concentration of substrate and alleviating substrate inhibition. Analysis of the aromatic compounds' structural characteristics indicated that substrates containing substituents of NH2 or OH were readily catalyzed. Furthermore, analysis of the relationship between natural bond orbital (NBO) charges on carbon atoms in benzene ring, as calculated by the density functional method, and the nitro product distribution characteristics, demonstrated that the favored nitration sites were the ortho and para positions of substituents in benzene ring, similar to the selectivity of chemical nitration.
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Kong
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Runan
authors.initials: R
authors.lastname: Dong
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China. Electronic address: hj_gao@bit.edu.cn.
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006841:Hydrocarbons, Aromatic / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D009574:Nitro Compounds / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D009930:Organic Chemicals / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism; D012977:Sodium Nitrite / Q000378:metabolism; D012997:Solvents; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D000814:Aniline Compounds; D006841:Hydrocarbons, Aromatic; D009574:Nitro Compounds; D009930:Organic Chemicals; D010636:Phenols; D012997:Solvents; D002244:Carbon; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D012977:Sodium Nitrite; D009584:Nitrogen
keywords: Aromatic compounds; Enzyme catalysis; Horseradish peroxidase; Nitration