Coupling reactions between reduced intermediates of insensitive munitions compound analog 4-nitroanisole

Warren M. Kadoya, Maria Reye Sierra Alvarez, Bhumasamudram Jagadish, Stanley Wong, Leif M Abrell, Eugene A Mash, James A Field

Research output: Contribution to journalArticle

Abstract

Explosives, pesticides, and pharmaceuticals contain toxic nitroaromatic compounds that may form even more toxic azo compounds if they encounter reducing conditions in the environment. We investigated the mechanism by which 4,4′-dimethoxyazobenzene forms in anaerobic sludge incubations of 4-nitroanisole, an analog for the insensitive munitions compound 2,4-dinitroanisole (DNAN). Because studies have reported the mechanism to involve the coupling of reduced nitroaromatic intermediates, specifically aromatic amines and nitrosoaromatics, by nucleophilic processes, we abiotically paired 10 mM 4-aminoanisole with 2 mM 4-nitrosoanisole in nitrogen-flushed microcosms. However, only 7 μM of 4,4′-dimethoxyazobenzene had formed after 24 h. We identified the major product to be 4-methoxy-4′-nitrosodiphenylamine. Repeating this experiment in phosphate buffer at pH 5.1, 7.1, and 8.6 demonstrated that the formation of this unexpected product is acid catalyzed. We found that 4-methoxy-4′-nitrosodiphenylamine is more toxic than 4,4′-dimethoxyazobenzene to the bioluminescent bacterium Aliivibrio fischeri, with IC 50 values of 0.1 μM and 0.5 μM, respectively. Both products are several orders of magnitude more toxic than reduced 4-nitroanisole intermediates 4-aminoanisole and 4-nitrosoanisole, as well as DNAN and its aromatic amine metabolites. Six-fold more 4,4′-dimethoxyazobenzene formed when we incubated 4-nitrosoanisole with ascorbic acid, a reducing agent, than when we incubated 4-nitrosoanisole with 4-aminoanisole in the absence of ascorbic acid. We therefore suspect that 4-hydroxylaminoanisole, the first reduction product of 4-nitrosoanisole, is a better nucleophile than 4-aminoanisole and couples more readily with 4-nitrosoanisole. Slightly basic and reducing conditions can prevent the formation and persistence of toxic coupling products on sites contaminated with nitroaromatics, i.e. DNAN-contaminated firing ranges.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
JournalChemosphere
Volume222
DOIs
StatePublished - May 1 2019

Fingerprint

Poisons
Ascorbic acid
Amines
Nucleophiles
Reducing agents
Metabolites
Pesticides
Drug products
ascorbic acid
Bacteria
Phosphates
Ascorbic Acid
Nitrogen
Azo Compounds
Aliivibrio fischeri
Acids
Reducing Agents
Sewage
Experiments
microcosm

Keywords

  • 2,4-Dinitroanisole (DNAN)
  • Aromatic amines
  • Azobenzenes
  • Insensitive munitions compound
  • Nitroaromatics
  • Nitrosoaromatics

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

Cite this

Coupling reactions between reduced intermediates of insensitive munitions compound analog 4-nitroanisole. / Kadoya, Warren M.; Sierra Alvarez, Maria Reye; Jagadish, Bhumasamudram; Wong, Stanley; Abrell, Leif M; Mash, Eugene A; Field, James A.

In: Chemosphere, Vol. 222, 01.05.2019, p. 789-796.

Research output: Contribution to journalArticle

@article{28e38cc024234df4a52350b3d332720b,
title = "Coupling reactions between reduced intermediates of insensitive munitions compound analog 4-nitroanisole",
abstract = "Explosives, pesticides, and pharmaceuticals contain toxic nitroaromatic compounds that may form even more toxic azo compounds if they encounter reducing conditions in the environment. We investigated the mechanism by which 4,4′-dimethoxyazobenzene forms in anaerobic sludge incubations of 4-nitroanisole, an analog for the insensitive munitions compound 2,4-dinitroanisole (DNAN). Because studies have reported the mechanism to involve the coupling of reduced nitroaromatic intermediates, specifically aromatic amines and nitrosoaromatics, by nucleophilic processes, we abiotically paired 10 mM 4-aminoanisole with 2 mM 4-nitrosoanisole in nitrogen-flushed microcosms. However, only 7 μM of 4,4′-dimethoxyazobenzene had formed after 24 h. We identified the major product to be 4-methoxy-4′-nitrosodiphenylamine. Repeating this experiment in phosphate buffer at pH 5.1, 7.1, and 8.6 demonstrated that the formation of this unexpected product is acid catalyzed. We found that 4-methoxy-4′-nitrosodiphenylamine is more toxic than 4,4′-dimethoxyazobenzene to the bioluminescent bacterium Aliivibrio fischeri, with IC 50 values of 0.1 μM and 0.5 μM, respectively. Both products are several orders of magnitude more toxic than reduced 4-nitroanisole intermediates 4-aminoanisole and 4-nitrosoanisole, as well as DNAN and its aromatic amine metabolites. Six-fold more 4,4′-dimethoxyazobenzene formed when we incubated 4-nitrosoanisole with ascorbic acid, a reducing agent, than when we incubated 4-nitrosoanisole with 4-aminoanisole in the absence of ascorbic acid. We therefore suspect that 4-hydroxylaminoanisole, the first reduction product of 4-nitrosoanisole, is a better nucleophile than 4-aminoanisole and couples more readily with 4-nitrosoanisole. Slightly basic and reducing conditions can prevent the formation and persistence of toxic coupling products on sites contaminated with nitroaromatics, i.e. DNAN-contaminated firing ranges.",
keywords = "2,4-Dinitroanisole (DNAN), Aromatic amines, Azobenzenes, Insensitive munitions compound, Nitroaromatics, Nitrosoaromatics",
author = "Kadoya, {Warren M.} and {Sierra Alvarez}, {Maria Reye} and Bhumasamudram Jagadish and Stanley Wong and Abrell, {Leif M} and Mash, {Eugene A} and Field, {James A}",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.chemosphere.2019.01.163",
language = "English (US)",
volume = "222",
pages = "789--796",
journal = "Chemosphere",
issn = "0045-6535",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Coupling reactions between reduced intermediates of insensitive munitions compound analog 4-nitroanisole

AU - Kadoya, Warren M.

AU - Sierra Alvarez, Maria Reye

AU - Jagadish, Bhumasamudram

AU - Wong, Stanley

AU - Abrell, Leif M

AU - Mash, Eugene A

AU - Field, James A

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Explosives, pesticides, and pharmaceuticals contain toxic nitroaromatic compounds that may form even more toxic azo compounds if they encounter reducing conditions in the environment. We investigated the mechanism by which 4,4′-dimethoxyazobenzene forms in anaerobic sludge incubations of 4-nitroanisole, an analog for the insensitive munitions compound 2,4-dinitroanisole (DNAN). Because studies have reported the mechanism to involve the coupling of reduced nitroaromatic intermediates, specifically aromatic amines and nitrosoaromatics, by nucleophilic processes, we abiotically paired 10 mM 4-aminoanisole with 2 mM 4-nitrosoanisole in nitrogen-flushed microcosms. However, only 7 μM of 4,4′-dimethoxyazobenzene had formed after 24 h. We identified the major product to be 4-methoxy-4′-nitrosodiphenylamine. Repeating this experiment in phosphate buffer at pH 5.1, 7.1, and 8.6 demonstrated that the formation of this unexpected product is acid catalyzed. We found that 4-methoxy-4′-nitrosodiphenylamine is more toxic than 4,4′-dimethoxyazobenzene to the bioluminescent bacterium Aliivibrio fischeri, with IC 50 values of 0.1 μM and 0.5 μM, respectively. Both products are several orders of magnitude more toxic than reduced 4-nitroanisole intermediates 4-aminoanisole and 4-nitrosoanisole, as well as DNAN and its aromatic amine metabolites. Six-fold more 4,4′-dimethoxyazobenzene formed when we incubated 4-nitrosoanisole with ascorbic acid, a reducing agent, than when we incubated 4-nitrosoanisole with 4-aminoanisole in the absence of ascorbic acid. We therefore suspect that 4-hydroxylaminoanisole, the first reduction product of 4-nitrosoanisole, is a better nucleophile than 4-aminoanisole and couples more readily with 4-nitrosoanisole. Slightly basic and reducing conditions can prevent the formation and persistence of toxic coupling products on sites contaminated with nitroaromatics, i.e. DNAN-contaminated firing ranges.

AB - Explosives, pesticides, and pharmaceuticals contain toxic nitroaromatic compounds that may form even more toxic azo compounds if they encounter reducing conditions in the environment. We investigated the mechanism by which 4,4′-dimethoxyazobenzene forms in anaerobic sludge incubations of 4-nitroanisole, an analog for the insensitive munitions compound 2,4-dinitroanisole (DNAN). Because studies have reported the mechanism to involve the coupling of reduced nitroaromatic intermediates, specifically aromatic amines and nitrosoaromatics, by nucleophilic processes, we abiotically paired 10 mM 4-aminoanisole with 2 mM 4-nitrosoanisole in nitrogen-flushed microcosms. However, only 7 μM of 4,4′-dimethoxyazobenzene had formed after 24 h. We identified the major product to be 4-methoxy-4′-nitrosodiphenylamine. Repeating this experiment in phosphate buffer at pH 5.1, 7.1, and 8.6 demonstrated that the formation of this unexpected product is acid catalyzed. We found that 4-methoxy-4′-nitrosodiphenylamine is more toxic than 4,4′-dimethoxyazobenzene to the bioluminescent bacterium Aliivibrio fischeri, with IC 50 values of 0.1 μM and 0.5 μM, respectively. Both products are several orders of magnitude more toxic than reduced 4-nitroanisole intermediates 4-aminoanisole and 4-nitrosoanisole, as well as DNAN and its aromatic amine metabolites. Six-fold more 4,4′-dimethoxyazobenzene formed when we incubated 4-nitrosoanisole with ascorbic acid, a reducing agent, than when we incubated 4-nitrosoanisole with 4-aminoanisole in the absence of ascorbic acid. We therefore suspect that 4-hydroxylaminoanisole, the first reduction product of 4-nitrosoanisole, is a better nucleophile than 4-aminoanisole and couples more readily with 4-nitrosoanisole. Slightly basic and reducing conditions can prevent the formation and persistence of toxic coupling products on sites contaminated with nitroaromatics, i.e. DNAN-contaminated firing ranges.

KW - 2,4-Dinitroanisole (DNAN)

KW - Aromatic amines

KW - Azobenzenes

KW - Insensitive munitions compound

KW - Nitroaromatics

KW - Nitrosoaromatics

UR - http://www.scopus.com/inward/record.url?scp=85061625374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061625374&partnerID=8YFLogxK

U2 - 10.1016/j.chemosphere.2019.01.163

DO - 10.1016/j.chemosphere.2019.01.163

M3 - Article

C2 - 30739063

AN - SCOPUS:85061625374

VL - 222

SP - 789

EP - 796

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

ER -