N-Methyl-4-nitroaniline: Physicochemical Properties, Degradation and Toxicity

General Description

N-Methyl-4-nitroaniline is a compound with significant environmental and toxicological relevance. Studies have shown that its physicochemical properties, such as aqueous solubility, octanol-water partition coefficient, and Henry's law constant, vary with temperature and ionic strength, influencing its environmental distribution and treatment processes. Notably, N-Methyl-4-nitroaniline's solubility decreases in the presence of electrolytes, suggesting reduced mobility in certain environments. Additionally, aerobic degradation by Pseudomonas sp. strain FK357 presents a promising bioremediation approach, converting N-Methyl-4-nitroaniline through a defined metabolic pathway into less harmful substances. Toxicity assessments reveal N-Methyl-4-nitroaniline's dose-dependent toxicity, with higher doses causing clear signs of toxicity without fatalities. These insights are crucial for managing N-Methyl-4-nitroaniline's environmental impact and occupational exposure, highlighting the importance of understanding both its physicochemical behavior and biological degradation pathways.

Figure 1. N-Methyl-4-nitroaniline

Physicochemical properties

N-Methyl-4-nitroaniline is a compound with significant implications for environmental science, particularly in understanding the fate and impact of organic contaminants. A study focused on determining its physicochemical properties, including aqueous solubility, octanol-water partition coefficient, and Henry's law constant across temperatures of 298.15 K to 318.15 K. These properties are crucial for predicting N-Methyl-4-nitroaniline's environmental distribution, potential for biotransformation, and treatment processes. The research revealed that N-Methyl-4-nitroaniline's solubility in water increases with temperature, a finding that aligns with the general behavior of many substances. However, the presence of electrolytes like NaCl and CaCl2 was found to decrease N-Methyl-4-nitroaniline's solubility, indicating ionic strength's role in affecting its environmental mobility. The study also applied the Van't Hoff equation to correlate the observed data, demonstrating a linear relationship between the physicochemical properties and reciprocal temperature. This linear relationship allowed for the calculation of enthalpy and entropy of phase transfer, providing deeper insight into N-Methyl-4-nitroaniline's behavior under varying environmental conditions. Such detailed understanding aids in predicting N-Methyl-4-nitroaniline concentrations in wastewater and air emanating from munitions facilities, especially considering operational conditions like melt pour techniques and facility cleaning with hot water or steam, where N-Methyl-4-nitroaniline concentrations could be higher due to temperature effects. ¹

Degradation

The aerobic degradation of N-Methyl-4-nitroaniline, a compound used to lower the melting temperature in the synthesis of insensitive explosives, has been successfully demonstrated by Pseudomonas sp. strain FK357 isolated from soil. This process marks a significant advancement as prior to this, only anaerobic biotransformation of N-Methyl-4-nitroaniline had been documented. The bacterium utilizes N-Methyl-4-nitroaniline as its sole source of carbon, nitrogen, and energy, showcasing an efficient microbial solution to degrade such environmental pollutants. Through HPLC and GC-MS analysis, the metabolic pathway was elucidated, revealing the formation of 4-nitroaniline (4-NA), 4-aminophenol (4-AP), and 1, 2, 4-benzenetriol (BT) as major intermediates. The initial step involves an N-demethylation reaction, transforming N-Methyl-4-nitroaniline into 4-NA and formaldehyde. Subsequently, 4-NA undergoes a monooxygenation to form 4-AP, followed by oxidative deamination to produce BT. The degradation of BT is facilitated by benzenetriol 1, 2-dioxygenase, a mechanism similar to that observed in the degradation of 4-nitrophenol. This research not only identifies a novel bacterium capable of N-Methyl-4-nitroaniline's aerobic degradation but also clarifies the metabolic pathways involved, offering potential strategies for the bioremediation of nitroaromatic pollutants. ²

Toxicity

N-Methyl-4-nitroaniline exhibits distinct toxicity profiles based on dosage and gender differences. In a study assessing its toxicity, males and females were administered single oral doses of N-Methyl-4-nitroaniline, with females receiving 300 mg/kg and both genders receiving 2000 mg/kg. Remarkably, no fatalities were observed at these dosages. However, at the higher dose of 2000 mg/kg, both male and female subjects displayed clear signs of toxicity immediately on the day of dosing. These findings suggest that while N-Methyl-4-nitroaniline can be tolerated up to a certain threshold without causing death, it becomes significantly toxic at higher concentrations, indicating a dose-dependent toxicity characteristic. This information is crucial for understanding N-Methyl-4-nitroaniline's safety profile and managing its environmental and occupational exposure risks effectively. ³

Reference

1. Boddu VM, Abburi K, Maloney SW, Damavarapu R. Physicochemical properties of an insensitive munitions compound, N-methyl-4-nitroaniline (MNA). J Hazard Mater. 2008;155(1-2):288-294.

2. Khan F, Vyas B, Pal D, Cameotra SS. Aerobic degradation of N-methyl-4-nitroaniline (MNA) by Pseudomonas sp. strain FK357 isolated from soil. PLoS One. 2013;8(10):e75046.

3. N-Methyl-4-nitroaniline. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 7483.