There has been a great focus on halogen-bonding as a unique interaction between electron-deficient halogen atoms with Lewis basic moieties. Although the application of halogen-bonded atoms in organic ...chemistry has been eagerly researched in these decades, the development of chiral molecules with halogen-bonding functionalities and their utilization in asymmetric catalysis are still in the\ir infancy. We have previously developed chiral halonium salts with amide functionalities, which behaved as excellent catalysts albeit in only two reactions due to the lack of substrate activation abilities. In this manuscript, we have developed chiral halonium salts with an
-nitrosamine moiety and applied them to the Mannich reaction of isatin-derived ketimines with malonic esters. The study focused on our novel bromonium salt catalyst which provided the corresponding products in high yields with up to 80% ee. DFT calculations of the chiral catalyst structure suggested that the high asymmetric induction abilities of this catalyst are due to the Lewis basic role of the
-nitrosamine part. To the best of our knowledge, this is the first catalytic application of
-nitrosamines.
In this study, the formation of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N-nitrosomethylamine, N-nitrosodi-n-propylamine, N-nitrosodi-n-butylamine, ...N-Nitrosopiperidine, N-Nitrosopyrrolidine, N-Nitrosomorpholine, were systematically evaluated with respect to seven N-nitrosamine precursors (dimethylamine, trimethylamine, 3-(dimethylaminomethyl)indole, 4-dimethylaminoantipyrine, ethylmethylamine, diethylamine, dipropylamine) and three disinfectants (monochloramine, free chlorine, peracetic acid) under variable dosages, exposure times, and pH in a drinking water system. Without the presence of the seven selected N-nitrosamine precursors N-nitrosamine formation was not observed under any tested condition except very low levels of N-Nitrosopyrrolidine under some conditions. With selected N-nitrosamine precursors present N-nitrosamines formed at different levels under different conditions. The highest N-nitrosamine formation was NDMA with a maximum concentration of 1180 ng/L by monochloramine disinfection with precursors present; much lower levels of N-nitrosamines were formed by free chlorine disinfection; and no detectable level of N-nitrosamines were observed by peracetic acid disinfection except low level of N-Nitrosodi-n-propylamine under some conditions. NDMA formation was not affected by pH while four other N-nitrosamine formations were slightly affected by sample pH tested between 7 and 9, with formation decreasing with increasing pH. Monochloramine exposure time study displayed fast formation of N-nitrosamines, largely formed in four hours of exposure and maximized after seven days. This was a systematic study on the N-nitrosamine formation with the seven major N-nitrosamine precursors presence and absence under different conditions, including peracetic acid disinfection which has not been studied elsewhere.
•Eight N-nitrosamine formations by different disinfections were studied.•No N-nitrosamines were formed without precursor addition in water samples.•NDMA formation increase with monochloramine dosage when precursors present.•Peracetic acid disinfection did not form N-nitrosamines except NDPA.
More than 24 N-nitrosamine compounds contribute to the total N-nitrosamine (TNA) burden monitored routinely to assess human exposure to this important group of known and suspected human carcinogens. ...A literature review (n = 122) identified multiple sources of human exposure to TNAs, including waters (40 ± 10.5 ng/L; average ± standard deviation), food and beverages (6.7 ± 0.8 ng/g), tobacco (16,100 ± 3650 ng/g) and personal care products (1500 ± 750 ng/g). Due to source control interventions, levels of TNAs in beer have dropped by about 96% between 1980 and 1990, whereas N-nitrosamine levels in other known sources have shown little to no change. Maximum daily TNA exposure in the U.S. in units of ng/d is estimated at 25,000 ± 4,950, driven by consumption of tobacco products (22,000 ± 4350), food (1900 ± 380), alcohol (1000 ± 200), and drinking water (120 ± 24). Behavioral choices of individuals in non-occupational settings were calculated to result in a spectrum of exposure values ranging from a lower bound of 1900 ± 380 ng/d to a higher bound of 25,000 ± 4950 ng/d, indicating opportunities for a possible 12-fold reduction in TNA exposure to 8% of the above maximum through deliberate choices in diet and lifestyle.
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•N-nitrosamines are found in tobacco, food, water and personal care products.•Exposure estimated at 1900 to 25,000 ng/day/person, excluding personal care.•6000 ± 2950 cancer cases per 1M persons attributable to N-nitrosamines.•1,940,000 ± 950,000 lifetime cancer cases in U.S. attributable to N-nitrosamines.•Up to 92% of exposure and cancer cases avoidable through lifestyle choices.
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•Formation of PCCC-derived N-nitrosamines and N-nitramines.•Emission and degradation of PCCC-derived N-nitrosamines and N-nitramines.•Toxicology and environmental impacts of ...N-nitrosamines and N-nitramines.•Destruction and removal of PCCC-derived N-nitrosamines and N-nitramines.•Future research perspectives for PCCC-derived N-nitrosamines and N-nitramines.
Amine-based post-combustion CO2 capture (PCCC) technology is regarded as one of the most viable solutions for the mitigation of CO2 emissions. It has been mature enough to be implemented on commercial scales. However, N-nitrosamines and N-nitramines can be formed as by-products of amine degradation during PCCC processes. They are suspected carcinogens and strictly regulated. With the development of PCCC technology across the global, PCCC facility may become a main source of N-nitrosamines and N-nitramines to the environment. Due to the possible adverse effects of N-nitrosamines and N-nitramines on the environment and human health, the interests in the occurrence, fate and mitigation of PCCC-derived N-nitrosamines and N-nitramines have been shared by a growing number of researchers recently. Therefore, this article provides a comprehensive review on the most recent efforts in this emerging field. In detail, this review focuses on (a) the formation, emission and degradation of N-nitrosamines and N-nitramines from amine-based PCCC processes, (b) the toxicology and environmental impact of PCCC-derived N-nitrosamines and N-nitramines, (c) the methods to destruct and remove N-nitrosamines and N-nitramines from PCCC waste, and (d) the future research perspectives.
► Significant variations in the rejection of NDMA by RO membranes have been reported. ► NDMA rejection by RO membranes ranges from negligible to as high as 86%. ► Effects of operating condition on ...rejection can explain for some of these variations. ► Future research areas to further explain these variations are proposed here. ► Little is known about the rejection of other N-nitrosamines and their precursors.
N-nitrosodimethylamine (NDMA) and several other N-nitrosamines have been identified as probable human carcinogens. Here, we review key aspects related to the occurrence and removal of N-nitrosamines by reverse osmosis (RO) membranes in the context of indirect potable water reuse. A comprehensive analysis of the existing data reveals significant variations in the rejection of NDMA by RO membranes reported in the literature, ranging from negligible up to 86%. This review article provides some insight into the reasons for such variations by examining the available data on the effects of operating conditions on NDMA rejection. Amongst several operating parameters investigated so far in the literature, feed temperature, membrane permeate flux, feed solution pH and ionic strength were found to have considerable impact on NDMA rejection by RO membranes. In particular, it has been recently shown that seasonal changes in feed temperature (e.g. from 20 to 30°C) can result in a significant decrease in NDMA rejection (from 49% to 25%). However, the combined effects of all operating parameters identified in the literature to date can only account for some of the variations in NDMA rejection that have been observed in full-scale RO plants. The impacts of membrane fouling and particularly chemical cleaning on the rejection of N-nitrosamines have not been fully investigated. Finally, this review article presents a roadmap for further research required to optimise the rejection of NDMA and other N-nitrosamines by RO membranes.
The detection of N-nitrosamine impurities in medicines and the recent emergence of nitrosamine drug substance related impurities (NDSRIs) has posed a great challenge to manufacturers of drug products ...and regulators alike. NDSRIs are primarily associated with reactions occurring in the drug product which brings particular complexity. This paper will explore the current technical knowledge surrounding the formation of these impurities, including the risk factors, reaction conditions, and potential mitigation strategies. Scientific understanding of these areas is still evolving, and we will highlight both the scientific progress made and discuss the significant gaps in mechanistic knowledge still remaining. These gaps render accurate predictions of NDSRI formation extremely challenging. The pharmaceutical industry should continue to work on potential mitigation strategies and generation of additional scientific data to address the mechanistic gaps. Regulatory guidance and policy will continue to advance and adapt in response to further changes in scientific understanding.
The source and fate of N-nitrosamines and their precursors in terms of formation potential (FP) was investigated quantitatively in the city level for the first time. Different sources of nitrosamines ...and their precursors were investigated in one city in the Yangtze River delta, China. The source water located downstream of the city contained 8.4 ng/L of N-nitrosodimethyamine (NDMA) and 153 ng/L of NDMA FP. The contribution of each discharge source was evaluated based on the concentration, the river water flux, and the amount of wastewater discharges. Textile printing and dyeing wastewater, and electroplating industrial wastewater contained high concentration of nitrosamines and were important discharge sources. Taking NDMA and NDMA FP attenuation by photolysis and biodegradation into consideration, the mass load calculation showed upstream surface water brought about 13 ± 4% of NDMA and 21 ± 3% of NDMA FP to downstream source water. Local wastewater discharges contributed 30 ± 8% of NDMA and 17 ± 2% of NDMA FP to downstream source water. Endogenous formation via amino acids metabolism could contribute 36% of NDMA FP (maximum) to downstream source water. Overall, this study provides a protocol for quantitative evaluation of the nitrosamine contribution to urban water supply from different contamination sources.
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•Fate of nitrosamines and precursors in an urban water system were investigated.•Nitrosamines and precursors of various wastewater discharges were characterized.•Upstream input and local wastewater discharges were important nitrosamine sources.•Upstream input, wastewaters and endogenous generation were major NDMA FP sources.
N-nitrosodimethylamine (NDMA), belonging to N-nitrosamines (NAs), was detected in several batches of aquatic products in Guangdong, China in 2019, making it urgent to monitor their contamination ...levels. A salting out homogeneous extraction coupled with GC-MS/MS method was developed for trace analysis of nine NAs in dry-cured mackerel. Results indicated calibration curves were linear from 0.5 to 200 μg/L with R2 higher than 0.9998. LODs and LOQs were in the range of 0.08–0.15 and 0.25–0.5 μg/kg, respectively. Matrix effects ranged from 0.98 to 1.17, which is within the commonly acceptable range. Favorable recoveries (77.1–112.9%) were obtained with RSDs below 7.4%. The proposed method shows rapid extraction time and favorable LODs, recoveries and RSDs which are comparable with other methods. The method was successfully applied for NAs determination in dry-cured mackerel, NDMA is widely detected in all samples with the concentration of 5.3–71.4 μg/kg and almost all kinds of NAs were detected in one sample.
•Developed a GC-MS/MS method for analysis of NAs firstly in dry-cured mackerel.•Salting out homogeneous extraction obtained high extraction recoveries for all NAs.•Method showed rapid extraction time and favorable LODs and precisions.•NDMA is widely detected in dry-cured mackerel (5.25–71.35, higher than 4 μg/kg).•Contamination of NAs in dry-cured mackerel is possibly related to dry-cured time.
Tea polyphenol (TP), apple polyphenol (AP), and cinnamon polyphenol (CP) are all enriched with antioxidant components, present enormous potential as natural antioxidants in meat products. The ...objective of this study was to evaluate the physicochemical properties, residual nitrites, and formation of N-nitrosamine (NA) in dry-fried bacons with three aforementioned plant polyphenols and ascorbic acid (AA). The results show that both plant polyphenols and AA significantly reduced pH, lipid oxidation and residual nitrite content when compared to the control (P < 0.05). Only AP exhibited a protective effect against protein oxidation-induced damage in bacon, and N-nitroso-methyl phenylamine (NMPhA) contents were significantly affected by plant polyphenols (P < 0.05). Bacon containing 300 mg/kg AP produced less thiobarbituric acid reactive substance (TBARS) (0.59 MDA/kg), carbonyl contents (2.30 nmol/mg protein) and NMPhA formation (1.211 ng/kg). In conclusion, plant polyphenols, particularly AP, have the potential to be used as natural antioxidants for reducing oxidation and nitrite application level while also improving the safety of bacon.
•Apple polyphenol (AP) was more effective in reducing nitrite and N-nitrosamine (NA) contents.•AP increased the bio-safety of smoked bacon in this study.•The optimal and recommended addition of AP in smoked bacon is 300 mg/kg.
N-nitrosamines (NAs), a class of emerging nitrogenous disinfection byproducts, have been detected remarkably in drinking/reclaimed water. There is a significant risk of excessive levels of NAs in the ...chlorination of the polluted source water, especially in the direct chlorination of nitrite-enriched groundwater. Considering the co-pollution of nitrite and micro-organic pollutants on groundwater, experiments were conducted on chlorination of nitrite-enriched water with precursor of antibiotics, and it was confirmed that the Cl2: N (molar ratio of chlorine to nitrite), contacting time, pH, and DO appreciably influenced the NAs formation potential. The molecular electric potential revealed that different dissociation status of precursors has a specific correlation with NAs formation potential (FP). The nitrite significantly increased the NAs FP because the reactive nitrogen species (RNS) formed in the oxidation process from nitrite to nitrate. Sequences of transformation products are determined to support the RNS promoted hypothesis of N-nitrosodimethylamine (NDMA) formation mechanism; furthermore, theoretical investigation in the reaction of dimethylamine (DMA) with different RNS verified the above hypothesis.
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•NDMA FP significantly promoted in chlorination of nitrite-enriched groundwater.•DO is not a key factor to NDMA formation in nitrite-enriched situation.•RNS enhanced-nitrosation pathway was proposed.•NDEA has been detected along with NDMA formation.
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