Ozonation of Gabapentin in Water─Investigating Reaction Kinetics and Transformation Mechanisms of a Primary Amine Using Isotopically Labeled Ozone.

Aliphatic amines are abundant micropollutants in wastewater treatment plant effluents. In order to mitigate such micropollutants, ozonation is one of the most commonly employed advanced treatment processes. Current research regarding ozone efficiency is heavily focusing on reaction mechanisms of different contaminant groups, including structures with amine moieties as reactive sites. This study analyzes pH-dependent reaction kinetics and pathways of gabapentin (GBP), an aliphatic primary amine with an additional carboxylic acid group. The transformation pathway was elucidated applying a novel approach using isotopically labeled ozone (18O) and quantum chemistry calculations. While the direct reaction of GBP with ozone is highly pH-dependent and slow at pH 7 (13.7 M-1 s-1), the rate constant of the deprotonated species (1.76 × 105 M-1 s-1) is comparable to those of other amine compounds. Pathway analysis based on LC-MS/MS measurements revealed that ozonation of GBP leads to the formation of a carboxylic acid group and simultaneous nitrate formation, which was also observed in the case of the aliphatic amino acid glycine. Nitrate was formed with a yield of approximately 100%. Experiments with 18O-labeled ozone demonstrated that the intermediate aldehyde does most likely not include any oxygen originating from ozone. Furthermore, quantum chemistry calculations did not provide an explanation for the C-N scission during GBP ozonation without ozone involvement, although this reaction was slightly more favorable than for respective glycine and ethylamine reactions. Overall, this study contributes to a deeper understanding of reaction mechanisms of aliphatic primary amines during wastewater ozonation.

Isotopically labeled ozone: A new approach to elucidate the formation of ozonation products.

As ozonation becomes a widespread treatment for removal of chemicals of emerging concern from wastewater treatment plant effluents, there are increasing concerns regarding the formation of ozonation products (OPs), and their possible impacts on the aquatic environment and eventually human health. In this study, a novel method was developed that utilizes heavy oxygen (18O2) for the production of heavy ozone ([18O1]O2, [18O2]O1, [18O3]) to actively label OPs from oxygen transfer reactions. To establish and validate this new approach, venlafaxine with a well-described oxygen transfer reaction (tertiary amine -> N-oxide) was chosen as a model compound. Observed 18O/16O ratios in the major OP venlafaxine N-oxide (NOV) correlated with expected 18O purities based on tracer experiments. These results confirmed the successful labeling with heavy oxygen and furthermore demonstrate the potential to monitor NOV as an indicator of 18O/16O ratios during ozonation. As a next step, 18O/16O ratios were used to elucidate the formation mechanism of previously described OPs from sulfamethoxazole (SMX). Seven OPs were detected including the frequently described nitro-SMX, which was formed with a maximum yield of 3.2% (of initial SMX). With the successful labeling of six of the seven OPs from sulfamethoxazole, it was possible to confirm their previously proposed formation pathways, and to distinguish oxygen transfer from electron transfer reactions. 18O/16O ratios in OPs indicate that hydroxylation of the aromatic ring and formation of nitro-groups mostly follows oxygen transfer reactions, while electron transfer reactions initiate the formation of hydroxylamine and the abstraction of NH2 leading to catechol.

Stable isotope labeling for detection of ozonation byproducts in effluent organic matter with FT-ICR-MS.

Despite effluent organic matter (EfOM) being a major consumer of ozone during wastewater treatment, little is known about ozonation byproducts (OBPs) produced from EfOM. To unambiguously identify OBPs, heavy ozone was used to ozonate EfOM, resulting in 18O labeled and unlabeled OBPs. Labeled OBPs mostly represent a single 18O transfer and were classified as either direct or indirect OBPs based on the 18O/16O intensity ratios of the isotopologues. Of the 929 labeled OBPs, 84 were unequivocally classified as direct OBPs. The remainder suggest a major contribution by indirect, hydroxyl radical induced formation of OBPs in EfOM. Overall, labelled OBPs possess a low degree of unsaturation and contributed most to OBP peak intensity - marking them as potential end products. A few direct and indirect OBPs with high peak intensity containing 18O and heteroatoms (N, S) were fragmented with CID FT-ICR-MS/MS and screened for indicative neutral losses carrying heavy oxygen. The neutral loss screening was used to detect the 18O location on the OBP and indicate the original functional group in EfOM based on known reaction mechanisms. We identified sulfoxide and sulfonic acid functional groups in selected OBPs - implying the presence of reduced sulfur in EfOM molecules - while no evidence for nitrogen containing functional groups reacting with ozone was found.