Assessing Photostability of mAb Formulations In Situ Using Light-Coupled NMR Spectroscopy.

Biopharmaceuticals, such as monoclonal antibodies (mAbs), need to maintain their chemical and physical stability in formulations throughout their lifecycle. It is known that exposure of mAbs to light, particularly UV, triggers chemical and physical degradation, which can be exacerbated by trace amounts of photosensitizers in the formulation. Although routine assessments of degradation following defined UV dosages are performed, there is a fundamental lack of understanding regarding the intermediates, transient reactive species, and radicals formed during illumination, as well as their lifetimes and immediate impact post-illumination. In this study, we used light-coupled NMR spectroscopy to monitor in situ live spectral changes in sealed samples during and after UV-A illumination of different formulations of four mAbs without added photosensitizers. We observed a complex evolution of spectra, reflecting the appearance within minutes of transient radicals during illumination and persisting for minutes to tens of minutes after the light was switched off. Both mAb and excipient signals were strongly affected by illumination, with some exhibiting fast irreversible photodegradation and others exhibiting partial recovery in the dark. These effects varied depending on the mAb and the presence of excipients, such as polysorbate 80 (PS80) and methionine. Complementary ex situ high-performance size-exclusion chromatography analysis of the same formulations post-UV exposure in the chamber revealed significant loss of purity, confirming formulation-dependent degradation. Both approaches suggested the presence of degradation processes initiated by light but continuing in the dark. Further studies on photoreaction intermediates and transient reactive species may help mitigate the impact of light on biopharmaceutical degradation.

The Z-Scheme MIL-88B(Fe)/BiOBr Heterojunction Promotes Fe(III)/Fe(II) Cycling and Photocatalytic-Fenton-Like Synergistically Enhances the Degradation of Ciprofloxacin.

The Z-scheme MIL-88B/BiOBr (referred to as MxBy, whereas x and y are the mass of MIL-88B(Fe) and BiOBr) heterojunction photocatalysts are successfully prepared by a facile ball milling method. By adding low concentration H2O2 under visible light irradiation, the Z-scheme heterojunction and photocatalytic-Fenton-like reaction synergistically enhance the degradation and mineralization of ciprofloxacin (CIP). Among them, M50B150 showed efficient photodegradation efficiency and excellent cycling stability, with 94.6% removal of CIP (10 mg L-1) by M50B150 (0.2 g L-1) under 90 min of visible light. In the MxBy heterojunctions, the rapid transfer of photo-generated electrons not only directly decomposed H2O2 to generate ·OH, but also improved the cycle of Fe3+/Fe2+ pairs, which facilitated the reaction with H2O2 to generate ·OH and ·O2 - radicals. In addition, the effects of photocatalyst dosages, pH of CIP solution, and coexisting substances on CIP removal are systematically investigated. It is found that the photocatalytic- Fenton-like reaction can be carried out at a pH close to neutral conditions. Finally, the charge transfer mechanism of the Z-scheme is verified by electron spin resonance (ESR) signals. The ecotoxicity of CIP degradation products is estimated by the T.E.S.T tool, indicating that the constructed photocatalysis-Fenton-like system is a green wastewater treatment technology.

Rational Design of Hydroxylated Thiazole Orange Photocages for Green Light-Triggered DNA Recombination.

The precise control of DNA recombination enables the cell- or time-dependent regulation of gene expression in studies of gene function. Caged estrogen receptor ligands combined with a Cre-ERT2/loxP system are useful tools for light-triggered DNA recombination. However, the photolysis of most caged compounds requires ultraviolet or blue light, which is toxic and displays low tissue penetration. Although a cyanine-based photo-responsive protecting group (PPG) can release estrogen receptor ligands with longer-wavelength light, its low photolytic efficiency requires long illumination times. We developed a caged estrogen receptor ligand with improved green light-responsive PPGs. The rational modification of Hydroxylated Thiazole Orange (HTO) photocages using electron-donating groups (EDGs), such as dimethoxy (DiMeO)-substituted HTO, resulted in high photolytic efficiency (up to ÏµΦ ≈320 M-1  cm-1 ). Theoretical calculations demonstrated that the enhanced photolytic efficiencies were derived from the increased intramolecular charge transfer by EDGs upon excitation. The efficient uncaging of estrogen receptor ligands enabled the control of gene recombination in a ligand-dependent Cre-ERT2/loxP system in live cells.

Electron-Induced Damage by UV Photolysis of DNA Attached to Gold Nanoparticles.

Photolysis of DNA attached to gold nanoparticles (AuNPs) with ultraviolet (UV) photons induces DNA damage. The release of nucleobases (Cyt, Gua, Ade, and Thy) from DNA was the major reaction (99%) with an approximately equal release of pyrimidines and purines. This reaction contributes to the formation of abasic sites in DNA. In addition, liquid chromatography-mass spectrometry/MS (LC-MS/MS) analysis revealed the formation of reduction products of pyrimidines (5,6-dihydrothymidine and 5,6-dihydro-2'-deoxyuridine) and eight 2',3'- and 2',5'-dideoxynucleosides. In contrast, there was no evidence of the formation of 5-hydroxymethyluracil and 8-oxo-7,8-dihydroguanine, which are common oxidation products of thymine and guanine, respectively. Using appropriate filters, the main photochemical reactions were found to involve photoelectrons ejected from AuNPs by UV photons. The contribution of "hot" conduction band electrons with energies below the photoemission threshold was minor. The mechanism for the release of free nucleobases by photoelectrons is proposed to take place by the initial formation of transient molecular anions of the nucleobases, followed by dissociative electron attachment at the C1'-N glycosidic bond connecting the nucleobase to the sugar-phosphate backbone. This mechanism is consistent with the reactivity of secondary electrons ejected by X-ray irradiation of AuNPs attached to DNA, as well as the reactions of various nucleic acid derivatives irradiated with monoenergetic very-low-energy electrons (∼2 eV). These studies should help us to understand the chemistry of nanoparticles that are exposed to UV light and that are used as scaffolds and catalysts in molecular biology, curative agents in photodynamic therapy, and components of sunscreens and cosmetics.

Near UV Photodegradation Mechanisms of Amino Acid Excipients: Formation of the Carbon Dioxide Radical Anion from Aspartate and Fe(III).

Carbon dioxide radical anion (•CO2-) is a powerful reducing agent that can reduce protein disulfide bonds and convert molecular oxygen to superoxide. Therefore, the generation of •CO2- can be detrimental to pharmaceutical formulations. Iron is among the most prevalent impurities in formulations, where Fe(III) chelates of histidine (His) can produce •CO2- upon exposure to near-UV light (Zhang and Schöneich, Eur. J. Pharm. Biopharm. 2023, 190, 231-241). Here, we monitor by spin-trapping in combination with electron paramagnetic resonance spectroscopy and/or high-performance liquid chromatography-mass spectrometry analysis the photochemical formation of •CO2- for a series of common amino acid excipients, including arginine (Arg), methionine (Met), proline (Pro), glutamic acid (Glu), glycine (Gly), aspartic acid (Asp), and lysine (Lys). Our results indicate that in the presence of Fe(III), Asp, and Glu produce significant yields of •CO2- under photoirradiation with near-UV light. Notably, Asp demonstrates the highest efficiency of •CO2- generation compared with that of the other amino acid excipients. Stable isotope labeling indicates that •CO2- exclusively originates from the α-carboxyl group of Asp. Mechanistic studies reveal two possible pathways for •CO2- formation, which involve either a ß-carboxyl radical or an amino radical cation intermediate.

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.

Mechanistic analysis of the photolytic decomposition of solid-state S-nitroso-N-acetylpenicillamine.

S-Nitroso-N-acetylpenicillamine (SNAP) is among the most common nitric oxide (NO)-donor molecules and its solid-state photolytic decomposition has potential for inhaled nitric oxide (iNO) therapy. The photochemical NO release kinetics and mechanism were investigated by exposing solid-state SNAP to a narrow-band LED as a function of nominal wavelength and intensity of incident light. The photolytic efficiency, decomposition products, and the photolytic pathways of the SNAP were examined. The maximum light penetration depth through the solid layer of SNAP was determined by an optical microscope and found to be within 100-200 µm, depending on the wavelength of light. The photolysis of solid-state SNAP to generate NO along with the stable thiyl (RS·) radical was confirmed using Electron Spin Resonance (ESR) spectroscopy. The fate of the RS· radical in the solid phase was studied both in the presence and absence of O2 using NMR, IR, ESR, and UPLC-MS. The changes in the morphology of SNAP due to its photolysis were examined using PXRD and SEM. The stable thiyl radical formed from the photolysis of solid SNAP was found to be reactive with another adjacent thiyl radical to form a disulfide (RSSR) or with oxygen to form various sulfonyl and sulfonyl peroxyl radicals {RS(O)xO·, x = 0 to 7}. However, the thiyl radical did not recombine with NO to reform the SNAP. From the PXRD data, it was found that the SNAP loses its crystallinity by generating the NO after photolysis. The initial release of NO during photolysis was increased with increased intensity of light, whereas the maximum light penetration depth was unaffected by light intensity. The knowledge gained about the photochemical reactions of SNAP may provide important insight in designing portable photoinduced NO-releasing devices for iNO therapy.

Study of the impurity profile of photodegradation in lomefloxacin hydrochloride ear drops using liquid chromatography combined with ion trap/time-of-flight mass spectrometry.

RATIONALE: Lomefloxacin hydrochloride ear drops are highly unstable to light and prone to produce photodegradation impurities. These impurities might be related to the phototoxicity of lomefloxacin, which could seriously threaten the health of patients. In this article, the photodegradation impurity profile in lomefloxacin hydrochloride ear drops was studied for further improvement of quality control of the drug. METHODS: By studying the chromatographic behavior of photodegradation impurities, the photodegradation impurities in lomefloxacin hydrochloride ear drops were separated and detected effectively. Liquid chromatography combined with ion trap/time-of-flight mass spectrometry was applied to characterize the structures of the photodegradation impurities in lomefloxacin hydrochloride ear drops. RESULTS: The structures of 17 impurities in lomefloxacin hydrochloride ear drops were elucidated based on high-resolution MSn data in positive ion mode, 12 of them being unknown impurities. CONCLUSIONS: The structural characteristics and fragmentation patterns of the photodegradation impurities were also studied. The study of the photodegradation impurity profile in lomefloxacin hydrochloride ear drops provides a scientific basis for quality control of these ear drops and ensures the safety of drug use by the public.

Identification, characterisation and in silico ADMET prediction of ozenoxacin and its degradation products using high-performance liquid chromatography-photodiode array and liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry.

RATIONALE: Ozenoxacin (OXC) is an antibiotic used topically to treat impetigo. This study aimed to evaluate the degradation products (DP) of OXC drug substance under different stress conditions, including hydrolysis, oxidation, thermal and photolysis, in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines Q1A(R2) and Q1B. The analytical technique was validated in compliance with ICH Q2(R1) requirements. METHODS: The drug substance underwent degradation under various forced degradation conditions, including thermal, oxidative, photolytic and hydrolytic (neutral, acidic and basic) degradation. Overall, four DPs were formed under oxidative stress conditions with AIBN. The formed DPs were identified and separated using a Shimadzu LC system with a reversed-phase Phenomenex Kinetex C18 column (4.6 × 250 mm, 5 µm), using 10 mM NH4 CH3 COOH buffer (pH -5.0) as mobile phase A and acetonitrile as mobile phase B at a detection wavelength of 254 nm. RESULTS AND CONCLUSION: The drug was found to be stable in neutral, acidic, basic and oxidative degradation conditions with hydrogen peroxide. Liquid chromatography-electrospray ionisation-quadrupole time-of-flight-tandem mass spectrometry- was employed in positive ionisation mode to analyse both the drug and the mass of the identified DP. The mechanism and the pathway of mass fragmentation have been proposed. The developed method was accurate, repeatable, linear and selective for further research. The ADMET Predictor software was applied to predict the in silico toxicity of the drugs and its DPs as well as their physicochemical characteristics.

LC/Q-TOF-MS-based structural characterization of enasidenib degradation products and establishment of a stability-indicating assay method: Insights into chemical stability.

RATIONALE: Enasidenib (EDB) is an orally active selective mutant isocitrate dehydrogenase-2 enzyme inhibitor approved by the U.S. Food and Drug Administration to treat acute myeloid leukemia. It lacks a reported forced degradation study and a stability-indicating assay method (SIAM). This study addresses this gap by establishing a degradation profile in accordance with the International Council for Harmonisation Q1A and Q1B (R2) guidelines and developing a validated SIAM for EDB. METHODS: EDB was exposed to forced degradation under various conditions (hydrolytic, photolytic, oxidative, and thermal stress). Degradation samples were analyzed using high-performance liquid chromatography on an Agilent ZORBAX Eclipse Plus C18 column with a mobile phase consisting of 0.1% formic acid in Milli-Q water and acetonitrile at a flow rate of 1 mL/min and detection at 270 nm. Liquid chromatography-quadrupole time-of-flight-high-resolution mass spectrometry (LC/Q-TOF HRMS) was used for the identification and characterization of degradation products. Nitrosamine risk assessment was conducted using a modified nitrosation assay procedure (NAP) test due to the presence of a secondary amine group in the drug, which is liable to forming nitrosamine drug substance-related impurities (NDSRI). RESULTS: The drug exhibited significant degradation under acidic, basic, photolytic, and oxidative conditions in the solution state. A total of nine degradation products (DP) were formed (DP-I, DP-III, and DP-IV: acidic conditions; DP-I and DP-III: basic conditions; DP-II, DP-V, DP-VI, and DP-VII: oxidative stress; and DP-VII, DP-VIII, and DP-IX: photolytic conditions), which were separated and identified using reversed-phase high-performance liquid chromatography and characterized using liquid chromatography-tandem mass spectrometry. The mechanism behind the formation of EDB degradation products has been discussed, and this study was the first to develop a degradation pathway for EDB. In addition, the possibilities of NDSRI formation for EDB were studied using a modified NAP test, which can contribute to the risk assessment of the drug. CONCLUSIONS: Forced degradation studies were conducted by establishing a SIAM for EDB. All the degradation products were characterized by mass spectral data obtained using LC/Q-TOF-HRMS.

Method validation and characterization of stress degradation products of azelastine hydrochloride using LC-UV/PDA and LC-Q/TOF-MS studies.

RATIONALE: Azelastine HCl is a second-generation H1 -receptor antagonist approved by the US Food and Drug Administration (US FDA) for treating seasonal allergic rhinitis and non-allergic vasomotor rhinitis. This study encompasses the validation of a liquid chromatography-ultra violet photo diode array (LC-UV/PDA) method for the drug and its extension to liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) studies for identification and characterization of various stress degradation products of the drug. METHODS: Stress degradation of azelastine HCl was undertaken under the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) prescribed conditions of hydrolytic, photolytic, oxidative, and thermal stress. The degraded drug solutions were analyzed using Ultra Performance Liquid Chromatography (UPLC) employing a C18 (100 × 4.6 mm; 2.6 µ, Kinetex) column by isocratic elution. Detection wavelength was 241 nm. The degradation products were identified and characterized using UPLC-MS/TOF studies, and an attempt was made to isolate one of the degradation products by solvent extraction. RESULTS: The drug was found to significantly degrade under acidic/alkaline/neutral photolytic, oxidative, and alkaline hydrolytic conditions. Six degradation products (I-VI) were identified through LC-Q/TOF-MS studies that were adequately resolved from the drug with the developed UPLC method. All degradation products (I-VI) were ionized in the total ion chromatogram (TIC) in the LC-MS studies, and these were identified and characterized, and the degradation pathway of the drug was postulated. One of the oxidation products isolated from the degraded drug solution was characterized through differential scanning calorimetry, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance spectral data. CONCLUSIONS: Six degradation products generated from stress degradation studies on azelastine HCl were adequately resolved through LC-UV/PDA studies followed by method validation. These were successfully identified and characterized through LC-Q/TOF-MS studies, and the degradation pathways for the generation of these products from the drug have been postulated.

Identification of degradation products of brivaracetam using liquid chromatography quadrupole time-of-flight tandem mass spectrometry: Degradation pathway elucidation.

RATIONALE: Pyrrolidone-based drugs find widespread use in treating conditions such as epilepsy and Alzheimer's disease, and in various other medical applications. Brivaracetam, the latest generation of pyrrolidone drugs, has exhibited significant promise owing to chemical structure modifications. Its affinity to the SV2A receptor is double that of the previous-generation drug, levetiracetam. Consequently, brivaracetam holds substantial potential for diverse applications. As a novel drug not yet included in the pharmacopeias of developed nations, comprehensive analysis and research are necessary to guarantee its safe utilization in clinical settings. METHODS: A liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC/QTOFMS) method has been developed to effectively separate, identify and characterize both the degradation products and process-related substances of brivaracetam. Stress testing of the sample was carried out following the guidelines outlined in ICH Q1A(R2). The structures of these impurities were identified through positive electrospray ionization QTOF high-resolution MS and NMR spectroscopy. Additionally, the formation mechanism of each degradation product is thoroughly discussed. RESULTS: Under the analytical conditions outlined in this paper, brivaracetam and its degradation products were effectively separated. Thirteen degradation products were detected and characterized, shedding light on their origins and degradation pathways. Among these, three degradation products align with previously reported impurities, and two unreported degradation products were synthesized and confirmed through NMR spectroscopy. The stress testing results revealed the instability of brivaracetam under acidic, alkaline, oxidative and thermal stress conditions, while it exhibited relative stability under photolytic stress conditions. CONCLUSION: The study developed an analytical method for brivaracetam that enabled the effective detection and separation of brivaracetam and its 13 degradation products. This method addresses a gap in both current domestic and foreign drug standards. The structures of all the major degradation products were characterized by high-resolution LC/QTOFMS, which is essential for quality control during the drug production process, stability evaluation and the establishment of proper storage conditions.

Analytical method development, identification, and characterization of stress degradation products of idelalisib by ultrahigh-performance liquid chromatography with photodiode array and ultrahigh-performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry studies.

RATIONALE: As per International Council for Harmonization (ICH) drug stability test guideline Q1A(R2), inherent stability characteristics of a drug should be studied. This work was designed to investigate inherent degradation characteristics of the drug idelalisib under ICH prescribed stress conditions, identify its degradation products, and postulate their corresponding degradation pathways. METHODS: Idelalisib was subjected to the ICH prescribed conditions of hydrolytic (neutral, acidic, and alkaline), photolytic, oxidative, and thermal stress according to ICH guideline Q1A(R2). An ultrahigh-performance liquid chromatography with photodiode array (UHPLC-PDA) method was developed to adequately resolve the drug from its degradation products, validated as per the ICH guidelines, and subsequently extended to UHPLC with electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS) studies to identify the degradation products. RESULTS: Significant degradation was noted under conditions of acidic/alkaline hydrolysis, acid photolysis, and oxidative stress. The UHPLC/ESI-QTOFMS studies revealed the generation of four degradation products (I-IV), which were satisfactorily resolved from the drug by UHPLC on a Kinetex® C18 (100 × 4.6 mm; 2.6 µm) column by the developed isocratic elution method. Detection wavelength was selected as 270 nm. All the degradation products (I-IV) could be identified and characterized from their mass spectral data. The degradation pathways for the generation of various products from the drug were postulated. CONCLUSIONS: A UHPLC-PDA method was developed and validated for idelalisib. Four degradation products of idelalisib were revealed through UHPLC/ESI-QTOFMS studies, and corresponding degradation pathways were postulated for the same.

Bio-based matrix photocatalysts for photodegradation of antibiotics.

Antibiotics development during the last century permitted unprecedent medical advances. However, it is undeniable that there has been an abuse and misuse of antimicrobials in medicine and cosmetics, food production and food processing, in the last decades. The pay toll for human development and consumism is the emergence of extended antimicrobial resistance and omnipresent contamination of the biosphere. The One Health concept recognizes the interconnection of human, environmental and animal health, being impossible alter one without affecting the others. In this context, antibiotic decontamination from water-sources is of upmost importance, with new and more efficient strategies needed. In this framework, light-driven antibiotic degradation has gained interest in the last few years, strongly relying in semiconductor photocatalysts. To improve the semiconductor properties (i.e., efficiency, recovery, bandgap width, dispersibility, wavelength excitation, etc.), bio-based supporting material as photocatalysts matrices have been thoroughly studied, exploring synergetic effects as operating parameters that could improve the photodegradation of antibiotics. The present work describes some of the most relevant advances of the last 5 years on photodegradation of antibiotics and other antimicrobial molecules. It presents the conjugation of semiconductor photocatalysts to different organic scaffolds (biochar and biopolymers), then to describe hybrid systems based on g-C3N4 and finally addressing the emerging use of organic photocatalysts. These systems were developed for the degradation of several antibiotics and antimicrobials, and tested under different conditions, which are analyzed and thoroughly discussed along the work.

Photodegradation of cannabidiol (CBD) and Δ9-THC in cannabis plant material.

Δ9-THC, the psychotropic cannabinoid in Cannabis sativa L., for many years has been the focus of all the pharmacological attention as the main promising principle of the plant. Recently, however, cannabidiol (CBD) has brought a sudden change in the scenario, exponentially increasing the interest in pharmacology as the main non-psychotropic cannabinoid with potential therapeutic, cosmetical and clinical applications. Although the reactivity of CBD and Δ9-THC has been considered, little attention has been paid to the possible photodegradation of these cannabinoids in the vegetal matrix and the data available in the literature are, in some cases, contradictory. The aim of the present work is to provide a characterization of the photochemical behaviour of CBD and Δ9-THC in three cannabis chemotypes, namely I (Δ9-THC 2.50%w/w), II (CBD:Δ9-THC 5.82%w/w:3.19%w/w) and III (CBD 3.02%w/w).

Reassessing the Quantum Yield and Reactivity of Triplet-State Dissolved Organic Matter via Global Kinetic Modeling.

Measuring the quantum yield and reactivity of triplet-state dissolved organic matter (3DOM*) is essential for assessing the impact of DOM on aquatic photochemical processes. However, current 3DOM* quantification methods require multiple fitting steps and rely on steady-state approximations under stringent application criteria, which may introduce certain inaccuracies in the estimation of DOM photoreactivity parameters. Here, we developed a global kinetic model to simulate the reaction kinetics of the hv/DOM system using four DOM types and 2,4,6-trimethylphenol as the probe for 3DOM*. Analyses of residuals and the root-mean-square error validated the exceptional precision of the new model compared to conventional methods. 3DOM* in the global kinetic model consistently displayed a lower quantum yield and higher reactivity than those in local regression models, indicating that the generation and reactivity of 3DOM* have often been overestimated and underestimated, respectively. The global kinetic model derives parameters by simultaneously fitting probe degradation kinetics under different conditions and considers the temporally increasing concentrations of the involved reactive species. It minimizes error propagation and offers insights into the interactions of different species, thereby providing advantages in accuracy, robustness, and interpretability. This study significantly advances the understanding of 3DOM* behavior and provides a valuable kinetic model for aquatic photochemistry research.

Interpretable Machine Learning and Reactomics Assisted Isotopically Labeled FT-ICR-MS for Exploring the Reactivity and Transformation of Natural Organic Matter during Ultraviolet Photolysis.

Isotopically labeled FT-ICR-MS combined with multiple post-analyses, including interpretable machine learning (IML) and a paired mass distance (PMD) network, was employed to unravel the reactivity and transformation of natural organic matter (NOM) during ultraviolet (UV) irradiation. FT-ICR-MS analysis was used to assign formulas, which were classified on the basis of their molecular compositions and structural categories. Isotope (deuterium, D) labeling was utilized to unequivocally determine the photochemical products and examine the development of OD radical-mediated NOM transformation. With regard to the reactive molecular formulas, CHOS formulas exhibited the highest reactivity (86.5% of precursors disappeared) followed by CHON (53.4%) and CHO (24.6%) formulas. With regard to structural categories, the degree of reactivity decreased in the following order: tannins > condensed aromatics > lignin/CRAMs. The IML algorithm demonstrated that the crucial features governing the reactivity of formulas were the molecular weight, DBE-O, NOSC, and the presence of heteroatoms (i.e., N and S), suggesting that the large and unsaturated compounds containing S and N are more prone to photodegradation. The reactomics approach using the PMD network further indicated that 11 specific molecular formulas in the CHOS and CHO class served as hubs, implying a higher photoreactivity and participation in a range of transformations. The isotope labeling analyses also found that, among the reactions observed, hydroxylation (i.e., +OD) is dominant for lignin/CRAMs and condensed aromatics, and formulas containing ≤10 D atoms were developed. Overall, this study, by adopting rigorous and interpretable techniques, could provide in-depth insights into the molecular-level dynamics of NOM under UV irradiation.

Photolysis of Dissolved Organic Matter over Hematite Nanoplatelets.

Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms of these reactions remain elusive. We examined the photolysis of chromophoric soil DOM coated onto hematite nanoplatelets featuring (001) exposed facets using a combination of molecular spectroscopies and density functional theory (DFT) computations. Reactive oxygen species (ROS) probed by electron paramagnetic resonance (EPR) spectroscopy revealed that both singlet oxygen and superoxide are the predominant ROS responsible for DOM degradation. DFT calculations confirmed that Fe(II) on the hematite (001) surface, created by interfacial electron transfer from photoexcited chromophores in DOM, can reduce dioxygen molecules to superoxide radicals (•O2-) through a one-electron transfer process. 1H nuclear magnetic resonance (NMR) and electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) spectroscopies show that the association of DOM with hematite enhances the cleavage of aromatic groups during photodegradation. The findings point to a pivotal role for organic matter at the interface that guides specific ROS generation and the subsequent photodegradation process, as well as the prospect of using ROS signatures as a forensic tool to help interpret more complicated field-relevant systems.

Heterogeneous Photodegradation Behavior of Liquid Crystal Monomers in Dust: Quantitative Structure-Activity Relationship and Product Identification.

The heterogeneous photodegradation behavior of liquid crystal monomers (LCMs) in standard dust (standard reference material, SRM 2583) and environmental dust was investigated. The measured photodegradation ratios for 23 LCMs in SRM and environmental dust in 12 h were 11.1 ± 1.8 to 23.2 ± 1.1% and 8.7 ± 0.5 to 24.0 ± 2.8%, respectively. The degradation behavior of different LCM compounds varied depending on their structural properties. A quantitative structure-activity relationship model for predicting the degradation ratio of LCMs in SRM dust was established, which revealed that the molecular descriptors related to molecular polarizability, electronegativity, and molecular mass were closely associated with LCMs' photodegradation. The photodegradation products of the LCM compound 4'-propoxy-4-biphenylcarbonitrile (PBIPHCN) in dust, including •OH oxidation, C-O bond cleavage, and ring-opening products, were identified by nontarget analysis, and the corresponding degradation pathways were suggested. Some of the identified products, such as 4'-hydroxyethoxy-4-biphenylcarbonitrile, showed predicted toxicity (with an oral rat lethal dose of 50%) comparable to that of PBIPHCN. The half-lives of the studied LCMs in SRM dust were estimated at 32.2-82.5 h by fitting an exponential decay curve to the observed photodegradation data. The photodegradation mechanisms of LCMs in dust were revealed for the first time, enhancing the understanding of LCMs' environmental behavior and risks.

Single-Particle Analysis of the Photodegradation of Submicron Polystyrene Particles Using Infrared Photothermal Heterodyne Imaging.

Sunlight irradiation is the predominant process for degrading plastics in the environment, but our current understanding of the degradation of smaller, submicron (<1000 nm) particles is limited due to prior analytical constraints. We used infrared photothermal heterodyne imaging (IR-PHI) to simultaneously analyze the chemical and morphological changes of single polystyrene (PS) particles (∼1000 nm) when exposed to ultraviolet (UV) irradiation (λ = 250-400 nm). Within 6 h of irradiation, infrared bands associated with the backbone of PS decreased, accompanied by a reduction in the particle size. Concurrently, the formation of several spectral features due to photooxidation was attributed to ketones, carboxylic acids, aldehydes, esters, and lactones. Spectral outcomes were used to present an updated reaction scheme for the photodegradation of PS. After 36 h, the average particle size was reduced to 478 ± 158 nm. The rates of size decrease and carbonyl band area increase were -24 ± 3.0 nm h-1 and 2.1 ± 0.6 cm-1 h-1, respectively. Using the size-related rate, we estimated that under peak terrestrial sunlight conditions, it would take less than 500 h for a 1000 nm PS particle to degrade to 1 nm.