Degradation Products Research Articles

The complete degradation of 1,2-dichloroethane in Escherichia coli by metabolic engineering

1,2-Dichloroethane (1,2-DCA), a widely utilized chemical intermediate and organic solvent in industry, frequently enters the environment due to accidental leaks and mishandling during application processes. Thus, the in-situ remediation of contaminated sites has become increasingly urgent. However, traditional remediation methods are inefficient and costly, while bioremediation presents a green, efficient, and non-secondary polluting alternative. In this study, an engineered strain capable of completely degrading 1,2-DCA was constructed. We introduced six exogenous genes of the 1,2-DCA degradation pathway into E. coli and confirmed their normal transcription and efficient expression in this engineered strain through qRT-PCR and proteomics. The degradation experiments showed that the strain completely degraded 2 mM 1,2-DCA within 12 h. Furthermore, the results of isotope tracing verified that the final degradation product, malic acid, entered the tricarboxylic acid cycle (TCA) of E. coli and was ultimately fully metabolized. Also, morphological changes in the engineered strain and control strain exposed to 1,2-DCA were observed under SEM, and the results revealed that the engineered strain is more tolerant to 1,2-DCA than the control strain. In conclusion, this study paved a new way for humanity to deal with the increasingly complex environmental challenges.

Synthesis of CuO, ZnO nanoparticles, and CuO-ZnO nanocomposite for enhanced photocatalytic degradation of Rhodamine B: a comparative study

Water pollution, arising from the presence of toxic dyes and chemicals, is a global challenge, urging the need for eco-friendly solutions in water decontamination. This study focused on the synthesis of copper oxide nanoparticles (CuO NPs), zinc oxide nanoparticles (ZnO NPs), and a bimetallic CuO-ZnO nanocomposite (CZ NC) through an environmentally friendly method employing Tragia involucrata L. leaf extract. Comprehensive analysis of structural and optical properties involved using various analytical techniques such as XRD, FT-IR, XPS, UV-DRS, PL, FE-SEM, EDAX, TEM, SAED, zeta potential, TGA, and BET. In comparison to pristine CuO and ZnO NPs, the CZ-NC demonstrated notably enhanced photocatalytic activity in the degradation of Rhodamine B dye (RhB). The optimum conditions for RhB degradation were found to be a pH of 9 and a catalyst dosage of 1 mg/mL for a concentration of 10 ppm. Under these conditions, CuO NPs, ZnO NPs, and CZ-NC demonstrated high efficiencies of 78%, 83%, and 96.1% respectively over 105 min. Through LC-HRMS, the identification of degradation products offered valuable insights into the pathway of photocatalytic degradation. Furthermore, toxicity analysis of intermediates, conducted through ECOSAR software, indicated the formation of non-toxic by-products (ChV/LC50/EC50 > 100) after the completion of the reaction. Furthermore, the recycled catalysts exhibited sustained stability for up to 4 cycles, with only a minor decrease in activity of up to 6.8%. This confirms their catalytic efficacy in purifying polluted water. This research significantly contributes to the progress of environmentally friendly nanocomposites, enhancing their efficacy in the realm of environmental remediation.

Engineering multi-degrading bacterial communities to bioremediate soils contaminated with pesticides residues

Parallel to the important use of pesticides in conventional agriculture there is a growing interest for green technologies to clear contaminated soil from pesticides and their degradation products. Bioaugmentation i. e. the inoculation of degrading micro-organisms in polluted soil, is a promising method still in needs of further developments. Specifically, improvements in the understanding of how degrading microorganisms must overcome abiotic filters and interact with the autochthonous microbial communities are needed in order to efficiently design bioremediation strategies. Here we designed a protocol aiming at studying the degradation of two herbicides, glyphosate (GLY) and isoproturon (IPU), via experimental modifications of two source bacterial communities. We used statistical methods stemming from genomic prediction to link community composition to herbicides degradation potentials. Our approach proved to be efficient with correlation estimates over 0.8 - between model predictions and measured pesticide degradation values. Multi-degrading bacterial communities were obtained by coalescing bacterial communities with high GLY or IPU degradation ability based on their community-level properties. Finally, we evaluated the efficiency of constructed multi-degrading communities to remove pesticide contamination in a different soil. While results are less clear in the case of GLY, we showed an efficient transfer of degrading capacities towards the receiving soil even at relatively low inoculation levels in the case of IPU. Altogether, we developed an innovative protocol for building multi-degrading simplified bacterial communities with the help of genomic prediction tools and coalescence, and proved their efficiency in a contaminated soil.

The role of ferroptosis as a regulator of oxidative stress in the pathogenesis of ischemic stroke.

Ferroptosis is a unique form of cell death that was first described in 2012 and plays a significant role in various diseases, including neurodegenerative conditions. It depends on a dysregulation of cellular iron metabolism, which increases free, redox-active, iron that can trigger Fenton reactions, generating hydroxyl radicals that damage cells through oxidative stress and lipid peroxidation. Lipid peroxides, resulting mainly from unsaturated fatty acids, damage cells by disrupting membrane integrity and propagating cell death signals. Moreover, lipid peroxide degradation products can further affect cellular components such as DNA, proteins, and amines. In ischemic stroke, where blood flow to the brain is restricted, there is increased iron absorption, oxidative stress, and compromised blood-brain barrier integrity. Imbalances in iron-transport and -storage proteins increase lipid oxidation and contribute to neuronal damage, thus pointing to the possibility of brain cells, especially neurons, dying from ferroptosis. Here, we review the evidence showing a role of ferroptosis in ischemic stroke, both in recent studies directly assessing this type of cell death, as well as in previous studies showing evidence that can now be revisited with our new knowledge on ferroptosis mechanisms. We also review the efforts made to target ferroptosis in ischemic stroke as a possible treatment to mitigate cellular damage and death.

Environmentally safe chemometric evaluation and data analysis for the kinetic investigation of mirabegron stability

The physicochemical characteristics of different pharmaceuticals may change with transportation, storage, and usage which directly affect their efficacy, quality, and other features. It is crucial to investigate the kinetic action of pharmaceutical compounds to produce predictive data that aid in the computation of their shelf lives. Several conventional analytical methods introduce unwanted dangerous risks, like employing unsafe solvents, that harm both the analyst and the environment. This created the motive for analysts to apply green approaches that consider using safe chemicals and producing as little waste as possible. In this study, powerful green assessment methods were investigated to study the kinetic process of Mirabegron (MIR) in different hydrolytic conditions giving its main degradation product. First, the optimal solvent was identified for the given kinetic procedures with the aid of Principal Component Analysis. Then two advanced chemometric methods were applied to estimate the kinetic parameters of the MIR degradation process namely: Multivariate Curve Resolution-Alternating Least Squares and Artificial Neural Networks. By data manipulation, both algorithms could provide an explanation of the MIR kinetic process in different hydrolytic conditions. Moreover, modified National Environmental Methods Index (NEMI), eco-scale, Hexagon algorithm, Complementary Green Analytical Procedure Index (Complex GAPI), and analytical greenness metric for sample preparation (AGREEprep) were adopted to ensure the greenness of the proposed study. Eventually, the presented investigation could successfully present an eco-friendly chemometric approach for monitoring the different kinetic processes of pharmaceutical compounds with minimum effort and solvent consumption and maximum time saving and analyst safety compared to other traditional methods.

LC and LC-MS/MS Studies for Identification and Characterisation of Related Substances and Degradation Products of Abrocitinib

In the pharmaceutical industry, Related Substances (RCs), impurities or Degradation Products (DPs) are associated with the Active Pharmaceutical Ingredient (API) in the final drug product. These compounds must be within permissible limits for safe therapeutic use for consumers. Hence there is a need to quantify these compounds using an appropriate analytical method. No method is reported in the literature for quantification of these compounds in abrocitinib which is a medical drug prescribed to treat severe atopic dermatitis in adults. This study includes the optimisation of stability indicating the HPLC method for resolution and subsequent quantification of abrocitinib RCs and structural characterisation of stressinduced DPs of abrocitinib. The method was optimised by varying mobile phase solvents, pH, flow rate and wavelength of the detector. The finalised conditions were validated and applied for the resolution and evaluation of stress-induced DPs. The stress was induced in abrocitinib pure drug HCl (0.1M), NaOH (0.1M), hydrogen peroxide (3%), 80°C in an air oven and 254nm in a UV chamber. The generated DPs were structurally characterised with the LCMS experiment. Abrocitinib and DPs along with known RCs were resolved on ACE Ultra Core Super C18 250mm column using 0.9mL/min gradient flow of methanol (Solvent A), acetonitrile and buffer (Solvent B). The resolved compounds were detected through a UV detector at 295nm and a mass detector at NMR positive mode. The method identifies 5.85min, 3.13min, 6.60min and 4.38min respectively for abrocitinib, related compounds 1 to 3 respectively with acceptable system suitability. A very high correlate (< 0.999) linear graph was achieved within 5 to 30 μg/mL concentration level for abrocitinib and 0.05 to 0.3μg/ mL for related compounds. Three DPs with molecular mass and formula of C10H13N5 (203.2 g/mol), C11H14N4 (202.2 g/mol) and C13H19N5O2S (309.3 g/mol) in acid-induced stress study and two DPs of C12H21N5O2S (299.3 g/mol) and C11H19N5O2S (285.3 g/mol) in peroxide-induced stress study and one DP of C10H14N4 (190.2 g/mol) in base induced stress study were successfully characterised. The method proposed in this study can effectively resolve unknown degradation products, and known related compounds along with abrocitinib and is hence applicable for quality control analysis of abrocitinib.

Simultaneous Determination of Fipronil, Permethrin, and Their Key Related Substances in a Topical Drug Product by a Single Stability-Indicating High-Performance Liquid Chromatography Method.

The topical veterinary drug product containing fipronil and permethrin provides an effective repellent protection and high insecticidal efficacy for dogs. The objective of this study was to develop a stability-indicating high-performance liquid chromatography (HPLC) method for simultaneous detection and quantification of fipronil, permethrin, their key degradation products, and butylated hydroxytoluene (BHT) in a topical drug product. The two active ingredients, their degradation products, and the antioxidant (BHT) were separated by a gradient elution on a Phenomenex Kinetex C18 column (150 × 3 mm, 2.6 µm particle size) maintained at 37°C with H2O acetonitrile isopropyl alcohol 85% H3PO4 (65.5 + 32.5 + 4/0.0053, v/v/v/v) as mobile phase A and acetonitrile (100%) as mobile phase B. The flow rate was 0.9 mL/min, and analytes were detected and quantified at 235 nm. The specificity of the method was demonstrated by adequate separation of fipronil, permethrin, their degradation products, and BHT in the forced degraded finished product. The linearity of the method was demonstrated in the range of 0.2% to 150% of target analytical concentration of both active ingredients and 50% to 150% for BHT. Excellent recoveries of fipronil, permethrin, and BHT in placebo spiked active ingredient solutions in the linearity range showed sufficient accuracy of the method. The LOQ and LOD of the method were determined to be 0.2% and 0.07% of the analytical concentration. A robustness study did not identify any critical parameter that adversely affected the separation and quantification. Here, we report the development and validation of a robust, stability-indicating HPLC method for identification and assay of fipronil, permethrin, and BHT, including estimation of fipronil's and permethrin's degradation products in a topical drug product for dogs. The new HPLC method permits the acquisition of data for all analytes of interest for a topical finished drug product containing fipronil, permethrin, and BHT.

Forced Degradation Products of Olmesartan Medoxomil and their In Vitro Genotoxicity Assessment by Comet Assay using HEK Cells

AbstractThis study designed to characterize major forced degradation products of Olmesartan Medoxomil (OM) and to perform genotoxicity profiling using acid, base, and hydrogen peroxide‐induced stress degradation studies. The isolation of degradation products was conducted on flash chromatography using FlashPure ECOFLEX C18 4 g column with gradient elution and diode array detection‐based fraction collection, and characterized by mass spectrometry. Three impurities (impurity‐1, 2, and 3) were identified with respective m/z values of 447.213, 461.229, and 463.208. The genotoxic potential of impurities was assessed by in silico prediction, and in vitro comet assay using HEK cells. The extent of DNA damage was analyzed using Comet Assay IV imaging software. For impurity‐1, head and tail lengths and their respective total intensities were significantly (p<0.001) larger than those of dimethyl sulfoxide (solvent) control and comparable to positive control. Other parameters such as mean grey level and total area of comet were statistically significant as compared with the solvent and positive controls. Overall, impurity‐1 was a possible genotoxic impurity and a known major degradation product in OM tablet dosage form. In silico prediction also revealed impurity‐1 as toxicity class 3, whilst impurities 2 and 3 were of toxicity class 4.

Direct Infusion Mass Spectrometry to Rapidly Map Metabolic Flux of Substrates Labeled with Stable Isotopes.

Direct infusion-high-resolution mass spectrometry (DI-HRMS) allows for rapid profiling of complex mixtures of metabolites in blood, cerebrospinal fluid, tissue samples and cultured cells. Here, we present a DI-HRMS method suitable for the rapid determination of metabolic fluxes of isotopically labeled substrates in cultured cells and organoids. We adapted an automated annotation pipeline by selecting labeled adducts that best represent the majority of 13C and/or 15N-labeled glycolytic and tricarboxylic acid cycle intermediates as well as a number of their derivatives. Furthermore, valine, leucine and several of their degradation products were included. We show that DI-HRMS can determine anticipated and unanticipated alterations in metabolic fluxes along these pathways that result from the genetic alteration of single metabolic enzymes, including pyruvate dehydrogenase (PDHA1) and glutaminase (GLS). In addition, it can precisely pinpoint metabolic adaptations to the loss of methylmalonyl-CoA mutase in patient-derived liver organoids. Our results highlight the power of DI-HRMS in combination with stable isotopically labeled compounds as an efficient screening method for fluxomics.

Degradation of pretilachlor and fenclorim and effects of these compounds on bacterial communities under anaerobic condition.

Pretilachlor and safener fenclorim are the main components of herbicides widely applied to control weeds. Although some pure cultures of bacteria and fungi which degraded these compounds under aerobic conditions were isolated, no isolated pretilachlor- and fenclorim-degrading bacterial strains under anaerobic condition had been available. In this study, the degradation of these compounds and the effects of them on bacterial community structures were investigated under anaerobic conditions. The dissipation rates of pretilachlor and fenclorim in slurries were in the order: soil from paddy field ≈ sediment from river > sediment from mangrove. Moreover, three pretilachlor-degrading bacterial strains (Pseudomonas sp. Pr1, Proteiniclasticum sp. Pr2 and Paracoccus denitrificans Pr3) and two fenclorim-degrading strains (Dechloromonas sp. Fe1 and Ralstonia pickettii Fe2) isolated from a slurry of paddy soil utilized the substrates as sole carbon and energy sources under anaerobic conditions. The degradation of pure pretilachlor and fenclorim at various concentrations by corresponding mixed pure cultures followed the Michaelis-Menten model, with the maximum degradation was 3.10 ± 0.31µM/day for pretilachlor, and 2.08 ± 0.18µM/day for fenclorim. During the degradation, 2-chloro-N-(2,6-diethylphenyl) acetamide and 2,6-dimethylaniline were produced in pretilachlor degradation, and benzene was a product of fenclorim degradation. The synergistic degradation of both substrates by all isolated bacteria reduced the metabolites concentrations accumulated in media. This study provides valuable information on effects of pretilachlor and fenclorim on bacterial communities in soil and sediments, and degradation of these substrates by isolated bacteria under anaerobic condition.

The global distribution of Isoprenoidal Glycerol Dialkyl Diethers (isoGDDs) is consistent with a predominant degradation origin

Glycerol dialkyl diethers (GDDs) are membrane lipids and a variation of the more commonly known glycerol dialkyl glycerol tetraethers (GDGTs). GDGTs include both archaeal and bacterial membrane lipids that are both frequently used for paleoclimate reconstruction in a range of terrestrial and aquatic environments. In contrast to GDGTs, GDDs lack one of the terminal glycerol moieties. Although both isoprenoidal (iso) and branched (br) GDDs have been found, this study focuses on isoGDDs. These lipids have been found in a few terrestrial and aquatic environments. However, the origin of isoGDDs is debated and the extent of their distribution across the surface of the Earth is poorly constrained. Based on a few single site studies, previous authors hypothesised that isoGDDs are degradation products of isoGDGTs, but more recent studies that isolated isoGDDs from cultured nitrososphaerota (formerly thaumarchaeota) proposed a biological source through direct archaeal biosynthesis. Here we compiled a global dataset of isoGDD and isoGDGT abundance in environmental samples to thoroughly investigate the distribution of isoGDDs and the correlation with isoGDGTs on a global scale and across a variety of environments (peat, mineral soils, lake sediments, and marine sediments). We find that isoGDDs are present in most samples that we analysed. Their abundance is strongly proportional to isoGDGT abundance (r2 = 0.85), dominated by the GDGT-crenarchaeol/GDD-crenarchaeol ratio (r2 = 0.94) and supported by individual compound isoGDGT/isoGDD ratios (r2 = 0.56–0.94). In addition, the degree of cyclisation of isoGDDs, reflected in the ring index, is positively correlated (r2 = 0.84) with that of isoGDGTs across all environments. We conclude that isoGDDs are abundant on the surface of the Earth and predominantly originate from the degradation of isoGDGTs.

New Insights in Metallurgical Manufacturing in the Caucasian Area: The Case Study of Artefacts from the Samshvilde Citadel Ruins (South Georgia)

An archaeometric approach was applied to the study of the hoard found in the Samshvilde fortress, one of the richest areas of archaeological artefacts in Caucasian Georgia, since it is representative of the historical events from the Neolithic period until the most recent epochs. In this context, four coins dated back to the 12th–13th centuries AD to the reign of King Giorgi III, Queen Tamar, and King Giorgi IV of Georgia underwent different analytical methods to collect information about the technological production process, the probable forge location, and their conservation state. Optical microscope observations provided details about the decorations, the stylistic aspects, and a preliminary evaluation of the conservation state. Portable X-ray fluorescence and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy analysis revealed a composition consisting almost exclusively of copper with a lower amount of tin, lead, and silver. Moreover, degradation products (copper chlorides and sulphates) and cuprite patina were identified. The metal-supplying areas could be related to the nearby Bolnisi Mining District, and the forge location could coincide with the hoard location in Samshvilde, but further data and analyses are necessary.

Multiple barriers as an efficient treatment for removing pesticides aiming direct potable reuse: A pilot scale study

Water reuse for potable purposes can represent a realistic source supply of drinking water in areas with water scarcity. Therefore, combining conventional wastewater treatment technologies with advanced technologies is necessary to remove contaminants and obtain high-quality and safe water. In this study, the pesticides and degradation products, atrazine (ATZ), hydroxyatrazine (ATZOH), deethylatrazine (DEA), deisopropylatrazine (DIA), simazine (SMZ), ametryn (AMT), diuron (DIU), 2,4-D, fipronil (FIP), fipronil sulfide (FIP-SF) and fipronil sulfone (FIP-SN) were evaluated in effluent after membrane bioreactor (MBR), effluent after advanced treatment by multiple barriers (MBR, reverse osmosis, UV/H2O2 and activated carbon), in tap water collected in the urban region of Campinas and in the Atibaia River (water supply source from city of Campinas). The pesticide concentrations in the Atibaia River and the post-MBR effluent ranged between 1 and 434 ng L−1 and 1 and 470 ng L−1, respectively. Therefore, the Atibaia River and the post-MBR effluent had the same magnitude pesticide concentrations. In the production of potable water reuse, after the multiple barriers processes, only fipronil (1 ng L−1) and atrazine (3 ng L−1) were quantified in some of the samples. In tap water from Campinas, atrazine, ATZOH, DEA, diuron, and 2,4-D were quantified in concentrations ranging between 3 and 425 ng L−1. Therefore, when comparing drinking water obtained from conventional treatment with potable water reuse, according to the pesticides studied, it is possible to conclude that the advanced treatment used on a pilot scale is promising for use in a potable water reuse plant. However, studies involving more microbiological and chemical parameters should be conducted to classify potable water reuse as drinking water.

Safety assessment and quality control of regenerated cellulose food packaging in different processes

Regenerated cellulose food packaging is increasingly widely used due to its renewable raw materials and excellent environmental performance. However, because its production process is complex, the safety of the regenerated cellulose food packaging needs to study carefully. In this study, we first collected the packages produced by traditional and new technology, and then HS-GC-MS was used to screen the volatile potential migrants in the package. Three food simulants were used for migration tests. The migrants from the regenerated cellulose food packaging during the contact with different foods were non-targeted screened and semi-quantitative by UPLC-QTOF-MS and GC-MS. The results show that 44 kinds of substances migrated to food simulants, and assessed their risk in conjunction with production processes. Glycerol or triethylene glycol as softeners, migrated in all three simulants and all types of packaging materials. Polyethylene glycol is detected in packaging materials with coatings, that come from adhesives. Allure red and its degradation products used for food coloring were detected in the transferable casing. The degradation product belongs to aromatic amine, which poses a high risk. Glycerol has the highest abundance among all migrants. By comparing the exposure and safety threshold values of migrants, it was found that polyethylene glycol and allure red pose health risks and should be paid more attention.

Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression

BackgroundHeart failure (HF) is a disease that poses a serious threat to individual health, and DNA methylation is an important mechanism in epigenetics, and its role in the occurrence and development of the disease has attracted more and more attention. The aim of this study was to evaluate the link between iodothyronine deiodinase 3 promoter region fragment FA27 (DIO3-FA27) methylation levels, biochemical indices, and HF.ResultsThe methylation levels of DIO3-FA27_CpG_11.12 and DIO3-FA27_CpG_23.24 significantly differed in HF patients with different degrees. Multivariate logistic regression analysis indicated that the relative HF risk in the third and fourth quartiles of activated partial thromboplastin time and fibrin degradation products. The results of the restricted cubic spline model showed that the methylation levels of DIO3-FA 27_CpG_11.12 and DIO3-FA 27_CpG_23.24 were associated with coagulation indicators, liver function, renal function, and blood routine.ConclusionsBased on the differential analysis of CpG methylation levels based on DIO3-FA27, it was found that biochemical indicators combined with DIO3-FA27 promoter DNA methylation levels could increase the risk of worsening the severity classification of HF patients, which provided a solid foundation and new insights for the study of epigenetic regulation mechanisms in patients with HF.

The metabolites of flavonoids with typical structure enhanced bioactivity through gut microbiota

The degradation of flavonoids helps to elucidate the mechanism of their biological activity, thus guiding individuals to better ingestion and utilization of these compounds. In this study, seven kinds of flavonoids with typical structures were in vitro fermented by fresh feces, and the degradation process of flavonoids were monitored by HPLC, and the gut microbiota constitutes were analyzed by 16 S rRNA microbiota sequencing. Results indicated that all seven kinds of flavonoids could be degraded by intestinal microbiota. In addition, the degradation products of flavonoids showed excellent antioxidant and anti-inflammatory activity, especially the degradation products of epicatechin at 24 h exhibited the strongest scavenging capacity for FRAP and ABTS free radicals, which were 287.494 ± 16.941 μM and 567.344 ± 13.477 μM, respectively. Moreover, compared with the corresponding control group, flavonoid treatment changed the composition of the gut microbiota, mainly by significantly reducing the abundance of harmful bacteria, such as Proteobacteria, and increasing the abundance of beneficial bacteria, such as Flavonifractor. This paper might provide theoretical basis and technical support for the nutritional and pharmacological applications of flavonoids.

The effect of topological design on the degradation behavior of additively manufactured porous zinc alloy

The advent of additively manufactured biodegradable porous metals presents a transformative opportunity to meet the criteria of ideal bone substitutes. Precisely tailoring their degradation behavior constitutes a pivotal aspect of this endeavor. In this study, we investigated the effects of topological designs on the degradation profile of laser powder bed fusion (LPBF) Zn scaffolds under dynamic in vitro immersion tests. Specifically, four types of Zn-0.4Mn-0.2Mg scaffolds (beam-based: diamond, face center cubic; surface-based: gyroid, schwarz-P) were designed and fabricated. The degradation mechanism of the scaffolds was comprehensively evaluated using both experimental and simulation methods. The results illuminate the profound impact of structural design on the degradation properties of the Zn alloy scaffolds. The beam-based diamond and face center cubic scaffolds exhibited a degradation rate of 0.08–0.12 mm per year with a relatively uniform degradation mode under dynamic immersion. On the contrary, the surface-based gyroid and Schwarz-P scaffolds demonstrated a notably reduced degradation rate due to lower permeability. This restricted the diffusion of medium ions within the pores, culminating in the accumulation of degradation products and more severe localized degradation. This study underscores the potential of topological design as a compelling strategy for tailoring the degradation profile of additively manufactured biodegradable scaffolds, thereby advancing their suitability as bone substitutes.

Forced Degradation Products of Liraglutide: A Comparative Study of Similarity Between Originator and Analogue Version by Liquid Chromatography–Mass Spectrometry

Forced Degradation Products of Liraglutide: A Comparative Study of Similarity Between Originator and Analogue Version by Liquid Chromatography–Mass Spectrometry

Influence of fluorine atoms on reactive oxygen species-mediated degradation of ophthalmic fluoroquinolones. Kinetic and cytotoxicity studies

Fluoroquinolones have been attractive broad-spectrum antibiotics for ophthalmic application. However, they have shown phototoxicity as a significant side effect, which is strongly dependent on fluoroquinolone structure and some environment conditions. Beyond their photo-reactivity, an indirect light-induced process deserves to be considered. The photosensitized action of molecules present in the ocular organ, such as Riboflavin, may produce reactive oxygen species (ROS) that could degrade fluoroquinolones. As a consequence, the antibiotics may lose their therapeutic action and/or produce degradation products with harmful effects on health.In this contribution, a kinetic analysis of ROS-mediated degradation processes of ophthalmic quinolones is addressed. Further, considering the evidence towards the structure-modulated phototoxicity, we evaluated the influence of structural fluorine atoms on these processes. The non-fluorinated precursor Nalidixic Acid and the fluoroquinolones (Ciprofloxacin, Norfloxacin and Lomefloxacin) were selected for this study. Cytotoxicity experiments in Vero cells were performed in order to investigate the potential toxicity of the ROS-mediated degradation products.Our results suggest that quinolones may be degraded by ROS and these processes are regulated by the ionization state of quinolone and the presence of fluorine atoms in their structure. Both effects increase the electron donor ability of the quinolones, which favor electron transfer processes and increase their reactivity towards species with an electrophilic character. Interestingly, this fluorine-dominated effect has been recently called “fluoromaticity”.Cytotoxicity assays indicated that neither the Qs nor their ROS-mediated degradation products presented injury on Vero cells under the current experimental conditions.

DFT investigation of Pt-doped CTF-1 covalent triazine frameworks for adsorption and sensing of SF6 decomposition products

We report a computational investigation of the gas adsorption and sensing properties of pristine covalent triazine framework CTF-1 and its platinum atom (Pt)-doped counterpart towards SF6 decomposition products (i.e., H2S, SO2, SOF2, and SO2F2 gases). For this purpose, density-functional theory calculations are employed with the TPSS exchange-correlation functional (with the Grimme-D3 empirical dispersion correction) and a 6-31+G**/Lanl2DZ mixed basis set. Pt was found to interact with a nitrogen atom, distorting the planar structure. Our results reveal that the electronic bandgap of the pristine CTF-1 lowers noticeably following surface doping with a Pt atom (3.48 vs. 1.06 eV for pristine vs. Pt-doped CTF-1, respectively), enhancing the electrical conductivity of the gas sensor. In contrast to pristine CTF-1, which displays weak adsorption performance (with adsorption energies of −0.25, −0.27, −0.31, and −0.18 eV for H2S, SO2, SOF2, and SO2F2, respectively), Pt-doped CTF-1 exhibits strong interactions with the gas species (with adsorption energies of −1.93, −2.41, −6.27, and −7.98 eV for H2S, SO2, SOF2, and SO2F2, respectively) and high sensitivity in detecting the target gas species under study. Moreover, a density of states (DOS) analysis is conducted to further characterize the mechanisms involved in gas adsorption and sensing. All four degradation products decrease the bandgap of pristine CTF-1 and increase the bandgap in Pt-doped CTF-1. The latter is generally more pronounced. We conclude that Pt-doped CTF-1 could be a novel SF6 decomposition gas adsorbent and sensor and provide experimentalists with the essential physicochemical characteristics of the designed materials for future work.