Parent Compound Research Articles

Formation and Reactions of Brønsted and Lewis Acid Adducts with Electron-Rich Heteroaromatic Compounds.

Electron-rich heteroaromatics, such as furan, thiophene and pyrrole, as well as their benzo-condensed derivatives, are of great interest as components of natural products and as starting substances for various products including high-tech materials. Although their reactions with Brønsted and Lewis acids play important roles, in particular as the primary step of various transformations, they are often disregarded and mechanistically not understood. The present publication gives a first overview about this chemistry focusing on the parent compounds. It comprises reactions with strong Brønsted acids forming adducts that can undergo intramolecular proton and/or substituent transfer reactions, ring openings or ring transformations into other heterocycles, depending on their structure. Interactions with weak Brønsted acids usually initiate oligomerizations/polymerizations. A similar behaviour is observed in reactions of these heteroaromatics with Lewis acids. Special effects are achieved when the Lewis acids are activated through primary protonation. Deuterated Brønsted acids allow straight forward deuteration of electron-rich heteroaromatics. Mercury salts as extremely weak Lewis acids cause direct metalation in a straight forward way replacing ring H-atoms yielding organomercury heterocycles. This review will provide comprehensive information about the chemistry of adducts of such heterocycles with Brønsted and Lewis acids enabling chemists to understand the mechanisms and the potential of this field and to apply the findings in future syntheses.

Non-target discovery and risk prediction of per- and polyfluoroalkyl substances (PFAS) and transformation products in wastewater treatment systems

Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1–3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.

Biotransformation of minocycline by a novel strain Kluyvera sp. DM13 isolated from municipal sludge: Performances, removal pathways, and toxicity

Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure. Therefore, it is necessary to find an efficient and environmentally friendly method to remove minocycline from the environment. This study screened and isolated a minocycline degrading strain DM13 from the activated sludge for municipal sewage pipeline, and optimized the biodegradation of minocycline by DM13 under various environmental conditions. The maximum biodegradation efficiency of 50 mg/L minocycline reached 93 % at 72 h with the temperature of 30 °C, the initial pH of 7.0, and the inoculation rate of 3 %. Two potential biotransformation pathways were proposed, including deamination, demethylation, and decarbonylation. The acute toxicity assessment showed that the biotransformation products of minocycline had lower toxicity than the parent compound. In addition, the first-generation tetracycline antibiotics could be removed, suggesting that strain DM13 has the potential for application in treating antibiotic wastewater.

Formulas of High MW Unknown Compounds from Accurate Mass Differences and Ranking of Best Candidates from First Principles.

The number of possible candidate formulas for high molecular weight unknown compounds (e.g., 7000-8000 Da for common 20-mer oligonucleotides) by high-resolution mass spectrometry is in the order of several hundred thousand even at the highest level of experimental accuracy. In demanding analytical applications involving new chemistries and synthetic routes where little is known about the chemical nature or mechanisms of formation of the unknown compounds (e.g., impurities), the generation of a short list of the most plausible formulas would be highly desirable. Such an approach has been developed in the current work. The concept of mass difference from a reference compound is introduced to simplify the approach and greatly reduce the number of possible formulas. The approach allows for the generation of candidate formulas by both the addition and subtraction of atoms to account for all possible molecular changes from the parent compound. A reduction of 3 orders of magnitude in the number of possible formulas has been achieved by the approach. Ranking of the formulas by the product of the sums of the absolute changes in the total number of all atoms and all heteroatoms in the proposed difference formula successfully ranked the correct formula within the top 10 from a list of 200-250 best candidate formulas. There is a tendency for the impurities to be formed involving the least change in the number of atoms and heteroatoms. ΔfHo and ΔfG'o values can be used as a complementary ranking system of the top candidates. The approach is applicable to unknowns in any other systems of high MW compounds.

Ca substitution effects on structure transformation and physical properties of (Eu,Ca)FeAs2 co-doped with La and Co

In this study, Ca substitution and carrier doping effect on phase formation temperature and physical/superconducting properties of (Eu0.9-xCaxLa0.1)(Fe0.97Co0.03)As2 ((Eu,Ca)112, x = 0–0.4) compounds were investigated. The best synthesis condition for obtaining pure phases vary (850–900 °C) depending on the Ca substitution amount. Ca substitution in the EuFeAs2 structure induced a structural transformation from orthorhombic I2mm to monoclinic P21/m symmetry. Single crystals of EuFeAs2 and (Eu0.9La0.1)FeAs2 were grown and their crystal structures were determined. Density functional theory calculations confirmed the transformation and stability of the La-doped Eu112 crystal structure with Ca substitution. Compared with the parent compound EuFeAs2, the effective substitution of Ca reduced the lattice constants. The magnetic and transport properties of (Eu0.9-xCaxLa0.1)(Fe0.97Co0.03)As2 compounds were studied using the temperature and field dependence of the magnetization and electrical resistivity measurements. Ca substitution suppressed the magnetic ordering of Eu and gradually reduced the Néel temperature TNEu. As determined by the magnetization and electrical resistivity data, the onset of critical temperature (Tc) values increased with Ca substitution increment from 26 K to 32.2 K and 31 K–34.8 K, respectively. Ca substitution slightly increased the upper critical field values, while the coherence length ξ values were slightly decreased. The Ca substitution and sintering temperature dependence of superconductivity, upper critical fields, lower critical fields, and Eu-related magnetic transitions were extracted. The new series of Eu-containing iron-based superconductors with high Tc provides an interesting playground in this field.

Design and synthesis of fluorescent BODIPY derivatives with D-A structure for cancer cell imaging

Boron-dipyrromethene (BODIPY) as a traditional fluorescent dye has received increasing attention because of its high molar extinction coefficient, easy modification, and good light stability. In this work, three BODIPY compounds (BDP-1, BDP-2 and BDP-3) were designed and synthesized by introducing PEG chains and a naphthalimide (NI) group onto the parent structure of BODIPY. Due to the electron-withdrawing properties of NI, the compounds of BDP-2 and BDP-3 formed a typical donor (D)-acceptor (A) structure, which led to the red-shifted absorption and fluorescence spectrum. The synthesized BODIPY exhibited intense green emission, with fluorescence quantum yield of 0.66, 0.29, and 0.19 for BDP-1, BDP-2 and BDP-3 respectively. The decrease in fluorescence of BDP-2 and BDP-3 was probably ascribed to the enhanced intramolecular charge transfer because of the introduction of the NI group. The good biocompatibility and low cytotoxicity of the synthesized BODIPY compounds were verified by the CCK-8 assay. The subcellular localization of the three compounds was further evaluated through a confocal laser scanning microscope. The results showed that these BODIPY derivatives were mainly localized in the lysosomes of cancer cells. Thus, the synthesized BODIPY fluorescent dyes show promising applications in tumor imaging benefiting from their good biocompatibility and strong fluorescence.

Phonon softening and atomic modulations in EuAl4

EuAl4 is a rare-earth intermetallic in which competing itinerant and/or indirect exchange mechanisms give rise to a complex magnetic phase diagram, including a centrosymmetric skyrmion lattice. These phenomena arise not in the tetragonal parent structure but in the presence of a charge-density wave (CDW), which lowers the crystal symmetry and renormalizes the electronic structure. Microscopic knowledge of the corresponding atomic modulations and their driving mechanism is a prerequisite for a deeper understanding of the resulting equilibrium of electronic correlations and how it might be manipulated. Here, we use synchrotron single-crystal x-ray diffraction, inelastic x-ray scattering, and lattice-dynamics calculations to clarify the origin of the CDW in EuAl4. We observe a broad softening of a transverse acoustic phonon mode that sets in well above room temperature and, at TCDW=142 K, freezes out in an atomic displacement mode described by the superspace group Immm(00γ)s00. In the context of previous work, our observation is a clear confirmation that the CDW in EuAl4 is driven by electron-phonon coupling. This result is relevant for a wider family of BaAl4 and ThCr2Si2-type rare-earth intermetallics known to combine CDW instabilities and complex magnetism. Published by the American Physical Society 2024

Machine learning assisted designing of conjugated organic chromophores, light absorption, and emission behavior prediction

Organic materials have several important characteristics that make them suitable for use in optoelectronics and optical signal processing applications. For absorption and emission maxima, the stabilities and photoactivities of conjugated organic chromophores can be tailored by selecting a suitable parent structure and incorporating substituents that predictably change the optical characteristics. However, a high-throughput design of efficient conjugated organic chromophores without using trial-and-error experimental approaches is required. In this study, machine learning (ML) is used to design and test the conjugated organic chromophores and predict light absorption and emission behavior. Many machine learning models are tried to select the best models for the prediction of absorption and emission maxima. Extreme gradient boosting regressor has appeared as the best model for the prediction of absorption maxima. Random forest regressor stands out as the best model for the prediction of emission maxima. Breaking Retrosynthetically Interesting Chemical Substructures (BRICS) is used to generate 10,000 organic chromophores. Chemical similarity analysis is performed to obtain a deeper understanding of the characteristics and actions of compounds. Furthermore, clustering and heatmap approaches are utilized.

Exploring the electronic structure of tetrathienylethene derivatives for OLED applications: A theoretical study

AbstractThe B3LYP/6‐31G(d,p) method is applied to investigate the structural and electronic properties of tetrathienylethene (TTE) derivatives, specifically for the properties of 14 distinct TTE derivatives. The results indicate that the T1–T14 derivatives exhibit numerous advantages over the parent TTE compound. Notably, substituents predominantly impact the LUMO energy level of the TTE parent compound. Additionally, all modified molecules exhibit lower energy band gaps (Egap) and improved charge transfer capacity relative to TTE. These findings suggest that the T1–T14 derivatives may be promising candidates for use as materials in OLED applications. The values of chemical hardness (η) indicate that all compounds T1–T14 manifest greater softness relative to the parent compound TTE. This correlation aligns with the calculated Egap values, wherein compounds T1–T14 consistently exhibit smaller Egap values compared to the TTE compound. These research findings indicate that compounds T1 and T10 display remarkable and harmonious charge transfer capabilities. This is evident from their corresponding values of λh and λe, which stand at 0.39/0.41 and 0.41/0.41 eV, respectively. Remarkably, compound T1 exhibits the most pronounced absorption peak, occurring at a wavelength of 441 nm. This absorption is accompanied by the highest oscillator strength recorded for the compound, reaching a value of 0.638.

Isolation, Chemical Modification and In vivo Pharmacological Screening of Piperine and its Derivatives

Piperine (1) extracted from black pepper was transformed into its derivatives piperic acid (2) and piperonal (3) with good yields (69-76%). Animal models were used to examine the compounds' in vivo peripheral as well as central analgesic and anti-inflammatory effects. In the peripheral analgesic experiment, compound 2 displayed remarkable action having writhing inhibition by 78% at 50 mg/kg dose, superior to that of 1 (74% writhing inhibition) when administered at the same dose and compared with standard diclofenac sodium (85%). Concerning central analgesic efficacy, piperonal outperformed compounds 1 and 2 at 25 mg/kg dose, with % tail-flick elongation times of 194%, 178%, and 178% at 30, 60, and 90 min, respectively. Conversely, at 50 mg/kg dose, piperic acid exhibited the highest activity, demonstrating % tail-flick elongation times of 231%, 213%, and 206% at 30, 60, and 90 min, respectively, as compared to the standard morphine (278%, 247%, and 160%) in the same duration. In anti-inflammatory property evaluation, piperonal portrayed outstanding effects with paw edema inhibitions of 57%, 66%, 76%, and 81%, respectively from 1st hour onwards, compared to standard aceclofenac (61%, 72%, 78%, and 89%) and parent compound piperine (20%, 34%, 51%, and 60%). This study suggests that piperine derivatives could act as promising leads for future drug development. Dhaka Univ. J. Pharm. Sci. 23(1): 13-22, 2024 (June)

Negative Thermal Expansion in ABC(MoO4)3 Compounds.

Negative thermal expansion (NTE) compounds provide a solution for the mismatch of coefficients of thermal expansion in highly integrated device design. However, the current NTE compounds are rare, and how to effectively design new NTE compounds is still challenging. Here, a new concept is proposed to design NTE compounds, that is, to increase the flexibility of framework structure by expanding the space in framework structure compounds. Taking the parent compound NaZr2(PO4)3 as a case, a new NTE system AIBIICIII(MoO4)3 (A = Li, Na, K, and Rb; B = Mg and Mn; C = Sc, In, and Lu) is designed. In these compounds, the large volume of MoO4 tetrahedron is used to replace the small volume of PO4 tetrahedron in NaZr2(PO4)3 to enhance structural space and NTE performance. Simultaneously, a joint study of temperature-dependent X-ray diffraction, Raman spectroscopy, and the first principles calculation reveals that the NTE in AIBIICIII(MoO4)3 series compounds arise from the coupled oscillation of polyhedral. Large-radius ions are conducive to enhancing the space and softening the framework structure to achieve the enhancement of NTE. The current strategy for designing NTE compounds is expected to be adopted in other compounds to obtain more NTE compounds.

Experimental investigation of intrinsic mechanism dominated anomalous Hall effect in hexagonal alloys Fe3-xMnxGe (x = 0.05, 0.1, 0.5)

Iron alloys are among the most fundamental and extensively studied alloys, particularly in recent years with the advancements in spintronics. The anomalous Hall effect based on intrinsic Berry curvature has sparked a significant research interest in magnetic materials. In this experimental study, we quantitatively elucidated the AHE mechanism in Fe3-xMnxGe (x = 0.05, 0.1, 0.5) alloy using the Tian-Ye-Jin model. It is found that the intrinsic mechanism associated with the band structure dominates the anomalous Hall effect of alloys, akin to the parent compound Fe3Ge. In addition, the total and separated intrinsic anomalous Hall conductivity decrease with the increase of doping level. The percentage of anomalous Hall conductivity in total anomalous Hall conductivity increases with increasing temperature and decreasing doping level. The percentage of intrinsic contribution was significantly higher than extrinsic contribution, confirming the intrinsic mechanism dominated anomalous Hall effect. This study provides a reference for tailoring transverse transport properties through doping.

Exploration of chitosan and its modified derivatives as vaccine adjuvant: A review

Chitosan is a natural polysaccharide that has earned much credit in the pharmaceutical field due to its broad implementation in drugs, antigens, and vaccine delivery. Owing to unique characteristics of biocompatibility, biodegradability, mucoadhesiveness, and less toxicity, chitosan holds promise as a vaccine adjuvant or vaccine delivery system. Furthermore, chitosan exhibits antiviral properties making it an ideal vaccine adjuvant and carrier for the delivery of vaccine. The presence of ridiculous functional groups in the parent structure of chitosan enables the creation of modified chitosan derivatives having improved physiochemical properties which provide enhanced vaccine adjuvant properties of chitosan. This review summarizes the potential of chitosan and its modified derivatives as an antiviral agent and vaccine adjuvant along with patents related to the application of chitosan as a vaccine adjuvant and vaccine carrier.

Electronic, magnetic and structural properties of CoFeVAl and CoFeV0.5Mn0.5Al

In this study, we present results of a comprehensive computational and experimental study of CoFeVAl and CoFeV0.5Mn0.5Al Heusler alloys. It is shown that while CoFeVAl exhibits a fairly large degree of spin polarization, this material is not half-metallic due to the presence of the vanadium spin-down states at the Fermi level. However, replacing 50% of vanadium with manganese results in a nearly half-metallic transition, largely due to the shift of the Fermi level towards occupied states. Moreover, the half-metallicity of CoFeV0.5Mn0.5Al is rather robust in a wide range of considered mechanical strain and under experimentally observed B2-type atomic disorder, thus making this alloy potentially suitable for practical spintronic applications. Both considered alloys exhibit ferromagnetic alignment at larger lattice constants, aside from a relatively small magnetic moment of vanadium which is anti-aligned with the magnetic moments of Co, Fe and Mn. We have synthesized both CoFeVAl and CoFeV0.5Mn0.5Al alloys in cubic structure with some structural disorder using arc melting and annealing. The structural and magnetic properties of the synthesized CoFeV0.5Mn0.5Al alloy are in good agreement with the theoretical calculations but vary slightly from the parent compound.

Identification of effective components in Flos Chrysanthemi Indici for alleviating gouty inflammation through integrated absorption and metabolism studies

Flos Chrysanthemi Indici (FCI) is a widely used edible flower and functional food resource, whose extract demonstrates a significant inhibitory effect on monosodium urate (MSU)-induced inflammation in mice. However, the main active components responsible for this effect have remained elusive. Understanding the bioavailability of these components is essential for ensuring the efficacy of functional foods. In this study, we aimed to identify the active components of FCI by examining their in vivo exposure, including absorbed compounds and their metabolites. Initially, we investigated the profiles of FCI extract and absorption and metabolism in rat plasma. Subsequently, through cellular experiments, we found that luteolin, apigenin, luteolin-3′-O-glucuronide, luteolin-7-O-glucuronide, acacetin-7-O-glucuronide, and apigenin-7-O-glucuronide exhibited anti-inflammatory effects against MSU-induced inflammation in THP-1 macrophage cells. The active-related parent compounds in FCI (linarin and luteolin-7-O-β-d-glucoside) were considered as quality control standards for the development of functional products targeting gout. This study characterized the active polyphenolics of FCI in vivo, which may contribute to its reported anti-gout properties, providing valuable insights into the health benefits of FCI polyphenols.

Formation of Inclusion Complexes of 2-Hydroxypropyl β-Cyclodextrin with 2-Hydroxychalcone: Experimental and Theoretical Study

The formation of inclusion complexes of 2-hydroxypropyl-β-cyclodextrin (HP β-CD) with 2-hydroxychalcone (2HOCH) in solution and solid state was investigated using UV–Visible, fluorescence, Fourier transform-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscope (SEM) techniques. The results obtained confirmed that 2HOCH formed the stable inclusion complex with HP β-CD. Moreover, the spectral data and Benesi–Hildebrand plots results indicated that the stoichiometry of the inclusion complex was 1:1. Theoretically, the structure of the inclusion complexes and the physical parameters such as complexation energy, highest occupied molecular orbital–lowest unoccupied molecular orbital, and energy gap were obtained using the DFT/B3LYP/6-311G method. It was found that the complexation energy for orientation B was lower than that for orientation A as evidenced by the theoretical calculations. Moreover, the carbonyl group of molecules was located outside of the cyclodextrin cavity while the hydroxyl group was located inside the cavity. The antioxidant capacity and antibacterial responses of the inclusion complexes and, for comparison, the parent compounds were also carried out.

Toxicokinetic relationship between the adducts in globin and their cleavage products in the urine: Implications for human biomonitoring

Globin adducts of various chemicals, persisting in organism over the whole lifetime of erythrocytes, have been used as biomarkers of cumulative exposures to parent compounds. After removal of aged erythrocytes from the bloodstream, cleavage products of these adducts are excreted with urine as alternative, non-invasively accessible biomarkers. In our biomonitoring studies on workers exposed to ethylene oxide, its adduct with globin, N-(2-hydroxyethyl)valine, and the related urinary cleavage product N-(2-hydroxyethyl)-L-valyl-L-leucine have been determined. To describe a toxicokinetic relationship between the above types of biomarkers, a general compartmental model for simulation of formation and removal of globin adducts has been constructed in the form of code in R statistical computing environment. The essential input variables include lifetime of erythrocytes, extent of adduct formation following a single defined exposure, and parameters of exposure scenario, while other possible variables are optional. It was shown that both biomarkers reflect the past exposures differently as the adduct level in globin is a mean value of adduct levels across all compartments (subpopulations of erythrocytes of the same age) while excretion of cleavage products reflects the adduct level in the oldest compartment. Application of the model to various scenarios of continuous exposure demonstrated its usefulness for human biomonitoring data interpretation.

Association between Volatile Organic Compound Exposure and Sex Hormones in Adolescents: The Mediating Role of Serum Albumin

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds.

Characterization and Metabolism of Drug Products Containing the Cocaine-Like New Psychoactive Substances Indatraline and Troparil.

With a rising demand of cocaine over the last years, it is likely that unregulated new psychoactive substances with similar effects such as indatraline ((1R,3S)-3-(3,4-dichlorophenyl)-N-methyl-2,3-dihydro-1H-inden-1-amine) and troparil (Methyl (1R,2S,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate) become popular as well. Both substances share a similar pharmacological profile as cocaine, while their potency is higher, and their duration of action is longer. This study investigated their metabolic fate in rat urine and incubations using pooled human liver S9 fraction (pHLS9). Indatraline formed two phase I and four phase II metabolites, with aromatic hydroxylation and glucuronidation being the main metabolic steps. All metabolites were detected in rat urine, while the parent compound was not detectable. Although low in abundance, indatraline metabolites were well identifiable due to their specific isotopic patterns caused by chlorine. Troparil formed four phase I and three phase II metabolites, with demethylation being the main metabolic step. Hydroxylation of the tropane ring, the phenyl ring, and combinations of these steps, as well as glucuronidation, were found. Phase I metabolites were detectable in rat urine and pHLS9, while phase II metabolites were only detectable in rat urine.

Heterogeneous catalytic ozonation of ciprofloxacin in wastewater with red mud: Characterization and performance

As a kind of solid waste, red mud (RM) contains various metal oxides, which have been proven to be effective as catalysts in different reactions. This study investigates the impact of RM on the catalytic ozonation for degrading ciprofloxacin (CIP). Compared to the single O3 system, the RM/O3 system improved CIP and Total Organic Carbon (TOC) removal rates by 44.8 % and 21.6 %, respectively, under identical conditions, and exceeded catalytic ozonation by most oxides. The influence factors, CIP degradation products, and reaction mechanisms were discussed in detail. The redox pairs of Fe2+/Fe3+ promoted the formation of oxygen vacancies (Ovac), and the hydroxyl groups and Ovac on the surface of RM were the active sites, facilitating ozone decomposition to reactive oxygen species (ROS). The scavenging experiments confirmed the presence of hydroxyl radical (·OH), peroxyl radical(·O2−), and singlet oxygen (1O2) in the RM/O3 system. Furthermore, toxicity assessment indicated reduced toxicity of intermediate products compared to the parent compound CIP. The catalytic performance of RM remained relatively stable after 5 cycles of experiments, with CIP removal remaining at 100 % and TOC removal decreasing by 5.3 %. This study offers a novel perspective on utilizing RM as an efficient catalyst in CIP ozonation, beneficial for both RM treatment and antibiotic pollution mitigation.