Diclofenac Derivatives Research Articles

NEW BIARYL DERIVATIVES OF DICLOFENAC DRUG: SYNTHESIS, MOLECULAR DOCKING AND THEIR BIOLOGICAL ACTIVITY STUDY AS ANTICANCER AND ANTIOXIDANT AGENTS

In this work, a series of diclofenac derivatives were synthesized via the Suzuki-Miyaura reaction and evaluated in vitro as anticancer and antioxidant agents. Structures of synthesized compounds were characterized by FT- IR, 1H NMR, 13C NMR spectra, and elemental analysis. The products have been screened in vitro for their anticancer activity against both cell lines HdFn and MCF-7 as well as they were investigated for their antioxidant activity. The cytotoxicity assay results revealed that derivatives 3a and 3d exhibited good inhibition for cell lines MCF-7 with IC50 values 33.1 and 38.2 µM, respectively while 3a and 3c exhibited acceptable inhibition for HdFn with IC50 values 68.7 and 72.6µM, respectively compared to the Tamoxifine drug. Molecular docking study of the target compounds confirmed the results of the cytotoxicity test. In addition, results of the DPPH investigation revealed good antioxidant activity for derivatives 3a, 3c and 3d with inhibition percentages of 83.14, 82.42, and 78.16%, respectively compared to ascorbic acid. For citation: Abdul-Rida N.A., Mohammed K.T. New biaryl derivatives of diclofenac drug: synthesis, molecular docking and their biological activity study as anticancer and antioxidant agents. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 12. P. 47-53. DOI: 10.6060/ivkkt.20246712.7071.

Pharmacological Evaluation of Diclofenac Derivatives: A Comprehensive Review of Their Antibacterial, Anti-inflammatory, and Anticancer activities.

Pharmacological Evaluation of Diclofenac Derivatives: A Comprehensive Review of Their Antibacterial, Anti-inflammatory, and Anticancer activities.

Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies.

Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies. The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches. Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program. Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-β in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue. The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

In-silico design, molecular docking, molecular dynamic simulations, Molecular mechanics with generalised Born and surface area solvation study, and pharmacokinetic prediction of novel diclofenac as anti-inflammatory compounds

The prostaglandins inside inflamed tissues are produced by cyclooxygenase-2 (COX-2), making it an important target for improving anti-inflammatory medications over a long period. Adverse effects have been related to the traditional usage of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation, mainly centered around gastrointestinal (GI) complications. The current research involves the creation of a virtual library of innovative molecules showing similar drug properties via a structure-based drug design. A library that includes five novel derivatives of Diclofenac was designed. Subsequently, molecular docking through the Glide module and determining the binding free energy implementing the Prime-MMGBSA module by the Schrödinger software package was used to identify compounds that showed marked specificity towards the COX-2 isoform. In addition, the ligands are subject to evaluation of their drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics using the QikProp module. Finally, molecular dynamics simulation has been calculated for the best molecule. The docking results indicated that all compounds own a predictive capability for specific binding to the COX-2 enzyme compared to the standard drug with a docking score range from -10.07 to -10.66 Kcal/mole, thus potentially overcoming the limitations imposed previously by the drugs currently used in clinical use. The ADMET analysis of the virtually active compounds demonstrated an acceptable drug-like profile and desirable pharmacokinetics properties. MM/GBSA calculation revealed that all the suggested compounds exhibited favorable free binding energies (-49.150 to - 60.185 Kcal/mole), indicating their strong potential to fit well into the COX-2 receptor. Finally, the MD simulation study revealed that compound 1 had perfect alignment with COX-2 receptor. The findings indicated that the compounds possess a predictive capability for specific binding to the COX-2 enzyme, thus potentially surmounting the restrictions imposed by the drugs currently employed in clinical use.

Analysis of the methodology described in the thermoanalytical characterization involving aceclofenac compounds and their derivatives: what does the literature say?

The thermoanalytical characterization of aceclofenac compounds and their derivatives is essential for understanding their physical and chemical properties. Thermoanalytical techniques offer critical insights into these compounds' thermal behavior, stability, and decomposition patterns, providing vital information for their formulation, processing, and storage. Aceclofenac, a diclofenac derivative, is a widely used nonsteroidal anti-inflammatory drug (NSAID) for treating inflammatory diseases. This physicochemical characterization is pivotal for assessing their stability, solubility, and bioavailability, involving various analytical techniques like melting point determination, decomposition temperature assessment, and heat capacity analysis. Thermoanalytical methods like thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) are frequently employed in pharmaceutical compound characterization, offering insights into thermal stability, decomposition kinetics, and molecular structure. This review summarizes recent literature on thermoanalytical methodologies characterizing Aceclofenac and its derivatives. A bibliographic review was conducted using the SciFinder web platform, resulting in the selection of ten relevant articles published between 2016 and 2023. The analysis reveals that thermal analysis is crucial for studying pharmaceuticals, providing insights into various physicochemical properties. Despite the importance of experimental methodologies in scientific publications, some studies lack adequate pre-experimental information, hindering reproducibility. In this review, it was observed that out of eight studies, twelve thermoanalytical techniques were employed for aceclofenac characterization, with DSC being the most used method. However, one author omitted crucial information about experimental procedures, highlighting the need for transparent reporting in scientific research.

Aceclofenac Derivatives: Synthesis, Characterization, and Determination of Anti‐oxidant and Anti‐inflammatory Activities by Chemiluminescence Assays and Molecular Docking Studies

AbstractAceclofenac (ACF) is a newer derivative of diclofenac, and one of the emerging NSAIDs for the treatment of various inflammatory diseases. In this research we have develop a set of 2‐(2‐(2‐((2,6‐dichlorophenyl)amino)phenyl)acetoxy)acetic acid derivatives (AR1‐AR12) using Fischer esterification in good yields and in an efficient manner. All the compounds were fully characterized physical (solubility and melting points) and chemical by spectral data analysis of FTIR, 1HNMR and 13CNMR and elemental analysis. In‐vitro anti‐inflammatory activity was performed by Chemiluminescence technique in which we found 2‐oxo‐1,2‐diphenylethyl2‐(2‐(2((2,6‐dichlorophenyl)amino)phenyl) acetoxy)acetate (AR2 71 %), 2‐(4‐formyl‐2‐methoxyphenoxy)‐2‐oxoethyl2‐(2‐((2,6 dichloro‐phenyl) amino)phenyl)acetate (AR3 74.7 %),2‐(2‐(2‐(2‐((2,6‐dichloropheny l)amino) phenyl) acetoxy) acetoxy)‐3‐(2‐(2‐(3‐((2,6‐dichlorophenyl) amino) phenyl) acetoxy)acetoxy)succinic acid (AR6 89.2 %), 2‐(4‐aminophenoxy)‐2‐oxoethyl2‐(2‐((2,6‐dichloro‐phenyl) amino) phenyl) acetate (AR8 71.1 %), 1,3‐dioxo‐2,3‐dihydro‐1H‐indene‐2,2‐diyl bis(2‐(2‐(2‐((2,6‐dichlorophenyl)amino)phenyl)acetoxy)acetate) (AR9 76.3 %) found more potent as compared to parent compound while AR3, AR6 and AR9 highly potent than standard reference ibuprofen (73.2 %). The current molecular docking study was performed In order to check the suitable method for the binding of target ligands and proteins Glide docking with extra precision (XP) mode. The hydrogen bonding interactions of Aceclofenac are prominent with Isoleucine moiety, those of compound AR‐6 shows hydrophobic interaction with active amino acid Leucine and Phenylalanine moieties. Anti‐oxidant activities were also performed, AR‐3 (79.30 %), AR‐5 (91.23 %), AR‐9 (83.43 %) AR‐12 (92.43 %) were found to be more anti‐oxidant as compared to aceclofenac (ACF) (66.46 %). These derivatives were synthesized with different aliphatic and aromatic alcohols and phenols.

Synthesis and Characterization of Novel Diclofenac (DCF) Derivatives

AbstractOver the years, scientific community has shown immense interest in the synthesis of novel, bioactive molecules with few adverse effects. Instead of painstaking multistep synthesis with hazardous synthetic reagents, also for clinical studies, it is better to enhance the activity and tuning by structural modification of the commercial drugs based on their structural and biological properties. It is demonstrated that diclofenac (DCF) be an effective analgesic and anti‐pyretic in the treatment of cancer‐related pain, but it has limitations and adverse effects as gastrointestinal irritation, small intestine damage, nausea, platelet dysfunction, and vertigo. Wherefore the main objective of the current research is to investigate new, novel, green methods of preparation of DCF derivatives, and structural characterization with the help of FT‐IR, UV‐Visible spectroscopy, MS spectrometry techniques.

Novel synthetic methodology of Diclofenac derivatives and its spectrochemical studies

To design the novel synthetic scheme, structural modification, characterization, and pharmacological evaluation of new derivatives of Diclofenac drugs is the main aim of the current research work. We describe the utility of novel reagents and green synthetic methodology to formulate the derivatives to enhance its biological action without undesirable effects. Diclofenac sodium is the phenylacetic acid salt and categorized under nonsteroidal anti-inflammatory drug (NSAID) with pain-relieving, antipyretic, and anti-inflammatory activity, but it has limits and adverse effects as gastrointestinal irritation, small intestine damage, nausea, platelet dysfunction and vertigo. Diclofenac amide derivatives are prepared with Sulphanilic acid and Naphthylamine by the following methods such as reflux and microwave irradiation method. Structural modification is carried out to build up the desired properties. The new synthesized derivatives were structurally characterized with the help of FT-IR, UV–Visible spectroscopy, and MS spectrometry techniques. Further we propose the pharmacological evaluation of Diclofenac derivatives will be carried out by in-vivo and invitro methods.

New bioisosteric derivative of diclofenac sodium resolute gastric ulcer in rats through regulation of pro-inflammatory cytokines “Tumor necrosis factor alpha and Inter-leukin-1”

Background and objective: Gastric ulcer is an important health risk for a human. It is a painful sore in the stomach lining. It is relatively easy to cure, but can cause significant problems if left un-treated. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for millions of people worldwide; however, as their consequences most of individuals suffer from gastric ulcers and related complications. Diclofenac sodium is a medication from NSAIDs class of drugs, is used to relieve joint pain from arthritis but when used chronically, it may cause bleeding and ulcers in the stomach or intestine. This study aimed to test the safety and the antiulcer activity of a new bioisosteric derivative of diclofenac sodium on a rat model. Methods: 2-Cumaranone 1 had been utilized to prepare the propanamides 2a-e then after the bioisosteric diaryl ethers 3a-e synthesized; then its purity was characterized on the basis of IR, 1HNMR and Mass spectral data. Acute toxicity on albino mice was performed to ensure the safety and an experimental rat model was used to evaluate the anti-ulcer activity. Kidney and liver functions tests were measured, ulcer measurements were reported and pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and Interleukin 1 beta (IL-1β) levels were tested. Results: Unlike diclofenac sodium, the bioisosteric diaryl ethers 3a-e is less acidic and produces less damage to the stomach wall. In addition, the structure of amide derivative is also bulky thus it is more selective to cyclooxygenase ΙΙ enzyme thus the risk of gastric ulcer was less than with diclofenac sodium itself. Conclusion: Unlike diclofenac, amide derivative of diclofenac is less acidic than diclofenac thus it produces less damage to the stomach wall.

Synthesis, biological evaluation, and molecular docking studies of novel diclofenac derivatives as antibacterial agents

In the recent years, interest in the synthesis of diclofenac derivatives has increased due to their exceptional biological activity. We present here the synthesis of some novel diclofenac derivatives through simple synthetic procedures, where the acylation of carbohydrazide compound 1 with chloroacetyl chloride in dioxane produced the compound 2. Chloroacetohydrazide compound 2 was further subjected to nucleophilic substitution reactions using different nucleophiles such as: hydrazine hydrate, thiosemicarbazide and p-aminobenzenesulfonamide to give the corresponding derivatives 3-5, respectively. Moreover, the reaction of the hydrazinyl compound 3 with active hydrogen species such as: ethyl acetoacetate and acetyl acetone in refluxed ethanol provided the corresponding pyrazolone derivatives 6 and 7, respectively. Furthermore, the reaction of previously reported diclofenac ester 8 with 1,2-diaminoethane gave the amino derivative 9. Finally, condensation reaction of the latter compound with benzaldehyde in dioxan furnished the corresponding Schiff's base compound 10, while its acylation with chloroacetyl chloride in dioxan produced 11. Different spectral (IR, NMR and Mass) and elemental analysis techniques were utilized to explore the structure of the synthesized compounds. All the synthesized compounds were tested for their in-vitro antibacterial activity against different strains of bacteria showing satisfactory results, and molecular docking study was performed to investigate the mode of action.

Development and Challenges of Diclofenac-Based Novel Therapeutics: Targeting Cancer and Complex Diseases.

Simple SummaryDiclofenac is a widely used drug for its anti-inflammatory and pain alleviating properties. This review summarizes the current understanding about the drug diclofenac. The potential applications of diclofenac beyond its well-known anti-inflammatory properties for other diseases such as cancer are discussed, along with existing limitations.Diclofenac is a highly prescribed non-steroidal anti-inflammatory drug (NSAID) that relieves inflammation, pain, fever, and aches, used at different doses depending on clinical conditions. This drug inhibits cyclooxygenase-1 and cyclooxygenase-2 enzymes, which are responsible for the generation of prostaglandin synthesis. To improve current diclofenac-based therapies, we require new molecular systematic therapeutic approaches to reduce complex multifactorial effects. However, the critical challenge that appears with diclofenac and other drugs of the same class is their side effects, such as signs of stomach injuries, kidney problems, cardiovascular issues, hepatic issues, and diarrhea. In this article, we discuss why defining diclofenac-based mechanisms, pharmacological features, and its medicinal properties are needed to direct future drug development against neurodegeneration and imperfect ageing and to improve cancer therapy. In addition, we describe various advance molecular mechanisms and fundamental aspects linked with diclofenac which can strengthen and enable the better designing of new derivatives of diclofenac to overcome critical challenges and improve their applications.

Design, Synthesis, Antimicrobial Activity, and Molecular Docking of Some New Diclofenac Derivatives

Due to the biological importance of diclofenac derivatives which are included in the composition of the active substance in many medicines used in the treatment of infections. Herein, we present a facile procedure for the synthesis of a new series of diclofenac analogous, in excellent isolated yields starting from the carbohydrazide precursor 1. Acylation and condensation of NH2 group in the starting material with different reagents delivered compounds (2–5). Moreover, the Nucleophilic substitution of chloromethyl derivative 5 with primary and secondary amines gave compounds (6a, 6b, and 7). Furthermore, the hydrazine compound (7) reaction with benzaldehyde and chloroacetylchloride produced derivatives (8, 9). The chemical structures of all newly synthesized compounds have been proved based on elemental and spectral analysis techniques (FTIR, 1HNMR, 13CNMR, and Mass spectroscopy). All synthesized compounds were investigated for their in-vitro antimicrobial activity against different strains of bacteria and fungi in moderate to high activity. A molecular docking approach was utilized to investigate the proposed molecular mechanism of the antibacterial and antifungal activity of the synthesized compounds.

Diclofenac derivatives as concomitant inhibitors of cholinesterase, monoamine oxidase, cyclooxygenase-2 and 5-lipoxygenase for the treatment of Alzheimer's disease: synthesis, pharmacology, toxicity and docking studies.

Targeting concomitantly cholinesterase (ChEs) and monoamine oxidases (MAO-A and MAO-B) is a key strategy to treat multifactorial Alzheimer's disease (AD). Moreover, it is reported that the expression of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is increased significantly in the brain of AD patients. Using the triazole of diclofenac 12 as a lead compound, we synthesized a variety of analogs as multipotent inhibitors concomitantly targeting COX-2, 5-LOX, AChE, BChE, MAO-A and MAO-B. A number of compounds showed excellent in vitro inhibition of the target biological macromolecules in nanomolar concentration. Compound 39 emerged as the most potent multitarget ligand with IC50 values of 0.03 μM, 0.91 μM, 0.61 μM, 0.01 μM 0.60 μM and 0.98 μM towards AChE, BChE, MAO-A, MAO-B, COX-2 and 5-LOX respectively. All the biologically active compounds were found to be non-neurotoxic and blood–brain barrier penetrant by using PAMPA assay. In a reversibility assay, all the studied active compounds showed reversibility and thus were found to be devoid of side effects. MTT assay results on neuroblastoma SH-SY5Y cells showed that the tested compounds were non-neurotoxic. An in vivo acute toxicity study showed the safety of the synthesized compounds up to a 2000 mg kg−1 dose. In docking studies three-dimensional construction and interaction with key residues of all the studied biological macromolecules helped us to explain the experimental results.

Diclofenac N-Derivatives as Therapeutic Agents with Anti-Inflammatory and Anti-Cancer Effect.

A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10, murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding that the most effective compound was compound 8c against all cell lines and both compounds 4 and 6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure because these products presented the lowest IC50 values in two of the three cancer cell lines assayed (B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line. Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing that the highest values were between 30 to 60%. Next, the effects of these two compounds were observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered by these compounds, mitochondrial potential was evaluated, indicating the possible activation of extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophages-monocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic concentrations were used to determine NO release at different incubation times. The greatest anti-inflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 µg·mL−1 concentration after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that inflammation may contribute to all states of tumorigenesis, the development of these new derivatives capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent new effective therapeutic strategies against these diseases.

Theoretical Study to Predict the Ability to Use Different Organic Substituents as Carrier Linkages for Diclofenac

The research includes unrestricted (UDFT) and (UPM3) quantum mechanical calculations for studying the reaction path of bonds rupture energies of (O-R) and (C-OAr) in twelve diclofenac derivatives containing different substituted organic groups. All the calculations were performed at the optimize geometries in vacuum phase by using Gaussian 09 program. Comparison was done between the studied diclofenac derivatives and the standard ionic diclofenac of sodium and potassium included geometrical structures, physical properties, total energies of the reactants and products, activation energies and transition states. The results showed that some substituted organic groups could be used to form good carrier bonds for the acidic drug diclofenac, while others were less efficient depending on the nature of the substituted carrier, and that there is a preference for carriers of the type (–R) over the carriers of the type (–Ar).

New Diclofenac Derivatives as Anti-Microbial, Anti-Inflammatory Agents: Design, Synthesis, Biological Screening, and Molecular Docking Study

New Diclofenac Derivatives as Anti-Microbial, Anti-Inflammatory Agents: Design, Synthesis, Biological Screening, and Molecular Docking Study

Synthesis, gastroprotective and acute toxicity of bio-isosteric derivative of diclofenac

Background and objective: Non-steroidal anti-inflammatory drugs (such as diclofenac1) had been widely prescribed for the treatment of different types of pain; however, they are not devoid of adverse effects. Therefore, synthesis of new bio-isosteric analogs4a-e of diclofenac1 with greater COX II selectivity and less gastrointestinal side effect is demanded. This study aimed to evaluate the acute toxicity and gastroprotective activity of the bio-isosteric derivative of diclofenac against ethanol-induced gastric ulceration in rats. Methods: 2-Cumaranone 2 had been utilized to prepare amides 3a-e then after the bio-isosteric derivatives 4a-esynthesized from them then used to study the biological activity by testing whether high doses of the prototype compound 4c are toxic or not on albino mice and measuring the gastroprotective effect on albino rats. Rats were divided into four groups. Group 1 orally administered with Tween 20; group 2 was orally administered with 20 mg/kg esomeprazole; groups 3 and 4 received 100 and 200 mg/kg of the compound, respectively. Absolute ethanol was given orally to the groups, and rats were sacrificed after one hour. Results: Few diarylethers 4a-ebio-isosteric to diclofenac had been prepared and fully characterized (including 1HNMR, 13CNMR, and IR spectroscopy). Serum biochemical parameters were reported to be normal. Hematological analysis of kidney and liver did not elicit any remarkable changes in the treated group compared to the control group. Thus, the 50% oral lethal dose (LD50) for the male and female mice was greater than 5 g/kg body weight. Anti-ulcer data showed a gastroprotective effect of the bio-isosteric diclofenac derivative 4c and presented the ulcer area inhibition, low stomach pH, and preserve the mucous content. Conclusion: Many bio-isosteric derivatives of diclofenac had been prepared with good yields. The synthesized derivative4c showed no toxicity, and the gastroprotective effect may possibly be due to the preservation of gastric wall mucus.

Optimization of the Synthesis of Diclofenac Derivatives with Hydrazone Structure and In Vitro Evaluation of the Anti-Inflammatory Potential

The aim of the study was to optimize the synthesis of diclofenac derivative with hydrazones structure in order to obtain higher yields and purity by variation of different parameters such as: ratio between reactants, solvent, catalyst, temperature, time of reaction and method used. The anti-inflammatory effects of diclofenac derivatives were evaluated using in vitro assays: albumin denaturation and erythrocyte membrane stability. The obtained results showed that the effect of the tested derivatives is increasing with the concentration, the best results being obtained at the concentration of 125 �g/mL (albumin denaturation assay), respectively 111.11 �g/mL (erythrocyte membrane stability assay). The most active compound was 4d which showed the highest inhibition effect on albumin denaturation and an appreciable effect on erythrocyte membrane stability, in comparation with diclofenac, used as drug reference.

Magnetic Ti3C2Tx (Mxene) for diclofenac degradation via the ultraviolet/chlorine advanced oxidation process

In this study, a magnetic titanium carbide (Ti3C2Tx) MXene was synthesized through a one-step chemical co-precipitation method using ammonium bifluoride as a mild etchant and was investigated for photocatalytic degradation of diclofenac (DCF) via the ultraviolet (UV)/chlorine process. The DCF degradation was enhanced by the generation of active radicals such as the hydroxyl radical and reactive chlorine species compared with that resulting from UV and chlorination treatment alone as well as UV/H2O2 processes at pH 7. The first-order rate constant of the UV/chlorine process was 0.1025 min−1, which is 12.7 and 6.8 times higher than those of the only UV and UV/H2O2 processes, respectively. Magnetic nanoparticles on the surfaces of Ti3C2Tx sheets not only enhanced the adsorption capacity of the synthesized composite but also increased the rate of electron transfer in solution. In addition, the effects of different operating conditions such as magnetic Ti3C2Tx dose, pH, and initial chlorine concentration on DCF degradation were investigated. Magnetic Ti3C2Tx showed high stability and photodegradation efficiency during seven consecutive degradation reaction cycles. The derivatives of DCF during the photocatalytic degradation process were also investigated based on the observed intermediate products and a degradation pathway was proposed. Thus the synthesized magnetic Ti3C2Tx is a simple and affordable photocatalyst, which can significantly enhance DCF degradation in the UV/chlorine advanced oxidation process.

The role of regioselective hydroxylation on toxicity of diclofenac and related derivatives

ABSTRACTDiclofenac and related derivatives become more toxic after biotransformation reactions in the body by electron or hydrogen transfers. The structure–reactivity study on regioselective hydroxylation of diclofenac acid was elucidated by using quantum chemistry calculations at level of DFT/B3LYP/6-31G(d,p). HOMO, ionisation potential, bond dissociation energy, and spin density distributions were used as chemical reactivity parameters. Also, some properties are related to lumiracoxib and fenclofenac. The higher flexibility of lumiracoxib can be responsible for the increase of COX2 selectivity. Diphenyl-amine moiety is responsible for their potent antioxidant capacity. Chloro atoms have a strong effect under electron transfer capacity when compared to acetic acid group. Hydroxylation for the 5-hydroxydiclofenac is more favoured in either electron or hydrogen transfers. Both hydroxylation increased the electron donation and antioxidant capacity. These properties were observed to the fenclofenac derivatives and can be related to their toxicity by redox mechanism.