Methylene Bridge Research Articles

Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro.

The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer-related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic dicarba-closo-dodecaboranes (carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. The di-tert-butylphenol derivative tebufelone represents a selective dual COX-2/5-LO inhibitor. The incorporation of meta- or para-carborane into the tebufelone scaffold resulted in eight carborane-based tebufelone analogs that show no COX inhibition but 5-LO inhibitory activity in vitro. Cell viability studies on HT29 colon adenocarcinoma cells revealed that the observed antiproliferative effect of the para-carborane analogs of tebufelone is enhanced by structural modifications that include chain elongation in combination with introduction of a methylene spacer resulting in higher anticancer activity compared to tebufelone. Hence, this strategy proved to be a promising approach to design potent 5-LO inhibitors with potential application as cytostatic agents.

Influence of resin on the formation and development of mesophase in fluid catalytic cracking (FCC) slurry oil

Resin is one of the key components of fluid catalytic cracking slurry oil which is the raw material to form high-quality mesophase pitch. The effect of resin variations on the formation of mesophase was investigated in this paper. The results showed when the resin addition was from 0 to 20 wt%, the formation rate of mesophase remained basically invariable, but it was beneficial to the development of mesophase pitch with higher order degree. However, excessive additions of resin (>20 wt%) sharply accelerated the formation of mesophase due to the high concentration of reactive sites in the system, which shortened the time to form pitch with mesophase content close to 100%, adversely it led to the generation of mesophase pitch with lower order degree. In addition, the approximate molecular structure model of resin was constructed by various characterization methods. The aromatic ring skeleton of resin was dominated by 3–4 ring aromatic hydrocarbons. Resin also possessed structural features such as higher aromaticity, higher N and S content, larger molecular size, longer branched chains, more cyclic alkane structures and methylene bridges, and higher concentration of reactive sites than FCC-exR. Furthermore, an explanation of the effect of resin on the formation and development of mesophase with respect to the molecular structure characteristics was presumed. This work has important implications for regulating the raw material properties of FCC slurry oil and the preparation of high-quality mesophase pitch.

Enhancing the Elasticity of Conjugated Polymers through Precise Control of the Spacing between the Backbone and Siloxane Side-Chains.

Intrinsically stretchable conjugated polymers (CPs) have extensively been studied for the development of novel flexible electronic devices. In this work, a method to control the elastic properties of CPs has been proposed via regulation of spacer length between the siloxane side-chain and the backbone. The target polymers were CP films with the structure P(mC-Si) for four different numbers of the spacer methylene groups, namely, m = 5, 6, 7, and 8. The effect of spacer length on the aggregation state as well as on electrical and elastic properties of the prepared films was then investigated. An adjustable lamellar spacing (dL-L), in addition to improved elastic properties, was achieved as the spacer length was changed in the prepared polymer films. Moreover, P(7C-Si) has a sufficient dL-L value of 35.77 Å, which provides enough space for inter-chain sliding to dissipate stress. This facilitated the dissipation of stress during the straining process. At a strain value of 100% in the vertical direction, the mobility of the P(7C-Si) film was 0.79 cm2 V-1 s-1 and reduced to 84.0% of the initial value without any applied strain. The study provides clear evidence that tuning the spacer length between the silicone endgroup and backbone is an effective way to improve the intrinsic stretchability of CPs with siloxane side chains.

A Potential Lead for Insect Growth Regulator: Design, Synthesis, and Biological Activity Evaluation of Novel Hexacyclic Pyrazolamide Derivatives.

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.

Bicyclo[1.1.1]pentane Embedded in Porphyrinoids.

We report a two-step approach to obtain synthetically versatile bicyclo[1.1.1]pentane (BCP) derivatives using Grignard reagents. This method allows the incorporation of BCP units in tetrapyrrolic macrocycles and the synthesis of a new class of calix[4]pyrrole analogues by replacing two bridging methylene groups with two BCP units. In addition, a doubly N-confused system was also formed in the presence of electron-withdrawing substituents at the BCP bridgeheads. The pyrrole rings in BCP containing macrocycles exist in 1,3-alternate or abab conformation, as observed from single-crystal X-ray diffraction analyses and 2D NMR spectroscopy.

Bicyclo[1.1.1]pentane Embedded in Porphyrinoids**

AbstractWe report a two‐step approach to obtain synthetically versatile bicyclo[1.1.1]pentane (BCP) derivatives using Grignard reagents. This method allows the incorporation of BCP units in tetrapyrrolic macrocycles and the synthesis of a new class of calix[4]pyrrole analogues by replacing two bridging methylene groups with two BCP units. In addition, a doubly N‐confused system was also formed in the presence of electron‐withdrawing substituents at the BCP bridgeheads. The pyrrole rings in BCP containing macrocycles exist in 1,3‐alternate or αβαβ conformations, as observed from single‐crystal X‐ray diffraction analyses and 2D NMR spectroscopy.

Removal of large class of organic pollutants and gold using Phloroglucinol/Resorcinol coupled Triazine-based porous organic polymer

Due to the various anthropogenic activities, the continuous release of organic pollutants is a serious global threat. Thus, developing effective removal and remediation technologies for hazardous pollutants is essential to minimize the adverse effects on human health and the environment. Herein, we developed hyper-crosslinked polymers (HCPs) via catalyst-free solvothermal Friedel-Crafts alkylation reaction using tris-phloroglucinol/tris-resorcinol substituted triazine and dimethoxymethane. The obtained HCPs (HCP-CPF, HCP-CRF) exhibit variation in the surface area, pore size and morphology. The cross-linking of Phloroglucinol-triazine-based planar monomers via methylene spacer leads to porous coral-like morphology with a high surface area (Sarea = 480 m2/g) in HCP-CPF. In contrast, the cross-linking of Resorcinol-substituted triazine-based monomers displayed a fibre network with comparatively low surface area (Sarea = 35.7 m2/g) in HCP-CRF. The presence of densely functionalized multiple hydroxyl groups, good surface area and aqueous dispersibility in HCPs facilitate the fast and efficient removal capacity of various cationic dyes and paraquat herbicide in water. The HCP-CPF displayed fast removal capacity towards the large class of different organic dyes, and it removed 100% of most of the dyes within 10 min from the aqueous solution. Furthermore, the recovery of gold from an aqueous solution is one of the essential and crucial tasks. HCP-CPF and HCP-CRF exhibited a good removal capacity towards Au3+ via in-situ reduction (Qmax = 497.5 mg/g for HCP-CPF and Qmax = 463.33 mg/g for HCP-CRF).

Complexes of a model trimeric acylphloroglucinol with a Cu2+ ion: a DFT study

Abstract Acylphloroglucinols (ACPLs, derivatives of phloroglucinol having at least one R−C=O group) are gaining increasing attention for their pharmacological potentialities. The presence of phenol OHs in their molecules confers antioxidant properties to ACPLs. Some ACPLs have already been identified as promising antioxidants for pharmaceutical purposes. Antioxidant properties may also be useful for a variety of other applications, including industrial ones. A viable option to verify and compare the antioxidant efficacy of compounds considers their ability to form complexes with a metal ion and reduce its charge. The present work considers a model structure maintaining all the identifying features of trimeric ACPLs (ACPLs containing three phloroglucinol moieties linked by methylene bridges) and studies the complexes of representative conformers with a Cu2+ ion, with the ion binding in turn to each of the available binding sites. Two series of calculations are performed at the DFT/B3LYP/6-31+G(d,p) level, without and with the Grimme’s D3 dispersion correction: the former series enables meaningful comparisons with previous calculations of complexes of other ACPLs, and the latter series is meant to evaluate the effect of taking dispersion into account on the estimation of the complexes’ properties. The results show that the Cu2+ ion is reduced to Cu+ ion. The molecule–ion interaction energy and the charge and spin density on the ion are comparable with those of complexes of known antioxidant ACPLs.

Novel Benzylamine Derivatives: Synthesis, Anti-Mycobacterium Tuberculosis Evaluation and Predicted ADMET Properties

Background: Tuberculosis (TB), a disease caused by the bacillus bacteria Mycobacterium tuberculosis is one of the major contributors of ill health in the world. TB is ranked in the top 10 causes of death globally and it is the leading killer associated with a single infectious agent. According to the World Health Organization (WHO), global number of deaths associated with TB have been slowly declining with 1.3 million in reported 2016 and 2017, and 1.2 million reported in 2018 and 2019. Objective: The synthesis, characterisation, biological evaluations, and the prediction of ADMET properties of the novel benzylamine derivatives. Methods: Commercially available reagents and solvents were purchased from Sigma Aldrich and Merck (South Africa). All chemicals were used as received, unless otherwise stated. The synthesised crude compounds were purified by flash silica gel column chromatography (5 – 30% ethyl acetate in hexane). The successful formation and purity of the synthesised compounds was confirmed by NMR, HRMS and melting point. Results: The respective organic compounds were synthesised by treating 3-ethoxysalcyladehyde, 5-bromo-3-ethoxysalcyladehyde, 5-chloro-3-ethoxysalcyladehyde with various aromatic amines and the products were obtained in good to excellent yields. The 1H and 13C NMR spectra of all the products showed the appearance of the methylene signals ranging from 3.88 – 4.68 ppm and 42.25 – 52.57 ppm respectively. Additionally, most compounds showed anti-Mycobacterium tuberculosis activity that ranged between 20 and 28 µM. Conclusion: A total of 36 compounds were synthesised and successfully biologically evaluated against Mycobacterium tuberculosis (Mtb) H37RV strain. All compounds showed activity against Mtb at concentrations of > 20 µM < 28 µM with the exception of compound one that was active against Mtb at higher concentration (MIC90 > 125 µM).

Aerobic degradation of tetramethyl bisphenol F (TMBPF) with activated sludge: Kinetics and biotransformation products

This study investigated the bio-degradation kinetics of tetramethyl bisphenol F (TMBPF), a non-estrogenic alternative to bisphenol A (BPA). Batch biotransformation experiments were performed whereby samples were inoculated with activated sludge and analysed using liquid chromatography-Orbitrap-tandem mass spectrometry (LC-Orbitrap-MS) utilising two non-targeted workflows (commercial and freely available online) for biotransformation products (BTP) identification. The degradation of TMBPF followed single first-order reaction kinetics and depended on the initial concentration (ci) with faster degradation -kt = 0.16, (half-life = 4.4 days) at lower concentrations ci = 0.1 mg L−1, compared with -kt = 0.02 (half-live = 36.4 days) at ci = 10.0 mg L−1. After 18 days, only 8% of the original TMBPF remained at the lowest tested concentration (0.1 mg L−1). Twelve BTPs were identified, three of which were workflow and one condition-specific. The highest relative quantities of BTPs were observed in nutrient-mineral and mineral media after ten days, while after 14 days, 36 and 31% of TMBPF (ci = 1 mg L−1) remained in the nutrient-mineral and mineral media, respectively. Also, the kinetics of TMBPF and its BTPs were the same with and without an additional carbon source. A newly proposed biodegradation pathway for TMBPF involves cleavage of the methylene bridge, hydroxylation with further oxidation, sulphation, nitrification, nitro reduction with further oxidation, acetylation, and glycine conjugation, providing a deeper insight into the fate of TMBPF during biological wastewater treatment.

Simultaneous reactions of sulfonation and condensation for high-yield conversion of polystyrene into carbonaceous material

Polystyrene (PS) was chemically treated with sulfuric acid to prepare stabilized precursors, which were converted into carbonaceous materials with high yield via subsequent carbonization. In addition to sulfuric acid, paraformaldehyde (PFA) was used to increase the crosslink density within the sulfonated PS chain networks by forming methylene bridges between phenyl rings via condensation. This transformed PS into a black glassy powder with increased crosslinking points. The carbon yield of the stabilized PS obtained after carbonization showed was considerably higher (45.3 wt%) than those of pristine PS (0 wt%) and sulfonated PS without PFA (22.4 wt%). This was attributed to its superior degree of crosslinks and the additional contribution of sulfur bridges to its thermal stability during carbonization. Further thermal treatment up to 2800 °C resulted in the formation of an intermediate structure between hard and soft carbons, which was directly revealed by microscopic images. These simultaneous reactions of sulfonation and condensation can be universally applied to various PS wastes, regardless of their shape and morphology. This suggests that the solid-to-solid transformation from PS to carbonaceous substances can be an effective and affordable method of upcycling general PS wastes.

Synthesis and Cytotoxicity Evaluation of Betulin Cycloolefin Derivatives by Ruthenium-Catalyzed Ring-Closing Metathesis.

The combination of ring-closing metathesis with betulin enables the design and synthesis of novel biomolecules representing a library of triterpenoid derivatives for potential pharmacological research. In this work, cyclic olefin betulin derivatives were attempted to be prepared by the combination of ring-closing metathesis with betulin. Dicyclohexyl carbodiimide coupling reaction allowed the transformation of betulin into two types of linear olefin derivatives that have different methylene spacer lengths between the olefin and ester groups. Subsequently, betulin-based cycloolefins were synthesized by ring-closing metathesis using Grubbs first-generation catalyst. The influence of different parameters including solvents, temperature, catalysts, and catalyst loading on ring-closing metathesis was investigated. Cytotoxicity results indicated that these betulin-based olefin derivatives, derived from renewable bioresources, have potential applications in the biomedical field.

Design, synthesis, structural investigation and binding study of 2-pyridone-based pharmaceutical precursor with DNA

Natural pyridones/pyridines and synthetic derivatives have shown different bio-activities and binding affinities with different receptors. Herein, we present the synthesis of four pyridone-based fleximers and characterization using SCXRD, 1HNMR, 13CNMR, and IR spectroscopy. Phthalimide is linked to different pyridines through a methylene bridge. Supramolecular self-assembly was studied with SCXRD and Hirshfeld analysis. Weak interactions were also analysed with IR study in solid and solution phases. More importantly, phthalimide and pyridine of all fleximers can bind with different receptors and are accessed with DNA binding interactions using ct-DNA. Compounds 1–4 exhibited interesting absorption shifts in the titration study with ct-DNA. In silico molecular docking of compounds, 1–4 was evaluated with B-DNA dodecamer (PDB ID: 1BNA). A docking score of -7.7 kcal/mol to -8.9 kcal/mol was observed from the docking results. Both results are promising for all compounds to go for in vivo/vitro study to develop a new drug.

Designing Excess Electron Compounds by Substituting Alkali Metals to a Small and Versatile Tetracyclic Framework: A Theoretical Perspective.

Organic compound-based nonlinear optical (NLO) materials have sparked a lot of attention due to their multitude of applications and shorter optical response times than those of inorganic NLO materials. In the present investigation, we designed exo-exo-tetracyclo[6.2.1.13,6.02,7]dodecane (TCD) derivatives, which were obtained by replacing H atoms of methylene bridge carbon with alkali metals (Li, Na, and K). It was observed that upon the substitution of alkali metals at bridging CH2 carbon, absorption within the visible region occurred. Moving from 1 to 7 derivatives, the maximum absorption wavelength of the complexes exhibited a red shift. The designed molecules showed a high degree of intramolecular charge transfer (ICT) and excess electrons in nature, which were responsible for rapid optical response time and significant large molecular (hyper)polarizability. Calculated trends also inferred that the crucial transition energy decreased in order that also played a key role in the higher nonlinear optical response. Furthermore, to examine the effect of the structure/property relationship on the nonlinear optical properties of these investigated compounds (1-7), we calculated the density of state (DOS), transition density matrix (TDM), and frontier molecular orbitals (FMOs). The largest first static hyperpolarizability (βtot) of TCD derivative 7 was 72059 au, which was 43 times greater than that of the prototype p-nitroaniline (βtot = 1675 au).

The Methylene Spacer Matters: The Structural and Luminescent Effects of Positional Isomerism of n-Methylpyridyltriazole Carboxylate Semi-Rigid Ligands in the Structure of Zn(II) Based Coordination Polymers.

Two Zn(II) coordination polymers (CPs) based on n-methylpyridyltriazole carboxylate semi-rigid organic ligands (n-MPTC), with n = 3 (L1) and 4 (L2), have been prepared at the water n-butanol interphase by reacting Zn(NO3)2·4H2O with NaL1 and NaL2. This allows us to systematically investigate the influence of the isomeric positional effect on their structures. The organic ligands were obtained by saponification from their respective ester precursors ethyl-5-methyl-1-(pyridin-3-ylmethyl)-1H-1,2,3-triazole-4-carboxylate (P1) and ethyl-5-methyl-1-(pyridin-4-ylmethyl)-1H-1,2,3-triazole-4-carboxylate (P2), resulting in their corresponding sodium salt forms, 3-MPTC, and 4-MPTC. The structure of the Zn(II) CPs determined by single-crystal X-ray diffraction reveals that both CPs have 2D supramolecular hydrogen bond networks. The 2D supramolecular network of [Zn(L1)]n (1) is built up by hydrogen bond interactions between oxygen and hydrogen atoms between neighboring n-methylpyridyltriazole molecules, whereas in [Zn(L2)·4H2O]n (2) the water molecules link 1D polymeric chains forming a 2D supramolecular aggregate. The structures of 1 and 2 clearly show that the isomeric effect in the semi-rigid ligands plays a vital role in constructing the Zn(II) coordination polymers, helped by the presence of the methylene spacer group, in the final structural conformation. The structures of 1 and 2 significantly affect their luminescent properties. Thus, while 2 shows strong emission at room temperature centered at 367 nm, the emission of 1 is quenched substantially.

Design, Synthesis, Antibacterial Evaluation and Docking Studies of Triazole and Tetrazole Linked 1,4‐benzodiazepine Nucleus via Click Approach

AbstractA novel series of 1,4‐triazole and 1H‐tetrazole pharmacophoric motifs embellished analogues linked to the privileged 1,4‐benzodiazepine nucleus through an amidophenylene, methylene and phenylene spacer were realized prodigiously through a domino click reaction. The structures of these compounds were established on the basis of their micro analytical IR, 1HNMR, 13C NMR and Mass spectral data. A noteworthy feature of this approach, over the variety of other methods available in the literature for the preparation of 1,4‐regioisomer of triazole and 1H‐tetrazole ring incorporated heterocyclic materials has been their easy access through a one pot strategy of Cu(I) catalyzed cycloaddition of a terminal alkyne with sodium azide. This Cu‐catalyzed click approach was applied for the synthesis of triazole and tetrazole incorporated 1,4‐benzodiazepine. Further, antibacterial activity and molecular docking studies were also performed to validate their biological potential.

Discovery of New Quinoline-Based Diarylamides as Potent B-RAFV600E/C-RAF Kinase Inhibitors Endowed with Promising In Vitro Anticancer Activity

The emergence of cancer resistance to targeted therapy represents a significant challenge in cancer treatment. Therefore, identifying new anticancer candidates, particularly those addressing oncogenic mutants, is an urgent medical demand. A campaign of structural modifications has been conducted to further optimize our previously reported 2-anilinoquinoline-diarylamides conjugate VII as a B-RAFV600E/C-RAF inhibitor. Considering the incorporation of a methylene bridge between the terminal phenyl and cyclic diamine, focused quinoline-based arylamides have been tailored, synthesized, and biologically evaluated. Among them, the 5/6-hydroxyquinolines 17b and 18a stood out as the most potent members, with IC50 values of 0.128 µM, 0.114 µM against B-RAFV600E, and 0.0653 µM, 0.0676 µM against C-RAF. Most importantly, 17b elicited remarkable inhibitory potency against the clinically resistant B-RAFV600K mutant with an IC50 value of 0.0616 µM. The putative binding mode of 17b and 18a were studied by molecular docking and molecular dynamics (MD). Moreover, the antiproliferative activity of all target compounds has been examined over a panel of NCI-60 human cancer cell lines. In agreement with cell-free assays, the designed compounds exerted superior anticancer impact over the lead quinoline VII against all cell lines at a 10 µM dose. Notably, both 17b and 18b showed highly potent antiproliferative activity against melanoma cell lines with growth percent under -90% (SK-MEL-29, SK-MEL-5, and UACC-62) at a single dose, while 17b maintained potency with GI50 values of 1.60-1.89 µM against melanoma cell lines. Taken together, 17b, a promising B-RAFV600E/V600K and C-RAF kinase inhibitor, may serve as a valuable candidate in the arsenal of anticancer chemotherapeutics.

Cyclopropane as an Unsaturation "Effect Isostere": Lowering the Melting Points in Lipid-like Ionic Liquids.

The replacement of unsaturation with a cyclopropane motif as a (bio)isostere is a widespread strategy in bacteria to tune the fluidity of lipid bilayers and protect membranes when exposed to adverse environmental conditions, e.g., high temperature, low pH, etc. Inspired by this phenomenon, we herein address the relative effect of the cyclopropanation, both cis and trans configurations, on melting points, packing efficiency, and order of a series of lipid-like ionic liquids via a combination of thermophysical analysis, X-ray crystallography, and computational modeling. The data indicate there is considerable structural latitude possible when designing highly lipophilic ionic liquids that exhibit low melting points. While cyclopropanation of the lipid-like ionic liquids provides more resistance to aerobic degradation than their olefin analogs, the impact on the melting point decrease is not as pronounced. Our results demonstrate that incorporating one or more cyclopropyl moieties in long aliphatic chains of imidazolium-based ionic liquids is highly effective in lowering the melting points of such materials relative to their counterparts bearing linear, saturated, or thioether side chains. It is shown that the cyclopropane moiety effectively disrupts packing, favoring formation of gauche conformer in the side chains, resulting in enhancement of fluidity. This was irrespective of the configuration of the methylene bridge, although marked differences in the effect of cis- and trans-monocyclopropanated ILs on the melting points were observed.

DNA sequence-specific ligands. XX. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric trisbenzimidazoles DB3P(n)

A new series of AT-specific minor groove DNA ligands (DB3P(n); n = 1,2,3,4) was synthesized and their spectral, biological and virological properties were investigated. With a methylene spacers of different lengths blocks of three AT pairs located at different distances from each other could be recognized. The compounds synthesized suppressed the activity of HIV-1 integrase at submicromolar concentrations (0.25–0.50 µМ). Also, DB3P(n) were found to be effective inhibitors of simplex virus type I and DNA topoisomerase I. The synthesized DB3P(n) demonstrated good solubility in water, could penetrate through cell and nuclear membranes, and stain DNA in live cells.Graphical Abstract

Polyfluorenes Bearing N,N-Dimethylpiperidinium Cations on Short Spacers for Durable Anion Exchange Membranes

Alicyclic quaternary ammonium cations having all the β-protons in a strain-free ring structure are in general highly base-resistant and are thus very attractive to employ for anion exchange membrane (AEM) applications. However, tethering cations such as N,N-dimethylpiperidinium (DMP) to polymer backbones without introducing any weak links is quite challenging. In the present study, we have attached pairs of piperidine rings in their 4-position to fluorene and 2,7-diphenylfluorene via methylene bridges using straightforward SN2 reactions. These fluorenes were subsequently utilized as monomers in polyhydroxyalkylations to prepare poly(fluorene alkylene)s with different contents of the piperidine groups. AEMs were cast after quaternizing the piperidine groups to introduce DMP and spirocyclic 6-azonia-spiro-[5,5]undecane-6-ium (ASU) cations, respectively. The AEMs reached very high hydroxide ion conductivities, 100–156 mS cm–1 at 80 °C, in the ion exchange capacity range 1.8–2.4 mequiv g–1. X-ray scattering showed ionomer peaks indicating ionic clustering with a characteristic distance d = 2.0–2.9 nm depending on the ion exchange capacity. The AEMs displayed high thermal stability, up to ∼250 °C, and 1H NMR data indicated no degradation after storage in 5 M aq NaOH during 168 h at 90 °C. However, degradation started under very severe conditions (10 M, 90 °C) with ∼75% of the total ionic loss in all the AEMs assigned to Hofmann β-elimination. The overall results show that fluorene-based AEMs carrying DMP and ASU cations via methylene bridges display an attractive combination of ionic phase separation, thermal and chemical stability, and hydroxide conductivity, making them viable alternatives for use in alkaline fuel cells and water electrolyzers..