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Acridine frameworks stand as pivotal architectural elements in pharmaceuticals and photocatalytic applications, owing to their chemical adaptability, biological activity, and unique excited‐state dynamics. Conventional synthetic routes often entail specialized starting materials, anaerobic or moisture‐free conditions, and elaborate multi‐stage manipulations for incorporating diverse functionalities. Herein, we present a convergent approach integrating photo‐excitation of readily available ortho‐alkyl nitroarenes with copper‐promoted cascade annulation. This innovative system enables an aerobic, one‐pot reaction of o‐alkyl nitroarenes with arylboronic acids, thereby streamlining the modular construction of a wide array of acridine derivatives with various functional groups. This encompasses symmetrical, unsymmetrical and polysubstituted varieties, some of which are otherwise exceptionally difficult to synthesize. Furthermore, it significantly improves the production of structurally varied acridinium salts, featuring enhanced photophysical properties, high excited state potentials (E*red=2.08–3.15 V), and exhibiting superior performance in intricate photoredox transformations. [ABSTRACT FROM AUTHOR]

Abstract Nanoparticles have emerged as a critical catalyst substrate due to their exceptional features, such as catalytic efficiency, high stability, and easy recovery. In our research, we have developed an innovative and environmentally friendly magnetic mesoporous nanocatalyst. Using the co-precipitation method, we produced magnetic nanoparticles (Fe3O4) and coated them with Zeolitic imidazolate frameworks (ZIFs) to enhance their surface area and chemical stability. The resulting substrate was functionalized with 1-aza-18-crown-6-ether and nickel metal. Our prepared catalyst has been rigorously evaluated using advanced techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmet-Teller (BET), vibrating sample magnetometry (VSM), scanning electron microscopy and energy dispersive X-ray (SEM-EDS), inductively coupled plasma (ICP), elemental mapping analysis (EMA), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). By synthesizing acridine derivatives, we have demonstrated the exceptional efficiency of our catalyst in organic compound synthesis. Through optimization, we have established the ideal parameters for catalytic processes, including catalyst amount, temperature, time, and ultrasonic use. Our catalyst has been proven to exhibit remarkable physical and chemical properties, such as porosity, temperature resistance, and recyclability. Notably, our heterogeneous nanocatalyst has shown outstanding performance and can be recycled six times without any loss in efficiency, affirming its potential in acridine.

the current investigation, 109 known ERα inhibitors have been developed in the current research; pharmacophore modeling, Molecular docking, MM‐GBSA, and MD study have been performed to investigate the binding affinity of 9‐anilinoacridines with heterocyclic substitutes as selective ERα inhibitors for breast carcinoma. Pharmacophore model have been developed by Schrodinger suite 2019–2 phasemodule. To predict binding free energy of the ligands in complex with PDB and post docked energy minimization was performed by Prime, MM‐GB/SA module. The Induced fit docking studies were performed on the ligand modulated dynamic behaviour of the protein molecular dynamics study. A statistical substantial 3D ‐ QSAR design was created using the pharmacophore hypothesis. 109 known ERα inhibitors have been developed with pIC50 values between 4.0 and 6.0 and were used in ligand‐based pharmacophore modelling and 3D‐QSAR analysis. R2 (0.8294), Q2 (0.7~0.8), and F value (83.5) were used to statistically validate the developed five‐point hypothesis DHRRR1 employing a minimum square of four. Molecular dynamics simulations were run to comprehend the conformational changes and ligand stability at the protein active pocket. The predicted 3D‐QSAR model significantly correlated with experimentally reported in‐vitro antitumor activity. These in‐silico discoveries will help in the future search for potent ERα inhibitors with desirable pharmacophoric properties. [ABSTRACT FROM AUTHOR]

9-Substituted-4,5-bifunctionalized acridines are common subunits of numerous drugs and fluorescent dyes, thus studies were carried out on a series of their potential precursors from the aspect of preparation, reactivity, chemical stability and potential applications. The syntheses of the new 9-fluoro-, 9-triflate and 9-lithiated derivatives of 4,5-dimethoxyacridine were reported. All the new intermediates supplemented with the recently synthetized 9-haloacridine analogues were compared and their applicability was discussed. The reactivity of the studied acridino-precursors was tested by using them as starting materials in Suzuki-Miyaura and Kharasch type cross-couplings as well as in Li-organic reactions. [ABSTRACT FROM AUTHOR]

Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine–azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320–420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine–isoxazole hybrids linked at the C9–C3 or C2–C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, o-xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl tert-butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine–azirine, acridine–isoxazole, and acridane–isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4). [ABSTRACT FROM AUTHOR]

The current research deals with the microwave-assisted green synthesis of two acridine-based libraries and in vitro urease inhibitory activities. The first library is based on 9-phenyl acridine 1–13 derivatives, while the second is based on 10H-acridin-9-one 14–33 derivatives. All compounds were characterized using FTIR, EI-MS, 1H-NMR, and CHNX techniques. As a result of in vitro evaluation of the synthesized derivatives, most compounds showed potent inhibitory activity against urease with IC50 values ranging from 0.91 to 11.84 µM. Thiourea was used as the standard (IC50 = 19.43 ± 0.18 µM). The structure–activity relationship (SAR) was established to identify key relationships between studied compounds' chemical structure and biological activity. The kinetic studies revealed a competitive mode of inhibition by the compounds. In addition, molecular docking and MD simulation studies were conducted to determine the different interactions between the ligands (compounds) and the enzyme's active site for the retention time of the ligand into the active pocket of the protein. Thus, it is well-known that inhibiting the urease enzyme activity effectively treats infections caused by Helicobacter pylori. This study has identified that these synthetic acridines may serve as promising lead candidates as urease inhibitors. [ABSTRACT FROM AUTHOR]

Acridines are a class of bioactive agents which exhibit high biological stability and the ability to intercalate with DNA; they have a wide range of applications. Pyridine derivatives have a wide range of biological activities. To enhance the properties of acridine and 2-amino-3-methylpyridine as the active pharmaceutical ingredient (API), 4-nitrobenzoic acid was chosen as a coformer. In the present study, a mixture of acridine and 4-nitrobenzoic acid forms the salt acridinium 4-nitrobenzoate, C13H10N+ ·C7H4NO4- (I), whereas a mixture of 2- amino-3-methylpyridine and 4-nitrobenzoic acid forms the salt 2-amino-3- methylpyridinium 4-nitrobenzoate, C6H9N2 + ·C7H4NO4- (II). In both salts, protonation takes place at the ring N atom. The crystal structure of both salts is predominantly governed by hydrogen-bond interactions. In salt I, C—H...O and N—H...O interactions form an infinite chain in the crystal, whereas in salt II, intermolecular N—H...O interactions form an eight-membered R2 ² (8) ring motif. A theoretical charge–density analysis reveals the charge–density distribution of the inter- and intramolecular interactions of both salts. An in-silico ADME analysis predicts the druglikeness properties of both salts and the results confirm that both salts are potential drug candidates with good bioavailability scores and there is no violation of the Lipinski rules, which supports the druglikeness properties of both salts. However, although both salts exhibit druglike properties, salt I has higher gastrointestinal absorption than salt II and hence it may be considered a potential drug candidate [ABSTRACT FROM AUTHOR]

Despite the important role that urease plays in the global nitrogen cycle, inhibition of its activity is demanded owing to the development of diseases such as stomach ulcers and some cancers. In the search for a potent urease inhibitor, imidazoacridine and pyrazoloacridine derivatives were synthesized and evaluated for their urease inhibitory potential. The desired compounds were obtained in two steps at high yields in basic media. Title compounds exhibited a variable degree of inhibitory interaction potential having IC50 values ranging between 14.83 ± 0.03 and 22.21 ± 0.6 μM compared with standard thiourea. To understand the binding interaction of most active analogs with ab active site of urease enzyme, molecular modeling of the complexes (ligand–enzyme) was also performed. [ABSTRACT FROM AUTHOR]

An expeditious strategy has been developed for the synthesis of diverse quinolines, indenoquinolines and acridines using KOtBu‐mediated reaction conditions. The designed process utilizes 2‐aminoaryl carbaldehydes/2‐aminoaryl ketones and methyl/methylene group containing ketones as readily available feedstock. The chemical transformation was affected at room temperature within a short duration of time to obtain diverse N‐heterocycles yields up to 92 %. The established process also exhibits considerable functional group tolerance with an operational simplicity. [ABSTRACT FROM AUTHOR]

Isatin, also known as indoline‐2,3‐dione, is a fused, N‐heterocyclic aromatic compound first isolated and purified in 1841. Since then, isatin and its derivatives emerged as a hot research topic for the scientific community. The number of research publications on isatin justifies their popularity. Researchers explored isatins and their derivatives as potential candidates in multidisciplinary research areas, including medicinal chemistry, synthetic organic chemistry, and polymer science. Synthetic chemists' perspective of tailoring isatin and its family members led to more efficient synthesis strategies in which ring‐opening reactions of isatins were particularly significant due to the product's importance. Our investigation aims to group the different types of cascade ring expansion reactions of isatin to synthesise fused heterocyclic compounds such as derivatives of quinolines, quinazolinones, acridines, acridones, and few spiro heterocyclic compounds, all of which highlight an inevitable role in the field of medicinal chemistry. [ABSTRACT FROM AUTHOR]

Acridine derivatives have exhibited great application prospects in organic photovoltaic devices. An efficient and atomically economical synthetic method was developed for the production of acridines from anthranils using arylboronic acids. This protocol features no catalysts, good functional group tolerance, and operational simplicity. This catalyst-free process afforded various acridines in moderate to good yields, providing an efficient platform for the investigation of untapped reactions at high temperatures. [ABSTRACT FROM AUTHOR]

Porous organic polymers (POPs) – the emergent hydrothermally stable, amorphous and porous materials – have proven to be invaluable for catalytic applications. Through a rational bottom‐up design, we have developed a Carboxy‐POP, a POP that is adorned by Bronsted acid (COOH) functionalities, for heterogeneous catalysis. The Carboxy‐POP has been comprehensively characterized by FT‐IR, solid‐state 13C NMR, SEM, TEM, etc. It exhibits a moderate porosity with a BET surface area of 381 m2 g−1 and acid concentration of 1.67 mmol/g. Its functional utility as an efficient heterogeneous catalyst for one‐pot synthesis of a variety of xanthenes and acridines in excellent isolated yields (up to 98 %) is demonstrated. In contrast to the conventional methods, the advantages of the reported metal‐free catalytic protocol include ease of operation, excellent isolated yields of the products, facile workup, and shorter reaction times. It is shown that the heterogeneous catalyst can be repetitively used with the catalytic activity almost intact even after 16 reaction cycles. [ABSTRACT FROM AUTHOR]

In this work, an efficient, novel, retrievable, and magnetic heterogeneous nanocatalyst, Fe3O4@CPTMS@Asp@Ni was successfully fabricated using Fe3O4 nanoparticles as the core that were coated with surfactant and 3‐chloropropyltrimethoxysilan and deposited asparagine and nickel metal that can be used in multicomponent reactions for the synthesis of acridines derivatives with high yield in short reaction times. The virtue of obtained nanocatalyst was identified using transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction analysis, energy dispersive X‐ray, Brunauer–Emmett–Teller, vibrating sample magnetometry, Raman, and thermogravimetric analysis. The X‐ray diffraction analysis studies demonstrate that the average crystallite sizes of the prepared nanocatalyst are estimated to be about 45.4 nm. Also, the vibrating sample magnetometry measurement shows saturation magnetization values (Ms) of 7 emu/g for Fe3O4@CPTMS@Asp@Ni nanocatalyst. Also, after the synthesis steps, the application of the prepared nanocatalyst in the preparation of acridine‐1,8(2H,5H)‐diones has been investigated. Then to evaluate and assess the efficiency of the nanocatalyst as mentioned above, and its effect on the synthesis of divergent acridines via a one‐pot, three‐component condensation reaction of cyclic 1,3‐dione, aryl glyoxal, with ammonium acetate in the water as green solvent was studied. Also, when investigating the reusability of this catalyst, it was observed that Fe3O4@CPTMS@Asp@Ni nanocatalyst could be reused at least five times without losing its efficiency. High efficiency, outstanding yields in quick intervals, easy separation using a magnetic field, and possessing reusability are significant benefits of the attained nanocatalyst. [ABSTRACT FROM AUTHOR]

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT). [ABSTRACT FROM AUTHOR]

Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine–azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320–420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine–isoxazole hybrids linked at the C9–C3 or C2–C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, o-xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl tert-butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine–azirine, acridine–isoxazole, and acridane–isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4).

A novel gentisic acid-based deep eutectic solvent (ETPPBr/GA-DES) was prepared by mixing of ethyltriphenylphosphonium bromide (ETPPBr) and gentisic acid (GA = 2,5-dihydroxy-benzoic acid), and its structure fully investigated by using the FT-IR, TGA/DTA, densitometer and 1HNMR techniques. Different mole ration of ETPPBr to GA were examined and the eutectic point phase diagram showed that the best ratio for the synthesis of a novel gentisic acid-based DES is the one-to-one mole ratio of the two starting materials (ETPPBr and GA).Then, ETPPBr/GA-DES was used as a novel and capable catalyst for the green synthesis of diverse N-substituted decahydroacridine-1,8-diones a(1−12) from the three-component condensation reaction of aromatic aldehyde, aromatic amine and dimedone in solvent-free conditions at 80 °C.

BackgroundTreatment of schistosomiasis, a neglected disease, relies on just one partially effective drug, praziquantel. We revisited the 9-acridanone hydrazone, Ro 15-5458, a largely forgotten antischistosomal lead compound.MethodsRo 15-5458 was evaluated in juvenile and adult Schistosoma mansoni-infected mice. We studied dose-response, hepatic shift and stage specificity. The metabolic stability of Ro 15-5458 was measured in the presence of human and mouse liver microsomes, and human hepatocytes; the latter also served to identify metabolites. Pharmacokinetic parameters were measured in naive mice. The efficacy of Ro 15-5458 was also assessed in S. haematobium-infected hamsters and S. japonicum-infected mice.ResultsRo 15-5458 had single-dose ED50 values of 15 and 5.3 mg/kg in mice harbouring juvenile and adult S. mansoni infections, respectively. An ED50 value of 17 mg/kg was measured in S. haematobium-infected hamsters; however, the compound was inactive at up to 100 mg/kg in S. japonicum-infected mice. The drug-induced hepatic shift occurred between 48 and 66 h post treatment. A single oral dose of 50 mg/kg of Ro 15-5458 had high activity against all tested S. mansoni stages (1-, 7-, 14-, 21- and 49-day-old). In vitro, human hepatocytes produced N-desethyl and glucuronide metabolites; otherwise Ro 15-5458 was metabolically stable in the presence of microsomes or whole hepatocytes. The maximum plasma concentration was approximately 8.13 μg/mL 3 h after a 50 mg/kg oral dose and the half-life was approximately 4.9 h.ConclusionsRo 15-5458 has high activity against S. mansoni and S. haematobium, yet lacks activity against S. japonicum, which is striking. This will require further investigation, as a broad-spectrum antischistosomal drug is desirable.

Nanomaterial-enabled chemiluminescence (CL) detection has become a growing area of interest in recent years. We review the development of nanomaterial-based CL detection strategies and their applications in bioanalysis. Much progress has been achieved in the past decade, but most attempts still remain in the proof-of-concept stage. This review highlights recent advances in nanomaterials in CL detection and organizes them into three groups based on their role in detection: as a sensing platform, as a signal probe, and applications in homogeneous systems. Furthermore, we have discussed the critical challenges we are facing and future prospects of this field.

In this study novel 2-(4-(1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide hybrids with fused 1,4-dihydropyridines such as acridines and tetrahydrodipyrazolo[3,4-b:4',3'-e]pyridines were successfully and efficiently prepared through a one-pot multi-component reaction of 2-(4-(4-formyl-1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide with dimedone, or 5-methyl-2,4-dihydro-3H-pyrazol-3-one at reflux. The tri-substituted methanes (TRSMs) were synthesized through the reaction of the appropriate aldehyde with 6-aminothiouracil and 4-hydroxycoumarin. The structures of novel compounds were confirmed based on spectral data. [ABSTRACT FROM AUTHOR]

Most metal–organic frameworks (MOFs) as heterogeneous catalytic systems limit their use in the catalytic process due to a lack of active functional sites. In this study, the novel modification of the Zr-MOF, UiO-66-NH2 was studied. Initially, UiO-66-NH2 was modified with 3,4 dihydroxybenzaldehyde to the creation of hydroxyl groups and subsequently reacts with di-n-butyl phosphate. The supported phosphate acid named UiO-66-N=CH-C6H3PO4H is introduced as a green, efficient, acidic-basic nanocatalyst. The structural and textural properties of the prepared UiO-66-N=CH-C6H3PO4H nanocatalyst were characterized by several techniques such as FTIR, XRD, FE-SEM, EDX, SEM elemental mapping, N2 adsorption–desorption, and TGA. Hydrogen phosphate groups on the surface are the main active catalytic sites. The performance of supported phosphate acid was applied for a one-pot, three-component approach to synthesize acridine derivatives using various aldehydes, ammonium acetate, and dimedone. The Brønsted acid and Brønsted base sites in phosphate acid and Lewis acid sites in the MOF were synergistically catalyzed the acridines synthesis. The nanocatalyst has important properties such as durability and robustness which are necessary parameters for the development of a new catalytic system for acid-catalyzed syntheses. This approach offers simple and optimum synthesis conditions, products with high efficiencies in short reaction times, and the ability to recover nanocatalyst for five consecutive cycles without a substantial decrease in catalytic efficiency. [ABSTRACT FROM AUTHOR]

Members of a novel class of anticancer compounds, exhibiting high antitumor activity, i.e. the unsymmetrical bisacridines (UAs), consist of two heteroaromatic ring systems. One of the ring systems is an imidazoacridinone moiety, with the skeleton identical to the structural base of Symadex. The second one is a 1-nitroacridine moiety, hence it may be regarded as Nitracrine's structural basis. These monoacridine units are connected by an aminoalkyl linker, which vary in structure. In theory, these unsymmetrical dimers should act as double-stranded DNA (dsDNA) bis-intercalators, since the monomeric units constituting the UAs were previously reported to exhibit an intercalating mode of binding into dsDNA. On the contrary, our earlier, preliminary studies have suggested that specific and/or structurally well-defined binding of UAs into DNA duplexes might not be the case. In this contribution, we have revisited and carefully examined the dsDNA-binding properties of monoacridines C-1305, C-1311 (Symadex), C-283 (Ledakrin/Nitracrine) and C-1748, as well as bisacridines C-2028, C-2041, C-2045 and C-2053 using advanced NMR techniques, aided by molecular modelling calculations and the analysis of UV–VIS spectra, decomposed by chemometric techniques. These studies allowed us to explain, why the properties of UAs are not a simple sum of the features exhibited by the acridine monomers. [ABSTRACT FROM AUTHOR]

Acridine and its derivatives (9-chloroacridine and 9-aminoacridine) are investigated here, supported on FAU type zeolite Y, as a delivery system of anticancer agents. FTIR/Raman spectroscopy and electron microscopy revealed successful drug loading on the zeolite surface, while spectrofluorimetry was employed for drug quantification. The effects of the tested compounds on cell viability were evaluated using in vitro methylthiazol-tetrazolium (MTT) colorimetric technique against human colorectal carcinoma (cell line HCT-116) and MRC-5 fibroblasts. Zeolite structure remained unchanged during homogeneous drug impregnation with achieved drug loadings in the 18–21 mg/g range. The highest drug release, in the µM concentration range, with favourable kinetics was established for zeolite-supported 9-aminoacridine. The acridine delivery via zeolite carrier is viewed in terms of solvation energy and zeolite adsorption sites. The cytotoxic effect of supported acridines on HCT-116 cells reveals that the zeolite carrier improves toxicity, while the highest efficiency is displayed by zeolite-impregnated 9-aminoacridine. The 9-aminoacridine delivery via zeolite carrier favours healthy tissue preservation while accompanying increased toxicity toward cancer cells. Cytotoxicity results are well correlated with theoretical modelling and release study, providing promising results for applicative purposes. [ABSTRACT FROM AUTHOR]

A series of novel 3,9-disubstituted acridines were synthesized and their biological potential was investigated. The synthetic plan consists of eight reaction steps, which produce the final products, derivatives 17a–17j, in a moderate yield. The principles of cheminformatics and computational chemistry were applied in order to study the relationship between the physicochemical properties of the 3,9-disubstituted acridines and their biological activity at a cellular and molecular level. The selected 3,9-disubstituted acridine derivatives were studied in the presence of DNA using spectroscopic (UV-Vis, circular dichroism, and thermal denaturation) and electrophoretic (nuclease activity, relaxation and unwinding assays for topoisomerase I and decatenation assay for topoisomerase IIα) methods. Binding constants (2.81–9.03 × 104 M−1) were calculated for the derivatives from the results of the absorption titration spectra. The derivatives were found to have caused the inhibition of both topoisomerase I and topoisomerase IIα. Molecular docking simulations suggested a different way in which the acridines 17a–17j can interact with topoisomerase I versus topoisomerase IIα. A strong correlation between the lipophilicity of the derivatives and their ability to stabilize the intercalation complex was identified for all of the studied agents. Acridines 17a–17j were also subjected to in vitro screening conducted by the Developmental Therapeutic Program of the National Cancer Institute (NCI) against a panel of 60 cancer cell lines. The strongest biological activity was displayed by aniline acridine 17a (MCF7–GI50 18.6 nM) and N,N-dimethylaniline acridine 17b (SR–GI50 38.0 nM). The relationship between the cytostatic activity of the most active substances (derivatives 17a, 17b, and 17e–17h) and their values of KB, LogP, ΔS°, and δ was also investigated. Due to the fact that a significant correlation was only found in the case of charge density, δ, it is possible to assume that the cytostatic effect might be dependent upon the structural specificity of the acridine derivatives. [ABSTRACT FROM AUTHOR]

Mild steel has been considerably exploited in various manufacturing and commercial fields due to its tremendous mechanical performance. However, mild steel's high susceptibility to corrosion under acidic conditions leads to vast economic losses and environmental consequences. Inhibitors used for steel corrosion in the acidic medium are ordinarily polar heteroaromatic molecules with electronegative atoms. Acridines are one type of inhibitor with several advantages, such as heteroatoms, functional groups and their polarity, double bond conjugation, and importantly efficient and non‐hazardous synthetic routes. The polar moieties of such inhibitors are considered to augment their adsorption on steel surface, thus creating a shielding to inhibit steel corrosion. Acridine analogs are N‐heterocyclic organic compounds that can be easily produced owing to impeccable inhibition capacity. The current review discusses the chemistry, synthesis, corrosion inhibition mechanism, and properties of acridines and their derivatives. [ABSTRACT FROM AUTHOR]

This review summarized the current breakthroughs in the chemistry of acridines as anti-cancer agents, including new structural and biologically active acridine attributes. Acridine derivatives are a class of compounds that are being extensively researched as potential anti-cancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is restricted or even excluded as a result of side effects. The photocytotoxicity of propyl acridine acts against leukaemia cell lines, with C1748 being a promising anti-tumour drug against UDP-UGT's. CK0403 is reported in breast cancer treatment and is more potent than CK0402 against estrogen receptor-negative HER2. Acridine platinum (Pt) complexes have shown specificity on the evaluated DNA sequences; 9-anilinoacridine core, which intercalates DNA, and a methyl triazene DNA-methylating moiety were also studied. Acridine thiourea gold and acridinone derivatives act against cell lines such as MDA-MB-231, SK-BR-3, and MCF-7. Benzimidazole acridine compounds demonstrated cytotoxic activity against Dual Topo and PARP-1. Quinacrine, thiazacridine, and azacridine are reported as anti-cancer agents, which have been reported in the previous decade and were addressed in this review article. [ABSTRACT FROM AUTHOR]

The phenomenon of corrosion threatens metallic components, human safety, and the economy. Despite being eco-friendly and promising as a corrosion inhibitor, acridine has not been explored to its full potential. In this review, we have discussed multiple biological activities that acridines have been found to show in a bid to prove that they are environmentally benign and much less toxic than many inhibitors. Some synthetic routes to acridines and substituted acridines have also been discussed. Thereafter, a multitude of acridines and substituted acridines as corrosion inhibitors of different metals and alloys in various corrosive media have been highlighted. A short mechanistic insight into how acridine-based compounds function as corrosion inhibitors have also been included. We believe this review will generate an impression that there is still much to learn about previously reported acridines. In the wake of recent surges to find efficient and non-toxic corrosion inhibitors, acridines and their analogs could be an appropriate answer. [ABSTRACT FROM AUTHOR]

The cocrystallization of active pharmaceutical ingredient naproxen with some acridines (acridine, 9-aminoacridine, 6,9-diamino-2-ethoxyacridine) has been explored and the conditions under which the crystallization can be carried out have been investigated. While the crystallization of acridine-based molecular crystals was widely studied under solution conditions, solvent-free and/or mechanochemical method potentialities are still unknown. To fill this gap, the cocrystallization of naproxen with the above-mentioned acridines was attempted using different approaches, e.g., by heat treatment of the dry mechanical mixture and by liquid-assisted grinding (LAG), as alternatives to the traditional precipitation by a proper solution. In the first case, the reaction is driven under dry conditions by the temperature and gave no results independently of the temperature used, below or above the melting point of the reactants. In the second case, the reaction is driven by the mechanical action of grinding assisted by a few drops of solvent to facilitate and improve the reaction. This screening allowed obtaining three new molecular crystals for naproxen coupled to acridine and a mono-aminoacridine and solved by single-crystal and powder X-ray diffraction (PXRD). Two host–guest structures were obtained by solution crystallization, while a layered structure was obtained under LAG conditions. Interconversion between molecular crystals formed by the same chemical species was hindered once a molecular crystal was obtained by a specific technique. Hirshfeld and energy framework calculations confirmed the remarkable structural differences between 1α and 1β packing and suggested that 1β is kinetically more stable. Variable-temperature PXRD, DSC and TGA were used to explore the stability of the compounds. 6,9-Diamino-2-ethoxyacridine proved to be too polar and/or too bulky to form crystals with naproxen regardless of the preparation method and the different stoichiometric ratios used. It is noteworthy that LAG allowed the preparation of the naproxen/acridine molecular crystal with a yield higher than 99% under almost solvent-free conditions. DSC indicated the formation of a eutectic between naproxen and acridine, with the possibility of recrystallizing the 1 : 1 complex also from the melt solution. [ABSTRACT FROM AUTHOR]

The present article presents a personalized Account on the synthesis of nitrogen heterocycles by combination of regioselective Pd-catalyzed cross-coupling reactions of polyhalogenated heterocycles, i.e., Suzuki–Miyaura and Sonogashira reactions, with acid-mediated cycloisomerization reactions. In many cases, the products constitute new heterocyclic core structures and show interesting optical and electronic properties. 1 Introduction 2 Acridines 3 Phenathridines 4 Azapyrenes 5 Thienoquinolines 6 Pyrrolonaphthyridines 7 6-Aza-ullazines 8 Conclusions [ABSTRACT FROM AUTHOR]

A practical nickel‐catalyzed protocol for the synthesis of sterically hindered 9‐arylacridines via Negishi type cross‐coupling was developed. The method enables a convenient approach to a set of active acridine photocatalysts starting from commercially available 9‐chloroacridine, inexpensive catalyst [NiCl2(Ph3P)2], and organozinc reagent with no need for additional ligands and precious metals. The synthetic protocol could be readily performed on a gram scale. The photocatalytic efficiency of obtained acridines was tested in decarboxylative thiolation and amination reactions. Structures of 19 acridines were studied by X‐ray analysis, which allowed to propose a steric descriptor relevant to the catalytic activity. [ABSTRACT FROM AUTHOR]

Base‐promoted formal [4+2] cycloaddition reaction of (Z)‐2‐(2‐hydroxy‐2‐alkylvinyl)quinoline‐3‐carbaldehydes and allenoates represents an efficient method for the synthesis of functionalized acridines through a sequential Michael addition, aldol condensation, and isomerization process in a mild condition. This new approach tolerates a wide range of (Z)‐2‐(2‐hydroxy‐2‐alkylvinyl)quinoline‐3‐carbaldehydes and allenoates and affords the functionalized acridines in good to excellent yields. The exclusive selectivity, high atom economy, and high bond‐formation efficiency of this method makes it a valuable approach for the synthesis of acridine backbones. [ABSTRACT FROM AUTHOR]

The present work deals with the synthesis, spectral characterization and the interaction of new tetracyclic imidazo[4,5-a]acridines with acetylcholinesterase (AChE) enzyme. This compound was obtained via hydrolysis in the CN group of 8-methoxy-3-methyl-3H-imidazo[4,5-a]acridine-11-carbonitrile in high yield. The target compound was synthesized from the reaction of 1-methyl-5-nitro-1H-benzo[d]imidazole with 2-(4-methoxyphenyl)acetonitrile in basic medium. The catalytic activity of AChE was investigated in the presence of title compound and inhibition constants were determined for the reversible enzyme–inhibitor complex. Based on the mixed inhibition model, inhibition constant for the title compound was 0.097 mM. Molecular modeling of the complex (ligand–enzyme) was used to determine amino acid residues of the active site involved in the interaction. In the presence of the ligand in some regions, such as residues 80 – 87, 328 – 347, 433 – 440, 484 – 492 and the N-terminal residues, the flexibility of the AChE residues has decreased. Also, the calculations show that the new ligand interacts with the active site of AChE. The Trp84, Phe330, and His440 residues play a role in this interaction. These residues are located in the cavity of the AChE binding site. Trp84 and His440 are located at the bottom of the cavity, and Phe330 occurs in the middle of the cavity. These residues exhibit hydrophobic interaction with the new ligand. Also, the ligand has altered the secondary structure of AChE. The helical secondary structure of AChE is most affected by the ligand. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity. In the present study, acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in OSCC cells. The mechanism of action, pharmacokinetics, and toxicity parameters of the most promising compound was further analyzed using in silico, in vitro, and in vivo methods. Among the derivatives, compound 4e was highly cytotoxic (29.99 µM) and selective (SI 2.9) at levels comparable and generally superior to chemotherapeutic controls. Besides, compound 4e proved to be non-hemolytic, stable, and well tolerated in animals at all doses tested. Mechanistically, compound 4e promoted cell death by apoptosis in the OSCC cell, and molecular docking studies suggested this compound possibly targets enzymes important for tumor progression, such as RSK2, PKM2, and topoisomerase IIα. Importantly, compound 4e presented a pharmacological profile within desirable parameters for drug development, showing promise for future preclinical trials. [ABSTRACT FROM AUTHOR]

In the title compound, C27H33NO5, a 3,3,6,6-tetramethyltetrahydroacridine-1,8-dione ring system carries an ethyl acetate substituent on the acridine N atom and an o-hydroxyphenyl ring on the central methine C atom of the dihydropyridine ring. The benzene ring is inclined to the acridine ring system at an angle of 80.45 (7)° and this conformation is stabilized by an intramolecular O—H...O hydrogen bond between the hydroxy substituent on the benzene ring and one of the carbonyl groups of the acridinedione unit. The ester C=O oxygen atom is disordered over major and minor orientations in a 0.777 (9):0.223 (9) ratio and the terminal –CH3 unit of the ethyl side chain is disordered over two sets of sites in a 0.725 (5): 0.275 (5) ratio. In the crystal, C—H...O hydrogen bonds combine to link the molecules into a three-dimensional network. van der Waals H...H contacts contribute the most to the Hirshfeld surface (66.9%) followed by O...H/H...O (22.1%) contacts associated with weak hydrogen bonds.

The photon upconversion based on triplet–triplet annihilation (TTA) is a mechanism that converts the absorbed low-energy electromagnetic radiation into higher energy photons also at extremely low excitation intensities, but its use in actual technologies is still hindered by the limited availability of efficient annihilator moieties. We present here the results obtained by the synthesis and application of two new fluorinated chromophores based on phenazine and acridine structures, respectively. Both compounds show upconverted emission demonstrating their ability as TTA annihilator. More interesting, the acridine-based chromophore shows an excellent TTA yield that overcomes the one of some of best model systems. By correlating the experimental data and the quantum mechanical modeling of the investigated compound, we propose an alternative efficient pathway for the generation of the upconverted emissive states involving the peculiar high-energy triplet levels of the dye, thus suggesting a new development strategy for TTA annihilators based on the fine tuning of their high-energy excited states properties. [ABSTRACT FROM AUTHOR]

The potential of acridines (amsacrine) as a topoisomerase II inhibitor or poison was first discovered in 1984, and since then, a considerable number of acridine derivatives have been tested as topoisomerase inhibitors/poisons, containing different substituents on the acridine chromophore. This review will discuss a series of studies published over the course of the last decade, which have investigated various novel acridine derivatives against topoisomerase II activity. This review will discuss a series of studies published over the course of the last decade, which have investigated of various novel acridine derivatives against topoisomerase II activity. Important recent studies have reported further interesting results concerning the effect of new acridine derivatives (4, 5, 24–27, 30, 33, 43–65, 68, 70–73, and 77) as inhibitors/poisons of topoisomerase IIα. The data presented in this article extended the potential activity of acridine derivatives to treating the Topo IIα as the universal target in drug discovery and development. [ABSTRACT FROM AUTHOR]

An efficient catalytic system has been developed on the basis of carbon-doped MoO3 (CPM-3) for the synthesis of 1,8-dioxodecahydroacridines by condensation of dimedone, aromatic aldehydes, and anilines in ethanol–water (3:1) under ultrasonication. The effects of addition of polyethylene glycol (PEG-400) and carbon (0, 1, 2, and 3 wt %) as substrates were investigated systematically to get the desired carbon-doped MoO3 material. The carbon source was prepared from the plant Acacia arabica, and the obtained samples were calcined at 500°C. The catalytic material was characterized by a number of sophisticated techniques such as XRD, SEM-EDS, FT-IR, TEM, NH3-TPD, and BET. The present protocol has several advantages, including the use of a non-corrosive, nontoxic, inexpensive, and recyclable catalytic material. [ABSTRACT FROM AUTHOR]

An efficient catalytic system has been developed on the basis of carbon-doped MoO3 (CPM-3) for the synthesis of 1,8-dioxodecahydroacridines by condensation of dimedone, aromatic aldehydes, and anilines in ethanol–water (3:1) under ultrasonication. The effects of addition of polyethylene glycol (PEG-400) and carbon (0, 1, 2, and 3 wt %) as substrates were investigated systematically to get the desired carbon-doped MoO3 material. The carbon source was prepared from the plant Acacia arabica, and the obtained samples were calcined at 500°C. The catalytic material was characterized by a number of sophisticated techniques such as XRD, SEM-EDS, FT-IR, TEM, NH3-TPD, and BET. The present protocol has several advantages, including the use of a non-corrosive, nontoxic, inexpensive, and recyclable catalytic material. [ABSTRACT FROM AUTHOR]

Human telomeres (HTs) can form DNA G-quadruplex (G4), an attractive target for anticancer and antiviral drugs. HT-G4s exhibit inherent structural polymorphism, posing challenges for understanding their specific recognition by ligands. Here, we aim to explore the impact of different topologies within a small segment of the HT (Tel22) on its interaction with BRACO19, a rationally designed G4 ligand with high quadruplex affinity, already employed in in-vivo treatments. Our multi-technique approach is based on the combined use of a set of contactless spectroscopic tools. Circular dichroism and UV resonance Raman spectroscopy probe ligand-induced conformational changes in the G4 sequence, while UV-visible absorption, coupled with steady-state fluorescence spectroscopy, provides further insights into the electronic features of the complex, exploiting the photoresponsive properties of BRACO19. Overall, we find that modifying the topology of the unbound Tel22 through cations (K + or Na + ), serves as a critical determinant for ligand interactions and binding modes, thus influencing the HT-G4's assembly capabilities. Furthermore, we show how fluorescence serves as a valuable probe for recognizing cation-driven multimeric structures, which may be present in living organisms, giving rise to pathological forms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

An attempted synthesis of 5-aryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline derivatives from 2,3-dihydroacridin-4(1H)-ones with 2-aminocarboxylic acid derivatives in presence of phosphorus oxychloride at 130˚C yielded a novel class of quin[1,2-b]acridine derivatives. The newly synthesized compounds showed a better cytotoxic activity against HeLa and MCF-7 cell lines during the structure–activity relationship (SAR) studies. To discover with the interactions of these molecules, we carried out molecular docking studies using the human protein kinase CK2 inhibitors. The molecular interaction results provided a number of elegant information for the outlook design of more potent inhibitors. [ABSTRACT FROM AUTHOR]

A series of novel 3,9-disubstituted acridines were synthesized and their biological potential was investigated. The synthetic plan consists of eight reaction steps, which produce the final products, derivatives 17a–17j, in a moderate yield. The principles of cheminformatics and computational chemistry were applied in order to study the relationship between the physicochemical properties of the 3,9-disubstituted acridines and their biological activity at a cellular and molecular level. The selected 3,9-disubstituted acridine derivatives were studied in the presence of DNA using spectroscopic (UV-Vis, circular dichroism, and thermal denaturation) and electrophoretic (nuclease activity, relaxation and unwinding assays for topoisomerase I and decatenation assay for topoisomerase IIα) methods. Binding constants (2.81–9.03 × 104 M−1) were calculated for the derivatives from the results of the absorption titration spectra. The derivatives were found to have caused the inhibition of both topoisomerase I and topoisomerase IIα. Molecular docking simulations suggested a different way in which the acridines 17a–17j can interact with topoisomerase I versus topoisomerase IIα. A strong correlation between the lipophilicity of the derivatives and their ability to stabilize the intercalation complex was identified for all of the studied agents. Acridines 17a–17j were also subjected to in vitro screening conducted by the Developmental Therapeutic Program of the National Cancer Institute (NCI) against a panel of 60 cancer cell lines. The strongest biological activity was displayed by aniline acridine 17a (MCF7–GI50 18.6 nM) and N,N-dimethylaniline acridine 17b (SR–GI50 38.0 nM). The relationship between the cytostatic activity of the most active substances (derivatives 17a, 17b, and 17e–17h) and their values of KB, LogP, ΔS°, and δ was also investigated. Due to the fact that a significant correlation was only found in the case of charge density, δ, it is possible to assume that the cytostatic effect might be dependent upon the structural specificity of the acridine derivatives.

Copper/dapsone cuvalented Fe3O4@SiO2‐propyl nanocomposite (Fe3O4@SiO2‐propyl@dapsone/Cu) was prepared using cheap compounds in simple immobilization methodology. This nanocompound was identified by X‐ray diffraction, FT‐IR, VSM, TEM, FE‐SEM, and TGA analyses and was found to be effective and green nanocomposite for the multicomponent reaction of aldehydes, dimedone, and dapsone. The catalyst is magnetically recoverable in the presence of an enormous magnetic bar and recycled for six rounds, without any obvious decrease in the efficiency of the catalyst. Moreover, it has been observed that this new class of dihydropyridines can be easily synthesized in this avenue in good yield and short reaction times. [ABSTRACT FROM AUTHOR]

The electrochemical behavior of two chemically related acridine compounds: tacrine (TAC) and 9-aminoacridine (9-AA) was investigated on a hanging mercury drop electrode (HDME). The electrochemical study was carried out by using Osteryoung square wave voltammetry (OSWV) and cyclic voltammetry (CV) techniques in the Britton-Robinson (B-R) buffer solution at pH = 2.0-12.0, KCl (0.1/0.2/0.3 M) and methanol (0.0-50%) mixture as supporting electrolyte. TAC showed maximum current at pH 7.5 while 9-AA at pH 10, KCl (0.3M), and 10% methanol. The study of electrochemical reduction of 9-AA and TAC on the HDME by using CV resulted in a quasi-reversibility, mainly diffusion-controlled reaction. The reaction involved 1e-/1H+ reduction at nitrogen atom in the case of the 9-AA while the second process involved the 2e-/2H+ reduction of the intra-cyclic azomethine group. The reduction peak potential of structurally related acridine compounds is influenced by the pH values and percentage of the organic solvent of the supporting electrolytes. Also, the study may provide insight into the electron transfer pathways of biological reactions of the acridines and their electrochemical behavior on the electrode. [ABSTRACT FROM AUTHOR]

We investigated the excited-state dynamics of bridged and non-bridged chiral helicene-like bidibenzo[c,h]acridines deposited as a thin film. Broadband UV/VIS−NIR transient absorption spectroscopy from the femtosecond to the microsecond time-scale and transient fluorescence measurements were employed to understand the photoinduced processes in these organic thin-film layers. Photoexcitation at 370 nm populates the S1 state, which has a lifetime of 15 and 36 ps for the non-bridged and bridged derivative, respectively. In both cases, the decay is governed by internal conversion (78% and 84%), whereas intersystem crossing represents only a smaller channel (21% and 15%), and the remaining 1% accounting for fluorescence. Fast repopulation of the S0 state leads to the generation of hot ground state molecules (S0*), with characteristic finger-type transient absorption features. The T1 state decays back to S0 by intersystem crossing with a time constant of 775 and 5500 ps, respectively. Even at high excitation fluence, there are no indications for higher-order processes, such as singlet–singlet annihilation or Förster energy transfer. Photoexcitation also launches coherent acoustic phonons in these films, appearing as damped oscillations in the transient absorption kinetics on the red and blue edge of each S0 absorption band, with a period of about 190 ps. [ABSTRACT FROM AUTHOR]

The phenomenon of corrosion threatens metallic components, human safety, and the economy. Despite being eco-friendly and promising as a corrosion inhibitor, acridine has not been explored to its full potential. In this review, we have discussed multiple biological activities that acridines have been found to show in a bid to prove that they are environmentally benign and much less toxic than many inhibitors. Some synthetic routes to acridines and substituted acridines have also been discussed. Thereafter, a multitude of acridines and substituted acridines as corrosion inhibitors of different metals and alloys in various corrosive media have been highlighted. A short mechanistic insight into how acridine-based compounds function as corrosion inhibitors have also been included. We believe this review will generate an impression that there is still much to learn about previously reported acridines. In the wake of recent surges to find efficient and non-toxic corrosion inhibitors, acridines and their analogs could be an appropriate answer.

Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity. In the present study, acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in OSCC cells. The mechanism of action, pharmacokinetics, and toxicity parameters of the most promising compound was further analyzed using in silico, in vitro, and in vivo methods. Among the derivatives, compound 4e was highly cytotoxic (29.99 µM) and selective (SI 2.9) at levels comparable and generally superior to chemotherapeutic controls. Besides, compound 4e proved to be non-hemolytic, stable, and well tolerated in animals at all doses tested. Mechanistically, compound 4e promoted cell death by apoptosis in the OSCC cell, and molecular docking studies suggested this compound possibly targets enzymes important for tumor progression, such as RSK2, PKM2, and topoisomerase IIα. Importantly, compound 4e presented a pharmacological profile within desirable parameters for drug development, showing promise for future preclinical trials.

Acridine derivatives are widely used as antiseptics, disinfectants, antibiotics, and fluorescent dyes as well as a subunit of optical sensor molecules of various analytical applications. We reported here the synthesis of several new 9-substituted-4,5-dimethoxyacridine derivatives (9-bromo-, 9-(p-methylphenyl)-, 9-(pbenzyloxyphenyl)-, 9-azido-, 9-phenyltriazole-, 9-[(trimethylsilyl) ethynyl]-, 9-nitrile-) as potential multifunctionalizable fluorescent precursors of sensor molecules, indicators or dyes including optimized procedures for preparation of 9-haloacridines and their cross-coupling reactions. Improved stability of several new compounds could be achieved by the synthetic modification at position 9 of the acridine unit compared to their unsubstituted acridine analogs. The basic spectroscopic characteristics of these useful intermediates were also determined. The new fluorescent compounds showed promising photochemical properties for optochemical-based applications in the future. The extremely large Stokes-shifts (above 15500 cm-1) should especially be emphasized. Moreover, the effects of the substituents at position 9 of the acridine unit on fluorescence signaling were studied by the examples of new precursors and their macrocyclic derivatives as known optical sensor molecules. Some interesting relationships between quantum yield and structural features were reported. [ABSTRACT FROM AUTHOR]

In the title compound, C27H33NO5, a 3,3,6,6-tetramethyltetrahydroacridine-1,8-dione ring system carries an ethyl acetate substituent on the acridine N atom and an o-hydroxyphenyl ring on the central methine C atom of the dihydropyridine ring. The benzene ring is inclined to the acridine ring system at an angle of 80.45 (7)° and this conformation is stabilized by an intramolecular O--H…O hydrogen bond between the hydroxy substituent on the benzene ring and one of the carbonyl groups of the acridinedione unit. The ester C=O oxygen atom is disordered over major and minor orientations in a 0.777 (9):0.223 (9) ratio and the terminal--CH3 unit of the ethyl side chain is disordered over two sets of sites in a 0.725 (5): 0.275 (5) ratio. In the crystal, C--H…O hydrogen bonds combine to link the molecules into a three-dimensional network. van der Waals H…H contacts contribute the most to the Hirshfeld surface (66.9%) followed by O…H/H…O (22.1%) contacts associated with weak hydrogen bonds. [ABSTRACT FROM AUTHOR]