Xanthene Derivatives Research Articles

Bio‐Based Hybrid Catalysts for the Synthesis of Pharmacologically Active Xanthenes

AbstractWe synthesized an efficient bio‐based nano‐catalyst, – Fe3O4@nano linear dextrin/Sb+5 (Fe3O4@NLD/Sb+5) – from nano linear dextrin and antimony pentachloride via straightforward steps. The nano‐catalyst was used to synthesize solvent‐free 14‐aryl‐14H‐ dibenzo[a, j]xanthene derivatives based on 2‐aminobenzimide and different aldehydes. The synthesized nano‐catalyst bears many critical advantages: nontoxicity, biocompatibility, affordability, easy work‐up method, environmentally friendliness, and high yields, as well as being solvent‐free and operable under green conditions.

Solvent-Free, One-Pot, Multicomponent Synthesis of Xanthene Derivatives

An efficient and environmentally benign one-pot condensation of cyclic diketones, aldehydes and naphthols was achieved with 1,4-diazabicyclo[2-2-2]octane supported on Amberlyst-15 as a novel catalyst, producing a variety of benzoxanthenones in good to excellent yields. The advantages of this multicomponent reaction include the use of a heterogeneous catalyst, solventless conditions and a simple methodology that is atom-economical and results in low E-factor values. A total of 17 xanthene derivatives, including two novel molecules, were synthesized and then characterized. Aromatic aldehydes carrying an electron-withdrawing group provided excellent yields. Appreciable results were also obtained using aliphatic aldehydes. The catalyst is fully recyclable and can be reused up to six times.

Development of ZnO/PANI/Ag nanocomposite for synthesis of bioactive xanthene‐1,8(2H)‐dione derivatives

In this work, we have developed an effective and novel heterogeneous ZnO/polyaniline (PANI)/Ag nanocomposite, which was characterized by X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FTIR), energy‐dispersive X‐ray spectroscopy (EDAX), X‐ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM). ZnO nanoparticles were prepared by coprecipitation method at low temperature. The obtained ZnO nanoparticles were used for its surface functionalization with PANI‐supported silver nanoparticles via self‐assembly redox polymerization method. Further, the high catalytic activity of ZnO/PANI/Ag nanocatalyst was investigated for the one‐pot synthesis of xanthene derivatives via condensation of 5,5‐dimethylcyclohexane‐1,3‐dione and different aromatic aldehydes under neat reaction condition. The advantage of this current work includes short reaction time, easy work‐up, solvent free, high product yield, good chemistry metrices values, easily recoverable and reusable catalyst up to six cycles.

NIR-II xanthene dyes with structure-inherent bacterial targeting for efficient photothermal and broad-spectrum antibacterial therapy.

Development of novel broad-spectrum sterilization is an efficient strategy that can overcome drug resistance and avoid antibiotics abuse toward bacterial-infected diseases. Photothermal therapy (PTT) in the second near-infrared (NIR-II) therapeutic window with an increased tissue penetration and elevated maximal permissible exposure has attracted considerable attention in antibacterial applications. However, the lack of bacterial-targeted photothermal agents limits their further development. Herein, we developed three xanthene derivatives (CNs) with intense light harvesting ability around 1180 nm. Their bulky planar conformations facilitated the formation of H-aggregates with outstanding photothermal conversion ability and good photostability in the NIR-II therapeutic bio window. By manipulating side chains of CNs, their liposomes exhibited different surface charges, ranging from negative to positive. Remarkably, the intermolecular hydrogen bonding of CN3 dimer drived the positively charged xanthene skeleton exposed to the periphery, which endowed it natural bacterial targeting potency. Therefore, CN3 possessed a good NIR-II photothermal and broad-spectrum sterilization against Gram-positive and Gram-negative bacteria. The photothermal antibacterial activities for S. aureus and E. coli were 99.4% and 99.2%, respectively, promoting significant wound healing in bacteria-infected mice with superior biocompatibility. This structure-inherent bacterial targeting strategy as a proof-of-concept shows an efficient broad-spectrum bacterial inactivation, indicating more encouraging NIR-II photothermal antibacterial therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT) in the second near-infrared region (NIR-II, 1000-1700 nm) enables the treatment of deep inflammation more satisfactory due to higher tissue penetration depth. In this work, three new NIR-II xanthene derivatives (CNs) with intense light harvesting ability around 1180 nm were developed. CNs showed typical H-aggregated performance with bulky planar conformations and outstanding photothermal conversion ability. Density functional theory calculations revealed that the intermolecular hydrogen bonding of CN3 dimer drived the exposure of positively charged xanthene skeleton to periphery of dimer. Therefore, CN3 NPs possessed natural bacterial targeting potency and excellent NIR-II photothermal and broad-spectrum sterilization, and so as to significantly promote the wound healing of Gram-positive / negative bacteria infected mice.

Brønsted Acid Catalyzed Friedel-Crafts Alkylation of Naphthols with In Situ Generated Naphthol-Derived ortho-Quinone Methides: Synthesis of Chiral and Achiral Xanthene Derivatives.

We disclose herein an enantioselective protocol for the Brønsted acid catalyzed addition of naphthols to in situ generated naphthol-derived ortho-quinone methides (o-QMs) followed by intramolecular cyclization, which delivers substituted chiral xanthene derivatives, in a one-pot reaction sequence under mild conditions. This process serves to convert naphthol-derived ortho-hydroxyl benzylic alcohols into reactive naphthol-derived o-QMs using a chiral phosphoric acid (CPA) catalyst. Moreover, it is helpful in controlling the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding followed by intramolecular cyclization. Additionally, for the first time, we observe a Brønsted acid catalyzed C(sp2)-C(sp3) bond cleavage of naphthol-derived ortho-hydroxyl benzylic alcohols for the synthesis of achiral xanthene (sigma plane containing) derivatives in good to excellent yields.

Design, fabrication and characterization of magnetic nickel copper ferrite nanocomposites and their application as a reusable nanocatalyst for sonochemical synthesis of 14-aryl-14-H-dibenzo[a,j]xanthene derivatives

Design, fabrication and characterization of magnetic nickel copper ferrite nanocomposites and their application as a reusable nanocatalyst for sonochemical synthesis of 14-aryl-14-H-dibenzo[a,j]xanthene derivatives

Photophysical investigation into room-temperature emission from xanthene derivatives.

The photophysical consequences of replacing the nitrogen heteroatom in phenothiazine with methylene are investigated for both solutions and crystalline solids. We analysed the excited state dynamics of four xanthene derivatives and observed an anomalous fluorescence from an energy level higher than the S1 state with lifetimes between 2.8 ns and 5.8 ns in solution and as solids. Additionally, the solid-state xanthene derivatives exhibited long-lived emission consistent with a triplet excited state, displaying millisecond lifetimes that ranged from 0.1 ms to 3.4 ms at ambient temperature in air. Our findings were supported by optical studies, crystallographic structural analyses, and DFT computations, which corroborated the photophysical measurements. It was concluded that the presence of the nitrogen atom in phenothiazine is crucial for achieving ultra-long emission lifetimes and that these results contribute to a deeper understanding of excited state dynamics which have potential implications for applications, such as display technologies, anticounterfeiting technologies, and sensors.

Synthesis and biological evaluation of 9-aryl-1,8-dioxo-octahydroxanthene derivatives as antileishmanial agents

In the current research, we designed and synthesized various derivatives of 9-aryl-1,8-dioxo-octahydroxanthene using flow chemistry technique and explored in vitro study for antileishmanial activity against the promastigote as well as amastigote form of Leishmania donovani strain. Among the tested analogs by various cell viability assays, six compounds exhibited antileishmanial activity with IC50 value ranging from 24.81 to 52.33 μM. Further, the functional dynamics study sheds light on the structural role of various functional groups presents in the xanthene derivatives for defining the actual antileishmanial activity. Molecular dynamics simulation data presented here attempts to provide a structural and mechanistic explanation of threonine synthase inhibition against Leishmania donovani by xanthene derivatives. Described structure–activity-relation advocates for further modification of the xanthene scaffolds for the accomplishment of challenging antileishmanial drugs.

Acid-catalysed intramolecular Friedel-Crafts annulation of hetero-atom-functionalized para-quinone methides: access to O-, S- and N-based heterocycles.

We describe here an acid-mediated one-pot approach to access substituted xanthene and thioxanthane derivatives from ortho-heteroaryl phenyl-substituted para-quinone methides via 1,6 intramolecular arylation. The scope of this work was further elaborated to the synthesis of 10H-indolo[1,2-a]indole-based heterocyclic systems using indole based para-quinone methides.

Assessing the pharmacological potential of selected xanthene derivatives

A convenient and efficient approach toward the synthesis of seven aromatically substituted xanthendiones 1?7 and one structurally-related xanthenone 8 through condensation of dimedone and the appropriate aromatic aldehyde is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, 1H-, 13C-NMR and UV?Vis spectroscopic methods. The relationship between the chemical structure and pharmacological activity was determined empirically using appropriate software packages and in vitro using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method. The results of in silico prediction suggested that all investigated compounds possess good oral bioavailability. The results of the ABTS assay indicate that five compounds possess the ability to scavenge the ABTS?+ radical cation. Based on the comparison of the IC50 values, the activity of the compounds was found to be as follows: 6 > 1 > 7 > 2 > 8. The effects of solvent dipolarity/ polarizability and solute solvent?hydrogen-bonding interactions on the shifts of the absorption maxima were rationalized by means of the linear solvation energy relationship concepts proposed by Kamlet?Taft and Catal?n.

Visible light irradiated photocatalytic C(sp3)-H phosphorylation of xanthenes and 9,10-dihydroacridines with P(O)-H compounds.

Photocatalytic C(sp3)-H phosphorylation of xanthenes and 9,10-dihydroacridines with P(O)-H compounds under the irradiation of 18 W blue LEDs at room temperature using fluorescein as the photocatalyst and molecular oxygen (O2) as the sole oxidant has been achieved. The newly developed reaction provides direct access to 9-phosphorylated xanthene derivatives with good functional group compatibility.

Continuous-flow Fe-zeolite-catalyzed temperature-directed synthesis of bioactive tetraketones and xanthenes using epoxides and cyclic-1,3-diketones via a Meinwald rearrangement

The continuous flow Fe-zeolite-catalyzed direct transformation of epoxides and cyclic-1,3-diketones to tetraketones and their subsequent catalytic cyclization to xanthene derivatives are described.

Xanthene Derivatives Targeting Bacterial Efflux Pumps, Quorum-Sensing, and Biofilm Formation

The rise of multidrug resistance (MDR) bacteria in nosocomial and health-care institutions is widespread and is currently recognized as a major medical challenge. Mechanisms of bacterial resistance, namely, quorum sensing (QS), biofilm formation, and efflux pumps, have been identified as critical biological processes in MDR bacteria. Following previous reports on the activity of phenothiazines against mechanisms of bacterial resistance, in this work we focus on the synthesis of xanthene derivatives aiming to discover phenothiazine bioisosteres with improved activity. Four compounds were obtained from the conjugation of xanthydrol with sulfonamides and aniline and were fully characterized. Their antibacterial activity was assessed considering their minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative strains, efflux pump inhibition, influence on biofilm formation and quorum-sensing (QS) inhibition. It was observed that the MIC of all the tested compounds was above 64 µg/mL The four 9-xanthenyl derivatives obtained, particularly the xanthene sulfonamide derivatives 3b and 3c, showed promising results on QS inhibition with a reduction of pigment production of 48 and 41 mm, and on biofilm formation with a reduction of 78 and 79%, respectively.

Synthesis of 14H-dibenzoxanthenes in green media using Sn(II)/nano silica as an efficient catalyst.

In this project, Sn(II)/nano silica has been prepared using a simple deposition of SnCl2.2.H2O on nano-silica. The prepared catalyst has been used as a green and reusable catalyst for synthesis of 14H-dibenzoxanthenes through a one-pot condensation reaction of β-naphthol with various aliphatic and aromatic aldehydes. Several xanthene derivatives have been synthesized using ethanol as the solvent, 10mol percent of the catalyst, at reflux condition, in 3h, and by 48%-94% yield. The structures of the synthesized derivatives are confirmed by melting point, FT-IR, 13C-NMR, and 1H-NMR analyses. Additionally, the nanocatalyst composition was confirmed by SEM, EDX, FT-IR, and XRD.

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst, and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions.

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene–aldehyde compound. Different xanthene concentrations (ca. 0.1–2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds’ adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.

Penicixanthene E, a new xanthene isolated from a mangrove-derived fungus Penicillium sp.

One new xanthene derivative, named penicixanthene E (1), together with one known compound 2, was isolated from the EtOAc extract of the endophytic fungus Penicillium sp. GXIMD 03101, which was identified from the mangrove Acanthus ilicifolius L. collected in the South China Sea. The structure of 1 was elucidated by 1D and 2D NMR spectral interpretation and HREISMS data. The absolute configurations of C-9 and C-11 in 1 were proposed based on electronic circular dichroism (ECD), but the configuration at C-3 in 1 was unassigned. Compound 1 represents a xanthene derivative that was first reported, in which carbon-carbon double bond has been reduced. The cytotoxic activities of all compounds were evaluated, the result showed that compound 1 has weak activity against pancreatic cancer SW1990.

Diastereoselective and Synergistic Gold‐Catalyzed Bispropargylation of Xanthones and Thioxanthones: An Access to Xanthene Derivatives

AbstractA gold‐catalyzed bispropargylation of xanthone derivatives is described. The use of propargylsilanes permits to achieve a deoxygenative bispropargylation through a double catalytic addition of the corresponding allenylgold intermediate to the synergistically activated carbonyl moiety. This methodology works in a diastereoselective manner either with xanthone or thioxanthone derivatives. Monopropargylated xanthydrol silyl ethers were isolated as reaction intermediates and these species could be transformed into symmetrical and non‐symmetrical bispropargylated xanthenes. The formation of non‐symmetrical bispropargylated xanthenes could also be achieved through an one‐pot procedure. Finally, other interesting structures, such as propargylxanthylidenes, propargylxanthenes and bispropargylated xanthenes replacing the silicon moiety, were accessible following different one‐pot synthetic methodologies. In addition, bispropargylated xanthenes could perform a carbonylative [2+2+1] formal cycloaddition.magnified image

Exploring the Role of Photosensitizer in Guanine Functionalization of Single-Wall Carbon Nanotubes

Single-walled carbon nanotubes (SWCNTs) have attracted a great deal of attention during the past two decades because of their unique optoelectronic properties and their potential applications in biomedical theranostics as well as nanoelectronics. It was recently discovered that it is possible to spatially modulate the exciton band gap of carbon nanotubes through a process known as guanine functionalization. In this reaction, the guanine nucleotides of an ssDNA strand wrapping a nanotube become covalently bonded to sidewall carbon atoms upon exposure to singlet oxygen.1 In the original work, the authors used xanthene derivatives such as rose bengal and erythrosine B as photosensitizers in order to generate singlet oxygen. It was assumed that this process was an independent step that did not involve the nanotube. However, we have found that rose bengal has a strong tendency to form a charge transfer complex with SWCNTs, and these complexes appear to be essential in the functionalization reaction.We have studied the complexation through a spectroscopic study of SWCNT fluorescence quenching and the appearance of a charge transfer absorption feature near 600 nm. Both are interpreted as results of nanotube p-doping when the dye adsorbs to the sidewall. We also observe that the charge transfer complex formation accelerates when the rose bengal is optically excited, apparently proceeding through the dye’s triplet state. A correlation between extent of guanine functionalization and the concentration of charge transfer complexes is found as ionic strength is changed. We infer that the functionalization reaction is enabled by adsorbed photosensitizers. Interestingly, the extent of SWCNT fluorescence quenching by rose bengal is found to vary significantly with (n,m) structure. This quenching effect therefore provides a simple approach to monitor structure-specific interactions between SWCNTs and coatings, including ssDNA and conventional ionic surfactants.(1) Zheng, Y.; Bachilo, S. M.; Weisman, R. B. Controlled Patterning of Carbon Nanotube Energy Levels by Covalent DNA Functionalization. ACS Nano 13, 5222 (2019). https://doi.org/10.1021/acsnano.9b03488.

BioMOF-Mn: An Antimicrobial Agent and an Efficient Nanocatalyst for Domino One-Pot Preparation of Xanthene Derivatives.

In this paper, a new Mn-based metal-organic framework [UoB-6] was obtained via a one-step ultrasonic irradiation method with the ligand (H2bdda: 4,4'-(1,4-phenylenebis(azaneylylidene))bis(methaneylylidene))dibenzoic acid. The structural integrity of the synthesized BioMOF-Mn was corroborated by FT-IR, EDX, ICP, XRD, TEM, DLS, FESEM, and BET-BJH analyses. The aerobic oxidative domino reaction of benzyl alcohols or aldehydes with dimedone derivatives was performed in the presence of the UoB-6 catalyst to produce xanthene derivatives in good yields. Hot filtration and Hg poisoning tests proved the heterogeneous nature of the catalyst. Novel synthesized xanthene-based bis-aldehydes were introduced as potent HDAC1 inhibitors according to molecular docking calculations. Finally, the inhibitory activities of Mn-MOF nanoparticles were evaluated on Escherichia coli and Candida albicans. The MIC, MBC, and MFC values were determined from 2048 to 4096 μg·mL-1 according to antimicrobial susceptibility testing methods. The inhibitory effects of antimicrobial agents can be exacerbated when loaded on BioMOFs.

Controlled Synthesis of Luminescent Xanthene Dyes and Use of Ionic Liquid in Thermochromic Reaction.

In this study, we demonstrate six novel xanthene derivatives and their spectroscopic and chemical properties. The presented synthesis examination allowed us to obtain two different compounds during one step, with open and closed lactone rings substituted with different length alkyl chains. Increasing the reaction efficiency to 77% was obtained using the microwave-assisted method. Moreover, the modification of O-alkylation synthesis in an ecofriendly way using a ball mill led to achieving exclusively one opened ring product. All of the synthesized compounds showed different spectroscopic behaviors in comparison with the different organic dyes; the typical concentration quenching of luminescence was not observed. The relationship between the length of the alkyl chain and the time of luminescence decay is presented. Synthetized closed forms of dyes turned out to be promising leuco dyes. For the first time, an ionic liquid was used as a developer of synthesized xanthene derivatives (as leuco dyes), which led to obtaining an irreversible thermochromic marker.