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Comprehensive Summary: A visible‐light‐induced decarboxylative radical cascade cyclization reaction between N‐(2‐cyanoaryl)‐acrylamides and alkyl N‐(acyloxy)phthalimide (NHPI esters) for the construction of phenanthridine derivatives has been developed. This approach utilizes lithium iodide (LiI) and triphenylphosphine (PPh3) as the redox catalysts and the alkyl radical is produced through the photoactivation of the electron donor‐acceptor (EDA) complex. A series of primary, secondary, and tertiary alkyl‐substituted phenanthridines are prepared in up to 82% yield without transition‐metal catalysts, chemical oxidants, or metal‐/organic dye‐based photocatalysts. [ABSTRACT FROM AUTHOR]

Phenanthridines are prevalent core in several natural products and staining agents that could be assembled in various manners. However, to our knowledge, the skeletal editing of azides via solid‐state melt rearrangement (SSMR) without catalysts, bases, and additives to access phenanthridines is not reported in the literature. Herein, we report solvent‐free and catalyst‐free thermolytic SSMR of azidofluorenes to phenanthridine derivatives. This protocol successfully demonstrates 21 examples of phenanthridines by SSMR of symmetrical and unsymmetrical azidofluorenes in good to excellent yields. The green metrics of the developed protocol are in good accordance with ideal green chemistry metrics. [ABSTRACT FROM AUTHOR]

Solar‐driven H2O2 production via the oxygen reduction reaction (ORR) and water oxidation reaction (WOR) dual channels is green and sustainable but severely restricted by the sluggish reaction kinetics. Constructing intriguing photocatalysts with effective active centers is a shortcut to breaking the kinetic bottleneck with great significance. Herein, we synthesize two novel neutral phenanthridine‐based covalent organic frameworks (PD‐COF1 and PD‐COF2) for photosynthesizing H2O2. Compared to the no phenanthridine counterpart (AN‐COF), the H2O2 photosynthetic activities of PD‐COF1 and PD‐COF2 are markedly boosted. In air and pure water without sacrificial agents, under Xe lamp and natural sunlight, the H2O2 photogeneration rate of PD‐COF2 is 6103 and 3646 μmol g−1 h−1, respectively. Further experimental and theoretical inspections demonstrate that introducing phenanthridine units into COFs smoothly modulates the charge carrier dynamics and thermodynamically favors the generation of crucial OOH* and OH* intermediates in the ORR and WOR paths, respectively. Additionally, this is the first time the neutral phenanthridine moiety serves as the photooxidation unit for 2e− WOR towards H2O2 photoproduction. The current work sheds light on exploring novel catalytic centers for high‐performance H2O2 evolution. [ABSTRACT FROM AUTHOR]

A nonlinear two-photon excited fluorescence photocatalytic system was constructed for the first time by integrating (ZnO)1−x(GaN)x photocatalyst and a fluorescence solution of phenanthridine derivatives. This work offers a strategy for increasing the photocatalytic solar spectral utilization rate and boosting the expectation for photocatalytic solar-to-hydrogen efficiencies. [ABSTRACT FROM AUTHOR]

Zanthoxylum simulans Hance, commonly known as Sichuan pepper, is a well-known medicinal plant recognized for its potential as a source of bioactive specialized metabolites. As part of our interest in natural antifungal compounds, the present study describes the discovery of an unreported N-alcoxycarbonylbenzo[c]phenanthridinium salt, N-methoxycarbonyl-9,12-dimethoxy-norchelerythrine 1 (a type-III benzo[c]phenanthridine), isolated from Z. simulans seedlings, which were propagated under controlled greenhouse conditions. Six-month seedlings were harvested and subjected to cold acid–base extraction. Chromatographic techniques achieved the isolation of 1 from raw alkaloid extract. The structural elucidation of 1 was accomplished through comprehensive spectroscopic analysis, including nuclear magnetic resonance and high-resolution mass spectrometry. Fusarium oxysporum, a fungal pathogen responsible for substantial agricultural losses, was exposed to different concentrations of the novel compound, exhibiting potent antifungal efficacy (IC50 < 3 µM) and fungicide effects. These findings highlight the potential of benzophenanthridines as antifungal leads and underscore the importance of exploring natural products for agricultural applications. [ABSTRACT FROM AUTHOR]

Herein, we report a copper‐catalyzed intramolecular benzylic C(sp3)−H oxidation of unprotected aniline derivatives under aerobic conditions, which enables the preparation of phenanthridine compounds. To the best of our knowledge, this is the pioneering reaction of dehydrogenative C(sp3)−N bond formation from unprotected anilines under a Cu/O2 system. Notably, various anilines possessing alkyl, methoxy, halogen (fluoride, chloride, bromide, and iodide), trifluoromethyl, trifluoromethoxy, cyano, ester, and acetal groups can also participate in the reaction. [ABSTRACT FROM AUTHOR]

This article provides an overview of photoredox-catalyzed C(sp2)–H bond functionalization reactions, which use low-energy photons to enable reactions under mild conditions. It discusses the contributions of researchers in advancing the field and explores the potential of using organic photocatalysts. The article focuses on the author's group's work in utilizing these reactions for C–H bond functionalizations, specifically in the context of enamides. The researchers explored various reactions, including the functionalization of enamide β-C(sp2)-H bonds, phosphorylation of alkenyl C(sp2)-H bonds, and bromination and alkylation of (hetero)arene C(sp2)-H bonds. These reactions have applications in the synthesis of natural products and pharmaceuticals, and further research is needed to develop new transformations and expand their applications. [Extracted from the article]

Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter's crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M−1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals. [ABSTRACT FROM AUTHOR]

Convenient access to 6‐alkylsulfonylmethyl phenanthridines has been demonstrated both under non‐catalytic thermal and visible‐light photoredox‐catalyzed conditions. A cascade of radical cyclization is triggered by the exposure of biphenyl vinyl azides to the in‐situ generated alkyl sulfonyl radicals from 4‐substituted Hanztsch esters in the presence of an SO2 surrogate. Transition metal‐free, mild reaction conditions, and broad substrate scope constitute some of the highlights of the approach. Also, the synthetic utility of the accessed 6‐alkylsulfonylmethyl phenanthridines has been demonstrated. [ABSTRACT FROM AUTHOR]

[Display omitted] An unprecedented transition metal-free visible light-induced autocatalytic intramolecular C–Hal (Hal = Cl, Br, I)/C–H bond activation leading to the formation of a new C–C bond between spatially converged benzene rings has been disclosed. In fact, irradiation of 5,6-diaryl-1 H -pyrrolo- [3,4- d ]pyrimidine-2,4-diones with 395 nm LED light at room temperature promotes their cyclization to pyrimido[5′,4′:3,4]- pyrrolo[1,2- f ]phenanthridine-12,14(11 H ,13 H)-diones in high yields, with the halogen nature being insignificant. [ABSTRACT FROM AUTHOR]

This article discusses the development of sustainable synthetic methods for the production of Active Pharmaceutical Ingredients (APIs) and other materials. The focus is on the synthesis of benzimidazole-fused phenanthridines, a class of heterocyclic compounds with various applications. The authors describe a new intramolecular radical C-N coupling reaction mediated by N-iodosuccinimide (NIS) in trifluoroethanol (TFE), which allows for the formation of these compounds in high yields. The document provides detailed procedures for the synthesis and characterization of specific compounds using this method, including their physical properties and spectroscopic data. The supporting information for the article is available online and includes control experiments, characterization data, and NMR spectra. [Extracted from the article]

The cyclization of 5,6-diarylpyrrolo[3,4-d]pyrimidine-2,4-diones containing a halogen atom in the ortho-position of one of the aryl rings, proceeding as intramolecular C–H arylation catalyzed by Ru(II) complexes, was studied. It was found that complexes Ru(NHC)(cymene)Cl2, where NHC = IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], IMes [1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene], and their derivatives containing substituents at positions 4 and 5 of the imidazole ring, exhibit high catalytic activity. Based on the reaction studied, new representatives of pyrimido[5',4':3,4]pyrrolo[1,2-f]phenanthridine were obtained. [ABSTRACT FROM AUTHOR]

The development of transition metal-free 2-isocyanobiaryl-based reactions has received much attention due to the widespread presence of phenanthidine frameworks as products in pharmacological chemistry and materials science. This review article focuses on the achievements from 2013 until now in various metal-free catalyzed reactions and discusses challenging mechanisms and features of the transformations. Isocyanides, in particular, 2-isocyanobiaryls have attracted extensive attention, due to their distinctive properties in the field of synthetic chemistry. The preparation of various phenanthridine-containing compounds from these scaffolds has been investigated in the two last decades. Hence, the synthesis of valuable bioactive phenanthridines via coupling reaction/cyclization of 2-isocyanobiaryls with many kinds of organic compounds is highlighted in this review. [ABSTRACT FROM AUTHOR]

A solvent-free three-component reaction between phenanthridine, acetylenic ketones, and bis(polyfluoroalkyl) H-phosphonates proceeded at room temperature for 20–24 h to stereoselectively give the corresponding E-N-acylethenyl-6-bis(polyfluoroalkyl)phosphoryl-5,6-dihydrophenanthridines in up to 82% yield. [ABSTRACT FROM AUTHOR]

The C═N bond is a critical structural piece of many N-donor ligand scaffolds and is central to the properties and reactivity of important coordination complexes. For example, C═N units play a key role in the "redox non-innocence" of α-diimine complexes and in making charge-transfer excited-state character available to complexes of N-heterocyclic ligands such as bipyridine. In N-heterocycles like pyridine, benzannulation can be used to extend the conjugated C═N-containing π-system to quinoline (2,3-benzopyridine) to acridine (2,3-benzoquinoline). This stabilizes the lowest unoccupied molecular orbital of the molecule and boosts its electron-accepting properties, but the position of the benzannulation matters. For example, phenanthridine (3,4-benzoquinoline), an asymmetric isomer of acridine, bears a similarly electronically accessible extended π-system but with a more chemically isolated "imine-like" C═N moiety. This award paper presents an overview of our work investigating the impact of such site-selective benzannulation on the chemistry and properties of phenanthridine as a molecule and ligand. [ABSTRACT FROM AUTHOR]

8,9-Dimethoxyphenanthridine derivatives, as potential antitumor drugs, need modification to improve their biocompatibility and water solubility. Reported here is a strategy to access C-heteroaryl glycosides by photoredox catalysis. C6-glycosylated phenanthridine derivatives are synthesized from biphenyl isocyanides and glycosyl bromides. The reaction conditions are mild and widely applicable, with anomeric α selectivity and good functional group tolerance. [ABSTRACT FROM AUTHOR]

Pt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors (RLPtCl) exhibit a promising in vitro therapeutic index compared with phenanthriplatin, a leading preclinical anticancer complex containing a monodentate phenanthridine ligand. Here, we report evidence for non-specific interactions of CF3LPtCl with DNA through intercalation-mediated turn-on luminescence in O2-saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of CF3LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of CF3LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate that CF3LPtCl efficiently mediates the generation of singlet dioxygen (1O2), highlighting the potential of RLPtCl in photodynamic therapy. [ABSTRACT FROM AUTHOR]

Phenanthridines are a privileged heterocyclic compound that exists in many natural products and has been known to exhibit a variety of pharmacological properties. In the last few decades, an incredible development has taken place to synthesise this scaffold. In this regard, 2‐isocyanobiphenyl has become one of the most exploited substrates that allow the direct formation of phenanthridine derivatives under various novel and conventional methods. The present review provides an overview of synthetic approaches for the preparation of phenanthridine, and their derivatives form 2‐isocyanobiphenyls′′. [ABSTRACT FROM AUTHOR]

Targeting thioredoxin reductase (TXNRD) with low-weight molecules is emerging as a high-efficacy anti-cancer strategy in chemotherapy. Sanguinarine has been reported to inhibit the activity of TXNRD1, indicating that benzophenanthridine alkaloid is a fascinating chemical entity in the field of TXNRD1 inhibitors. In this study, the inhibition of three benzophenanthridine alkaloids, including chelerythrine, sanguinarine, and nitidine, on recombinant TXNRD1 was investigated, and their anti-cancer mechanisms were revealed using three gastric cancer cell lines. Chelerythrine and sanguinarine are more potent inhibitors of TXNRD1 than nitidine, and the inhibitory effects take place in a dose- and time-dependent manner. Site-directed mutagenesis of TXNRD1 and in vitro inhibition analysis proved that chelerythrine or sanguinarine is primarily bound to the Sec498 residue of the enzyme, but the neighboring Cys497 and remaining N-terminal redox-active cysteines could also be modified after the conjugation of Sec498. With high similarity to sanguinarine, chelerythrine exhibited cytotoxic effects on multiple gastric cancer cell lines and suppressed the proliferation of tumor spheroids derived from NCI-N87 cells. Chelerythrine elevated cellular levels of reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress. Moreover, the ROS induced by chelerythrine could be completely suppressed by the addition of N-acetyl-L-cysteine (NAC), and the same is true for sanguinarine. Notably, Nec-1, an RIPK1 inhibitor, rescued the chelerythrine-induced rapid cell death, indicating that chelerythrine triggers necroptosis in gastric cancer cells. Taken together, this study demonstrates that chelerythrine is a novel inhibitor of TXNRD1 by targeting Sec498 and possessing high anti-tumor properties on multiple gastric cancer cell lines by eliciting necroptosis. [ABSTRACT FROM AUTHOR]

Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of papaveraceae, corydalis, and rutaceae. Biological activities and clinical studies have shown that benzophenanthridine alkaloids have inhibitory effects on many cancers. Considering that the anticancer activities and mechanisms of many natural benzophenanthridine alkaloids have been discovered in succession, the purpose of this paper is to review the anticancer effects of benzophenanthridine alkaloids and explore the application potential of these natural products in the development of antitumor drugs. A literature survey was carried out using Scopus, Pubmed, Reaxys, and Google Scholar databases. This review summarizes and analyzes the current status of research on the antitumor activity and antitumor mechanism of natural products of benzophenanthridine from different sources. The research progress of the antitumor activity of natural products of benzophenanthridine from 1983 to 2023 was reviewed. The antitumor activities of 90 natural products of benzophenanthridine and their related analogues were summarized, and the results directly or indirectly showed that natural products of benzophenanthridine had the effects of antidrug-resistant tumor cell lines, antitumor stem cells, and inducing ferroptosis. In conclusion, benzophenanthridine alkaloids have inhibitory effects on a variety of cancers and have the potential to counteract tumor resistance, and they have great application potential in the development of antitumor drugs. [ABSTRACT FROM AUTHOR]

Two novel conjugate molecules were designed: pyrene and phenanthridine-amino acid units with a different linker length between the aromatic fragments. Molecular modelling combined with spectrophotometric experiments revealed that in neutral and acidic buffered water solutions conjugates predominantly exist in intramolecularly stacked conformations because of the π–π stacking interaction between pyrene and phenanthridine moieties. The investigated systems exhibited a pH-dependent excimer formation that is significantly red-shifted relative to the pyrene and phenanthridine fluorescence. While the conjugate with a short linker showed negligible spectrophotometric changes due to the polynucleotide addition, the conjugate with a longer and more flexible linker exhibited a micromolar and submicromolar binding affinity for ds-polynucleotides and inactivated a mutant of dipeptidyl peptidase enzyme E451A. Confocal microscopy revealed that the conjugate with the longer linker entered the HeLa cell membranes and blue fluorescence was visualized as the dye accumulated in the cell membrane.

Treatment of 2‐(2‐bromoaryl)‐ and 2‐(2‐bromovinyl)benzimidazoles with cyclohexane‐1,3‐diones in DMF in the presence of reusable Fe3O4@SiO2@MOF‐199 along with L‐proline and Cs2CO3 afforded 2,3‐dihydrobenzo[4,5]imidazo[1,2‐f]phenanthridin‐4(1H)‐ones and 2,3‐dihydrobenzo[4,5]imidazo[1,2‐a]quinolin‐4(1H)‐ones, respectively, in moderate to good yields. Such C(sp2)−C coupled and cyclized scaffolds were aromatized to benzo[4,5]imidazo[1,2‐f]phenanthridines and benzo[4,5]imidazo[1,2‐a]quinolines in good yields by a one‐pot sequential treatment with NaBH4, POCl3/pyridine, and DDQ. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) with precise designable structures are becoming popular semiconductor materials for photocatalytic applications. In this study, a hydrazone-linked COFs (TFPT-ODH) material was constructed from the reversible polycondensation of 2,4,6-tris(4-formylphenyl)-1,3,5-triazine with oxalohydrazide. Thanks to the bottom-up strategy, the as-prepared TFPT-ODH exhibited satisfactory crystallinity, high thermal and chemical stability. The benefit of the combined effects of narrow band gap and efficient separation of photogenerated carriers, the photofunctional TFPT-ODH further demonstrated outstanding photocatalytic activity, stability, and recyclability in the photocatalytic cyclization reactions of 2-isocyanodiaryl compounds with phenylhydrazine. The photocatalytic mechanism for the photocyclization approach to phenylphenanthridines was proposed based on experimental data and spectrum techniques. Our work also demonstrates application in developing COFs-based photocatalysts for the photocatalytic cyclization of bioactive PAHs derivatives. [ABSTRACT FROM AUTHOR]

The precise activation of C–H bonds will eventually provide chemists with transformative methods to access complex molecular architectures. Current approaches to selective C–H activation relying on directing groups are effective for the generation of five-membered, six-membered and even larger ring metallacycles but show narrow applicability to generate three- and four-membered rings bearing high ring strain. Furthermore, the identification of distinct small intermediates remains unsolved. Here, we developed a strategy to control the size of strained metallacycles in the rhodium-catalysed C−H activation of aza-arenes and applied this discovery to tunably incorporate the alkynes into their azine and benzene skeletons. By merging the rhodium catalyst with a bipyridine-type ligand, a three-membered metallacycle was obtained in the catalytic cycle, while utilizing an NHC ligand favours the generation of the four-membered metallacycle. The generality of this method was demonstrated with a range of aza-arenes, such as quinoline, benzo[f]quinolone, phenanthridine, 4,7-phenanthroline, 1,7-phenanthroline and acridine. Mechanistic studies revealed the origin of the ligand-controlled regiodivergence in the strained metallacycles. The ability to selectively functionalize different sites on simple starting materials is a constant pursuit in organic chemistry. Here, the authors report a catalytic system to regioselectively differentiate and alkynylate different positions on azaarenes via rhodium catalysis. [ABSTRACT FROM AUTHOR]

A mild, efficient, photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity in metal-free conditions, using low-cost Rose Bengal as a catalyst and sustainable air as a terminal oxidant at room temperature and providing the desired products in moderate to good yields. [ABSTRACT FROM AUTHOR]

A procedure has been developed for the direct Csp2–H functionalization of phenanthridine with a 1H-benzotriazole residue in the presence of Selectfluor® to build up Csp2–N bond. The procedure makes it possible to synthesize 6-(1H-benzotriazol-1-yl)phenanthridine in one step using commercially available starting materials and reagents. The product is an important substrate for further chemical transformations. [ABSTRACT FROM AUTHOR]

Carbon‐carbon bond formation in the phenanthridine 7‐position was achieved by microwave‐assisted Claisen rearrangement of 8‐allyloxyphenanthridines. The reactions took place with excellent regioselectivity and high chemical yields. If the 7‐position was substituted, rearrangement to C‐9 took place, but the reaction occurred less readily. Rearrangements of 8‐allyloxy‐5,6‐dihydrophenanthridines (phenanthridines with a saturated B‐ring) gave a mixture of 7‐ and 9‐substituted products. The experimental results were supported by DFT (density functional theory) calculations. [ABSTRACT FROM AUTHOR]

Due to the increasing need for fluorine-containing drugs, the synthesis of organofluorine scaffolds has become a highly researched area of synthetic organic chemistry. The introduction of the trifluoromethyl group into the structure of an organic molecule has considerable potential and several advantages concerning the characteristics of the fluorinated pharmaceuticals. The incorporation of a CF3 group at multiple bonds containing a nitrogen heteroatom is a relatively new field and currently it is an expanding area of synthetic chemistry. This short review summarizes, for the first time, recent developments in trifluoromethylation reactions of isonitriles. 1 Introduction 2 Trifluoromethylation Reactions of Isonitriles 2.1 Synthesis of Trifluoromethylated Phenanthridine Derivatives 2.2 Synthesis of Trifluoromethylated Quinoline Derivatives 2.3 Synthesis of Trifluoromethylated Isoquinoline Derivatives 2.4 Synthesis of Trifluoromethylated Indole Derivatives 2.5 Synthesis of Trifluoromethylated Pyridine Derivatives 3 Summary and Outlook [ABSTRACT FROM AUTHOR]

An efficient and convenient palladium-catalyzed reductive system by employing sodium hydride as the hydrogen donor and acetic anhydride as an activator has been developed for transfer hydrogenation and acetylation of a wide range of N -heteroarenes including quinoline, phthalazine, quinoxaline, phenazine, phenanthridine, and indole. Moreover, acridine substrates could be directly reduced without the use of acetic anhydride. This protocol provides a simple method for the preparation of various saturated N -heterocycles. [ABSTRACT FROM AUTHOR]

In both of the title compounds, C26H19NO2S2, (I), and C25H19NO2S2, (II), the benzothiophene rings are essentially planar with maximum deviations of 0.026 (1) and -0.016 (1) A ° for the carbon and sulfur atoms in compounds (I) and (II), respectively. In (I), the thiophene ring system is almost orthogonal to the phenyl ring attached to the sulfonyl group, subtending a dihedral angle of 88.1 (1)°, and the dihydropyridine ring adopts a screw-boat conformation. In both compounds, the molecular structure is consolidated by weak C--H· · ·O intramolecular interactions formed by the sulfone oxygen atoms, which generate S(5) ring motifs. In the crystal of II, molecules are linked via C--H· · ·O hydrogen bonds, generating C(7) chains running along the [100] direction. No significant intermolecular interactions are observed in I. [ABSTRACT FROM AUTHOR]

A practical electrochemical Minisci‐type reaction for the synthesis of silylated heterocycles is described. Using N‐hydroxyphthalimide (NHPI) as the hydrogen atom transfer (HAT) catalyst and trialkylsilanes as the silyl radical sources, a wide range of electron‐deficient heterocycles in‐cluding quinoline, quinoxaline, phthalazine, 3,6‐dichloropyridazine, phenanthridine, 6‐chloroimidazo[1,2‐b]pyridazine and coumarin, etc. were easily converted to the corresponding silylated products in 37–83% yields. [ABSTRACT FROM AUTHOR]

An Ag/Au‐catalyzed divergent cascade reaction of alkyne embedded diazoketones with indoles has been described. Preliminary mechanistic studies indicate that the reaction goes through a [4+2]‐cycloaddition of an in situ formed isobenzopyrylium intermediate with indole, followed by a sequential retro‐Michael addition/carbene N−H insertion process to give the benzo[i]phenanthridines products with gold catalysis; whereas a dearomatization/rearomatization sequence occurs favourably when the reaction is catalyzed by a silver catalyst, delivering benzo[b]carbazoles in generally high to excellent yields. Notably, this is a rare example of using indole as the dienophile for cycloaddition with the isobenzopyrylium species, providing a concise and practical approach for the selective construction of N‐doped polycyclic aromatic hydrocarbons (PAHs) with structural diversity and broad functional‐group compatibility. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate a regioselective intramolecular C–N cross-coupling for the synthesis of 14H-quinazolino[3,2-f]phenanthridin-14-one by using 9-mesityl-10-methylacridinium perchlorate as the visible-light (450–470 nm) photocatalyst. The experiments with BHT, TEMPO, and Stern–Volmer quenching studies helped to rationalize a radical pathway via a SET mechanism. [ABSTRACT FROM AUTHOR]

Phenanthridine readily undergoes one-pot N-acylvinylation/C-phosphorylation in the terminal acetylenic ketone—secondary phosphine oxide system at room temperature (acetonitrile, 48–72 h) in the absence of a catalyst to stereoselectively form (E)-N-acylvinyl-6-diorganylphosphoryl-5,6-dihydrophenanthridines in up to 88% preparative yield. Under similar conditions, secondary phosphine sulfides form a difficult-to-separate mixture of N-vinylation/C-phosphorylation products and adducts of phosphine sulfides with acetylenic ketones, while bis(2-phenylethyl)phosphine selenide gives only an adduct with acetylenic ketone in 78% yield. [ABSTRACT FROM AUTHOR]

A new protocol for the direct transformation of secondary amides (N -acyl- o -xenylamines) to phenanthridines under mild conditions is reported. The method features trifluoromethanesulfonic anhydride (Tf2 O)/2-fluoropyridine as the efficient amide activation system and MeCN or CH2 Cl2 as the solvent. For some substrates, MeCN participated in the reaction, which affords a mild access to polysubstituted quinazolines. By employing a Tf2 O/2,4,6-tri- tert -butylpyrimidine (TTBP) combination, the method was extended to an N -formyl- o -xenylamine, which represents a recalcitrant amide substrate type for the dehydrative cyclization reaction. More importantly, a one-pot method was established for the direct and divergent synthesis of four types of phenanthridinoids from o -xenylamines, which features both a tert - N -formyl- o -xenylamine and phenanthridinium salt as key and versatile intermediates. The investigation has resulted in one of the shortest and the most efficient total syntheses of the three natural products trisphaeridine, 5,6-dihydrobicolorine, and N -methylcrinasiadine, and in the formal total syntheses of three other ones: 3-hydroxytrisphaeridine, bicolorine, and zephycandidine A. [ABSTRACT FROM AUTHOR]

The isomerization of iridium(III) complexes with metalated N-heterocyclic carbene (NHC) ligands was studied. The fac isomers of complexes with 1-phenyl-3-methylbenzimidazolin-2-ylidene or 1-phenyl-3-benzylbenzimidazolin-2-ylidene ligands are transformed cleanly into the mer isomers when solutions of the complexes are treated with first HNTf2 and then NEt3. The transformation can be accomplished within a few minutes and the side product (NEt3H)(NTf2) is easy to separate. Spectroscopic and structural analyses indicate that the isomerization proceeds by protonation of the carbene ligand at the metalated phenyl group, accompanied by a fac → mer rearrangement of the carbene donors. An iridium complex with a 1-phenyl-1,2,4-triazolo[4,3-f]phenanthridine-based carbene ligand could not be isomerized under similar conditions, most likely because of its reduced conformational flexibility. [ABSTRACT FROM AUTHOR]

[Display omitted] • For the first time an efficient mechanochemical route was developed for the synthesis of Phenanthridine derivative. • Probe (L) displayed a colorimetric response for Th4+ and a fluorescence OFF response for Th4+ and Hg2+ ions with LODs of 125.5 pM and 1.94 nM. • Colorimetric sequential detection of Cys and His was achieved by L -Hg2+ ensemble. • An open-source, economical, device was built for on-site application. • Colorimetric, ratiometric and fluorometric detection of thorium and mercury in solid state. A new phenanthridine-based multifunctional chemosensor (L), was synthesised via a green synthetic route and characterised using FT-IR, NMR and HRMS analysis. The sensing application of L towards metal ions in both solution and solid-state was studied using UV–vis and fluorescence spectroscopy, which exhibits dual-sensing behaviour for Th4+ and Hg2+ ions with good recyclability. In aqueous acetonitrile, L showed rapid response for the detection of environmental toxic metal ions and has a very low analytical detection limit of 125.5 pM and 1.94 nM for Th4+ and Hg2+ions respectively, which is remarkably lower than the World Health Organization standard. The cation binding property of the L with Th4+ and Hg2+ions was investigated by Job plot, 1H NMR titration, HR-MS and DFT calculation. The in-situ formed ensemble L-Hg2+ was further applied in the naked-eye detection of Cys (Cystine) and His (Histidine) over other common amino acids. The utility of L for real-time detection of Hg2+ and Th4+ ions was explored in various sources of environmental water samples, test paper strips, fingerprint imaging, fluorescent ink and smartphone-assisted sensing techniques, demonstrating the promising on-site visualization of the probe in controlling the toxicity levels in wastewater sources without resorting to expensive instruments. [ABSTRACT FROM AUTHOR]

Abnormal changes in the mitochondrial microenvironment can cause a variety of diseases. Consequently, based on the twisted intramolecular charge transfer (TICT) theory, three hemicyanine fluorescent probes 1a-c were designed and developed by linking the phenanthridine group with different electron donor groups for the dynamic detection of mitochondrial viscosity in this paper. They have the advantages of near-infrared emission, excellent pH stability and viscosity sensitivity. Optical experiments showed that the maximum absorption and emission wavelengths of the probes in different solvents located at 411 − 529 nm and 623 − 684 nm with large Stokes shifts of 133 – 230 nm. In addition, when the viscosity increased from 0.89 cP to 856 cP, their fluorescence intensities in glycerol enhanced by 115-fold, 83-fold and 303-fold compared with water, respectively. The fluorescence intensities of probes showed excellent fit to the Forster Hoffmann equation, and exhibited nearly OFF-ON response to viscosity. Moreover, the probe 1a with good photostability and low cytotoxicity could target mitochondria. It was verified that 1a also could detect variation in mitochondrial viscosity during autophagy by modelling starvation and drug-induced (rapamycin and nystatin) in HeLa cells. Therefore, this study provides a useful probe for the analysis of mitophagy process in HeLa cells by the viscosity variation of mitochondria. [Display omitted] • NIR probes based on the phenanthridine moiety. • Viscosity sensitivity and mitochondria targetability. • Applied to starvation and drug-induced mitochondrial autophagy. [ABSTRACT FROM AUTHOR]

Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties. [Display omitted] • The mutagenicity of the photodegradation product of azilsartan, APP , was evaluated. • QSAR predicted the mutagenicity of APP owing to the 6-aminophenanthridine ring. • However, the in vitro mutagenicity assay revealed that APP was nonmutagenic. • The bulky benzimidazolylmethyl group prevents APP reaction with DNA. [ABSTRACT FROM AUTHOR]

[Display omitted] • The phenanthridine sensor (TPTA) has been developed for the ratiometric detection of SOCl 2 and (COCl) 2. • The sensor TPTA exhibited remarkable anti-interference character over other competing analytes. • The detection process is facilitated by a dual (ESIPT & ICT) process. • TPTA is also applied for the detection of SOCl 2 and (COCl) 2 in liquid and vapor phases. As fatal and potentially accessible reagents, oxalyl and thionyl chloride have become severe concerns for public safety. Therefore, it is essential to develop effective methods to discriminate them. Herein, a new fluorescent sensor, 2-(7,8,13,14-tetrahydrodibenzo[a, i]phenanthridin-5-yl)-4,6-di(thiophen-2-yl)aniline (TPTA) has been designed with the incorporation of classical phenanthridine fluorophore and o -aniline functionality to explore the versatile sensing capabilities. Due to the electrophilic character of chlorocarbonyls, the detection process occurs between TPTA and SOCl 2, (COCl) 2 via nucleophilic addition and subsequent cyclization, which produces new, green emissive cyclic adducts. An inhibited excited-state intramolecular proton transfer (ESIPT) followed by the ICT process endows sensitive ratiometric detection of oxalyl and thionyl chloride with a low limit of detection (4.15 and 2.93 nM). The limit of quantification (LOQ) was calculated to be (9.81 and 13.8 nM for SOCl 2 and (COCl) 2 , which is far lower than the LD 50 values. Because of its reaction-based sensing mechanism, robust selectivity with rapid response time has been achieved towards SOCl 2 and (COCl) 2 (<5 sec) with good stability. The anti-interference properties reveal that the sensor TPTA can efficiently detect SOCl 2 and (COCl) 2 even in the presence of other analytes. Further, the detection mechanism of the TPTA induced by oxychlorides was studied and well supported by NMR, HRMS, and DFT theoretical calculations. Remarkably, smartphone-assisted concentration-dependent test kit experiments enhance the practical utility of TPTA and facilitate the real-time detection of oxychlorides. Hence, TPTA has proven to be an inevitable and promising tool for the sensitive recognition oxychloride species. [ABSTRACT FROM AUTHOR]

The persistent mutation of the novel coronavirus presents a continual threat of infections and associated illnesses. While considerable research efforts have concentrated on the functional proteins of SARS-CoV-2 in the development of anti-COVID-19 therapeutics, the structural proteins, particularly the N protein, have received comparatively less attention. This study focuses on the N protein, a critical structural component of the virus, and employs advanced deep learning models, including EMPIRE and DeepFrag, to optimize the structures of phenanthridine-based compounds. More than 10,000 small molecules, derived through deep learning, underwent high-throughput virtual screening, resulting in the synthesis of 44 compounds. Compound 38 showed a binding potential energy of −8.2 kcal/mol in molecular docking. Surface Plasmon Resonance (SPR) and Microscale Thermophoresis (MST) validation yielded dissociation constants of 353 nM and 726 nM, confirming strong binding to the N protein. Compound 38 demonstrated antiviral activity in vitro and exhibited anti-COVID-19 effects by interfering with the binding of N proteins to RNA. This research underscores the potential of targeting the SARS-CoV-2 N protein for therapeutic intervention and illustrates the efficacy of deep learning model in the design of lead compounds. The application of these deep learning models represents a promising approach for accelerating the discovery and development of antiviral agents. [Display omitted] • Research on coronavirus drugs has predominantly focused on functional proteins, with comparatively less emphasis on structural proteins. Nevertheless, our study specifically targets the SARS-CoV-2 N protein, offering a novel approach to coronavirus treatment. • Based on the molecular backbone of the SARS-CoV-2 N protein and phenanthridine, deep learning models were utilized for structure optimization. Subsequently, high-throughput screening of the resulting compounds was conducted to accelerate drug development. • As a final result of this study, a compound that binds strongly to the N protein and shows anti-SARS-CoV-2 viral activity in vitro was successfully obtained. [ABSTRACT FROM AUTHOR]

Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine‐based fluorophores (i.e. B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163 nm, which results in organic fluorophore‐based full‐color piezochromism. Moreover, both B1 and F1 exhibit an aggregation‐caused quenching (ACQ) behavior, while T1 is an aggregation‐induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring. [ABSTRACT FROM AUTHOR]

An efficient and facile strategy for the synthesis of 6‐(sulfonylmethyl)phenanthridines and its derivatives has been developed via tandem sulfonylation cyclization of vinyl azides under mild conditions in the absence of any catalysts and additives. The reaction simply utilizes easily accessible and cheap K2S2O5 as the sulfur dioxide source, delivering functionalized phenanthridines in moderate to excellent yields with operational simplicity and gram‐scale synthesis, as well as good functional‐group tolerance. [ABSTRACT FROM AUTHOR]

An efficient and facile strategy for the synthesis of 6‐(sulfonylmethyl)phenanthridines and its derivatives has been developed via tandem sulfonylation cyclization of vinyl azides under mild conditions in the absence of any catalysts and additives. The reaction simply utilizes easily accessible and cheap K2S2O5 as the sulfur dioxide source, delivering functionalized phenanthridines in moderate to excellent yields with operational simplicity and gram‐scale synthesis, as well as good functional‐group tolerance. [ABSTRACT FROM AUTHOR]

Nitrenes and nitrenoids are highly reactive species and the proposed key intermediates in nitrogen‐containing heterocyclic compound synthesis. In this work, we developed a practical method for the synthesis of phenanthridines by the reaction of oximes and Grignard reagents (with or without diethylzinc) via ring‐expansion of magnesium coordinated nitrenoid complex as the key step. The method has been used to synthesize optically active planar chiral ferrocenyl phenanthridines. [ABSTRACT FROM AUTHOR]

Here we report a simple and efficient method for the preparation of CF2H‐substituted pyrido[4,3,2‐gh]phenanthridines under photoredox conditions. The reactions are triggered by addition of a CF2H radical to a carbon–carbon double bond to form three different types of bonds via a cascade radical difluoromethylation/cyano insertion/cyclization. This difluoromethylated transformation exhibits good functional group compatibility, leading to the construction of the desired ring‐fused phenanthridine derivatives in moderate to excellent yields. [ABSTRACT FROM AUTHOR]