Pyrylium Research Articles

Two-component design strategy: TADF-Type organic afterglow for time-gated chemodosimeters

Organic afterglow materials exhibit strong capability to avoid fluorescence interference for their applications in highly sensitive analysis. However, afterglow materials with specific analysis properties are less explored. For example, among the reported studies, afterglow materials with chemodosimeter functions towards specific substances remain elusive even in a proof-of-concept demonstration level. The key to address this issue is to develop reactive organic dyes that can be processed into room-temperature afterglow materials. Here, by doping reactive pyrylium salts into phenyl benzoate matrices, we report the fabrication of TADF-type organic afterglow materials which feature a moderate kRISC of 100-102 s−1 to efficiently harvest triplet energies, significantly improve afterglow efficiency and simultaneously maintain afterglow emission lifetimes. The obtained materials possess afterglow quantum yields up to 48%, which is among the highest values in the reported studies, and can function as time-gated chemodosimeters specifically towards amine-containing compounds even in the presence of strong fluorescence backgrounds.

Selectivity, Speciation, and Substrate Control in the Gold-Catalyzed Coupling of Indoles and Alkynes.

A convenient and mild protocol for the gold-catalyzed intermolecular coupling of substituted indoles with carbonyl-functionalized alkynes to give vinyl indoles is reported. This reaction affords 3-substituted indoles in high yield, and in contrast to the analogous reactions with simple alkynes which give bisindolemethanes, only a single indole is added to the alkyne. The protocol is robust and tolerates substitution at a range of positions of the indole and the use of ester-, amide-, and ketone-substituted alkynes. The use of 3-substituted indoles as substrates results in the introduction of the vinyl substituent at the 2-position of the ring. A combined experimental and computational mechanistic study has revealed that the gold catalyst has a greater affinity to the indole than the alkyne, despite the carbon–carbon bond formation step proceeding through an η2(π)-alkyne complex, which helps to explain the stark differences between the intra- and intermolecular variants of the reaction. This study also demonstrated that the addition of a second indole to the carbonyl-containing vinyl indole products is both kinetically and thermodynamically less favored than in the case of more simple alkynes, providing an explanation for the observed selectivity. Finally, a highly unusual gold-promoted alkyne dimerization reaction to form a substituted gold pyrylium salt has been identified and studied in detail.

Condensation of pyrylium salts with mixed anhydrides: aryl ethers, aryl amines and sterically congested aromatics

Condensation of 2,4,6-triaryl pyrylium salts with mixed anhydrides, formed in situ from α-functionalized sodium acetates and an anhydride solvent, leads in good yields to the corresponding 2,4,6-triaryl benzenes functionalized at their 1-position.

Pyrylium salts acting as both energy transfer and electron transfer photocatalysts for E → Z isomerization of activated alkenes and cyclization of cinnamic or biaryl carboxylic acids

Here we report that 2,4,6-triarylpyrylium salts could perform both energy transfer and electron transfer photocatalysis modes for E → Z isomerization of activated alkenes and cyclization of cinnamic or biaryl carboxylic acids.

Stereoselective O-Glycosylations by Pyrylium Salt Organocatalysis.

Despite many years of invention, the field of carbohydrate chemistry remains rather inaccessible to non-specialists, which limits the scientific impact and reach of the discoveries made in the field. Aiming to increase the availability of stereoselective glycosylation chemistry for non-specialists, we have discovered that several commercially available pyrylium salts catalyze stereoselective O-glycosylations of a wide range of phenols and alkyl alcohols. This catalytic reaction utilizes trichloroacetimidates, an easily accessible and synthetically proven electrophile, takes place under air and only initiates when all three reagents are mixed, which should provide better reproducibility by non-specialists. The reaction exhibits varying degrees of stereospecificity, resulting in β-selective glycosylations from α-trichloroacetimidates, whilst an α-selective glycosylation proceeds from β-trichloroacetimidates. A mechanistic study revealed that the reaction likely proceeds via an SN 2-like substitution on the protonated electrophile.

Stereoselective O‐Glycosylations by Pyrylium Salt Organocatalysis**

AbstractDespite many years of invention, the field of carbohydrate chemistry remains rather inaccessible to non‐specialists, which limits the scientific impact and reach of the discoveries made in the field. Aiming to increase the availability of stereoselective glycosylation chemistry for non‐specialists, we have discovered that several commercially available pyrylium salts catalyze stereoselective O‐glycosylations of a wide range of phenols and alkyl alcohols. This catalytic reaction utilizes trichloroacetimidates, an easily accessible and synthetically proven electrophile, takes place under air and only initiates when all three reagents are mixed, which should provide better reproducibility by non‐specialists. The reaction exhibits varying degrees of stereospecificity, resulting in β‐selective glycosylations from α‐trichloroacetimidates, whilst an α‐selective glycosylation proceeds from β‐trichloroacetimidates. A mechanistic study revealed that the reaction likely proceeds via an SN2‐like substitution on the protonated electrophile.

Heteroatom‐Embedded Approach to Vinylene‐Linked Covalent Organic Frameworks with Isoelectronic Structures for Photoredox Catalysis

AbstractEmbedding heteroatoms into the main backbones of polymeric materials has become an efficient tool for tailoring their structures and improving their properties. However, owing to comparatively harsh heteroatom‐doping conditions, this has rarely been explored in covalent organic frameworks (COFs). Herein, upon aldol condensation of a trimethyl‐substituted pyrylium salt with a tritopic aromatic aldehyde, a two‐dimensional oxonium‐embedded COF with vinylene linkages was achieved, which was further converted to a neutral pyridine‐cored COF by in situ replacement of oxonium ions with nitrogen atoms under ammonia treatment. The two heteroatom‐embedded COFs are conceptually isoelectronic with each other, featuring similar geometric structures but different electronic structures, rendering them capable of catalyzing the visible‐light‐promoted multi‐component synthesis of tri‐substituted pyridine derivatives with good recyclability.

Heteroatom-Embedded Approach to Vinylene-Linked Covalent Organic Frameworks with Isoelectronic Structures for Photoredox Catalysis.

Embedding heteroatoms into the main backbones of polymeric materials has become an efficient tool for tailoring their structures and improving their properties. However, owing to comparatively harsh heteroatom-doping conditions, this has rarely been explored in covalent organic frameworks (COFs). Herein, upon aldol condensation of a trimethyl-substituted pyrylium salt with a tritopic aromatic aldehyde, a two-dimensional oxonium-embedded COF with vinylene linkages was achieved, which was further converted to a neutral pyridine-cored COF by in situ replacement of oxonium ions with nitrogen atoms under ammonia treatment. The two heteroatom-embedded COFs are conceptually isoelectronic with each other, featuring similar geometric structures but different electronic structures, rendering them capable of catalyzing the visible-light-promoted multi-component synthesis of tri-substituted pyridine derivatives with good recyclability.

A simple and straightforward polymer post-modification method for wearable difluoroboron β-diketonate luminescent sensors

Boron-containing polymeric materials represent an important class of functional polymers, whereas their preparation usually requires multiple synthetic steps. Here we report a simple and straightforward polymer post-modification method to attach difluoroboron β-diketonate (BF2bdk) luminescent moieties onto polymer chains as side groups. The post-modification, using poly (N-vinyl carbazole) (PVK) as aromatic substrates, has been found to occur at ambient conditions via a cascade manner in the presence of acetic anhydride and boron trifluoride diethyl etherate. The obtained PVK-BF2bdk polymeric materials have been found to function as wearable luminescent sensors to display switching-on property upon exposing to alcohol and show switching-off behavior in organic acid environment. Detailed studies reveal that the post-modification also produces crosslinking points formed by pyrylium salt structures. The pyrylium structures, which are well solvated in organic acids and show UV–vis absorption largely overlapped with BF2bdk emission, cause the switching-off behaviour of the PVK-BF2bdk polymeric materials.

Evaluation of suitable onium tetrafluoroborates for cationic polymerization of epoxides

AbstractEpoxides are frequently used in coatings due to their great adhesion to most materials, high resistance towards chemicals and well‐defined material properties. Onium salts such as iodonium and sulfonium salts are one of the most widespread classes of initiators used in light‐induced cationic polymerization of such epoxides. We successfully synthesized onium salts based on group 14 to 16 elements in the periodic table. They were then characterized using cyclic voltammetry and UV–visible spectroscopy before determining their reactivity in epoxy‐based resins. Using commercial bisphenol‐A‐based resins, thiopyrylium, bismuithonium and pyrylium salts show good reactivity and epoxy group conversions above 60% in simultaneous thermal analysis. Photochemically interesting new cationic initiators were identified to be oxonium, thiopyrylium and selenonium salts. Additionally, bismuthonium and stibonium salts show great potential towards sensitization with anthracene. © 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Combining the Katritzky Reaction and Paper Spray Ionization Mass Spectrometry for Enhanced Detection of Amino Acid Neurotransmitters in Mouse Brain Sections.

This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

α-Active Pyrylium Salt 2,4,5-Triphenylpyrylium for Improved Mass Spectrometry-Based Detection of Peptides

Pyrylium salts are considered efficient chemical tags for amino groups. However, the apparent steric selectivity of pyrylium salts limits their application in the field of chemical labeling, especially during the labeling of sterically hindered compounds like amino acids, peptides, and proteins. Herein, we have investigated the effects of the α-substitution of pyrylium salts on their reactivity. We have also investigated the mechanism of nucleophilic reactions with pyrylium salts and further proposed that the reactivity of pyrylium salts mainly depends on the position and type of their substituents. A series of pyrylium salts were synthesized, and a highly active α-monosubstituted pyrylium salt, 2,4,5-triphenylpyrylium, was developed for efficient chemical labeling. All of the 15 amino acids studied were efficiently labeled under optimized reaction conditions. The 2,4,5-triphenylpyrylium salt was highly efficient in comparison to the previously reported 2,4,6-triphenylpyrylium salt developed for lysine-specific modifications. Furthermore, we successfully used 2,4,5-triphenylpyrylium salt for the hydrophobic labeling of peptides and protein hydrolysates. The most striking observation was that the ionization efficiency of short-chain multilabeled peptides in mixed samples, after derivatization, increased by up to 60 times. The increase in ionization efficiency gradually decreased with increasing peptide chain length. During the "soft" collision-induced dissociation (CID) process, the peptide was tagged at the N-terminus with 2,4,5-triphenylpyrylium, producing abundant a-type ions and b-type ions (Δ = 28), which eases the peptide resequencing process and assists in cracking the peptide codes. Moreover, 2,4,5-triphenylpyrylium has been utilized for the proteomic analysis of HeLa cell digests. In addition, 215 additional proteins were identified in the labeled products and the coverage of most proteins was improved.

Highly Strained Nanoscale Bicyclophane Monolayers Entering the Third Dimension: A Combined Synthetic and Scanning Tunneling Microscopy Investigation.

Invited for this month's cover are the collaborating groups of Prof. Dr. Sigurd Höger and Dr. Stefan-S. Jester from Rheinische Friedrich-Wilhelms-Universität Bonn, Germany. The cover picture shows a bicyclophane that forms a two-dimensional supramolecular nanopattern on graphite at the solid/liquid interface. After adsorption, the central unit points towards the volume phase. Read the full text of the article at 10.1002/cplu.202000711.

Redox-Neutral 1,3-Dipolar Cycloaddition of 2H-Azirines with 2,4,6-Triarylpyrylium Salts under Visible Light Irradiation.

A novel visible light mediated redox-neutral 1,3-dipolar cycloaddition of 2H-azirines with 2,4,6-triarylpyrylium tetrafluoroborate salts providing tetrasubstituted pyrroles has been developed. The 2,4,6-triarylpyrylium salt acts as dipolarophile as well as photosensitizer in the reaction, under blue light irradiation. The control experiments indicated single electron oxidation of 2H-azirines by photoexcited pyrylium salts, followed by coupling between an azaallenyl radical cation and triarylpyranyl radical as the key mechanistic feature. The mild conditions, wide substrate scope, and complete regioselectivity are the noticeable attributes of the reaction.

Continuous-Flow Synthesis of Pyrylium Tetrafluoroborates: Application to Synthesis of Katritzky Salts and Photoinduced Cationic RAFT Polymerization.

Katritzky salts have emerged as effective alkyl radical sources upon metal- or photocatalysis. These are typically prepared from the corresponding triarylpyrylium ions, in turn an important class of photocatalysts for small molecules synthesis and photopolymerization. Here, a flow method for the rapid synthesis of both pyrylium and Katrizky salts in a telescoped fashion is reported. Moreover, several pyrylium salts were tested in the photoinduced RAFT polymerization of vinyl ethers under flow and batch conditions.

Regioselective synthesis of functionalized pyrazole-chalcones via a base mediated reaction of diazo compounds with pyrylium salts.

A base-mediated reaction of triaryl/alkyl pyrylium tetrafluoroborate salts with α-diazo-phosphonates, sulfones and trifluoromethyl compounds affords the corresponding functionalized pyrazole-chalcones as 5-P-5 and 3-P-3 tautomeric mixture. The reaction proceeds through an initial nucleophilic addition of diazo substrates to pyrylium salts followed by a base-mediated pyrylium ring-opening and intramolecular 1,5-cyclization to afford formal 1,3-dipolar cycloaddition products. The products underwent a Nazarov-type cyclization upon hydride reduction followed by acidic-workup, furnishing the corresponding indenyl-pyrazoles in high yields.

Fluorescent styrylpyrylium probes for the imaging of mitochondria in live cells.

Eight styrylpyrylium tetrafluoroborate salts have been synthesized and fully optically characterized by UV-vis absorption and fluorescence steady-state/time-resolved spectroscopies. The new dyes exhibit strong emission bands with yellow-orange colours, depending on the substituents present in the structure. Notably, the Stokes shift recorded for some of them exceeds 100 nm, a very valuable feature for biological imaging. Four of them have been assayed as biological imaging agents by confocal laser scanning microscopy (CLSM) in the human hepatoma cell line Hep3B. It has been found that all the compounds efficiently stain intracellular structures which have been identified as mitochondria through colocalization assays with MitoView (a well-known mitochondrial marker) and using carbonyl cyanide m-chlorophenyl hydrazone (CCCP) as a mitochondrial membrane potential uncoupler. Additionally, the potential ability of the studied dyes as cytotoxic drugs has been explored. The inhibitory concentration (IC50) against Hep3B was found to be in the range of 4.2 μM-11.5 μM, similar to other described anticancer drugs for the same hepatoma cell line. The combined features of a good imaging agent and potential anticancer drug make the family of the studied pyrylium salts good candidates for further theranostic studies. Remarkably, despite the extensive use of pyrylium dyes in several scientific areas (from photocatalysis to optics), there is no precedent description of a styrylpyrylium salt with potential theranostic applications.

Efficient cascade reactions for luminescent pyrylium biolabels catalysed by light rare-earth elements

Luminescent pyrylium salts have been efficiently synthesized from cascade reactions, coupled to supramolecular assembly and used for protein labeling.

Acylation of indolyl subsituted β-ketonitriles. The way to new indolo[2,3-c]pyrilium and β-carboline derivatives

Aim. To synthesize 4-cyanoindolo[2,3-c]pyrilium salts and examine their reactivity towards N-nucleophiles.Results and discussion. The acylation reaction of 2-(indolyl-3)-2-aroylacetonitriles under acid catalysis conditions was studied. 4-Cyanoindolo[2,3-c]pyrillium borofluorides were obtained, and ketonitrile enolacylates were isolated as by-products of the reaction. Treatment of the 4-cyanoindolo[2,3-c]pyrilium salts with ammonia led to 4-cyano-β-carbolines while the interaction of the salts with hydrazine hydrate resulted in formation of pyrazolo[3’,4’:5,6]pyrido[3,4‑b]indoles – derivatives of a new heterocyclic system. The latter are formed via recyclization involving the pyran ring and the cyano group.Experimental part. Upon the treatment of 2-(indolyl-3)-2-aroylacetonitriles with acetic anhydride/tetrafluoroboric acid mixture, the acylation of the indole fragment in position 2 was followed by cyclization, resulting in formation of 4-сyanoindolo[2,3-c]pyrilium salts. The reactivity of the pyrylium salts was studied on the examples of their interaction with N-nucleophiles – ammonia and hydrazine hydrate. The structure of the compounds synthesized was confirmed by 1H NMR, IR spectroscopy and elemental analysis.Conclusions. It has been found that moderate yields of 4-сyanoindolo[2,3-c]pyrilium salts are the result of competing acylation of the hydroxyl group of enol ketonitrile, which blocks the pyran ring formation. Recylization of the salts with ammonia leads to 4-cyano-β-carbolines. Transformation of the pyran ring with hydrazine hydrate proceeds with the participation of the cyano group as a tandem reaction with formation of pyrazolo[3’,4’:5,6]pyrido[3,4-b]indoles.Received: 22.06.2020 Revised: 03.10.2020 Accepted: 23.10.2020

Catalytic Enantioselective Reactions with (Benzo)Pyrylium Salts.

The use of (benzo)pyrylium salts as versatile synthetic building blocks has become an attractive platform for the preparation of valuable heterocyclic compounds. Besides other numerous direct applications of (benzo)pyryliums, the intrinsic electrophilic nature of these species or the dipole character of the related oxidopyrylium derivatives have been exploited towards the development of enantioselective transformations such as nucleophilic dearomatization and cycloaddition reactions. This review aims at providing an overview on the relevant catalytic enantioselective methodologies developed in the past years, which are presented considering the involved metal- and/or organic catalytic system, as well as the type of reaction.