Two series of novel T‐shaped 8‐substituted psoralen derivatives bearing (hetero)aryl and arylethynyl substituents were synthesized via Suzuki and Sonogashira coupling starting from 8‐methoxypsoralen (8‐MOP). Predominantly, electron‐donating substituents such as anisyl and phenothiazine were introduced at the 8‐position of the psoralen for increasing the electron density in comparison to 8‐MOP. Photophysical properties were studied by absorption and emission spectroscopy in solution and in the solid state. Increasing the donor strength of the substituent causes a bathochromic shift of both absorption and emission maxima. The absorption behavior can be correlated with Hammett substituent parameters of remote substituents at the p‐aryl moieties that are directly or by ethynyl spacing positioned at the 8‐position of psoralen. In most cases, fluorescence in the solid state is more pronounced than in solution. One derivative also displays significant aggregation‐induced emission. For two amino‐substituted psoralen derivatives, positive emission solvatochromism was observed and associated with a considerable change of dipole moment upon photonic excitation according to Lippert–Mataga analysis. Furthermore, the pKa value of the T‐shaped dimethylaminophenyl psoralen derivative was determined from absorption spectra. In addition, emission quenching is caused by protonation on the nitrogen atom. TD‐DFT (time‐dependent density functional theory) calculations are in good agreement with experimental data and rationalize the electronic structure.

The strategic combination of Suzuki coupling and Buchwald–Hartwig amination in consecutive (pseudo‐)four‐component syntheses provides a highly efficient and modular route to meta‐ and ortho‐biaryl‐substituted triarylamines (m‐ and o‐bTAA), thereby expanding a substance library that has previously focused on para‐bTAA. The broad range of novel bTAA enables comprehensive investigations of their electronic properties and reveals highly tunable emission in solution from blue to yellow, with quantum yields up to 55%, and up to 26% in the solid state. The bTAA also show strong potential as stimulus‐responsive luminophores due to their pronounced positive emission solvatochromism, which indicates substantial charge transfer character—particularly in the m‐bTAA—as well as aggregation‐induced emission in DMSO/water mixtures with with intensity enhancements of up to 75‐fold. Quantitative 2D Hammett correlations combined with quantum‐chemical calculations systematically rationalize substituent effects not only on the emission properties but also on the low, reversible redox potentials determined by cyclic voltammetry. Cyclic voltammetry further reveals irreversible dimerization processes in certain unsubstituted bTAA. In addition to para‐substituents, the biaryl substitution pattern (meta, ortho, or para) also proves to be a finely tunable parameters, opening new opportunities for the rational design of tailored bTAA emitters with predictable structure–property relationships.

A palladium-catalyzed domino sequence has been unlocked through the advent of a hitherto unreported class of ortho-X-allenyl tethered aryl isocyanides, highly reactive scaffolds that enable streamlined access to fused polycyclic heterocycles, including 2-substituted benzoxazoles, benzothiazoles, and benzimidazoles. The transformation forges two C-X and four C-C bonds in a single sequence and proceeds with broad functional-group tolerance, delivering the products in moderate to good yields. Mechanistic studies support a domino sequence involving allene isomerization, isocyanide insertion, migratory cycloisomerization, and a final [4 + 2] cycloaddition reaction, as validated by control experiments. This work unveils an unprecedented reactivity mode of functionalized isocyanides and provides a concise strategy for assembling densely fused heterocyclic frameworks.

Furo[2,3-c]isoquinolines are tricyclic heteroaromatic structures that can be obtained by coupling the Ugi reaction with a complex Pd-mediated secondary transformation. These compounds are usually blue emitters, which can be converted to green emitters by modulating the electronic properties of the substituents as well as their position on the scaffold. Here, we present a different strategy for tuning the emission properties, which is the extension of the conjugation of the scaffold after the formation of the tricyclic heterocycle. This allowed us to synthesize a new library of highly conjugated and structurally complex fluorophores displaying considerable emission light-up upon induced aggregation. The electronic structure of absorption and emission of the chromophores was rationalized by cLR-CAM-B3LYP calculations.

Twelve donor-aniline-thiophene-acceptor chromophores with varying acceptor moieties were synthesized via consecutive lithiation-borylation-Suzuki-coupling sequence as potential hybridized localized and charge transfer (HLCT) dyes. Cyclic voltammetry measurements reveal one or two reversible oxidation processes with thermodynamic stability of radical cations. The photophysical properties of these potential HLCT systems display blue to yellow luminescence in the solid state, in solution, and in a poly(methyl methacrylate) film, showing increased emission quantum yield in degassed media up to 68%. Solvatochromism studies reveal an underlying charge transfer character and variable temperature emission spectroscopy accounts for the absence of a thermally activated delayed fluorescence mechanism.

Acid chlorides, alkynes, amines, and N-thiosuccinimides react in a consecutive four-component alkynylation-addition-sulfenylation sequence to give alpha-sulfenylated enaminones in good to excellent yields. The terminal sulfenylation step is catalyzed by Yb(OTf)3 and both N-arylthiosuccinimides and N-alkylthio succinimides can be successfully employed. Most products are solid-state luminescent with fluorescence quantum yields up to 84 % and lifetimes up to 4.9 ns. Additionally, TD-DFT calculations rationalize the electronic structure of the absorption characteristics of the dyes.

Three regioisomeric N ‐ para ‐fluorophenyl bis[1]benzothieno[1,4]thiazines (BBTT) are selectively oxidized under mild conditions to give the corresponding BBTT‐ S ‐oxides, which were fully characterized by single crystal structural analysis. The newly formed S ‐oxide is uniformly oriented in a pseudo‐axial S ‐ extra position, whilst the N ‐aryl substituent adopts an N ‐ intra conformation. In comparison to the diminished planarization of the BBTT scaffold according to DFT calculations, the structures are considerably planarized in the crystal. Only the anti ‐ anti ‐BBTT‐ S ‐oxide emits intensively and the electronic structure of the absorption and emission spectra can be elucidated by TDDFT calculations. This blue emission, both in solution (Φ f = 17%) and in the solid state (Φ f = 66%), is significant and qualifies this isomer as an attractive emitter.

The synthesis of an anionic [Ge,N]-bidentate ligand based on the combination of an amidopyridinato group with an anionic germolide ring is reported. The potential of the germolide part of this ligand to switch between η1-(via Ge) and η5-(via C4Ge) coordination modes makes this ligand an interesting synthetic target. Salt metathesis reactions of the potassium salt of this ligand with GeCl2 dioxane and SnCl2 allow the synthesis of bis-germolyl-substituted germylenes and stannylenes with the tetrel atoms in a distorted square pyramidal coordination environment.

The equistoichiometric three-component reaction of an acid chloride, an alkyne, and an ortho -amino- or ortho -hydroxyphenylboronic ester proceeds smoothly to give phenanthridines or benzo[ c ]chromenes, respectively, with good to quantitative yields in the sense of a Sonogashira-Suzuki-Michael cyclization sequence. In the coupling of ortho -amidophenylboronates, interestingly, after ring closure a subsequent an acyl migration occurs to give 6-(2-(acyloxy)vinyl)phenanthridines.

For the preparation of novel 5‐styryl‐substituted 9‐hydroxy‐1H‐phenalen‐1‐ones, a sequential Pd‐catalyzed Heck vinylenation–Suzuki arylation one‐pot strategy was established, providing efficient access to a library of donor–acceptor chromophores. These multifunctional conjugates are characterized by a planar, highly conjugated backbone extended through vinyl substitution at the 5‐position. The obtained compounds were comprehensively investigated with respect to their electrochemical and photophysical properties. Cyclic voltammetry demonstrates that the reduction potentials remain largely unaffected by substituents, whereas the oxidation potentials show a pronounced dependence on the electronic nature of the aryl groups. UV–vis and fluorescence spectroscopy revealed bathochromic shifts of absorption and emission maxima for electron‐donating substituents, while electron‐withdrawing groups induce hypsochromic responses. Complementary Hammett correlations confirm the dominance of resonance effects, with the strongest linear relationships observed for the extended σp+ parameter, highlighting mesomeric stabilization as the decisive factor in modulating electronic transitions. Quantum‐chemical (TD)DFT calculations reproduce the spectroscopic trends and provide detailed insight into orbital contributions and charge‐transfer characteristics. Solvatochromic analyses further evidence the polar nature of the excited states, supporting a pronounced intramolecular charge‐transfer character.

Ene reactions are inter‐ or intramolecular addition reactions between a four‐electron "ene" component and a two‐electron enophile functionality, in which two π‐bonds and a C–H (or metal–C) σ‐bond are rearranged into one π‐bond and two σ‐bonds. One of the newly formed σ‐bonds is a carbon–carbon bond, while the other is the rearranged a C–H (or metal–C) bond. This transformation enables the formation of structurally and functionally complex ene products in a single step. Originally, ene reactions were discovered as concerted and stepwise pericyclic elementary processes. However, increasing mechanistic insight—gained through both experimental and computational studies—along with extensive empirical methodological work, has paved the way to a plethora of ene‐type reactions involving carbon enophiles. Since 2012, the already well‐established transition metal‐catalyzed variants of ene reactions have significantly expanded. Moreover, highly reactive aryne intermediates—generated in situ either by fluoride induced elimination from ortho‐silyl aryltriflates at room temperature, or by hexadehydro‐Diels–Alder reaction of a 1,3‐diyne with an alkyne (both inter‐ and intramolecularly)—find increasing application in novel ene‐type sequences. Propargyl ene reactions also gain traction, particularly because the resulting ene‐allenes serve as highly valuable intermediates in the design of domino sequences that lead to complex polycyclic fused structures. Finally, the implementation of ene reactions in polymer chemistry for the synthesis of functionalized polymers and renewable unsaturated raw materials has emerged as a promising alternative to the use of purely petrochemistry based substrates.

Recent developments in the synthesis of substituted polyacetylenes have considerably benefitted from advancements in organometallic catalysis; however, most important developments rely on the advent of Rh-catalyzed living polymerizations. The latter not only allow the tailoring of well-defined degrees of polymerization with low and narrow polydispersity but also enable access to stereochemical well-defined cis-transoidal polymers with a helical structure. These novel polymers open new avenues for application in photonics and electronics. Rh-catalyzed living polymerizations are mild and concise metal-catalyzed polymer syntheses that not only allow for the decoration of sidechains with multiple functionalities, including chiral units, but also enable enantioselective induction of helical chirality, memory of chirality, well-defined copolymerization, and end-group functionalization at both termini. This review summarizes recent developments in metal-catalyzed syntheses of substituted polyacetylenes, with a special focus on Rh-catalyzed living polymerizations.

Pyrazoles are rarely found in nature but are traditionally used in the agrochemical and pharmaceutical industries, while other areas of use are also actively developing. However, they have also found numerous other applications. The search for new and efficient syntheses of these heterocycles is therefore highly relevant. The modular concept of multicomponent reactions (MCR) has paved a broad alley to heteroaromatics. The advantages over traditional methods are the broader scope and increased efficiency of these reactions. In particular, traditional multistep syntheses of pyrazoles have considerably been extended by MCR. Progress has been made in the cyclocondensation of 1,3-dielectrophiles that are generated in situ. Limitations in the regioselectivity of cyclocondensation with 1,3-dicarbonyls were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern cross-coupling and radical chemistry, as well as providing versatile synthetic approaches to pyrazoles. This overview summarizes the most important MCR syntheses of pyrazoles based on ring-forming sequences in a flashlight fashion.

Using the established synthetic methods, aroyl-S,N-ketene acetals and subsequent bi- and multichromophores can be readily synthesized. Aside from pronounced AIE (aggregation induced emission) properties, these selected examples possess distinct complexometric behavior for various metals purely based on the underlying structural motifs. This affects the fluorescence properties of the materials which can be readily exploited for metal ion detection and for the formation of different metal-aroyl-S,N-ketene acetal complexes that were confirmed by Job plot analysis. In particular, gold(I), iron(III), and ruthenium (III) ions reveal complexation enhanced or quenched emission. For most dyes, weakly coodinating complexes were observed, only in case of a phenanthroline aroyl-S,N-ketene acetal multichromophore, measurements indicate the formation of a strongly coordinating complex. For this multichromophore, the complexation results in a loss of fluorescence intensity whereas for dimethylamino-aroyl-S,N-ketene acetals and bipyridine bichromophores, the observed quantum yield is nearly tripled upon complexation. Even if no stable complexes are formed, changes in absorption and emission properties allow for a simple ion detection.

Germaaluminocenes are formed by salt metathesis reactions of dipotassium germacyclopentadienediides with pentamethylcyclopentadienylaluminum dichloride. The reactivity pattern of these sandwich complexes is determined by the electrophilic central aluminum atom and by the nucleophilic dicoordinated germanium center. Surprisingly, the products formed by reactions with Lewis acids, Lewis bases, amphiphiles and compounds with polar double bonds are those expected from the reaction of a hypothetical aluminagermapentafulvene with these types of reagents. This suggests that germaaluminocenes are synthetic equivalents to these pentafulvenes.

We present a new pathway toward cationic N,N′-diaryl-substituted quinazolin-4-one derivatives, which act as precursors for the synthesis of new N,N′-diaryl-amino-amido carbenes 5a,b that are stable under inert conditions. A tetrafluoro analogue 5c withstands isolation but can be prepared and employed in situ. The new NHCs exhibit a strong σ-donor capacity as well as strong π-accepting properties according to NMR and IR spectroscopic investigations indicated by the coupling constants 1JC,H (210–214 Hz) and 77Se NMR resonances (545–654 ppm) of suitable derivatives. Remarkably, replacement of the hydrogen atoms of the anellated benzene ring by fluorine atoms exerts only a small effect on the overall donor properties of the carbene, as suggested by a small shift of the TEP values from 2053 cm–1 (5a) to 2055 cm–1 (5c). An ambiphilic reactivity of the NHCs 5 is supported by their reactions with isonitriles to provide the respective ketenimines 13, which show unprecedented rearrangement reactions, induced by either water or heat. The NHCs 5 also react with amines or methanol in N–H and O–H bond activations. The mechanisms of these activation reactions were investigated by quantum chemical calculations. Due to the apparent blue emission of the selected derivatives, the photophysical properties were exemplarily characterized in solution and solid state and assigned to the underlying electronic transitions by (TD)-DFT calculations.

Meriolin derivatives represent a new class of kinase inhibitors with a pronounced cytotoxic potential. Here, we investigated a newly synthesized meriolin derivative (termed meriolin 16) that displayed a strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. Meriolin 16 induced apoptosis in rapid kinetics (within 2–3 h) and more potently (IC 50 : 50 nM) than the previously described derivatives meriolin 31 and 36 [ 1 ]. Exposure of Ramos cells to meriolin 16, 31, or 36 for 5 min was sufficient to trigger severe and irreversible cytotoxicity. Apoptosis induction by all three meriolin derivatives was independent of death receptor signaling but required caspase-9 and Apaf-1 as central mediators of the mitochondrial death pathway. Meriolin-induced mitochondrial toxicity was demonstrated by disruption of the mitochondrial membrane potential (ΔΨm), mitochondrial release of proapoptotic Smac, processing of the dynamin-like GTPase OPA1, and subsequent fragmentation of mitochondria. Remarkably, all meriolin derivatives were able to activate the mitochondrial death pathway in Jurkat cells, even in the presence of the antiapoptotic Bcl-2 protein. In addition, meriolins were capable of inducing cell death in imatinib-resistant K562 and KCL22 chronic myeloid leukemia cells as well as in cisplatin-resistant J82 urothelial carcinoma and 2102EP germ cell tumor cells. Given the frequent inactivation of the mitochondrial apoptosis pathway by tumor cells, such as through overexpression of antiapoptotic Bcl-2, meriolin derivatives emerge as promising therapeutic agents for overcoming treatment resistance.

A key feature of cancer is the disruption of cell cycle regulation, which is characterized by the selective and abnormal activation of cyclin-dependent kinases (CDKs). Consequently, targeting CDKs via meriolins represents an attractive therapeutic approach for cancer therapy. Meriolins represent a semisynthetic compound class derived from meridianins and variolins with a known CDK inhibitory potential. Here, we analyzed the two novel derivatives meriolin 16 and meriolin 36 in comparison to other potent CDK inhibitors and could show that they displayed a high cytotoxic potential in different lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells. In a kinome screen, we showed that meriolin 16 and 36 prevalently inhibited most of the CDKs (such as CDK1, 2, 3, 5, 7, 8, 9, 12, 13, 16, 17, 18, 19, 20). In drug-to-target modeling studies, we predicted a common binding mode of meriolin 16 and 36 to the ATP-pocket of CDK2 and an additional flipped binding for meriolin 36. We could show that cell cycle progression and proliferation were blocked by abolishing phosphorylation of retinoblastoma protein (a major target of CDK2) at Ser612 and Thr82. Moreover, meriolin 16 prevented the CDK9-mediated phosphorylation of RNA polymerase II at Ser2 which is crucial for transcription initiation. This renders both meriolin derivatives as valuable anticancer drugs as they target three different Achilles' heels of the tumor: (1) inhibition of cell cycle progression and proliferation, (2) prevention of transcription, and (3) induction of cell death.

The concatenation of Suzuki coupling and two-fold Buchwald-Hartwig amination in sequentially palladium-catalyzed consecutive multicomponent syntheses paves a concise, convergent route to diversely functionalized para-biaryl-substituted triarylamines (p-bTAAs) from simple, readily available starting materials. An extensive library of p-bTAAs permits comprehensive investigations of their electronic properties by absorption and emission spectroscopy, cyclic voltammetry, and quantum chemical calculations, which contribute to a deep understanding of their electronic structure. The synthesized p-bTAAs exhibit tunable fluorescence from blue to yellow upon photonic excitation with quantum yields up to 98 % in solution and 92 % in the solid state. Furthermore, a pronounced bathochromic shift of the emission maxima by increasing solvent polarity indicates positive emission solvatochromism. Aggregation-induced enhanced emission (AIEE) in dimethyl sulfoxide (DMSO)/water mixtures causes the formation of intensely blue fluorescent aggregates. Cyclic voltammetry shows reversible first and second oxidations of p-bTAAs at low potentials, which are tunable by variation of the introduced para substituents. 3D Hammett plots resulting from the correlation of oxidation potentials and emission maxima with electronic substituent parameters emphasize the rational design of tailored p-bTAAs with predictable electrochemical and photophysical properties. A single palladium catalyst catches two birds with one stone by multicomponent Suzuki and Buchwald-Hartwig coupling to give a library of redox-active triarylamine (TAA) luminophores. Redox potentials, absorption and emission energies together with (TD)DFT calculations of the electronic structure set the stage for structure-property relationships for a rational design of tunable TAAs. image

AbstractEine neue Generation löslicher Phenothiazinyl‐Merocyanin‐substituierter Polyacetylene wurde mittels Rhodium‐katalyisierter Polymerisation der entsprechenden 3‐Ethinyl‐Phenothiazine dargestellt. Die Monomere sind über Sonogashira‐Kupplung und Knoevenagel‐Kondensation zugänglich. UV/Vis‐ und fluoreszenzspektroskopische Untersuchungen der 7‐Acceptor‐substituierten Phenothiazinyl‐Polyacetylene zeigen, dass diese Polymere mit konjugiert verknüpften Merocyaninen in Lösung mit positiver Emissionssolvatochromie lumineszieren und in bestimmten Fällen eine ausgeprägte Festkörperlumineszenz aufweisen.