Ring Fusion Research Articles

Synthesis of Acenaphthene Fused Dithiaporphyrin(3.1.1.1)s and N‐Fused Triphyrin(3.1.1)s in One‐Pot Condensation

Two different types of novel nonaromatic acenaphthene fused macrocycles such as acenaphthene fused dithiaporphyrin(3.1.1.1)s and acenaphthene fused N‐fused triphyrin(3.1.1)s were synthesized in one pot condensation reaction using 5,6‐dibromoacenaphthene as a key precursor. The X‐ray analysis revealed the oval core‐shaped structure for dithiaporphyrin(3.1.1.1)s and intramolecular ring fusion in N‐Fused triphyrin(3.1.1)s. The NMR, absorption and DFT studies suggested the non‐aromatic nature of both macrocycles which absorb strongly in visible‐NIR region. Both macrocycles were stable under electrochemical conditions and showed their electron‐rich nature.

Stable, aromatic, and electrophilic azepinium ions: Design using quantum chemical methods.

Cyclic nitrenium ions containing five-membered and six-membered rings are available, however, the seven-membered cyclic nitrenium ions (azepinium ions) are rare. The chemistry of these species is related to their stability originating from the aromaticity due to 6π electrons. Very few theoretical and experimental studies have been conducted on the azepinium ions. Related clozapine and olanzapine cations (diazepinium ions) were observed during drug metabolism studies. In this work, quantum chemical analysis has been carried out to estimate the stability, aromaticity, and electrophilicity of several derivatives of azepinium ions. A few of the designed azepinium ions carry ΔES-T values in the range of 50 kcal/mol favoring singlet state; π donating groups at the 2nd position increase the singlet-triplet energy differences. Most of the substituents reduce the NICS(1) values compared to the parent system. Ring fusion with heterocyclic five-membered rings generally increases the aromaticity and the stability of the azepinium ion ring systems. The electrophilicity parameters estimated in terms of HIA, FIA, and ω values indicate that it is possible to fine-tune the chemical properties of azepinium ions with appropriate modulation.

Furano‐ and Thieno‐Fused Carbazole‐Containing Azaborines and Their π‐Extension: Synthesis, Structures, and Properties

AbstractA series of carbazole‐containing azaborines, furano‐fused 1–2F and 1–3F and thieno‐fused 1–2T and 1–3T, were efficiently synthesized from a common carbazole boronic acid ester in two steps. The structural effects of the fused ring moieties and the patterns of the ring fusion were clarified. According to X‐ray crystal structure analysis, the furano‐ and thieno‐fused carbazole azaborines had planar structures and generally formed 1D columns. UV–vis analysis revealed that their absorption properties were significantly affected by the fused ring moieties. In contrast, the fluorescence properties were affected by the ring fusion patterns. π‐Extended derivatives of 1–2T and 1–3T, benzothieno‐fused 1–2BT and 1–3BT and phenyl‐substituted 1–2T‐Ph2 and 1–3T‐Ph2 were synthesized, and the effects of π‐extension on physical properties were also investigated. All the π‐extended compounds showed red‐shifts in absorption and fluorescence spectra compared with the pristine 1–2T and 1–3T. The color of solid‐state emission of the synthesized azaborines was tuned from purple to green without electron‐rich or ‐deficient substituents. The structural effects on the electronic structures were also discussed based on theoretical calculations.

Peripheral Fusion of Carbon-Based Aromatic Rings to B4N4-Heteropentalene Leading to Close π-Stacking in the Solid State.

π-Electronic molecules with a BN-heterocyclic and carbon-based aromatic hybrid ring system (h-CBN) are interesting in that they potentially exhibit synergistic properties arising from the two different π-systems. Here we report the synthesis and properties of a h-CBN-type molecule (1) having a bicyclic B4N4-heteropentalene core fused with extended aromatic rings. This molecule exhibits excellent chemical stability despite the absence of bulky substituents for kinetic protection, which in turn provides effective stacking of the π-system upon crystallization. Depending on the crystallization solvent, 1 forms two polymorphs, i. e., the α- and β-phases. While both phases have one-dimensional columnar structures, the π-stacking geometries associated with the transfer integrals of the frontier orbitals are different, resulting in a twofold difference in the electrical conducting properties. We also found that upon thermal vacuum deposition, 1 gives an amorphous film, which serves as a host material for a red phosphorescent OLED device (maximum external quantum efficiency: 15.5 and 13.3 % at 0.1 and 2.5 mA, respectively).

Four-Membered Ring-Embedded Cycloarene Enabling Anti-Aromaticity and Ultra-Narrowband Emission.

The synthesis of fully fused π-conjugated cycloarenes embedded with nonbenzenoid aromatics is challenging. In this work, the first example of four-membered ring-embedded cycloarene (MF2) was designed and synthesized in single-crystal form by macrocyclization and ring fusion strategies. For comparison, single bond-linked chiral macrocycle MS2 without two fused four-membered rings and its linear-shaped polycyclic benzenoid monomer L1 were also synthesized. The pronounced anti-aromaticity of four-membered rings significantly adjusts the electronic structures and photophysical properties of cycloarene, resulting in an enhancement of the photoluminescence quantum yield (PLQY) from 10.66 % and 10.74 % for L1 and MS2, respectively, to 54.05 % for MF2, which is the highest PLQY among the reported cycloarenes. Notably, owing to the embedded anti-aromatic four-membered rings that reduce structural displacements, MF2 exhibits an ultra-narrowband emission with a single-digit full-width at half-maximum (FWHM) of only 7 nm (0.038 eV), which sets a new record among all reported organic narrowband luminescent molecules, and represents the first example of ultra-narrowband emission in conventional polycyclic aromatic hydrocarbons (PAHs) devoid of heteroatoms.

Adjustable Regioselectivity for the Diels-Alder Reactions of Sulfolenodipyrrins upon Molecular Engineering on H-Bonds.

The Diels-Alder reactions of sulfolenodipyrrins prove to be an efficient way to construct aromatic ring-fused dipyrrins. However, adjustable annulation is still hard to achieve. To address this, molecular engineering on the H-bond has been employed. The α-position aryl group-modified sulfolenodipyrrins have been synthesized to react with various dienophiles in Diels-Alder reactions, affording the monoannulation products with different regioselectivity in good yields (45-76%). The remaining sulfolenopyrrole in monoadducts can undergo further fusion in the presence of dienophiles and TEMPO, giving the bisadducts with a lactam subunit in an appropriate yield. According to the crystal structures and theoretical calculations, the intramolecular H-bonds between the α-substituent and the nearby pyrrole confine the conjugation pathway of the dipyrrin core. With respect to the normal NH-sulfolenopyrrole, the imino-type one features low aromaticity, from which SO2 extrusion generates more stable dipyrrin-diene, achieving regioselectivity. In addition, aromatic ring fusion results in red-shifted absorption and emission spectra, and the annulation units regulate the emission intensity. This work shows the versatility of intramolecular H-bonds in regulating the reaction through confinement of the conjugation system.

High‐Yielding Nanobelt Formation by Chirality‐Assisted Synthesis

Shape‐persistent Conjugated nanobelts are fascinating synthetic targets. However, in most cases these are made in low overall yields by applying strategies of macrocyclization followed by (multiple) ring fusion reactions for nanobelt formation. Here, we describe the high yielding synthesis of enantiopure chiral nanobelts in 84% yield by applying chirality‐assisted synthesis (CAS). The chiral nanobelts were investigated by UV/vis and CD spectroscopy. By DFT calculations the aromaticity of these structures is discussed.

High-Yielding Nanobelt Formation by Chirality-Assisted Synthesis.

Shape-persistent Conjugated nanobelts are fascinating synthetic targets. However, in most cases these are made in low overall yields by applying strategies of macrocyclization followed by (multiple) ring fusion reactions for nanobelt formation. Here, we describe the high yielding synthesis of enantiopure chiral nanobelts in 84% yield by applying chirality-assisted synthesis (CAS). The chiral nanobelts were investigated by UV/vis and CD spectroscopy. By DFT calculations the aromaticity of these structures is discussed.

FuBay: An Integrated Fusion Framework for Hyperspectral Super-Resolution Based on Bayesian Tensor Ring.

Fusion with corresponding finer-resolution images has been a promising way to enhance hyperspectral images (HSIs) spatially. Recently, low-rank tensor-based methods have shown advantages compared with other kind of ones. However, these current methods either relent to blind manual selection of latent tensor rank, whereas the prior knowledge about tensor rank is surprisingly limited, or resort to regularization to make the role of low rankness without exploration on the underlying low-dimensional factors, both of which are leaving the computational burden of parameter tuning. To address that, a novel Bayesian sparse learning-based tensor ring (TR) fusion model is proposed, named as FuBay. Through specifying hierarchical sprasity-inducing prior distribution, the proposed method becomes the first fully Bayesian probabilistic tensor framework for hyperspectral fusion. With the relationship between component sparseness and the corresponding hyperprior parameter being well studied, a component pruning part is established to asymptotically approaching true latent rank. Furthermore, a variational inference (VI)-based algorithm is derived to learn the posterior of TR factors, circumventing nonconvex optimization that bothers the most tensor decomposition-based fusion methods. As a Bayesian learning methods, our model is characterized to be parameter tuning-free. Finally, extensive experiments demonstrate its superior performance when compared with state-of-the-art methods.

Four‐Membered Ring‐Embedded Cycloarene Enabling Anti‐Aromaticity and Ultra‐Narrowband Emission

AbstractThe synthesis of fully fused π‐conjugated cycloarenes embedded with nonbenzenoid aromatics is challenging. In this work, the first example of four‐membered ring‐embedded cycloarene (MF2) was designed and synthesized in single‐crystal form by macrocyclization and ring fusion strategies. For comparison, single bond‐linked chiral macrocycle MS2 without two fused four‐membered rings and its linear‐shaped polycyclic benzenoid monomer L1 were also synthesized. The pronounced anti‐aromaticity of four‐membered rings significantly adjusts the electronic structures and photophysical properties of cycloarene, resulting in an enhancement of the photoluminescence quantum yield (PLQY) from 10.66 % and 10.74 % for L1 and MS2, respectively, to 54.05 % for MF2, which is the highest PLQY among the reported cycloarenes. Notably, owing to the embedded anti‐aromatic four‐membered rings that reduce structural displacements, MF2 exhibits an ultra‐narrowband emission with a single‐digit full‐width at half‐maximum (FWHM) of only 7 nm (0.038 eV), which sets a new record among all reported organic narrowband luminescent molecules, and represents the first example of ultra‐narrowband emission in conventional polycyclic aromatic hydrocarbons (PAHs) devoid of heteroatoms.

Endothelial Cells Increase Mesenchymal Stem Cell Differentiation in Scaffold-Free 3D Vascular Tissue.

In this study, we present a versatile, scaffold-free approach to create ring-shaped engineered vascular tissue segments using human mesenchymal stem cell-derived smooth muscle cells (hMSC-SMCs) and endothelial cells (ECs). We hypothesized that incorporation of ECs would increase hMSC-SMC differentiation without compromising tissue ring strength or fusion to form tissue tubes. Undifferentiated hMSCs and ECs were co-seeded into custom ring-shaped agarose wells using four different concentrations of ECs: 0%, 10%, 20%, and 30%. Co-seeded EC and hMSC rings were cultured in SMC differentiation medium for a total of 22 days. Tissue rings were then harvested for histology, Western blotting, wire myography, and uniaxial tensile testing to examine their structural and functional properties. Differentiated hMSC tissue rings comprising 20% and 30% ECs exhibited significantly greater SMC contractile protein expression, endothelin-1 (ET-1)-meditated contraction, and force at failure compared with the 0% EC rings. On average, the 0%, 10%, 20%, and 30% EC rings exhibited a contractile force of 0.745 ± 0.117, 0.830 ± 0.358, 1.31 ± 0.353, and 1.67 ± 0.351 mN (mean ± standard deviation [SD]) in response to ET-1, respectively. Additionally, the mean maximum force at failure for the 0%, 10%, 20%, and 30% EC rings was 88.5 ± 36. , 121 ± 59.1, 147 ± 43.1, and 206 ± 0.8 mN (mean ± SD), respectively. Based on these results, 30% EC rings were fused together to form tissue-engineered blood vessels (TEBVs) and compared with 0% EC TEBV controls. The addition of 30% ECs in TEBVs did not affect ring fusion but did result in significantly greater SMC protein expression (calponin and smoothelin). In summary, co-seeding hMSCs with ECs to form tissue rings resulted in greater contraction, strength, and hMSC-SMC differentiation compared with hMSCs alone and indicates a method to create a functional 3D human vascular cell coculture model.

Unlocking the Potential of Glutinol: Structural Diversification and Antifungal Activity against Phytopathogenic Fusarium Strains.

Unlike most common pentacyclic plant triterpenes, glutinol has a methyl group at position C-9 and a Δ5 double bond. At the same time, it lacks a methyl at C-10. These features significantly modify its chemical behavior compared to other triterpenes, particularly under oxidative conditions. Although the isolation of glutinol from various plant species has been documented, its chemistry remains largely unexplored. In this study, glutinol was isolated from the bark of Balfourodendron riedelianum as a starting material for top-down strategies of structural diversification, which included ring fusion, oxidation, aromatization, and ring cleavage reactions. Glutinol, together with a library of 22 derivatives, was evaluated for antifungal activity against three phytopathogenic Fusarium strains, F. solani, F. graminearum, and F. tucumaniae. Some of the derivatives displayed antifungal activity; in particular, compound 12, featuring a triazine ring, displayed the best fungicidal properties against F. solani and F. graminearum, while the ring B cleavage product 23 showed the best activity against F. tucumaniae. This study highlights the potential of glutinol as a scaffold for structural diversification, and these results may contribute to the design of novel fungicidal agents against phytopathogenic strains.

Design, synthesis, and optimization of novel PD-L1 inhibitors and the identification of a highly potent and orally bioavailable PD-L1 inhibitor

In this paper we report the discovery of structurally novel and highly potent programmed cell death-ligand 1 (PD-L1) inhibitors targeting surface and intracellular PD-L1. A ring fusion design utilizing dimethoxyphenyl indazole derivatives was used, followed by structural extension, which further improved potency by inducing the formation of additional symmetrical interactions within the PD-L1 binding site, leading to the discovery of novel and highly active tetra-aryl-scaffold inhibitors. Key optimizations involved polar tail chain modifications that improve potency and minimize cell cytotoxicity. In addition, druggability issues that exist outside the rule-of-five chemical space were addressed. CB31, a representative compound, was found to exhibit outstanding activity in blocking programmed cell death-1 (PD-1)/PD-L1 interactions (IC50 = 0.2 nM) and enhancing T-cell functions, with minimal cell cytotoxicity. CB31 also displayed favorable oral pharmacokinetic properties, consistent with its high passive permeability and insusceptibility to efflux transporters, as well as its high metabolic stability. Additionally, CB31 demonstrated mechanistically differentiated features from monoclonal antibodies by inducing PD-L1 internalization, intracellular retention of PD-L1 with altered glycosylation pattern, and PD-L1 degradation. It also demonstrated greater effects on tumor size reduction and tumor cell killing, with enhanced T-cell infiltration, in a 3D tumor spheroid model. Overall, results show that CB31 is a promising small-molecule PD-L1 inhibitor that can inhibit PD-1/PD-L1 interactions and promote PD-L1 degradation.

Unexpectedly Regioselective Diels-Alder Reactions of New Unsymmetrical Benzoquinones: A Convenient Synthetic Entry to Uniquely Substituted Decalins.

We report flexible synthesis of new unsymmetrically 2,6-disubstituted benzoquinones (33 examples) and a systematic study of their reactivity in the Diels-Alder reaction. The Diels-Alder reactions of selected unsymmetrical benzoquinones with seemingly similar substituents were found to proceed with high regioselectivity and the formation of selected experimentally observed main products was rationalized by theoretical (DFT) calculations. The findings can be exploited in the convenient preparation of densely substituted and stereochemically defined decalins with unique angular substituents at ring fusion. We also demonstrate the usefulness of this methodology in complex molecule synthesis through the total synthesis of a novel forskolin analog possessing an ethyl group at the fusion of the rings B and C.

Ring Fusion Elevates the Electronic Mobility of Azabenzannulated Perylene Diimide.

The backwardness of n-type organic semiconductors still exists compared with the p-type counterparts. Thus, the development of high-performance n-type organic semiconductors is of great importance for organic electronic devices and their integrated circuits. In recent years, azabenzannulated perylene diimide (PDI), as one of immense bay-region-annulated PDI derivatives, has drawn considerable attentions. However, the electronic mobilities of azabenzannulated PDI derivatives are barely satisfactory. In this contribution, the peripheral benzene ring in azabenzannulated PDI 2 was fused to the ortho position by intramolecular C-H arylation cyclization. This endows the resultant azabenzannulated PDI 4 a planar configuration as well as electron deficient pentagonal ring. As a result, the electronic mobility of 4 is almost two orders of magnitude higher than that of the nonfused azabenzannulated PDI 2. This work shall pave a new avenue in elevating the performance of azabenzannulated PDI in organic electronics.

Tuning Molecular Packing and Boosting Self-Assembling Properties via Ring Fusion Strategy in Naphthalimide-Based A-D-A Conjugated Systems.

Two fully fused acceptor-donor-acceptor (A-D-A) architecture conjugated derivatives (NPF and NCF) comprising an electron-withdrawing naphthalimide (NMI) and two different electron-donating cores, phenanthrene and carbazole, respectively, were conveniently synthesized by bismuth(III)-catalyzed selective cyclization of vinyl ethers. Compared with their corresponding single bond-linked A-D-A molecules NPS and NCS, both having a moderately twisted aromatic configuration, the ring fusion strategy leads to fully coplanar conjugated skeletons and greatly changes the electronic structures, photophysical properties, self-assembling behaviors, and molecular packing motifs. In particular, the naphthalimide/carbazole derivative NCF exhibits intriguing 2D brickwork packing and significantly enhanced self-assembling properties.

Effect of π-Bridge Ring Fusion on the Wide-Bandgap Donor and Its Application for High-Efficiency All Small-Molecule Tandem Solar Cells

Effect of π-Bridge Ring Fusion on the Wide-Bandgap Donor and Its Application for High-Efficiency All Small-Molecule Tandem Solar Cells

Novel imidazolone derivatives as potential dual inhibitors of checkpoint kinases 1 and 2: Design, synthesis, cytotoxicity evaluation, and mechanistic insights

Applying various drug design strategies including ring variation, substituents variation, and ring fusion, two series of 2-(alkylthio)-5-(arylidene/heteroarylidene)imidazolones and imidazo[1,2-a]thieno[2,3-d]pyrimidines were designed and prepared as dual potential Chk1 and Chk2 inhibitors. The newly synthesized hybrids were screened in NCI 60 cell line panel where the most active derivatives 4b, d-f, and 6a were further estimated for their five dose antiproliferative activity against the most sensitive tumor cells including breast MCF-7 and MDA-MB-468 and non-small cell lung cancer EKVX as well as normal WI-38 cell. Noticeably, increasing the carbon chain attached to thiol moiety at C-2 of imidazolone scaffold elevated the cytotoxic activity. Hence, compounds 4e and 4f, containing S-butyl fragment, exhibited the most antiproliferative activity against the tested cells where 4f showed extremely potent selectivity toward them. As well, compound 6a, containing imidazothienopyrimidine core, exerted significant cytotoxic activity and selectivity toward the examined cells. The mechanistic investigation of the most active cytotoxic analogs was achieved through the evaluation of their inhibitory activity against Chk1 and Chk2. Results revealed that 4f displayed potent dual inhibition of both Chk1 and Chk2 with IC50 equal 0.137 and 0.25 μM, respectively. It also promoted its antiproliferative and Chk suppression activity via EKVX cell cycle arrest at S phase through stimulating the apoptotic approach. The apoptosis induction was also emphasized by elevating the expression of Caspase-3 and Bax, that are accompanied by Bcl-2 diminution. The in silico molecular docking and ADMET profiles of the most active analogs have been carried out to evaluate their potential as significant anticancer drug candidates.

Multifaceted effects of ring fusion on the stability of charged dialkoxyarene redoxmers

Due to their almost unlimited scalability, redox flow batteries can make versatile and affordable energy storage systems. Redox active materials (redoxmers) in these batteries largely define their electrochemical performance, including the life span of the battery that depends on the stability of charged redoxmers. In this study, we examine the effects of expanding the π-system in the arene rings on the chemical stability of dialkoxyarene redoxmers that are used to store positive charge in RFBs. When 1,4-dimethoxybenzene is π-extended to 1,4-dimethoxynaphthalene, a lower redox potential, improved kinetic stability, and longer cycling life are observed. However, when an additional ring is fused to make 9,10-dimethoxyanthracene, the radical cation undergoes rapid O-dealkylation possibly due to increased steric strain that drives methoxy out of the arene plane thus breaking the π-conjugation with O 2p orbitals. On the other hand, the planar structure of 1,4-dimethoxynaphthalene may facilitate second-order reactions of radical cations leading to their neutralization in the bulk. Our study suggests that extending the π-system changes reactivity in multiple (sometimes, opposite) ways, so lowering the oxidation potential through π-conjugation to improve redoxmer stability should be pursued with caution.

Anthraquinone fused sulfolenoporphyrins: Regulation of reactivity and property through annulations

The sulfolenoporphyrin-based Diels-Alder reaction is an efficient strategy in the construction of aromatic ring-fused porphyrins. However, the structure-reactivity relationship is still less explored. Here, we have synthesized the mono-, bis- and tri-anthraquinone fused sulfolenoporphyrins and explore the effect of anthraquinone fusion on their further Diels-Alder reactions. As a result, more anthraquinone fusions lead to higher reactivity but lower annulation yield. Theoretical calculation discloses that anthraquinone fusion has the HOMO of the dienes (i.e., the intermediates after extrusion of SO2 from sulfolenoporphyrins) raised owing to the [Formula: see text]-extension, affording high reactivity. However, as the number of ring fusions increases, the LUMO energy levels of dienes are reduced, which seems to benefit the side reaction (i.e., the dimer/oligomerization owing to the Diels-Alder reaction among porphyrin dienes), leading to the rapid consumption of dienes and low yields. Besides, the influence of the peripheral anthraquinone units on molecular stacking, absorption as well as aromaticity was investigated experimentally and computationally. In brief, this work has investigated the structure-reactivity relationship of sulfolenoporphyrins in the Dies-Alder reaction, which will help construct [Formula: see text]-extended porphyrin rationally.