Organic Small Molecules for Photonics and Electronics from the [2.2]Paracyclophane Scaffold

In the search for molecules for organic photonics and electronics, several strategies have been used to modulate physical and chemical properties of [2.2]paracyclophane derivatives by sequential functionalization of their three-dimensional cores. This review summarizes the major design and synthetic strategies for tuning paracyclophane-containing small molecules by introducing various moieties featuring (hetero)aromatic rings directly connected to each other, as well as alternating (hetero)aryl and ethylene or ethynylene units. Several examples are presented that elucidate the structural, optical, and electronic consequences of incorporating these fragments in the aromatic decks, particularly relating to applications in organic optoelectronics.     

High-Pressure Diels-Alder Reaction: Preparation of [2.2]Paracyclophane Derivatives

High-pressure Diels-Alder cycloaddition reactions of 5-ethenyl[2.2]indeno-paracyclophane (1) with 1,4-benzoquinone (2), N-phenylmaleimide (3), and 2-inden-1-one (4) have been studied. Attempts to convert the cycloadducts into the corresponding aromatic helicenophanes failed. All new compounds were characterized by extensive nuclear magnetic resonance (NMR) investigations.     

[2.2]Paracyclophane-Derived Planar-Chiral Hydrogen-Bond Receptors

The development of planar-chiral hydrogen-bond donors based on the [2.2]paracyclophane scaffold is discussed. General strategies to access functionalized enantiopure [2.2]paracyclophane derivatives are briefly reviewed, with the focus on suitable precursors for the synthesis of planar-chiral thiourea derivatives. The synthesis of fourteen hydrogen-bond donors is described. The interaction of four thiourea derivatives with hydrogen-bond acceptors (DMSO and tetramethylammonium chloride) was investigated by ¹H NMR spectroscopy and X-ray crystallography. A selection of enantiomerically pure planar-chiral derivatives was applied in asymmetric hydrogen-bond catalysis.     

Metal‐Free Catalytic Hydrogenation of Imines with Recyclable [2.2]Paracyclophane‐Derived Frustrated Lewis Pairs Catalysts

A series of [2.2]paracyclophane‐derived frustrated Lewis pairs (FLPs) with reversible, metal‐free hydrogen activation was synthesized and successfully applied in the hydrogenation of imines in moderate to good yields. The high stability of the novel FLP system enables effective recycling of the metal‐free catalysts. This reaction could also be compatible with a larger scale and developed into a pharmaceutical synthesis of cinacalcet {(R)‐N‐[1‐(1‐naphthyl)ethyl]‐3‐[3‐(trifluoromethyl)phenyl]propan‐1‐amine} without heavy metal residues.

     

Synthesis of through-space conjugated polymers containing the pseudo-<Emphasis Type="Italic">ortho</Emphasis>-linked [2.2]paracyclophane moiety

New through-space conjugated polymers comprising the pseudo-ortho-linked [2.2]paracyclophane moiety were synthesized by the Sonogashira coupling reaction. All the synthesized polymers were soluble in common organic solvents and could form thin films. The UV–vis absorption spectra of the synthesized polymers revealed an extension of the conjugation length owing to the through-space interactions. The polymers exhibited a blue-light emission in both solution and film states.     

[2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists

Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site.     

Entropy-controlled thermal back-reaction of photochromic [2.2]paracyclophane-bridged imidazole dimer

A [2.2]paracyclophane-bridged imidazole dimer having bulky 3′,4′,5′-triphenyl-1,1′:2′,1″-terphenyl substituents was synthesized and the photochromic properties were investigated. The half-life of the colored species generated by the UV irradiation of the parent imidazole dimer was 1.0 ms at 298 K in benzene. Although such bulky substituents are introduced on the imidazole dimer, the fast thermal back-reaction can be observed as found in other [2.2]paracyclophane-bridged imidazole dimers. Herein, enthalpy and entropy of the activation energies (?H^‡ and ?S^‡, respectively) for the thermal back-reaction of the present molecule were compared with other [2.2]paracyclophane-bridged imidazole dimers in order to investigate the generality and the limitation of the molecular design of the photochromic imidazole dimer along with the correlation between bulkiness of the substituents and the rate constant of the thermal back-reaction. Finally, we referred to a new method for controlling the rate constant of the thermal back-reaction of [2.2]paracyclophane-bridged imidazole dimers.     

Exploring the Assembly of Resorc[4]arenes for the Construction of Supramolecular Nano-Aggregates

Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone endowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized several architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phenomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV–visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.     

Supramolecular Capsules Derived from Resorcin[4]arenes by H-Bonding and Metal Coordination: Synthesis,Characterization, and Single-Molecule Force Spectroscopy

Self-assembly by H-bonding and by metal-coordination of functionalized calix[4]arenes and cavitands to large supramolecular capsules is described. In addition, a new method of analyzing supramolecular recognition processes at the single molecule level is discussed. By measuring interaction forces in a hydrogen-bonded assembly using single-molecule force spectroscopy (SMFS), the dynamics of the self-assembly process can be evaluated. In the future, consequent application of this new technique will influence supramolecular design principles and the use of non-covalent interactions as construction elements in the field of nanotechnology.     

Dimeric Resorcin[4]arene Capsules in the Solid State

Supramolecular chemistry research is focused on the study of weak non-covalent intermolecular — that is, supramolecular — interactions as the driving force in self-assembly and molecular recognition. Dimeric resorcin[4]arenes capsules have been a focus of our research for the last 15 years. This review describes the solid state complexation studies of unsubstituted phenolic resorcin[4]arenes and pyrogall[4]arenes towards the formation of dimeric capsules and assemblies using ionic and neutral species as guest molecules and templates. The multitude of different crystal structures obtained during these studies demonstrates the versatile nature of resorcin[4]arenes and pyrogall[4]arenes (2-hydroxy-resorcin[4]arenes) as supramolecular hosts in crystal engineering.     

A Rapid and Highly Efficient Microwave-Promoted Four-Component Domino Reaction for the Synthesis of Novel Spiro[benzo[a]chromeno[2,3-c]phenazine] Derivatives Under Solvent-Free Conditions

p-Toluenesulfonic acid was applied as an efficient, non-toxic and solid acid catalyst for the one-pot, four-component condensation between 2-hydroxy-1,4-naphthoquinone, benzene-1,2-diamine, cyclic 1,3-dicarbonyl compounds and isatin or ninhydrin to afford the corresponding novel spiro[benzo[a]chromeno[2,3-c]phenazine] derivatives via a new two-step domino protocol under conventional heating and microwave irradiation. This solvent-free process produces biologically considerable heterocycles with the formation of five new bonds (two C–C, two C?N, and one C–O) and two new rings in a single operation and this effective green process provides considerable advantages such as: operational simplicity, very short reaction time, high yields, absence of any tedious process or purification, and it avoids hazardous reagents/solvents.     

Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis,Formulation and Characterization

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed.     

Cucurbit[n]urils-related Multitopic Supramolecular Components: Design,Properties, and Perspectives

Cucurbit[n]urils (CBns) are an intriguing family of macrocyclic hosts whose chemistry has undergone rapid developments in recent decades. The initial interest in the synthesis, modifications and binding properties has shifted to areas focused on applications in drug storage, delivery, and release, external-stimuli responsive devices, and molecular nano-reactors. Since CBns are fruitfully complemented by cyclodextrins (CDs) in such systems, guest molecules that contain several binding sites are needed. These multitopic guests provide not only a scaffold for holding CBns and CDs together in appropriate arrangements but also allow for manipulation with supramolecular aggregates, e. g., reorganization or release of macrocycles. In this review, we summarize recent studies related to the design of multitopic guests. Binding motifs properties, the role of attractive or repulsive lateral interactions, the competition-compensation effect, and rotaxane versus pseudorotaxane manner are discussed.     

Cucurbit[n]uril Host-Guest Complexes of Acids,Photoacids, and Super Photoacids

The supramolecular chemistry of host-guest complexes of cucurbit[n]urils (CB[n]) with acidic guests in the ground (HG⁺) and excited states (HG⁺*) are reviewed. The effects of CB[n] complexation on the guests’ pK_a and/or pK_a* values are related to relative binding constants and host-guest structures of the acid form of the guest and its conjugate base. Included are carbon acids, guests of biological and medicinal interest, dyes and related polyaromatic guests, and other organic and organometallic guests. The applications of the pK_a shifts to the solubility, stability, and bioavailabilty of drug molecules, the stability and enhanced spectral properties of dyes, and in pH-induced self-sorting, micelle formation, host-guest shuttling, and controlled guest release, are discussed.     

The Effect of Cucurbit[7]uril on the Antitumor and Immunomodulating Properties of Oxaliplatin and Carboplatin

Cucurbit[7]uril (CB[7]) is a molecular container that may form host–guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]–oxaliplatin complex and the mixture of CB[7] and carboplatin (1:1) on viability and proliferation of a primary cell culture (peripheral blood mononuclear cells), two tumor cell lines (B16 and K562) and their activity in the animal model of melanoma. At the same time, we studied the impact of platinum (II) drugs with CB[7] on T cells and B cells in vitro. Although the stable CB[7]–carboplatin complex was not formed, the presence of cucurbit[7]uril affected the biological properties of carboplatin. In vivo, CB[7] increased the antitumor effect of carboplatin, but, at the same time, increased its acute toxicity. Compared to free oxaliplatin, its complex with CB[7] shows a greater cytotoxic effect on tumor cell lines B16 and K562, while in vivo, the effects of the free drug and encapsulated drug were comparable. However, in vivo studies also demonstrated that the encapsulation of oxaliplatin in CB[7] lowered the toxicity of the drug.     

Carbene Rearrangements, 60.‡ Supramolecular Structure‐Reactivity Relationships: Photolysis of a Series of Aziadamantane@Cyclodextrin Inclusion Complexes in the Solid State

Photolyses of the α‐, β‐ and γ‐cyclodextrin complexes of 2‐aziadamantane ( 1 ) in the solid state afforded markedly different product distributions, as determined by quantitative GC and HPLC analyses. The results are discussed with respect to the structures of the inclusion complexes.     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

Recent trends in the chemistry of aminobenzo[b]thiophenes

The chemistry of aminobenzo[b]thiophenes has gained increased interest in both synthetic organic chemistry and biological fields and has considerable value. Some of the reactions have been successfully applied for the production of various fused heterocycles. The present review covers the literature up to date for the synthesis, reactions and applications of such compounds.     

An Abbreviated Synthesis of 7,12-Dimethylbenz[ a ]anthracene and Benzo[ c ]chrysene Metabolites Using the Suzuki Reaction

Efficient syntheses of important metabolites of 7,12-dimethylbenz[ a ]anthracene (DMBA) and benzo[ c ]chrysene (B[ c ]C), via Suzuki coupling reaction are described. This approach provides an excellent method for the preparation of 3-methoxy-DMBA 5 , 10-methoxy-B[ c ]C 14 and 2-methoxy B[ c ]C 20 , and hence for the corresponding dihydrodiols 6 , 15 , and 21 . Following a similar Suzuki reaction, DMBA-6(5 H )-one 8 was also synthesized in high yield.     

Dual-Targeted Supramolecular Vesicles Based on the Complex of Galactose Capped Pillar[5]Arene and Triphenylphosphonium Derivative for Drug Delivery

In this study, a dual targeted supramolecular glycol-vesicle based on the host-guest complexation of galactose capped pillar[5]arene ( GALWP5 ) and triphenylphosphonium derivative ( D-TPP ) have been constructed ( GALWP5⊃D-TPP ), which showed dual target potential (cell and mitochondria targeting) resulting from its galactose units and TPP units, respectively. The dual targeted glycol-vesicle displays ignorable cytotoxicity and good mitochondria targeting. Our work presents a good example of rational design for an effective cell and subcellular organelles dual targeted delivery system.