Cage-like Compounds Research Articles

Anion Recognition-Directed Supramolecular Catalysis with Functional Macrocycles and Molecular Cages.

ConspectusThe development of supramolecular chemistry has provided a variety of host molecules and noncovalent tools for boosting catalytic processes, stimulating the emergence and advance of supramolecular catalysis, among which macrocyclic and cage-like compounds have attracted great attention due to their possession of an enzyme-mimetic cavity and recognition ability. While the privileged scaffolds such as crown ethers, cyclodextrins, cucurbiturils, calixarenes, and metal-coordinated cages have been widely used, their skeletons usually do not contain a directional binding site; binding and activation mainly rely on cation-associated interactions or hydrophobic effects. In this context, the recent advance of anion supramolecular chemistry has drawn our attention to developing an anion recognition-directed approach by using tailor-made functionalized macrocycles and cages. Anions are important widely existing species in both biological and chemical systems and play an important role in regulating the structure and function of enzymes. We envisioned that by taking advantage of anions, including their rich variety, diverse geometry, and multiple interaction sites, the sophisticated cooperation of multiple noncovalent interactions can be manipulated in a confined cavity for directing efficient and selective catalysis.Following this concept, we initiated our study by introducing typical thiourea H-bonding groups to design and synthesize a series of bis-thiourea macrocycles, especially chiral macrocycles, by incorporating chiral linkers. Taking advantage of the obtained strong, cooperative anion binding, a macrocycle-enabled counteranion trapping strategy was developed, which afforded greatly enhanced catalytic efficiency and excellent stereocontrol in acid-catalyzing reactions. Furthermore, inspired by sulfate-induced macrocyclic dimerization assembly, we built a substrate-induced assembly system, enabling an induced-fit cooperative activation network for efficient and enantioselective catalysis. In addition, anion recognition-driven chirality gearing with a more sophisticated trithiourea cage was revealed, which could provide a basis for implementing anion-triggered allosteric catalysis within the induced helical space. Not limited to hydrogen bonding, the emerging anion-π interactions were largely exploited. A series of triazine-based prism cages containing three V-shaped electron-deficient π-cavities were constructed, and their anion-π binding properties were studied. Based on this system, cooperative anion-π activation was established for driving highly efficient and selective catalysis, which paved a way to push anion-π interactions toward more practical and useful catalyst design.These results demonstrated that the anion-recognition direction can serve as a powerful, versatile approach for boosting highly efficient and selective supramolecular catalysis. It is feasible not only for employing exogenous anions (e.g., counteranion) as a handle but also for recognition and regulation of anionic active intermediates/transition states, from use in conventional H-bonding to emerging anion-π recognition.

Guest-Mediated Hierarchical Self-Assembly of Dissymmetric Organic Cages to Form Supramolecular Ferroelectrics

Guest-Mediated Hierarchical Self-Assembly of Dissymmetric Organic Cages to Form Supramolecular Ferroelectrics

Molecular cages for biological applications.

Artificial receptors able to recognise biologically relevant molecules or ions have gained interest in the chemical community because they offer a plethora of posibilities. Molecular cage compounds are polycyclic compounds with a cavity designed for the encapsulation of guest species. Once inside the host cavity, the substrate can be transported through membranes and protected from the action of enzymes or other reactive species, thus offering the possibility of interfering with biological systems. Commonly, enzymes have been an inspiration for chemists in the search and design of defined cavities for different purposes. However, the chemical preparation of molecular cages has struggled with many synthetic challenges but this effort is worthwhile as they are a very promising tool for many applications ranging from sensing, delivery, purification or even promotion of/prevention from chemical modifications. Since the early reports at the end of the 60s, this field has experienced a growing interest; this review summarises the progress in the preparation and study of cage-like compounds highlighting their importance in biological applications.

Chiral Self-sorting in Cage-like Compounds

Chiral self-sorting in cage-like compounds is drawing increasing attention in recent years. It is of great importance in controlling the chirality of the formed cages and their chirality related pr...

Recent applications of ninhydrin in multicomponent reactions.

Ninhydrin (1,2,3-indanetrione hydrate) has a remarkable breadth in different fields, including organic chemistry, biochemistry, analytical chemistry and the forensic sciences. For the past several years, it has been considered an important building block in organic synthesis. Therefore, there is increasing interest in ninhydrin-based multicomponent reactions to rapidly build versatile scaffolds. Most of the works described here are simple reactions with readily available starting materials that result in complex molecular architectures. Some of the synthesized compounds exhibit interesting biological activities and constitute a new hope for anticancer agents. The present review aims to highlight the multicomponent reactions of ninhydrin towards diverse organic molecules during the period from 2014 to 2019.

New Cu4Na4- and Cu5-Based Phenylsilsesquioxanes. Synthesis via Complexation with 1,10-Phenanthroline, Structures and High Catalytic Activity in Alkane Oxidations with Peroxides in Acetonitrile

Self-assembly of copper(II)phenylsilsesquioxane assisted by the use of 1,10-phenanthroline (phen) results in isolation of two unusual cage-like compounds: (PhSiO1,5)12(CuO)4(NaO0.5)4(phen)4 1 and (PhSiO1,5)6(PhSiO1,5)7(HO0.5)2(CuO)5(O0.25)2(phen)3 2. X-Ray diffraction study revealed extraordinaire molecular architectures of both products. Namely, complex 1 includes single cyclic (PhSiO1,5)12 silsesquioxane ligand. Four sodium ions of 1 are additionally ligated by 1,10-phenanthrolines. In turn, “sodium-less” complex 2 represents coordination of 1,10-phenanthrolines to copper ions. Two silsesquioxane ligands of 2 are: (i) noncondensed cubane of a rare Si6-type and (ii) unprecedented Si7-based ligand including two HOSiO1.5 fragments. These silanol units were formed due to removal of phenyl groups from silicon atoms, observed in mild conditions. The presence of phenanthroline ligands in products 1 and 2 favored the π–π stacking interactions between neighboring cages. Noticeable that in the case of 1 all four phenanthrolines participated in such supramolecular organization, unlike to complex 2 where one of the three phenanthrolines is not “supramolecularly active”. Complexes 1 and 2 were found to be very efficient precatalysts in oxidations with hydroperoxides. A new method for the determination of the participation of hydroxyl radicals has been developed.

Discovery of diazahexa/hepta cyclic cage-like compounds with broad-spectrum antifungal activity against Candida and Cryptococcus species.

Invasive fungal infections caused by Candida and Cryptococcus species lead to life threating infections in immunocompromised individuals. Furthermore, increasing incidence of fungal strains resistant to FDA-approved antifungal drugs along with the paucity of antifungal drugs warrants novel drugs to treat invasive fungal infections. In this study, we investigated the antifungal activity of a novel series of diazahexa/hepta cyclic cage-like compounds. Results indicate that compounds with unsubstituted and o-methyl substitution on aryl rings exhibit potent broad-spectrum antifungal activity against various fungal strains. In addition, these compounds showed significant inhibitory activity against Candida hyphae and biofilm formation. Collectively, results from this study indicate that these compounds are promising candidates to develop as novel antifungal drugs to treat drug-resistant fungal infections.

Facial one-pot synthesis of D3h symmetric bicyclocalix[2]arene[2]triazines and their layered comb self-assembly

A number of D3h symmetric bicyclocalix[2]arene[2]triazine core compounds were synthesized via a general and good-yielding (43–48% yield) facile protocol starting from cyanuric halides, phloroglucinol and K2CO3 under very mild reaction conditions. These cage-like compounds are tolerante with different reaction conditions and can be derived with other functional groups in high yields. The X-ray crystal structures show these compounds have slightly distorted D3h symmetric structures. Due to the unique molecular topological structure, bicyclocalix[2]arene[2]triazine molecules form unique layered comb networks when hydrogen bond groups exist (such as CO2H, B(OH)2), which represent a new kind of building block unit for supramolecular architectures.

Synthesis of penta- and tetra-cyclic cage-like compounds and dispiro heterocycles through microwave-assisted solvent-free multi-component domino reactions

Novel penta- and tetra-cyclic cage-like compounds and dispiro heterocycles were obtained as a result of a microwave-assisted three-component domino reaction.

A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid.

The microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields.

Multicomponent [3+2] cycloaddition strategy: stereoselective synthesis of novel polycyclic cage-like systems and dispiro compounds

The syntheses of novel structurally intriguing hexacyclic cage-like compounds have been achieved from the three-component tandem [3+2] cycloaddition–intramolecular annulation reactions of ninhydrin, α-amino acids and (E)-3-arylidene-1-methylpiperidin-4-ones. On the other hand the four-component reactions of ninhydrin, o-phenylenediamine, α-amino acids and (E)-3-arylidene-1-methylpiperidin-4-ones afforded novel polycyclic dispiro compounds.

Donor–acceptor cyclopropanes with Lawesson's and Woollins' reagents: formation of bisthiophenes and unprecedented cage-like molecules

Furan-derived donor-acceptor-substituted cyclopropanes were reacted with Lawesson's reagent. Depending on the reaction conditions either bisthiophenes or unprecedented cage-like molecules were obtained. Woollins' reagent always led to the respective selenium-containing cage-like compounds.

C3i-Symmetric Octanuclear Cadmium Cages: Double-Anion-Templated Synthesis, Formation Mechanism, and Properties

A series of C(3i)-symmetric bicapped trigonal antiprismatic Cd(8) cages [2X@Cd(8)L(6)(H(2)O)(6)]⋅n Y⋅solvents (X = Cl(-), Y = NO(3)(-), n = 2: MOCC-4; X = Br(-), Y = NO(3)(-), n = 2: MOCC-5; X = NO(3)(-), Y = NO(3)(-), n = 2: MOCC-6; X = NO(3)(-), Y = BF(4)(-), n = 2: MOCC-7; X = NO(3)(-), Y = ClO(4)(-), n = 2: MOCC-8; X = CO(3)(2-), n = 0: MOCC-9), doubly anion templated by different anions, were solvothermally synthesized by means of a flexible ligand. Interestingly, the CO(3)(2-) template for MOCC-9 was generated in situ by two-step decomposition of DMF solvent. For other MOCCs, spherical or trigonal monovalent anions could also play the role of template in their formation. The template abilities of these anions in the formation of the cages were experimentally studied and are discussed for the first time. Anion exchange of MOCC-8 was carried out and showed anion-size selectivity. All of the cage-like compounds emit strong luminescence at room temperature.

P02-411 - Analgesic and anticonvulsive activity new compounds with norbornene and adamantane fragments

IntroductionThe present work deals with analgesic and anticonvulsive activity of four novel aminoalcohols C-81, C-78, C-115 and C-120 synthesized on basic glycidylcamphorimide (Gly-CI), exo- and endo-aminomethylnorbornenes, aminoethyladamantan (remantadin) and aminoethylnorbornan (deitiforin).AimsSynthesis cage-like compounds with excellent analgesic and anticonvulsive activity. Methods: Experiments have been carried out on both genders adult white mice at the dozes of 1/10 LD50. Investigated substances were entered intraperitoneally. Preparations have been entered as a water suspension on TWEEN-40. Acute toxicity of compounds (LD50) has been measured by Litchfield & Wilcoxon method in Prozorovsky V.B. modification and amounts 370–1196 mg/kg.ResultsThe most toxic compound is aminoalcohol C-115 with adamantane fragment. Investigation of analgesic activity has been carried out by determination of pain threshold by thermal irritation method (hot plate) at 55°C. Anticonvulsive activity has been studied by corazole spasm test. The activity has been calculated in percentage in relation to control group of animals.ConclusionsAll aminoalcohols have shown analgesic and (except for compound C-81) anticonvulsive activity. For exo-aminoalcohol C-81 the most intense activity are analgesic (195.0%) and for endo-isomer C-78 - anticonvulsive activity (213.3%). Compounds C-115 and C-120 shows medium analgesic (67.1 and 58.5%) and anticonvulsive activity (13.4 and 67.5%).

1H and 13C NMR spectral data of bioactive cage‐like polycyclic compounds

Bioactive cage-like polycyclic compounds have attracted the attention of several research groups because of their unique appearance and their biological activities. Their structures were established on the basis of (1)H NMR and (13)C NMR spectroscopic data. The (1)H and (13)C signal assignments and most homonuclear hydrogen coupling constants were assigned by use of techniques such as 1D (1)H and (13)C NMR and 2D gCOSY, non-edited gHSQC and gHMBC. The gNOESY experiments proved the endo-stereochemistry.

Kinetics and mechanism of unimolecular heterolysis of cage-like compounds: XXI. Solvent effect on the realtive rate of heterolysis of 2-methyland 2-phenyl-2-haloadamantanes. Role of activation parameters

The kinetics of heterolysis of 2-chloro-2-methyladamantane, 2-bromo-2-methyladamantane, 2-chloro-2-phenyladamantane, and 2-bromo-2-phenyladamantane in isopropyl alcohol, tert-butyl alcohol, acetonitrile, nitromethane, cyclohexanone, and γ-butyrolactone were studied using the verdazyl technique. The rate constant ratio kPh/kMe decreases from three orders of magnitude to unity in the solvent series BuOH > i-PrOH > t-BuOH > MeCN > PhNO2 > cyclohexanone > γ-butyrolactone > sulfolane, which results from weakening of conjugation between the phenyl group and emerging carbocationic center. The effect of solvent on the entropy and enthalpy of heterolysis in going from 2-methyl-substituted 2-haloadamantanes to their 2-phenyl analogs is discussed.

Study of the contact charge transfer behavior between cryptophanes ( A and E) and fullerene by absorption, fluorescence and 1H NMR spectroscopy

A group of novel cage-like compounds cryptophanes A and E were synthesized from vanillin by a three-step method. The intermolecular interaction between cryptophanes ( A and E) and fullerene (C 60) was investigated in detail by absorption, fluorescence and 1H NMR spectroscopy. The absorption of C 60 at 410–650 nm decreased in the presence of cryptophanes A or E. The decrease in absorption intensity was proportional to the concentration of cryptophanes A or E. On the other hand, the fluorescence intensity of cryptophanes A or E decreased and the emission maxima were blue-shifted with the increase in C 60 concentration. These results suggest that contact charge transfer (CCT) complexes can be formed from C 60 with cryptophanes A or E. In addition, the electrochemical behavior of cryptophanes ( A and E) and C 60 was studied by cyclic voltammetry. The redox currents of cryptophanes ( A and E) decreased and the peak potentials were shifted on addition of C 60. The changes in the chemical shifts (Δ δ) of aromatic protons of cryptophanes ( A and E) in their NMR spectra further support that CCT complexes were formed with cryptophanes as the electron donors and C 60 as the electron acceptor.

Reactions of Unsaturated Azides; Part 22: The Alkyne Azide Click Chemistry as a Synthetic Tool for the Generation of Cage-Like Triazole Compounds

The applicability of the copper(I)-catalyzed click reaction of terminal trialkynes with triazides to the synthesis of cage-like triazole compounds was determined. A number of starting materials were prepared and several monotriazoles as well as macrocyclic bistriazoles were obtained from the triazide trialkyne reaction. Finally, a tristriazole macrobicyclic compound was synthesized from the previously formed triazole precursors.

Synthesis and Biological Evaluation of Rigid Polycyclic Derivatives of the Diels-Alder Adduct Tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione

Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed by an evaluation of their biological activity.

Kinetics and mechanism of unimolecular heterolysis of cage-like compounds: XIX. Effect of the nucleofuge nature on the activation parameters of heterolysis of 1-halo-1-methylcyclohexanes in cyclohexane. Heterolysis rate ratio in aprotic and protic solvents

Heterolysis of 1-bromo-1-methylcyclohexane in cyclohexane (E1 reaction) involves solvation of the transition state (ΔS≡ = −81 J mol−1K−1), while heterolysis of 1-chloro-1-methylcyclohexane is characterized by desolvation of the transition state (ΔS≡ = 92 J mol−1K−1). The probability for the formation of transition state (interaction between cationoid intermediate and solvent cavity) increases in the first case due to enhanced stability of the solvated intermediate, and in the second, due to reduction in its size. The bromide/chloride heterolysis rate ratio decreases as the ionizing power of aprotic solvent decreases and that of protic solvent increases.