Cage Architectures Research Articles

Enhanced kinetic stability of [Pd2L4](4+) cages through ligand substitution.

There is considerable interest in exploiting metallosupramolecular cages as drug delivery vectors. Recently, we developed a [Pd2L4](4+) cage capable of binding two molecules of cisplatin. Unfortunately, this first generation cage was rapidly decomposed by common biologically relevant nucleophiles. In an effort to improve the kinetic stability of these cage architectures here we report the synthesis of two amino substituted tripyridyl 2,6-bis(pyridin-3-ylethynyl)pyridine () ligands (with amino groups either in the 2-() or 3-() positions of the terminal pyridines) and their respective [Pd2()4](4+) cages. These systems have been characterised by (1)H, (13)C and DOSY NMR spectroscopies, high resolution electrospray mass spectrometry, elemental analysis and, in one case, by X-ray crystallography. It was established, using model palladium(ii) N-heterocyclic carbene (NHC) probe complexes, that the amino substituted compounds were stronger donor ligands than the parent system ( > > ). Competition experiments with a range of nucleophiles showed that these substitutions lead to more kinetically robust cage architectures, with [Pd2()4](4+) proving the most stable. Biological testing on the three ligands and cages against A549 and MDA-MB-231 cell lines showed that only [Pd2()4](4+) exhibited any appreciable cytotoxicity, with a modest IC50 of 36.4 ± 1.9 μM against the MDA-MB-231 cell line. Unfortunately, the increase in kinetic stability of the [Pd2()4](4+) cages was accompanied by loss of cisplatin-binding ability.

A versatile hard-soft N/S-ligand for metal coordination and cluster formation.

Deprotonation of the thialdiphosphazane [S[double bond, length as m-dash]PH(μ-N(t)Bu)]2 with a range of metal-bases gives the stable dianion [S-P(μ-N(t)Bu)]2(2-), which is valence-isoelectronic with the widely-used [RN-P(μ-NR)]2(2-) ligand. Structural studies show that the new ligand has adaptable hard-soft character with respect to the coordinated metal centre and that its multidentate nature can be exploited to construct large cage architectures.

A diaryl-linked [Pd2L4]4+ metallosupramolecular architecture: synthesis, structures and cisplatin binding studies

A diaryl-linked tripyridyl ligand (L), 2,6-bis[4-(3-pyridinyl)phenyl]-4-(hydroxymethyl)pyridine, was synthesised in good yield (57%) exploiting the Pd-catalysed Suzuki cross-coupling method and used to assemble a new [Pd2L4]4+ metallosupramolecular cage architecture. These systems have been characterised by NMR, IR and UV–vis spectroscopies, mass spectrometry, elemental analysis and by X-ray crystallography. It was shown using NMR spectroscopy and X-ray crystallography that the cage acts as a host for anions. However, efforts to bind the anticancer drug cisplatin within the central cavity of the cage were unsuccessful. This appears to be connected to steric effects caused by the aryl spacer units of the ligands forming the cage.

Heterometallic Na6Co3 Phenylsilsesquioxane Exhibiting Slow Dynamic Behavior in its Magnetization

A heterometallic phenylsilsesquioxane [(PhSiO1,5)22(CoO)3(NaO0.5)6]⋅(EtOH)6⋅(H2O) 1 cage architecture of Co(II) ions in a triangular topology exhibits a slow dynamic behavior in its magnetization, induced by the freezing of the spins of individual molecules.

Iron binding to human heavy-chain ferritin.

Maxi-ferritins are ubiquitous iron-storage proteins with a common cage architecture made up of 24 identical subunits of five α-helices that drive iron biomineralization through catalytic iron(II) oxidation occurring at oxidoreductase sites (OS). Structures of iron-bound human H ferritin were solved at high resolution by freezing ferritin crystals at different time intervals after exposure to a ferrous salt. Multiple binding sites were identified that define the iron path from the entry ion channels to the oxidoreductase sites. Similar data are available for another vertebrate ferritin: the M protein from Rana catesbeiana. A comparative analysis of the iron sites in the two proteins identifies new reaction intermediates and underlines clear differences in the pattern of ligands that define the additional iron sites that precede the oxidoreductase binding sites along this path. Stopped-flow kinetics assays revealed that human H ferritin has different levels of activity compared with its R. catesbeiana counterpart. The role of the different pattern of transient iron-binding sites in the OS is discussed with respect to the observed differences in activity across the species.

Water-Soluble Phosphine Capable of Dissolving Elemental Gold: The Missing Link between 1,3,5-Triaza-7-phosphaadamantane (PTA) and Verkade's Ephemeral Ligand.

We herein describe a tricyclic phosphine with previously unreported tris(homoadamantane) cage architecture. That water-soluble, air- and thermally stable ligand, 1,4,7-triaza-9-phosphatricyclo[5.3.2.1(4,9)]tridecane (hereinafter referred to as CAP) exhibits unusual chemical behavior toward gold and gold compounds: it readily reduces Au(III) to Au(0), promotes oxidative dissolution of nanocrystalline gold(0) with the formation of water-soluble trigonal CAP-Au(I) complexes, and displaces cyanide from [Au(CN)2](-) affording triangular [Au(CAP)3](+) cation. From the stereochemical point of view, CAP can be regarded as an intermediate between 1,3,5-triaza-7-phosphaadamantane (PTA) and very unstable aminophosphine synthesized by Verkade's group: hexahydro-2a,4a,6a-triaza-6b-phosphacyclopenta[cd]pentalene. The chemical properties of CAP are likely related to its anomalous stereoelectronic profile: combination of strong electron-donating power (Tolman's electronic parameter 2056.8 cm(-1)) with the low steric demand (cone angle of 109°). CAP can be considered as macrocyclic counterpart of PTA with the electron-donating power approaching that of strongest known phosphine electron donors such as P(t-Bu)3 and PCy3. Therefore, CAP as sterically undemanding and electron-rich ligand populates the empty field on the stereoelectronic map of phosphine ligands: the niche between the classic tertiary phosphines and the sterically undemanding aminophosphines.

Synthesis of sexithiophene-bridged cage compound: a new class of three-dimensionally expanded oligothiophenes.

A bicyclo-type cage-shaped compound consisting of three sexithiophenes was successfully synthesized and characterized by NMR, HRMS, and X-ray crystallographic analysis. The strained cage architecture was reflected in the blue-shifted absorption spectrum relative to its linear analogue. Intramolecular interaction between three-dimensionally fixed sexithiophenes was suggested by electrochemical analysis.

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents.

Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size.

Analisis Budaya Pekandangan : Sistem Beternak Kerbau Berkelanjutan di Kecamatan Cerenti dan Singingi Kabupaten Kuantan Singingi

Buffalo breeding system in pekandangan culture in Kuantan Singingi Regencycontains diversity patterns of adaptation to the environment and the values of local wisdomwhich is a form of knowledge that is combined with traditional norms, cultural values andenvironmental management activities that guide the community in meeting the needs of liveand interact with their environment is still very relevant to the current conditions, and shouldbe preserved, adapted or even developed further in accordance with the concept ofsustainability. This study aims to analyze the forms of local wisdom in pekandangan culturein accordance with the concept of sustainable buffalo breeding systems, analyze activity andcultural barriers in pekandangan culture, and analyze public perceptions of the pekandanganculture. The method used in this study is a qualitative research method approach. Datacollection using observation, interview and documentation. In-depth interviews conductedwith key informants: breeders, chairman of the group of pekandangan, traditional leaders,community leaders, village chiefs and Dinas Peternakan of Kuantan Singingi Regencyofficials. Structured interview was conducted to determine the public perception of therespondents were community residing 0.5-3 km of pekandangan area.The results of the studyas follows: (1) The forms of local wisdom in accordance with the concept of sustainablebuffalo breeding systems in the pekandangan culture is cage architecture uses the directsunlight, the cage material is made of organic or renewable materials, utilizing buffalo dunginto manure, bonfire material from organic ingredients, free fodder pesticides, buffalograzing by means of foot, and the existence of regular meeting of pekandangan groups /societies and mutual help activities. (2) Public perception of pekandangan culture is goodbecause it provides benefits and economic advantages, can improve people's lives and have asocial system.

Efficient and modular synthesis of new structurally diverse functionalized [n]paracyclophanes by a ring-distortion strategy.

With the goal of synthesizing new [n]paracyclophanes, the expansion of the scope of a strategy originally disclosed by Winterfeldt et al., was investigated. This approach involves sequential Diels-Alder/retro-Diels-Alder reactions, the applications of which have been constrained so far to steroid derivatives. An efficient access to new functionalized [9]-, [10]-, and [16]paracyclophanes, including original cage architectures, was developed from readily available building blocks using thermal electrocyclization and a cycloaddition/cycloreversion sequence as the key steps.

Efficient and Modular Synthesis of New Structurally Diverse Functionalized [n]Paracyclophanes by a Ring‐Distortion Strategy

AbstractWith the goal of synthesizing new [n]paracyclophanes, the expansion of the scope of a strategy originally disclosed by Winterfeldt et al., was investigated. This approach involves sequential Diels–Alder/retro‐Diels–Alder reactions, the applications of which have been constrained so far to steroid derivatives. An efficient access to new functionalized [9]‐, [10]‐, and [16]paracyclophanes, including original cage architectures, was developed from readily available building blocks using thermal electrocyclization and a cycloaddition/cycloreversion sequence as the key steps.

Complex Cage Architecture Incorporating All Ring Sizes from Three to Seven

Complex Cage Architecture Incorporating All Ring Sizes from Three to Seven

Synthesis of porous micro-sized titania cages and their photocatalytic property

Micro-sized TiO2 cage consisted of anatase nanoparticles on the edges of each cube, was synthesized using TTIP as the reagent and NaF submicrometer sized cubes as the template. When a salt of cube was adopted as the template, the reactants prefer to grow on the active sites, edges and corners of the cube, after removing the NaF template, the skeleton of the cube remain as the cage-shaped materials. The hierarchical structures with nano-sized anatase particles and micro scaled cage architecture markedly enlarge the surface area and enhance the light harvesting by light scattering of TiO2 frame, resulting in great photo-catalytic performance, which leads to the photo-degradation of methylene blue by 40% higher than that was achieved by crushed nanoparticles.

ChemInform Abstract: Reactivity of Cyclohexene Epoxides Toward Intramolecular Acid‐Catalyzed Cyclizations for the Synthesis of Naturally Occurring Cage Architectures

AbstractReview: 31 refs.

Incorporation of Thrombin Cleavage Peptide into a Protein Cage for Constructing a Protease-Responsive Multifunctional Delivery Nanoplatform

Protein cages are spherical hollow supramolecules that are attractive nanoscale platforms for constructing cargo delivery vehicles. Using ferritin isolated from the hyperthermophilic archaeon Pyrococcus furiosus (Pf_Fn), we developed a multifunctional protein cage-based delivery nanoplatform that can hold cargo molecules securely, deliver them to the targeted sites, and release them to the targeted cells. The release is triggered by cleavage induced by the protease, thrombin. The thrombin cleavage peptide (GGLVPR/GSGAS) was inserted into the flexible loop region of Pf_Fn, which is located at a 4-fold axis of symmetry exposed on the surface of protein cages (Thr-Pf_Fn). Subsequently, the C-terminal glycine, which is situated in the interior cavity, was substituted with cysteine (G173C) to permit site-specific conjugation of cargo molecules. The introduced cysteine (G173C) was labeled with a fluorescent probe (F5M-Thr-Pf_Fn) for cell imaging and cargo release monitoring. The surface of F5M-Thr-Pf_Fn was further modified with biotins (F5M-Thr-Pf_Fn-NPB) as targeting ligands. The specific binding of dual functionalized F5M-Thr-Pf_Fn-NPB to the MDA MB 231 cell line, which overexpresses biotin-specific receptors on its surface, was confirmed by fluorescence microscopic analyses. The inserted thrombin cleavage peptides were effectively cleaved by thrombin, resulting in the release of the C-terminal helix in buffer and on the targeted cells without disruption of the cage architecture. Protein cage scaffolds that combine genetic and chemical modifications may serve as stimulus-responsive delivery nanoplatforms and provide opportunities for developing new types of theranostic nanoplatforms.

Reactivity of cyclohexene epoxides toward intramolecular acid-catalyzed cyclizations for the synthesis of naturally occurring cage architectures

Abstract This account compiles our results on the reactivity of cyclohexene epoxides toward the synthesis of naturally occurring cage architectures, in particular, the one found in harringtonolide. Bicyclic and branched monocyclic functional triads (hydroxy-epoxy-esters) were synthesized with the aim of undertaking cascade processes toward the formation of lactone and/or cycloether bridges, through a central epoxide opening. This work successfully culminated in the cascade cyclization of the fully oxygenated bridge-structure of harringtonolide, by using a dual Bronsted-Lewis acid complex.

Periodic negative differential conductance in a single metallic nanocage

We report a bi-polar multiple periodic negative differential conductance (NDC) effect on a single cage-shaped Ru nanoparticle measured using scanning tunneling spectroscopy. This phenomenon is assigned to the unique multiply-connected cage architecture providing two (or more) defined routes for charge flow through the cage. This, in turn, promotes a self- gating effect, where electron charging of one route affects charge transport along a neighboring channel, yielding a series of periodic NDC peaks. This picture is established and analyzed here by a theoretical model.

Manipulating the Size of Hen Lysozyme Nanoparticles Created by Controlled Self-Assembly

Natural protein-based nanostructures like viral capsids, ferritin present attractive platforms for vaccine development, catalysis, nanomaterial synthesis, drug/gene delivery owing to their biocompatability and rich functional chemistry. These container-like protein cage architectures possess multiple interfaces (interior, exterior and between subunits) for imparting functionality. However, assembling such structures artificially, with defined molecular dimensions has proved challenging. Current approaches do not permit spatial tuning, yielding bulky nanostructures (>50 nm).

Monte Carlo Temperature Basin Paving with Effective Fragment Potential: An Efficient and Fast Method for Finding Low-Energy Structures of Water Clusters (H2O)20 and (H2O)25

Determining low-energy structures of large water clusters is a challenge for any optimization algorithm. In this work, we have developed a new Monte Carlo (MC)-based method, temperature basin paving (TBP), which is related to the well-known basin hopping method. In the TBP method, the Boltzmann weight factor used in MC methods is dynamically modified based on the history of the simulation. The states that are visited more are given a lower probability by increasing their temperatures and vice versa. This allows faster escapes from the states frequently visited in the simulation. We have used the TBP method to find a large number of low-energy minima of water clusters of size 20 and 25. We have found structures energetically same to the global minimum structures known for these two clusters. We have compared the efficiency of this method to the basin-hopping method and found that it can locate the minima faster. Statistical efficiency of the new method has been investigated by running a large number of trajectories. The new method can locate low-energy structures of both the clusters faster than some of the reported algorithms for water clusters and can switch between high energy and low-energy structures multiple times in a simulation illustrating its efficiency. The large number of minima obtained from the simulations is used to get both general and specific features of the minima. The distribution of minima for these two clusters based on the similarity of their oxygen frames shows that the (H(2)O)(20) can have different variety of structures, but for (H(2)O)(25), low-energy structures are mostly cagelike. Several (H(2)O)(25) structures are found with similar energy but with different cage architectures. Noncage structures of (H(2)O)(25) are also found but they are 6-7 kcal/mol higher in energy from the global minimum. The TBP method is likely to play an important role for exploring the complex energy landscape of large molecules.

Mechanism of the order–disorder phase transition, and glassy behavior in the metal-organic framework [(CH 3 ) 2 NH 2 ]Zn(HCOO) 3

Transitions associated with orientational order–disorder phenomena are found in a wide range of materials and may have a significant impact on their properties. In this work, specific heat and 1 H NMR measurements have been used to study the phase transition in the metal-organic framework (MOF) compound [(CH 3 ) 2 NH 2 ]Zn(HCOO) 3 . This compound, which possesses a perovskite-type architecture, undergoes a remarkable order–disorder phase transition at 156 K. The (DMA + ) cationic moieties that are bound by hydrogen bonds to the oxygens of the formate groups (N─H⋯O ∼ 2.9 Å ) are essentially trapped inside the basic perovskite cage architecture. Above 156 K, it is the orientations of these moieties that are responsible for the disorder, as each can take up three different orientations with equal probability. Below 156 K, the DMA + is ordered within one of these sites, although the moiety still retains a considerable state of motion. Below 40 K, the rotational motions of the methyl groups start to freeze. As the temperature is increased from 4 K in the NMR measurements, different relaxation pathways can be observed in the temperature range approximately 65–150 K, as a result of a “memory effect.” This dynamic behavior is characteristic of a glass in which multiple states possess similar energies, found here for a MOF. This conclusion is strongly supported by the specific heat data.