Anionic Host Research Articles

Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action.

It is becoming increasingly clear that plants ranging across the plant kingdom produce anionic host defence peptides (AHDPs) with potent activity against a wide variety of human cancers cells. In general, this activity involves membrane partitioning by AHDPs, which leads to membranolysis and / or internalization to attack intracellular targets such as DNA. Several models have been proposed to describe these events including: the toroidal pore and Shai-Matsuzaki-Huang mechanisms but, in general, the mechanisms underpinning the membrane interactions and anticancer activity of these peptides are poorly understood. Plant AHDPs with anticancer activity can be conveniently discussed with reference to two groups: cyclotides, which possess cyclic molecules stabilized by cysteine knot motifs, and other ADHPs that adopt extended and α-helical conformations. Here, we review research into the anticancer action of these two groups of peptides along with current understanding of the mechanisms underpinning this action.

Formation of Self‐Templated 2,6‐Bis(1,2,3‐triazol‐4‐yl)pyridine [2]Catenanes by Triazolyl Hydrogen Bonding: Selective Anion Hosts for Phosphate

AbstractWe report the remarkable ability of 2,6‐bis(1,2,3‐triazol‐4‐yl)pyridine (btp) compounds 2 with appended olefin amide arms to self‐template the formation of interlocked [2]catenane structures 3 in up to 50 % yield when subjected to olefin ring‐closing metathesis in CH2Cl2. X‐ray diffraction crystallography enabled the structural characterization of both the [2]catenane 3 a and the non‐interlocked macrocycle 4 a. These [2]catenanes showed selective triazolyl hydrogen‐bonding interactions with the tetrahedral phosphate anion when screened against a range of ions; 3 a,b are the first examples of selective [2]catenane hosts for phosphate.

Formation of Self-Templated 2,6-Bis(1,2,3-triazol-4-yl)pyridine [2]Catenanes by Triazolyl Hydrogen Bonding: Selective Anion Hosts for Phosphate.

We report the remarkable ability of 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) compounds 2 with appended olefin amide arms to self-template the formation of interlocked [2]catenane structures 3 in up to 50 % yield when subjected to olefin ring-closing metathesis in CH2 Cl2 . X-ray diffraction crystallography enabled the structural characterization of both the [2]catenane 3 a and the non-interlocked macrocycle 4 a. These [2]catenanes showed selective triazolyl hydrogen-bonding interactions with the tetrahedral phosphate anion when screened against a range of ions; 3 a,b are the first examples of selective [2]catenane hosts for phosphate.

An Unusual 3D Zinc‐Organic Framework Constructed from Paddle‐Wheel‐Based Carboxylate Sheets Bridged by Acetate Ions

AbstractA zinc‐2,6‐naphthalenedicarboxylate metal‐organic framework, (H2NEt2)[Zn2(AcO)(NDC)2]·nDEF (1) (DEF = N,N‐diethylformamide, AcO = acetate), was solvothermally synthesized in the presence of small amounts of acetic acid and characterized by single‐crystal and powder X‐ray diffraction and thermogravimetric analysis. Compound 1 is an anionic 3D paddle‐wheel MOF, in which the zinc‐naphthalenedicarboxylate sheets are linked together by bridging acetate ions. Compound 1 exhibits large square channels (13 × 13 Å), which contain DEF molecules and, alternatively, charge‐balancing diethylammonium cations in situ generated by the hydrolysis of DEF under the solvothermal conditions used. The anionic host framework of 1 is unstable upon removal of guest DEF molecules suggesting that host‐guest hydrogen bond interactions are crucial for maintaining the structural integrity of this compound.

Chlorodiphenyltin(IV) dithiocarbamate complexes as chemodosimeters and host for anions and neutral compounds in solution

The chlorodiphenyltin(IV) dithiocarbamate complexes 1–5 with general formula {(Ph2SnCl)dtc} (dtc=R1R2NCS2−; 1, R1=Bn, R2=9-anthrylmethyl; 2, R1=Bn, R2=9-phenanthrylmethyl; 3, R1=Bn, R2=1-pyrenylmethyl; 4, R1=1-naphthylmethyl, R2=1-pyrenylmethyl; 5, R1=R2 1-pyrenylmethyl) have been tested as host for anions and neutral amines in acetonitrile by spectrophotometric UV/Vis titrations. In addition, the titrations of the complexes 1 and 5 were studied in chloroform by 1H and 119Sn NMR spectroscopy. It was found that anions as acetate, benzoate, and dihydrogen phosphate cause a displacement of the dithiocarbamate ligands of metallic center independently of the aromatic nature of the substituents on the nitrogen atom functioning as chemodosimeters in which the indicator is displaced. However, some aliphatic amines and aromatic methylene amines and its aromatic analogs can act as guests with binding constants in the range of 103 to 106M−1. Also, in these cases compound 5 functions as chemodosimeter without displacement of the indicator. According to 1H, 13C, 119Sn NMR data and using DFT (B3LYP) and Poisson–Boltzmann (PB) to model the solvent, structures of the complexes are proposed in which the hydrophobic and π–π interactions are suggested as the dominant interactions.

Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.

Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.

Cationic gemini guests promote the efficient self-assembly of capsular entities in water at neutral pH

The binding features of a sulfonato-calix[4]arene with pyridinium-based gemini guests have been investigated in water at physiological condition by NMR spectroscopy. Results provided converging evidence showing that guests having different size, shape and flexibility formed water-soluble homodimeric supramolecular capsules. The remarkably large encapsulation efficiency of the anionic calixarene host towards these bis(pyridinium) gemini guests results from the favourable combination of electrostatic and hydrophobic interactions. The introduction of short and rigid spacers between the two positively charged heads of the guest improves the efficiency of the capsule formation. The insertion of a substituent into the pyridinium ring of the guest dramatically affects both the association constants and the binding modes.

Hydrogen-Bonded Anionic Host Lattices Constructed with Isocyanurate and Thiourea/Urea

A series of seven inclusion complexes containing the isocyanurate ion, thiourea/urea, and selected quaternary ammonium ions as templates, namely, (CH3)4N+C3H2N3O3–· 3(NH2)2CS·H2O (1), (CH3)4N+C3H2N3O3–·(NH2)2CS (2), (C2H5)4N+C3H2N3O3–·(NH2)2CS (3), (n-C3H7)4N+C3H2N3O3–·(NH2)2CS·H2O (4), 3[(n-C4H9)4N+C3H2N3O3–]·5(NH2)2CS·3H2O (5), (C2H5)4N+C3H2N3O3–·(NH2)2CO (6) and (n-C3H7)4N+C3H2N3O3–·2(NH2)2CO·H2O (7), have been prepared and characterized by X-ray crystallography. Complex (1) features a hydrogen-bonded molecular cage in which two (CH3)4N+ cations can be accommodated. Complexes (2) and (7) are channel-type inclusion compounds. In (2), the thiourea sulfur atom does not participate in host lattice construction, while (7) contains several intersecting channel systems that are formed by the cross-linkage of two sets of isocyanurate–urea–water ribbons. Complexes (3)–(6) exhibit layer-type architectures. The host layers of complexes (3) and (6) are constructed by two distinct rosette motifs produced by isocyan...

Aromatic oligureas as hosts for anions and cations.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Spectroscopic and computational investigations on the origin of charge transfer between included neutral guest molecules and a functionalized anionic layered host.

Layered double hydroxides (LDHs) or anionic clays are an important class of ion-exchange materials, well known for drug and gene delivery and several other applications including catalysis, bioactive nanocomposite, electroactive and photoactive materials. Their structure is based on positively charged brucite-like inorganic sheets with the interlamellar space being occupied by charge-compensating exchangeable anions. In spite of having a vast scope many of the applications of LDHs are restricted as their host-guest chemistry is limited to ion-exchange reactions. Recently we have shown for the first time that charge-transfer interactions can be used as a driving force for the insertion of neutral guest molecules (ortho- and para-chloranil) within the galleries of an Mg-Al LDH by forming a charge-transfer complex with aniline pre-intercalated as p-aminobenzoate anion. Here, we have performed quantum chemical calculations in combination with molecular dynamics simulations to elucidate the nature of interactions, arrangement and the evaluation of electronic and Raman spectral signatures of the chloranil charge-transfer complex included within the galleries of the Mg-Al LDH. The natural bond orbital (NBO) analysis has been used to understand the nature and origin of the unidirectional charge-transfer that lead to the unusual insertion of chloranil in the galleries of the Mg-Al LDH. The NBO analysis reveals that a considerable amount of electronic charge redistribution occurs from the p-aminobenzoate to the chloranil during latter's insertion within the LDH galleries with a very negligible amount of back donation. This work is expected to pave the way for understanding the host-guest chemistry and targeted and controlled delivery of poorly soluble drugs.

Construction of a novel INHIBIT logic gate through a fine-tuned assembly of anthryl fluorophores via selective anion recognition and host–guest interactions

A novel ligand containing of anthryl fluorophore was achieved. The assembly and disassembly of anthryl fluorophore by Pi and β-CD as chemical inputs and emission around 500 nm as output resulted in the construction of novel INHIBIT gate.

Halogen bonding anion recognition.

A halogen bond is an attractive non-covalent interaction between an electrophilic region in a covalently bonded halogen atom and a Lewis base. While these interactions have long been exploited as a tool in crystal engineering their powerful ability to direct supramolecular self-assembly and molecular recognition processes in solution has, until recently, been overlooked. During the last decade however an ever-increasing number of studies on solution-phase halogen-bond-mediated anion recognition processes has emerged. This Feature Article summarises advancements which have been made thus far in this rapidly developing research area. We survey the use of iodoperfluoroarene, haloimidazolium and halotriazole/triazolium halogen-bond-donor motifs in anion receptor design, before providing an account of our research into the application of mechanically interlocked rotaxane and catenane frameworks as halogen bonding anion host systems.

Cyanide-bridged mixed-valence copper(II/I) coordination polymers: Unique 7-connected sev-type 3D network versus anionic 2D host network encapsulated with cationic complex

Reactions of CuCl2, K2[Ni(CN)4]/K3[Co(CN)6], and 5-amino-1H-tetrazole led to cyanide-bridged mixed-valence Cu(II/I) complexes, [Cu(H2O)3Cu3(CN)5] (1) and [Cu(H2O)4][Cu4(CN)6] (2).The uncommon semi-closed {Cu2(CN)3} dimmers in 1 are bridged by μ3-C,C,N cyanide ligands to afford rare 1D centipedal-like chain motifs, which are further bridged by μ2-C,N and metalloligand “CN–Cu(4)–CN” to finish sophisticated zeolite-like 3-D structure. Topologically, 1 is the first example of uninodal 7-connected sev-like cyanide-bridged network. Compound 2 consists of two-dimensional honeycomb-related anionic layers [Cu4(CN)6]2−, within which the [Cu(H2O)4]2+ cations are intercalated into alternate interlamellar space. Compound 1 shows antiferromagnetic couple arising from pure ground-state configuration of Cu(II) mediated by diamagnetic bridges –CN–CuI–CN−. The inclusion compound 2 shows blue photoluminescence originated from Cu(I) center to the unoccupied π* orbital of the cyanide ligand (MLCT) charge transfer.

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.

Chloride-Anion-Templated Synthesis of a Strapped-Porphyrin-Containing Catenane Host System.

The synthesis, structure and anion-recognition properties of a new strapped-porphyrin-containing [2]catenane anion host system are described. The assembly of the catenane is directed by discrete chloride anion templation acting in synergy with secondary aromatic donor–acceptor and coordinative pyridine–zinc interactions. The [2]catenane incorporates a three-dimensional, hydrogen-bond-donating anion-binding pocket; solid-state structural analysis of the catenane⋅chloride complex reveals that the chloride anion is encapsulated within the catenane’s interlocked binding cavity through six convergent CH⋅⋅⋅⋅Cl and NH⋅⋅⋅Cl hydrogen-bonding interactions and solution-phase 1H NMR titration experiments demonstrate that this complementary hydrogen-bonding arrangement facilitates the selective recognition of chloride over larger halide anions in DMSO solution.

Synthesis of coumarin-appended cyclophanes and evaluation of their complexation with myoglobin

Coumarin-appended cyclophanes bearing positively or negatively charged side chains were synthesized as a water-soluble host (1a or 1b, respectively). Host 1a and 1b showed fluorescence bands with fluorescence maxima at 404 nm originated from coumarin moiety. As a host for guest molecules by using macrocyclic cavity, cationic host 1a binds anionic guests such as 6-p-toluidinonaphthalene-2-sulfonate (TNS), 6-anilinonaphthalene-2-sulfonate (2,6-ANS), and 8-anilinonaphthalene-1-sulfonate (1,8-ANS) more strongly than anionic host 1b, reflecting intermolecular electrostatic interactions. In addition, both host 1a and 1b showed protein surface recognition and fluorescence response toward myoglobin, a small and globular protein. The fluorescence intensity originating from the hosts decreased upon the addition of myoglobin, reflecting the formation of 1a- and 1b-myoglobin complexes. On the other hand, such fluorescence response of 1a and 1b was almost negligible for other proteins such as egg white albumin, bovine serum albumin, human albumin, concanavaline A, fibrinogen, γ-globlin, peanut agglutinin, trypsin, and lysozyme.

Metallacycles Capabilities in Host-Guest Chemistry.

The perfect host for anions! The nature of host–guest interactions in metallacycle-based complexes was determined by various methodologies. Additionally, by plotting the atomic multipole moment tensors, a clear representation of the higher-order electrostatic interactions within the studied systems, such as dipole–quadrupole and quadrupole–quadrupole forces, was obtained.

Participation of aliphatic C–H hydrogen bonding in anion recognition

Enthalpically and entropically favorable anion receptors 1 and 2 are developed. The receptors 1 and 2 utilize 4 hydrogen bonds to bind halide anions. Receptor 1 utilizes two imidazolium (C–H)+⋯A− hydrogen bonds, one aliphatic methine C–H⋯A− hydrogen bond, and one aromatic C–H⋯A− hydrogen bond for anion binding, while receptor 2 utilizes one aliphatic methine C–H⋯A− hydrogen bond and one aromatic C–H⋯A− hydrogen bond, and two aliphatic(methyl) C–H⋯A− hydrogen bonds instead of imidazolium (C–H)+⋯A− hydrogen bond for anion binding. By comparing anion affinity for these anion receptors it has been found that aliphatic C–H⋯A− hydrogen bonds are comparable in strength to their imidazolium (C–H)+⋯A− counterparts and well designed aliphatic C–H hydrogen bond could be a viable hydrogen bond interaction motif for anion host design.

Synthesis of Spherical Graphite Particles Possessing a Definable Size and Their Application in Dual-Graphite Cells

Graphitic carbon provides a redox-amphoteric character, which leads to the capability to intercalate a broad range of different cations and anions between its planar graphene sheets, resulting in so-called graphite intercalation compounds (GICs). Graphite intercalation compounds, formed by cations are called donor-type GICs and those intercalated by anions are called acceptor type GICs [1-4]. A well-known application for a donor-type GIC is lithium-intercalated graphite (LiC6) as the anode material in lithium-ion batteries. In recent publications, we reported an electrochemical energy storage system using graphite as both anion and cation intercalation host. During charge, cations and anions, stemming from the electrolyte, are intercalated into the graphitic lattice structure of negative and positive electrode, respectively. During discharge, they are released back into the electrolyte. Hence, the electrolyte can be considered as active material, as it does not only act as charge carrier for lithium ions [4, 5]. Since a high oxidative stability of the electrolyte is mandatory, it is most likely composed of an ionic liquid and a suitable conductive salt, possessing the same anion as the ionic liquid. This system has been proposed as dual-graphite cell [6]. The electrolyte of the dual-graphite system used in this work is composed of the ionic liquid N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesul-fonyl) imide (Pyr14TFSI) using lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) as conductive and electro-active salt. This work deals with the synthesis of spherical graphite particles, their physical characterization and the application as active material in dual-graphite cells. First, carbon spheres, possessing different sizes, are synthesized by a hydrothermal bottom-up synthesis from glucose as precursor. Afterwards, a heat treatment at 1200 °C under argon atmosphere was performed in order to decompose the glucose structure to a soft carbon structure. Finally, the resulting soft carbon spheres were heat treated at different temperatures above 2000 °C in order to investigate the graphitization degree as well as the influence of the carbonaceous material structure to the electrochemical performance for application in a dual-graphite cell. The structure of the novel materials was characterized by X-ray diffraction, Raman spectroscopy, specific surface area investigations, scanning electron microscopy and electrochemical measurements.

Crystalline Inclusion Compounds: Thiourea and Bis-quaternary Ammonium Salts

Two new inclusion compounds, namely 3(CH3)3N+(CH2)3N+(CH3)3·6Br–·8(NH2)2CS·H2O (1) and (CH3)3N+(CH2)4N+(CH3)3·2Br–·2(NH2)2CS (2), have been prepared and characterized by X-ray crystallography. In the crystal structure of 1, uni-directional double channels with peanut-shaped cross-section running paralleling to the a axis are generated by N–H···S and N–H···Br hydrogen bonds between thiourea molecules and bromide anions, and trimethylenebis(trimethylammonium) dications are arranged separately in each hemisphere of the double channel. In 2, tetramers comprising pairs of thiourea molecules and bromide anions by N–H···S and N–H···Br hydrogen bonds are joined with the methyl groups of tetramethylenebis(trimethylammonium) dications to generate similar quasi-rectangle channels. The present study shows that new anionic host lattices can be constructed from thiourea molecules and bromide anions as building blocks, which readily adopt different topologies for the accommodation of bis-quaternary ammonium dications of various sizes. Hydrogen bonding constitutes a principal driving force that dominates the crystal packing of the two compounds, in which weak hydrogen bonds are of particular significance in the construction. In the crystal structure of 1, uni-directional double channels with peanut-shaped cross-section running paralleling to the a axis are generated by N–H···S and N–H···Br hydrogen bonds between thiourea molecules and bromide anions, and trimethylenebis(trimethylammonium) dications are arranged separately in each hemisphere of the double channel. In 2, tetramers comprising pairs of thiourea molecules and bromide anions by N–H···S and N–H···Br hydrogen bonds are joined with the methyl groups of tetramethylenebis(trimethylammonium) dications to generate similar quasi-rectangle channels.