Protein interactions with nanosized hydrotalcites of different composition

Nanosized hydrotalcite-like compounds (HTlc) with different chemical composition were prepared and used to study protein adsorption. Two soft proteins, myoglobin (Mb) and bovine serum albumin (BSA), were chosen to investigate the nature of the forces controlling the adsorption and how these depend on the chemical composition of the support. Both proteins strongly interact with HTlc exhibiting in most cases a Langmuir-type adsorption. Mb showed a higher affinity for Nickel Chromium (NiCr-HTlc) than for Nickel Aluminum (NiAl-HTlc), while for BSA no significant differences between supports were found. Adsorption experiments in the presence of additives showed that proteins exhibited different types of interactions onto the same HTlc surface and that the adsorption was strongly suppressed by the addition of disodium hydrogen phosphate (Na₂HPO₄). Atomic force microscopy images showed that the adsorption of both proteins onto nanoparticles was followed by the aggregation of biocomposites, with a more disordered structure for BSA. Fluorescence measurements for adsorbed Mb showed that the inorganic nanoparticles induced conformational changes in the biomolecules; in particular, the interactions with HTlc surface quenched the tryptophan fluorescence and this process was particularly efficient for NiCr-HTlc. The adsorption of BSA onto the HTlc nanoparticles induced a selective quenching of the exposed fluorescent residues, as indicated by the blue-shift of the emission spectra of tryptophan residues and by the shortening of the fluorescence decay times.     

Opening Two‐Dimensional Materials for Energy Conversion and Storage: A Concept

The development of two‐dimensional (2D) materials is experiencing a renaissance since the adventure of graphene. 2D materials typically exhibit strong in‐plane covalent bonding and weak out‐of‐plane van der Waals interactions through the interlayer gap. Opening 2D materials is an effective way to alter the physical and chemical properties, such as band gap, conductivity, optical property, thermoelectric property, photovoltaic property and superconductivity. A larger interlayer distance means more accessible active sites for catalysis, an ion‐accessible surface in the interlayer space, which may greatly enhance the performance of 2D materials for energy conversion and storage. Moreover, opening 2D materials by intercalation can change the band filling state and the Fermi level. This review mainly focuses on the opening of 2D materials and their subsequent applications in energy conversion and storage fields, expecting to promote the development of such a new class of materials, namely expanded 2D materials. The exciting progresses of these expanded materials made in both energy conversion and storage devices including solar cells, thermoelectric devices, electrocatalyst, supercapacitors and rechargeable batteries, is presented and discussed in depth. Furthermore, prospects and further developments in these exciting fields of the expanded 2D materials are also commented.     

Structural limitations on the bifunctional intercalation of diacridines into DNA

An homologous series of diacridines containing two 9-aminoacridine chromophores linked via a simple methylene chain has been studied in order to investigate the minimum interchromophore separation required to permit bifunctional intercalation. Viscometric, sedimentation, and electric dichroism experiments show that compounds having one to four methylene groups in the linker are restricted to monofunctional intercalation, whereas the interaction becomes bifunctional when the chain length is increased to six carbons or more. The results indicate that bifunctional reaction occurs with an interchromophore distance not exceeding 8.8 A, implying that intercalation by these compounds is not subject to neighbor exclusion if the mode of binding is of the classical intercalation type.     

Designing synthetic materials to control stem cell phenotype

The micro-environment in which stem cells reside regulates their fate, and synthetic materials have recently been designed to emulate these regulatory processes for various medical applications. Ligands inspired by the natural extracellular matrix, cell-cell contacts, and growth factors have been incorporated into synthetic materials with precisely engineered density and presentation. Furthermore, material architecture and mechanical properties are material design parameters that provide a context for receptor-ligand interactions and thereby contribute to fate determination of uncommitted stem cells. Although significant progress has been made in biomaterials development for cellular control, the design of more sophisticated and robust synthetic materials can address future challenges in achieving spatiotemporal control of cellular phenotype and in implementing histocompatible clinical therapies.     

The interactions of substituted pyrido[1,2-e]purines with oligonucleotides depend on the amphiphilic properties of their side chain.

Three pyrido[1,2-e]purines of increasing hydrophilicity have been synthesized to evaluate as anticancer agents. These drugs interact quite differently with a synthetic oligodeoxynucleotide d(CGATCG)2. [1] is very hydrophobic due to a phenyl residue in its side chain. It only shows limited interactions with the minihelix without any evidence of intercalation. [2] and [3], on the other hand, have one ([2]) or two ([3]) hydroxyl groups in their acyl chain and present rather amphiphilic properties. The result is a similar intercalation of these derivatives between C and G base pairs as revealed by intermolecular nOe, 1H and 31P chemical shift variations. Models for the intercalation of [2] are proposed using energy minimizations and molecular dynamics (MD) calculations subject to restraints from nOe connectivities. Simulations and experiments indicate weak stability and thus fast exchange of [2] in its intercalation site.     

Synthesis and biological activity of novel bifunctional isoxazolidinyl polycyclic aromatic hydrocarbons

This paper reports the synthesis and the biological properties of two novel pyrene-bearing isoxazolidinyl derivatives able to exhibit antitumor activity by DNA intercalation. The synthetic approach exploits a consolidated protocol based on 1,3-dipolar cycloaddition reaction. The intercalating properties have been determined by combining electrophoresis studies with molecular docking, while the antitumor activity has been evaluated over five carcinoma cell lines. The obtained compounds show also a good affinity towards silver cations; the presence of a 2-hydroxybenzyl appendage on the isoxazolidine ring ensures a good affinity and selectivity in the binding.     

The intercalation of imidazoacridinones into DNA induces conformational changes in their side chain

Imidazoacridinones (IAs) are a new group of highly active antitumor compounds. The intercalation of the IA molecule into DNA is the preliminary step in the mode of action of these compounds. There are no experimental data about the structure of an intercalation complex formed by imidazoacridinones. Therefore the design of new potentially better compounds of this group should employ the molecular modelling techniques. The results of molecular dynamics simulations performed for four IA analogues are presented. Each of the compounds was studied in two systems: i) in water, and ii) in the intercalation complex with dodecamer duplex d(GCGCGCGCGCGC)2. Significant differences in the conformation of the side chain in the two environments were observed for all studied IAs. These changes were induced by electrostatic as well as van der Waals interactions between the intercalator and DNA. Moreover, the results showed that the geometry of the intercalation complex depends on: i) the chemical constitution of the side chain, and ii) the substituent in position 8 of the ring system.     

The interaction of benzimidazole compounds with DNA: intercalation and groove binding modes.

Benzimidazole compounds (Fig. 1) have been synthesized to study their DNA-binding properties. Results obtained with spectroscopy and viscosity measurements indicate that the binding mode varies from intercalation to groove-binding, depending on the number of benzimidazole rings (conformation and size of compounds).     

Foldamers with hybrid biological and synthetic sequences as selective DNA fluorescent probes

Foldable polymers with alternating single-strand deoxyribonucleic acid (ssDNA) and planar fluorescent organic chromophores can self-organize into folded nanostructures and hence are hybrid foldamers with biological sequences and synthetic properties. The biological sequence provides highly specific molecular recognition properties, while the physical properties of synthetic chromophores offer sensitive fluorescence detection. In this paper, we describe that rational designed hybrid foldamers exhibit potential in the detection of polynucleotides. Under strictly controlled laboratory conditions, fluorescence measurements indicate that configuration change due to binding of polynucleotides with one or two mismatched bases can be readily distinguished. These results shed light on the design and construction of nanostructured foldamers with actuator and sensory properties, which may find important applications as biological probes.     

First generation TREN dendrimers functionalized with naphthyl and/or dansyl units. Ground and excited state electronic interactions and protonation effects.

We report the photophysical properties (absorption and emission spectra, quantum yield, and lifetime) of five dendrimers of first generation based on a TREN (tris(2-aminoethyl)amine) skeleton functionalized at the periphery with naphthyl and/or 5-dimethylamino-1-naphthalenesulfonamide (hereafter called dansyl) chromophores. Each dendrimer comprises one tertiary amine unit in the core and three branches carrying a sulfonimido unit at the periphery, each one substituted by two identical or different moieties. In particular, TD6 and TN6 contain dansyl (D) or naphthyl (N) units, respectively, while TD3B3, TN3B3 and TN3D3 contain dansyl, naphthyl or benzyl (B) units at the periphery. The spectroscopic behaviour of these dendrimers has been investigated in acetonitrile solution and compared with that of reference compounds. For all dendrimers the absorption bands are red shifted compared to those of monomeric naphthyl and dansyl reference compounds. Moreover, the intense naphthyl and dansyl fluorescence is greatly quenched because of strong interactions between the two aromatic moieties linked by a sulfonimido unit. Protonation of the amine units of the dendrimers by addition of CF(3)SO(3)H (triflic) acid causes a decrease in intensity of the luminescence and a change in the shape of the emission bands. The shapes of the titration curves depend on the dendrimer, but in any case the effect of acid can be fully reversed by successive addition of base (tributylamine). The obtained results reveal that among the intradendrimer interactions the most important one is that taking place (via mesomeric interaction) between the various chromophores and a pair of sulfonimido groups.     

The effect of synthetic antioxidants,anphen derivatives,on erythrocyte morphology

The effect of new synthetic antioxidants, anphens, on erythrocyte morphology was studied. Insignificant cell transformations induced by the hydrophilic derivative of anphen-1 into echinocytes, as well as cell transformations into stomatocytes under the action of hydrophobic derivatives of anphens-2, 3, and 4 were revealed. The data we obtained indicate the intercalation of these compounds into the erythrocyte membrane. The distribution of compounds in the intra-membrane space depends on their hydrophobicity. A hydrophilic compound, anphen-1, is predominantly located in the outer monolayer of the membrane, while hydrophobic derivatives occur in the inner monolayer. It is proposed that the biological activities of anphen-3 and anphen-4 can occur in both monolayers as they move through the membrane, while the hydrophilic compound, anphen-1, exerts an insignificant membranotropic effect and can act only in the outer monolayer of the membrane. Variability in the efficiency of the concentration-dependent modifying action of the compounds with different hydrophobic properties has been found.     

The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: molecular dynamics simulations

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i) in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.     

Use of the exciton chirality method in the investigation of ligand-gated synthetic ion channels

The objective of this brief highlight is to point out the central role of the exciton chirality method to gain insights on the structural basis of the recently achieved ligand gating of synthetic ion channels. This unprecedented ligand gating was achieved with an equally unprecedented transmembrane rigid-rod pi-stack architecture that is designed to adopt a closed conformation with helically stacked naphthalenediimide (NDI) acceptors. The intercalation of the complementary electron-rich dialkoxynaphthalene ligands then stimulates the untwisting of the closed pi-helices into hollow barrel-stave supramolecules. During this helix-barrel transition, the angle between the transition moments of the exciton-coupled NDI chromophores decreases toward zero. The corresponding disappearance of the split CD provides, according to the exciton chirality method, the otherwise elusive experimental support that ligand-gated ion channel formation really occurs by this rationally designed helix-barrel transition.     

Fluorescence and binding properties of phenazine derivatives in complexes with polynucleotides of various base compositions and secondary structures

The interactions of two phenazine derivatives, one with a neutral chromophore (glycoside) and the other with a cationic one (quaternary salt), with various synthetic single- and double-stranded polynucleotides and natural DNA were studied by fluorescence techniques, conducting measurements of steady-state fluorescence intensity and polarization degree as well as fluorescence lifetime. These dyes show fluorescence quenching upon intercalation into the GC sequences of the double-stranded nucleic acids and an increase in fluorescence emission and lifetime upon incorporation into the AT and AU sequences. GC base pairs in continuous deoxynucleotide sequences were found to be preferred as binding sites for both phenazines, in contrast to AT base pairs. On the contrary, the continuous ribonucleotide GC sequence binds the phenazines more weakly than does the AU sequence. With regard to the interaction of the phenazines with single-stranded polynucleotides, a stacking interaction of the dye chromophores with the nucleic bases was observed. In that case the guanine residue quenches the cationic phenazine fluorescence, while the stacking interaction with the other bases results in an increase in the fluorescence quantum yield. Unlike the cationic dye, the fluorescence of the neutral phenazine was quenched by both purine bases.     

Molecular Mechanics Studies of Montmorillonite Intercalated with Tetramethylammonium and Trimethylphenylammonium

The intercalation of organoammonium cations into smectite structure is the important step in the technology of non-linear optical materials. In this study we investigated the structure of montmorillonite (MMT), intercalated with two organoammonium cations : tetramethylammonium (TMA) and trimethylphenylammonium (TMPA) using molecular mechanics simulations. The studies were focused to following aspects: arrangement of organoammonium cations in the interlayer, their positions and orientation with respect to silicate layers and their anchoring to the layers. The calculated (basal) d-spacings for MMT with TMA 14.29 Å and 15.36 Å for MMT with TMPA are in good agreement with X-ray diffraction data.     

Manipulating Adsorption–Insertion Mechanisms in Nanostructured Carbon Materials for High‐Efficiency Sodium Ion Storage

Hard carbon is one of the most promising anode materials for sodium‐ion batteries, but the low Coulombic efficiency is still a key barrier. In this paper, a series of nanostructured hard carbon materials with controlled architectures is synthesized. Using a combination of in situ X‐ray diffraction mapping, ex situ nuclear magnetic resonance (NMR), electron paramagnetic resonance, electrochemical techniques, and simulations, an “adsorption–intercalation” mechanism is established for Na ion storage. During the initial stages of Na insertion, Na ions adsorb on the defect sites of hard carbon with a wide adsorption energy distribution, producing a sloping voltage profile. In the second stage, Na ions intercalate into graphitic layers with suitable spacing to form NaC _x compounds similar to the Li ion intercalation process in graphite, producing a flat low voltage plateau. The cation intercalation with a flat voltage plateau should be enhanced and the sloping region should be avoided. Guided by this knowledge, nonporous hard carbon material has been developed which has achieved high reversible capacity and Coulombic efficiency to fulfill practical application.     

Photophysical characterization of methyl viologen ion-exchanged within a zirconium phosphate framework

The photophysical properties of 1,1′-dimethyl-4,4′dipyridinium (methyl viologen, MV²⁺) intercalated within zirconium phosphate (ZrP) were investigated. The intercalation of MV²⁺ within ZrP was achieved by ion-exchange using a hydrated form of ZrP with six water molecules per formula unit and an interlayer distance of 10.3 Å. The intercalation yields a new phase with an interlayer distance up to 10.6 Å. The MV²⁺-exchanged ZrP material was characterized using elemental analysis, XRPD and IR data. The MV²⁺-exchanged ZrP materials show a red shift in the UV-Vis spectra in contrast with solution. The photoexcitation of nitrogen purged, MV²⁺-exchanged ZrP water suspensions with UV light leads to fluorescence emission with a maximum at 337 nm. The photoexcitation of MV²⁺-exchanged ZrP suspensions without nitrogen purging yields two fluorescence emissions with maxima at 337 and 450 nm. The emission in the visible region can be attributed to a photodecomposition product. The fluorescence quantum yields indicate that the emission of MV²⁺-exchanged ZrP is of the same order of magnitude as that of MV²⁺ in water indicating a strong deactivation of the excited state by non-radiative pathways.     

Intercalative DNA binding of model compounds derived from metabolites of 7,12-dimethylbenz[a]anthracene

The DNA binding of nonreactive model compounds of metabolites of 7,12-dimethylbenz[a]-anthracene (DMBA)1 was studied in fluorescence quenching and fluorescence lifetime experiments. The model compounds examined were DMA and 8,9,10,11-tetrahydro-BA. DMA is a pi electron model of a highly carcinogenic bay region epoxide of DMBA, 8,9,10,11-tetrahydro-BA is a model compound of a less carcinogenic DMBA epoxide. The results indicate that the binding of DMA occurs primarily via intercalation. In 15% methanol the binding constant is 3.1 x 10(3) M-1. In 15% methanol and at DNA phosphate levels of 5.0 x 10(-4) M the intercalative binding of DMA is reduced by a factor of 6.2 when 5.0 x 10(-4) M Mg+2 is added. The DMA binding constant for intercalation is reduced by more than a factor of 4 when the methanol content of the solvent is increased from 0% to 20%. Finally DMA binding arising from pi interactions with the DNA bases is reduced more than 15 times when the DNA is denatured. For 8,9,10,11-tetrahydro-BA in 15% methanol the binding constant for intercalation is 6 times lower than that for DMA. These results along with previously reported binding data on other model compounds suggest that bay region metabolites of DMBA readily participate in physical pi stacking interactions with DNA.     

Design and synthesis of efficient fluorescent dyes for incorporation into DNA backbone and biomolecule detection

We report here the design and synthesis of a series of pi-conjugated fluorescent dyes with D-A-D (D, donor; A, acceptor), D-pi-D, A-pi-A, and D-pi-A for applications as the signaling motif in biological-synthetic hybrid foldamers for DNA detection. The Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel condensation were demonstrated as the optimum ways for construction of long pi-conjugated systems. Such rodlike chromophores have distinct advantages, as their fluorescence properties are not quenched by the presence of DNA. To be incorporated into the backbone of DNA, the chromophores need to be reasonably soluble in organic solvent for solid-phase synthesis, and therefore a strategy of using flexible tetraethylene glycol (TEG) linkers at either end of these rodlike dyes was developed. The presence of TEG facilitates the protection of the chain-growing hydroxyl group with DMTrCl (dimethoxytrityl chloride) as well as the activation of the coupling step with phosphoramidite chemistry on an automated DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six synthetic chromophores with blue to red fluorescence have been developed, and those with orthogonal fluorescent emission were chosen for incorporation into DNA-chromophore hybrid foldamers.