Dendrimeric siRNA for Efficient Gene Silencing

Programmable molecular self‐assembly of siRNA molecules provides precisely controlled generation of dendrimeric siRNA nanostructures. The second‐generation dendrimers of siRNA can be effectively complexed with a low‐molecular‐weight, cationic polymer (poly(β‐amino ester), PBAE) to generate stable nanostructures about 160 nm in diameter via strong electrostatic interactions. Condensation and gene silencing efficiencies increase with the increased generation of siRNA dendrimers due to a high charge density and structural flexibility.     

Nature of cationic poly(propylenimine) dendrimers in aqueous solutions as studied using versatile indicator dyes

Aqueous solutions of four cationic poly(propylenimine) low-generation dendrimers of different architecture and hydrophobicity have been examined as media for acid-base reactions of indicator dyes. The cationic dendrimers in solution can be considered as oligomers of cationic polyelectrolytes, or surfactant-like species, able to form micelles through self-association or sometimes even as unimolecular micelles. The dendrimers influence the ionization constants, tautomeric equilibria, and absorption/emission/excitation spectra of indicator dyes. The p K a values of the majority of the indicator dyes decrease in dendrimer solutions, often by 1-2 p K a units, similar to effects registered in micellar solutions of cationic surfactants. Analogously, the shifts of absorption band maxima indicate that the microenvironments of the dyes bound to the dendrimers are less polar than in water. However, some spectral effects denote the specificity of the dendrimers. The greatest difference between the dendrimers and spherical surfactant micelles is revealed by kinetic processes, especially of bromophenol blue alkaline fading in a dendrimer solution but not in a micellar surfactant solution. Within the dendrimer series, the most significant differences were observed for substances possessing n-dodecyl tails on the one hand and those without such hydrophobic portions on the other. For the last-named, the decrease in p K a's of indicators, band shifts of their anions, and in particular displacement of tautomeric equilibria compared with aqueous solutions are much smaller than for more hydrophobic dendrimers.     

Polyvalent scaffolds. Counting the number of seats available for eosin guest molecules in viologen-based host dendrimers

We have prepared and investigated two dendrimers based on a 1,3,5-trisubstituted benzenoid-type core, containing 9 and 21 viologen units in their branches, respectively, and terminated with tetraarylmethane derivatives. We have shown that, in dichloromethane solution, such highly charged cationic species give rise to strong host-guest complexes with the dianionic form of the red dye eosin. Upon complexation, the absorption spectrum of eosin becomes broader and is slightly displaced toward lower energies, whereas the strong fluorescence of eosin is completely quenched. Titration experiments based on fluorescence measurements have shown that each viologen unit in the dendrimers becomes associated with an eosin molecule, so that the number of positions ("seats") available for the guest molecules in the hosting dendrimer is clearly established, e.g., 21 for the larger of the two dendrimers. The host-guest interaction can be destroyed by addition of chloride ions, a procedure which permits eosin to escape from the dendrimer's interior in a controlled way and to regain its intense fluorescence. When chloride anions are precipitated out by addition of silver cations, eosin molecules re-enter the dendrimer's interior and their fluorescence again disappears.     

In Situ Synthesis of a Supramolecular Hydrogelator at an Oil/Water Interface for Stabilization and Stimuli‐Induced Fusion of Microdroplets

Supramolecular hydrogels are expected to have applications as novel soft materials in various fields owing to their designable functional properties. Herein, we developed an in situ synthesis of supramolecular hydrogelators, which can trigger gelation of an aqueous solution without the need for temperature change. This was achieved by mixing two precursors, which induced the synthesis of a supramolecular gelator and its instantaneous self‐assembly into nanofibers. We then performed the in situ synthesis of this supramolecular gelator at an oil/water interface to produce nanofibers that covered the surfaces of the oil droplets (nanofiber‐stabilized oil droplets). External stimuli induced fusion of the droplets owing to disassembly of the gelator molecules. Finally, we demonstrated that this stimuli‐induced droplet fusion triggered a synthetic reaction within the droplets. This means that the confined nanofiber‐stabilized droplets can be utilized as stimuli‐responsive microreactors.     

The Formation of Organogels and Helical Nanofibers from Simple Organic Salts

Simple organic salts based on aniline‐derived cations and D ‐tartrate anions formed organogels and helical nanofibers. The organic salt (p‐fluoroanilinium)(D ‐tartrate) was found to generate an organogel despite the absence of a hydrophobic alkyl chain, whereas (p‐iodoanilinium)(D ‐tartrate) formed helical nanofibers in braided ropelike structures through a rolling‐up process. The helicity of these nanofibers could be reversed by changing the growth solvent. The driving forces responsible for the formation of the nanofibers were determined to be 1D O?H???O^? hydrogen‐bonding interactions between D ‐tartrate anions and π stacking of anilinium cations, as well as steric hindrance between the hydrogen‐bonded chains.     

Amphiphilic diblock copolymers bearing pendant aromatic acetal groups: Synthesis and tunable pH‐triggered assembly/disassembly transition behavior

A novel aromatic acetal‐based acid‐labile monomer 2‐phenyl‐5‐ethyl‐5‐acryloxymethyl‐1,3‐dioxacyclohexane (HEDPA) was synthesized and polymerized by reversible addition fragmentation chain transfer (RAFT) polymerization using alkynyl functional chain transfer agent (CTA‐Alk). Afterward, a series of amphiphilic diblock copolymers composed of fixed hydrophobic poly(2‐phenyl‐5‐ethyl‐5‐acryloxymethyl‐1,3‐dioxacyclohexane) (PDAEP) segments and various lengths of hydrophilic mPEG segments were prepared through click reaction between alkynyl‐terminated PDAEP and azido‐terminated mPEG. The self‐assembly behaviors of the diblock copolymers were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence spectroscopy, and ¹H NMR. These results indicated that the diblock copolymers could self‐assemble into nano‐sized micelles with PDAEP cores and PEG coronas in aqueous solution. DLS, fluorescence spectroscopy and UV–vis spectroscopy were used to monitor the pH‐triggered assembly/disassembly transition of the micelles. These results showed that the assembly/disassembly transition behaviors of the diblock copolymers micelles can be adjusted by changing the lengths of the mPEG segments. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1537–1547     

Mercapto thiadiazole-based sensor with colorimetric specific selectivity for AcO- in aqueous solution

A novel acetate selective anion sensor 3 based on azophenol and mercapto thiadiazole had been designed and synthesized. Sensor 3 behaves a single selectivity and sensitivity in the recognition for AcO(-) anion over other anions such as F(-), Cl(-), Br(-), I(-), H(2)PO(4)(-), HSO(4)(-) and ClO(4)(-) by naked-eyes and UV-vis spectra changes in aqueous solution (H(2)O/DMSO, 5:5, v/v). The color of the solution containing sensor 3 had an obvious change from colorless to orange only after the addition of AcO(-) in aqueous solution while other anions did not cause obvious color change. (1)H NMR titration results revealed that the binding process includes two steps: (i) hydrogen bonding interactions (for small quantities of acetate) and (ii) proton transfer between the sensor 3 and the coordinated anion (for high quantities of acetate). The association constant K(a) was 7.35×10(3) M(-1). The detection limitation of AcO(-) with the sensor 3 was 1.0×10(-6) mol L(-1).     

Metal ion-dependent molecular inclusion chemistry: inclusion of aromatic anions by coordinated 1,4,7,10-tetrakis((S)-2-hydroxy-3-phenoxypropyl)-1,4,7,10-tetraazacyclododecane

The ability of the pendant donor macrocyclic ligand 1,4,7,10-tetrakis((S)-2-hydroxy-3-phenoxypropyl)-1,4,7,10-tetraaza- cyclododecane((S)-thphpc12) (or [Cd((S)-thphpc12)](2+)) to act as a metal ion-dependent receptor for aromatic anions has been investigated in solution and in the solid state. [Cd((S)-thphpc12)](2+) adopts a stable conical conformation with a large hydrophobic cavity, which has been shown to contain, via complementary multiple hydrogen bonding, p-nitrophenolate, aromatic carboxylates, p-toluenesulfonate, certain aromatic amino acid anions, phenoxyacetate, and acetate. In the case of p-nitrophenolate only, one or two anions can be contained within the receptor cavity. The crystal structure of [Cd((S)-thphpc12)(p-nitrophenolate)(2)] shows a coplanar arrangement of the p-nitrophenolates, where each is retained in the cavity by a pair of hydrogen bonds to cis hydroxyl groups. The crystal structure of the p-aminobenzoate inclusion complex indicates retention of the guest via a pair of hydrogen bonds to each oxygen atom of the carboxylate moiety. The crystal structure of the (L)-phenylalaninate inclusion complex indicates that the amino acid is retained by five hydrogen bonds, two involving the nitrogen atom and three to the oxygen atoms of the carboxylate moiety. Binding constants (10(3)-10(5) M(-1)) for the inclusion of some of the aforementioned anions in [Cd((S)-thphpc12)](2+) and related receptors were measured by (1)H NMR titration in DMSO-d(6) at 298 K.     

Cd(II) determination in the presence of aqueous micellar solutions

The equilibrium constants and molar absorptivities for the fast formation of a 1:3 complex between cadmium(II) (Cd(II)) and dithizonate anion, in the presence of cationic and non-ionic surfactants, allowed a simple and fast spectrophotometric determination of total cadmium. Indeed, the molar absorptivities of the Cd(II)-dithizone (Dz) complex formed in the presence of the neutral Triton X-100 and cationic cetyltrimethylammonium bromide (CTAB) surfactants are almost twice the value observed in the standard method and the maxima of absorption are shifted by about 40 nm when compared with the standard method. Clearly, the use of neutral and cationic surfactants promotes a higher value of the molar absorptivities of the complex, resulting in an increase in the sensitivity of the method. Application of the method to the desorption of Cd(II) ions from clays is illustrated.     

New insights into the interactions between dendrimers and surfactants by two dimensional NOE NMR spectroscopy

The interactions between polyamidoamine dendrimers and different surfactants including sodium dodecyl sulfate (SDS) and dodecyltrimethyl ammonium bromide in aqueous solutions have been investigated by a NOESY NMR technique. Strong NOE cross-peaks between hydrophobic chain protons of SDS and methylene protons of cationic dendrimers were found, suggesting a strong tendency for the long hydrophobic tails of SDS to associate with the hydrophobic pockets of dendrimers. The hydrophilic head of SDS localizes near the core or the boundary of each generation of dendrimers, and the hydrophobic chain of SDS localizes in the relative nonpolar pockets of dendrimers. The encapsulation of surfactant monomers by dendrimers is dependent on the charge type of the surfactants, the surface functionality, and the generation of dendrimers. The NOESY analysis provides a new insight into interactions between dendrimers and surfactants in comparison with previous investigations.     

A novel acetate selective chromogenic chemosensor based on phenanthroline

A novel colorimetric anion-chemosensor based on 1,10-phenanthroline-2,9-dicarbonyl-p-nitro-phenylhydrazine has been synthesized. Among the different anions tested, it shows the best selectivity towards AcO(-). The addition of acetate causes the color to change from yellow to red, which could be detected with naked eyes. The binding ability of chemosensor 1 with anions has been investigated through UV-vis spectral titrations. In addition, (1)H NMR experiment was carried out to explore the nature of interaction between chemosensor 1 and acetate.     

Photo‐controlled Hierarchical Assembly and Fusion of Coumarin‐containing Polydiacetylene Vesicles

Herein, we synthesize a coumarin‐substituted diacetylene monomer (CODA) and report the novel photo‐controlled reversible assembly and disassembly behavior of the polymerized CODA (PCODA) vesicles. The photo‐triggered dimerization and cleavage reactions of the coumarin groups within the surface of the adjacent PCODA vesicles can be utilized as the driving force to induce assembly and disassembly of PCODA vesicles. Moreover, the boundary of PCODA vesicles in the aggregates becomes more obscure when the irradiation time exceeds 30 min. Fusion occurs upon close docking of target membranes, driven by sufficient dimerization of the coumarin groups within the surface of PCODA vesicles.     

Direct Assembly of Metal-Phenolic Network Nanoparticles for Biomedical Applications

Coordination assembly offers a versatile means to developing advanced materials for various applications. However, current strategies for assembling metal-organic networks into nanoparticles (NPs) often face challenges such as the use of toxic organic solvents, cytotoxicity because of synthetic organic ligands, and complex synthesis procedures. Herein, we directly assemble metal-organic networks into NPs using metal ions and polyphenols (i.e., metal-phenolic networks (MPNs)) in aqueous solutions without templating or seeding agents. We demonstrate the role of buffers (e.g., phosphate buffer) in governing NP formation and the engineering of the NP physicochemical properties (e.g., tunable sizes from 50 to 270 nm) by altering the assembly conditions. A library of MPN NPs is prepared using natural polyphenols and various metal ions. Diverse functional cargos, including anticancer drugs and proteins with different molecular weights and isoelectric points, are readily loaded within the NPs for various applications (e.g., biocatalysis, therapeutic delivery) by direct mixing, without surface modification, owing to the strong affinity of polyphenols to various guest molecules. This study provides insights into the assembly mechanism of metal-organic complexes into NPs and offers a simple strategy to engineer nanosized materials with desired properties for diverse biotechnological applications.     

A selective chromogenic molecular sensor for acetate anions in a mixed acetonitrile-water medium

Quinonehydrazone compound , as a new chromogenic anion sensor, can selectively detect AcO(-) over F(-) and other anions in mixed acetonitrile-water media. The deprotonation of the N-H proton of the sensor is responsible for the drastic color change. An acidic C-H group in the receptor, probably acting as an accessorial binding site, is essential to the selectivity and affinity for sensing the acetate anions.     

Functionalized guanidinium chloride based colourimetric sensors for fluoride and acetate: single crystal X-ray structural evidence of -NH deprotonation and complexation

A series of new symmetrically functionalized guanidinium chlorides (S1-S10) are synthesized in good yields and their sensing ability toward anions is studied in MeCN-DMF (24?:?1) (v/v). The absorption bands of these molecules in the presence of anions are tuned by varying the functional groups attached to the guanidinium moiety (which resembles urea) with respect to (i) aromaticity (S1-S4), (ii) electron induction effect (S1, S5-S9), (iii) positional isomeric effect (S7-S9), (iv) indole functionality (S10) of the conjugated aryl units. Anions that are above Cl(-) in the Hofmeister series (F(-), AcO(-), H(2)PO(4)(-)) are eligible as an analyte in this series of molecules whereas less basic anions than Cl(-) do not cause any interference. Thus, this series of molecules are suitable for the detection of anions in the narrow window of the Hofmeister series. Out of all the anions, only fluoride causes vivid colour changes from yellow to red to reddish orange and finally to blue, irrespective of the increasing aromaticity, induction and positional isomeric effect of the substituent that is attached to the guanidinium moiety. Interestingly, S9 has shown the ability to sense distinctly both F(-) and AcO(-) colourimetrically. Further S10, a sensor attached with indole functionality shows selective sensing of F(-) colourimetrically with a NIR signature at ～930 nm though both these outputs are very unstable in nature. Stability constants for complex formation of S1-S10 (except S5) with F(-), AcO(-) are calculated by UV-vis titration experiments. Finally single crystal X-ray structural studies on the species 1 formed upon treating S6 with sodium fluoride confirms -NH deprotonation, whereas the reaction of S6 and S2 with sodium benzoate shows 1:1 host:guest binding that results in complexes 2 and 3 respectively.     

pH-controlled reversible assembly of peptide-functionalized gold nanoparticles

The assembly/disassembly process of carboxylated peptide-functionalized gold nanoparticles (peptide-GNPs) was studied within the pH interval of 2.5 to 10. The assembly process was not well controlled at pH 2.5, leading to the formation of 3D structures of GNPs, whereas at pH 4 we observed controlled assembly with the formation of only a network of 1D chains. In the pH range of 2.5 to 4, the assembly proceeded with the formation of a combination of two extremes (i.e., having both 1D and 2D nanostructures). The assembly process was reversed on changing the pH of the medium to 10. The assembly/disassembly process was monitored using UV-vis spectroscopy and finally confirmed by TEM analysis. This assembly resulted from the intermolecular H-bonding between two carboxylic acid groups of peptides bound to the two adjacent GNPs and were confirmed by FTIR spectroscopy.     

Roles of anionic and cationic template components in biomineralization of CdS nanorods using self-assembled DNA-membrane complexes

Complexes of anionic DNA and cationic liposomes self-assemble into a multilamellar structure where two-dimensional lipid sheets confine a periodic one-dimensional lattice of parallel DNA chains, between which Cd(2+) ions can condense, and be subsequently reacted with H(2)S to form CdS nanorods. In this work, we identify the synergistic roles of the anionic and cationic components within the DNA-membrane template; DNA is highly anionic and condenses the Cd(2+) ions, while the cationic membrane modulates the concentration of condensed Cd(2+) ions to control the final CdS nanorod dimensions. Due to the strong electrostatic interactions between the DNA sugar-phosphate backbone and the Cd(2+) ions, crystallographic control of CdS nanostructures is possible using these simple DNA-membrane templates, which we demonstrate using nanobeam electron diffraction experiments on individual templated CdS nanorods.     

Modular functional integration of a two-input INH logic gate with a fluorophore-spacer-receptor1-spacer-receptor2 conjugate

The synthesis and photophysical characterization of a fluorophore-spacer-receptor 1-spacer-receptor 2 system, which combines the 1,8-naphthalimide fluorophore with amine and urea receptor units, is reported. Photoinduced electron transfer (PET) from the amino group was blocked by protonation, leading to a drastic fluorescence enhancement (ca. 20 times). Interaction of the urea receptor with anions (F (-), AcO (-), H 2PO 4 (-)) via hydrogen bonding or urea NH deprotonation resulted in significant fluorescence quenching of the 1,8-naphthalimide chromophore in an appropriately chosen model compound (ca. 30-45%). In the presence of both chemical input species, protons and anions, the fluorescence was also quenched. The binding of the anions by NH (+) ammonium receptor has been assumed. The apparent anion binding constants of the protonated conjugate follow the basicity trend of the anions: AcO (-) approximately F (-) > H 2PO 4 (-). The investigated system constitutes an example for the flexible and modular realization of functionally integrated INH logic at the molecular level, using protons and anions as chemical input species and the fluorescence of a PET-active signaling unit as output.     

Synthesis and esterolytic activity of catalytic peptide dendrimers

Peptide dendrimers were prepared by solid-phase peptide synthesis. Monomeric dendrimers were first obtained by assembly of a hexapeptide sequence containing alternate standard alpha-amino acids with diamino acids as branching units. The monomeric dendrimers were then dimerized by disulfide-bridge formation at the core cysteine. The synthetic strategy is compatible with functional amino acids and different diamino acid branching units. Peptide dendrimers composed of the catalytic triad amino acids histidine, aspartate, and serine catalyzed the hydrolysis of N-methylquinolinium salts when the histidine residues were placed at the outermost position. The dendrimer-catalyzed hydrolysis of 7-isobutyryl-N-methylquinolinium followed saturation kinetics with a rate constant of catalysis/rate constant without catalysis (k(cat)/k(uncat)) value of 3350 and a rate constant of catalysis/Michaelis constant (k(cat)/K(M)) value 350-fold larger than the second-order rate constant of the 4-methylimidazole-catalyzed reaction; this corresponds to a 40-fold rate enhancement per histidine side chain. Catalysis can be attributed to the presence of histidine residues at the surface of the dendrimers.