Reaction of 2,5-dihydroxy-[1,4]-benzoquinone with nucleophiles - -substitution addition/elimination.

2,5-Dihydroxy-[1,4]-benzoquinone (DHBQ) reacts readily with secondary amines to 2,5-diamino compounds and with thiols to the corresponding 2,5-dithioether derivatives. The literature has been inconclusive about the detailed mechanism, as both ipso-substitution at C-2/C-5 and the sequence of C-3/C-6 addition and C-2/C-5 elimination would give exactly the same products. By means of selectively 13C isotopically labelled DHBQ it was demonstrated that the reaction with morpholine is an ipso-substitution, while the reaction with benzenethiol and 1-hexanethiol proceeds according to the addition/elimination mechanism, and the reaction with the respective thiolates according to both mechanisms in parallel.

High-Yielding Syntheses of Crown Ether-Based Pyridyl Cryptands.

Pyridinium bis(trifluoromethylsulfonyl)imide (PyTFSI)-templated syntheses of 2,6-pyridyl cryptands of cis(4,4')-dibenzo-30-crown-10 (3a), the p-bromobenzyloxy derivative 3b, bis(m-phenylene)-32-crown-10 (5), cis(4,4')-dibenzo-27S-crown-9 (7), cis(4,4')-dibenzo-27L-crown-9 (9), and cis(4,4')-dibenzo-24-crown-8 (11) are reported. Here we provide a fast (12 h), high-yielding (89%, 74%, 80%, and 62% for 3a, 3b, 5, and 9, respectively) templation method without the use of a syringe pump. The yields for 7 (19%) and 11 (26%) were lower than with the previous pseudo-high-dilution method, indicating ineffective templation in these cases.

Morphology selection via geometric frustration in chiral filament bundles.

In assemblies, the geometric frustration of a locally preferred packing motif leads to anomalous behaviours, from self-limiting growth to defects in the ground state. Here, we demonstrate that geometric frustration selects the equilibrium morphology of cohesive bundles of chiral filaments, an assembly motif critical to a broad range of biological and synthetic nanomaterials. Frustration of inter-filament spacing leads to optimal shapes of self-twisting bundles that break the symmetries of packing and of the underlying inter-filament forces, paralleling a morphological instability in spherical two-dimensional crystals.

Preparation of Bottlebrush Polymers via a One-Pot Ring-Opening Polymerization (ROP) and Ring-Opening Metathesis Polymerization (ROMP) Grafting-Through Strategy.

Bottlebrush polymers are synthesized using a tandem ring-opening polymerization (ROP) and ring-opening metathesis polymerization (ROMP) strategy. For the first time, ROP and ROMP are conducted sequentially in the same pot to yield well-defined bottlebrush polymers with molecular weights in excess of 10(6) Da. The first step of this process involves the synthesis of a polylactide macromonomer (MM) via ROP of d,l-lactide initiated by an alcohol-functionalized norbornene.

Highly Conductive and Thermally Stable Ion Gels with Tunable Anisotropy and Modulus.

A new liquid-crystalline ion gel exhibits unprecedented properties: conductivity up to 8 mS cm(-1) , thermal stability to 300 °C, and electrochemical window to 6.1 V, as well as adjustable transport anisotropy (up to 3.5×) and elastic modulus (0.

Dendritic Elastin-like Peptides: The Effect of Branching on Thermoresponsiveness.

Elastin-like peptides (ELPs) have been used widely to confer thermoresponsive characteristics onto various materials, but to this point mostly linear ELPs have been studied. A class of linear and dendritic (branched) ELPs based on the GLPGL pentamer repeat unit was synthesized using an on-resin divergent strategy. The effect of peptide topology on the transition temperature (Tt) was examined using circular dichroism to study the peptide secondary structure transition and turbidity to measure the macroscopic phase transition (coacervation).

Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers.

Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.

Diffusion of Drug Delivery Nanoparticles into Biogels Using Time-Resolved MicroMRI.

Nanoparticle-based therapeutic agents can in some cases provide selective delivery to tumors, yet this field would greatly benefit from more detailed understanding of particle transport into and within tumor tissue. To provide fundamental information for optimizing interstitial transport of polymeric nanoparticles, we have developed a quantitative approach employing real-time analysis of nanoparticle diffusion into bulk biological hydrogels using microMRI. We use two distinct imaging approaches to probe the migration of two novel "theranostic" polymeric agents (combining drug delivery and contrast agent functions) into bulk hydrogels.

Peptide-based hydrogen sulphide-releasing gels.

An aromatic peptide amphiphile was designed for delivery of the signaling gas H2S. The peptide self-assembled in water into nanofibers that gelled upon charge screening. The non-toxic gel slowly released H2S over 15 hours, and the presence of H2S in endothelial cells was verified using a fluorescent H2S probe.

Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers.

Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC50 (0.

Lanthanide-containing polycations for monitoring polyplex dynamics via lanthanide resonance energy transfer.

Theranostic nanomaterials have emerged in the past decade that combine therapeutic delivery and diagnostic imaging into one package. Such materials offer the opportunity to aid diagnosis, track therapeutic biodistribution, and monitor drug release. We have developed a series of nucleic acid delivery polymers containing oligoethylene amines that are able to be protonated at physiological pH (for binding/compacting pDNA) and a lanthanide-chelating domain, which imparts diagnostic functionality.

Observation of separate cation and anion electrophoretic mobilities in pure ionic liquids.

Ionic liquids (ILs) continue to show relevance in many fields, from battery electrolytes, to carbon capture, to advanced separations. These highly ion-dense fluids present unique challenges in understanding their electrochemical properties due to deviations in behavior from existing electrolyte theories. Here we present a novel characterization of ILs using electrophoretic NMR (ENMR) to determine separate cation and anion mobilities.

Humidity-modulated phase control and nanoscopic transport in supramolecular assemblies.

Supramolecular assembly allows for enhanced control of bulk material properties through the fine modulation of intermolecular interactions. We present a comprehensive study of a cross-linkable amphiphilic wedge molecule based on a sulfonated trialkoxybenzene with a sodium counterion that forms liquid crystalline (LC) phases with ionic nanochannel structures. This compound exhibits drastic structural changes as a function of relative humidity (RH).

Cation and anion transport in a dicationic imidazolium-based plastic crystal ion conductor.

Here we investigate the organic ionic plastic crystal 1,2-bis[N-(N'-hexylimidazolium-d2(4,5))]ethane 2PF6(-) in one of its solid plastic crystal phases by means of multinuclear solid-state (SS) NMR and pulsed-field-gradient NMR diffusometry. We quantify distinct cation and anion diffusion coefficients as well as the Arrhenius diffusion activation energies (Ea) in this dicationic imidazolium-based plastic crystal. Our studies suggest a change in transport mechanism for the cation upon varying thermal and magnetic treatment (9.

Quantitation of Complexed versus Free Polymers in Interpolyelectrolyte Polyplex Formulations.

The quantity of free polymer in a polymer/DNA complex (polyplex) formulation critically impacts its gene transfection efficiency, cellular uptake, and toxicity. In this study, the compositions of three interpolyelectrolyte polyplex formulations were quantified by a facile NMR method. Using careful integration of a 1D H NMR spectrum with a broad spectral width, the quantities of unbound polymer and polyplexes in solution were determined.

Poly(trehalose): sugar-coated nanocomplexes promote stabilization and effective polyplex-mediated siRNA delivery.

When nanoparticles interact with their environment, the nature of that interaction is governed largely by the properties of its outermost surface layer. Here, we exploit the exceptional properties of a common disaccharide, trehalose, which is well-known for its unique biological stabilization effects. To this end, we have developed a synthetic procedure that readily affords a polymer of this disaccharide, poly(methacrylamidotrehalose) or "poly(trehalose)" and diblock copolycations containing this polymer with 51 repeat units chain extended with aminoethylmethacrylamide (AEMA) at three degrees of polymerization (n = 34, 65, and 84).

Synthesis and Properties of Sulfonium Polyelectrolytes for Biological Applications.

Sulfonium macromolecules displayed for the first time nucleic acid binding and transfection in vitro. Conventional and controlled radical polymerization techniques coupled with subsequent alkylation generated a sulfonium homopolymer, poly(DMSEMA), and a sulfonium diblock copolymer, poly(OEG--DMSEMA). DNA gel shift assays probed the ability of sulfonium macromolecules to complex nucleic acids, and luciferase assays examined the transfection efficiency and cytotoxicity of both sulfonium macromolecules.

Unraveling the local energetics of transport in a polymer ion conductor.

We compare diffusion activation energy measurements in a hydrated perfluorosulfonate ionomer and aqueous solutions of triflic acid. These measurements provide insight into water transport dynamics on sub-nm length scales, and gauge the contribution of the polymer sidechain terminal group. Future membrane materials design will hinge on detailed understanding of transport dynamics.

Phosphonium-containing diblock copolymers for enhanced colloidal stability and efficient nucleic acid delivery.

RAFT polymerization successfully controlled the synthesis of phosphonium-based AB diblock copolymers for nonviral gene delivery. A stabilizing block of either oligo(ethylene glycol(9)) methyl ether methacrylate or 2-(methacryloxy)ethyl phosphorylcholine provided colloidal stability, and the phosphonium-containing cationic block of 4-vinylbenzyltributylphosphonium chloride induced electrostatic nucleic acid complexation. RAFT polymerization generated well-defined stabilizing blocks (M(n) = 25000 g/mol) and subsequent chain extension synthesized diblock copolymers with DPs of 25, 50, and 75 for the phosphonium-containing block.

Crystallinity and motional dynamics study of a series of poly(arylene ether sulfone) segmented copolymer analogues.

Solid-state NMR spectroscopy was utilized to study the crystallinity and its correlation to the motional dynamics of a series of biphenol based poly(arylene ether sulfone) (PAES) copolymer analogues obtained by incorporating flexible aliphatic blocks. Introduction of a series of conformationally flexible aliphatic blocks into the rigid aromatic PAES blocks in the copolymer sequence had increased the crystallinity of the polymer matrix because the copolymer system with aliphatic blocks provided a decrease in the glass transition temperature (Tg) while maintaining a nonvariant melting temperature (Tm). Modified PAES copolymer systems with aliphatic blocks had yielded shorter (1)H T1 relaxation times and longer (1)H T1ρ relaxation times relative to the neat aromatic PAES copolymer.

Sterically Crowded Anionic Polyelectrolytes with Tunable Charge Densities Based on Stilbene-Containing Copolymers.

Anionic polyelectrolytes with various charge densities and a well-defined chain architecture have great industrial and fundamental importance. In this article, we describe the synthesis and characterization of new sterically crowded conformationally constrained anionic polyelectrolytes with tunable charge densities based on highly functionalized stilbene-maleic anhydride/maleimide comonomers. Polyelectrolyte precursors with -butyl carboxylate protecting groups are first prepared by radical polymerization and readily characterized by H NMR, SEC, TGA, and DSC without the complications normally arising with charged macromolecules.

TBAF and cellulose esters: unexpected deacylation with unexpected regioselectivity.

Tetrabutylammonium fluoride has been found to catalyze the deacylation of cellulose esters. More surprisingly, the deacylation is highly regioselective. Even more remarkably, in contrast with the C-6 regioselectivity of other reactions of cellulose and its derivatives, this deacylation shows substantial selectivity for the removal of the acyl groups from the esters of the secondary alcohols at C-2 and C-3, affording cellulose-6-O-esters with high regioselectivity by a simple one-step process employing no protective groups.

DNA-inspired hierarchical polymer design: electrostatics and hydrogen bonding in concert.

Nucleic acids and proteins, two of nature's biopolymers, assemble into complex structures to achieve desired biological functions and inspire the design of synthetic macromolecules containing a wide variety of noncovalent interactions including electrostatics and hydrogen bonding. Researchers have incorporated DNA nucleobases into a wide variety of synthetic monomers/polymers achieving stimuli-responsive materials, supramolecular assemblies, and well-controlled macromolecules. Recently, scientists utilized both electrostatics and complementary hydrogen bonding to orthogonally functionalize a polymer backbone through supramolecular assembly.

Cationic glycopolymers for the delivery of pDNA to human dermal fibroblasts and rat mesenchymal stem cells.

Progenitor and pluripotent cell types offer promise as regenerative therapies but transfecting these sensitive cells has proven difficult. Herein, a series of linear trehalose-oligoethyleneamine "click" copolymers were synthesized and examined for their ability to deliver plasmid DNA (pDNA) to two progenitor cell types, human dermal fibroblasts (HDFn) and rat mesenchymal stem cells (RMSC). Seven polymer vehicle analogs were synthesized in which three parameters were systematically varied: the number of secondary amines (4-6) within the polymer repeat unit (Tr4(33), Tr5(30), and Tr6(32)), the end group functionalities [PEG (Tr4(128)PEG-a, Tr4(118)PEG-b), triphenyl (Tr4(107)-c), or azido (Tr4(99)-d)], and the molecular weight (degree of polymerization of about 30 or about 100) and the biological efficacy of these vehicles was compared to three controls: Lipofectamine 2000, JetPEI, and Glycofect.

Poly(glycoamidoamine)s: a broad class of carbohydrate-containing polycations for nucleic acid delivery.

In the era of nucleic acid therapeutics, there is an urgent need for non-viral delivery vehicles that can cross the extracellular and intracellular barriers and deliver nucleic acids to specific intracellular regions. This paper reviews the development of a subclass of polymer-based delivery vehicles termed poly(glycoamidoamine)s (PGAAs). The general design of this family consists of carbohydrate residues copolymerized with oligoethyleneamine units, which have proven to be an effective motif that promotes polyplex formation, efficient cellular internalization, high gene expression and low cytotoxicity with cultured cell lines and primary cell types.