Dendritic molecular capsules for hydrophobic compounds

Reichardt's dye, a highly solvatochromic dye, was encapsulated within poly (glycerol succinic acid) ([Gn]-PGLSA-OH) dendrimers to investigate the interior environment of these dendritic macromolecules. The absorption maximum for the encapsulated Reichardt's dye in water was indicative of a relatively high dielectric constant present within the dye/dendrimer complex. (1)H NMR of the encapsulated complex showed the presence of aromatic protons from Reichardt's dye along with the aliphatic protons of the dendrimer. Additionally, there were substantial changes in T(1) and T(2) times of the encapsulated dye when compared with the free dye, and (1)H NOESY spectra for the complex showed a significant number of intermolecular NOE cross-peaks. These data reveal the close through-space proximity of the dye to the dendrimer and the restricted motion of the encapsulated dye. To demonstrate the potential use of these macromolecules as drug delivery vehicles, the poorly water-soluble anticancer drug 10-hydroxycamptothecin (10HCPT) was encapsulated within a carboxylated PGLSA dendrimer ([G4]-PGLSA-COONa). Cytotoxicity assays with human breast cancer cells showed a significant reduction of cell viability, demonstrating that 10HCPT retains activity upon encapsulation.     

Synthesis and characterization of carbohydrate-based phospholipids

Novel carbohydrate-based phospholipids containing two saturated C(12) (dilauroyl ribo-phosphocholine) (DLRPC), C(14) (dimyristoyl ribo-phosphocholine) (DMRPC), and C(20) (diarachadonyl ribo-phosphocholine) (DARPC) carboxylic acid chains were synthesized. The physical properties of the supramolecular structures formed by these compounds were compared to those formed by their direct glycerol analogues dilauroyl phosphocholine (DLPC), dimyristoyl phosphocholine (DMPC), and diarachadonyl phosphocholine (DAPC). Modulated differential scanning calorimetry (MDSC) and X-ray diffraction data indicated that with chain lengths < or =14 carbons, the carbohydrate backbone increased the thermal stability of the bilayer below the phase-transition temperature (T(m)) as compared to the glycerol-based lipids. With longer chains (C(20)), the bilayer structure was destabilized as compared to glycerol-based lipids. NMR studies of a DMRPC vesicle dispersion reveal split choline headgroup signals and distinct magnetization transfer effects arising from the "inner" and "outer" surfaces of the bilayer vesicle. Modulated differential scanning calorimetry also demonstrated that glycerol- and carbohydrate-based lipids mix, as evidenced by a single intermediate T(m). In addition, carbohydrate-based lipid/cholesterol mixtures exhibited a decrease in enthalpy with an increase in cholesterol concentration. Unlike glycerol phospholipids, carbohydrate lipids were resistant to enzymatic degradation by phospholipase A(2) (PLA(2)).     

Synthesis and characterization of fluorenone-, anthraquinone-, and phenothiazine-labeled oligodeoxynucleotides: 5'-probes for DNA redox chemistry

A facile and automated procedure for the synthesis of oligodeoxynucleotides possessing derivatives of 9-fluoreneone, 9,10-anthraquinone, and phenothiazine is described. The phosphoramidite approach is used to attach these redox and spectroscopic probes to the 5'-terminus of oligodeoxynucleotides in high yield (>95%). Thermal denaturation studies of labeled oligodeoxynucleotides show a slight enhancement in duplex stability relative to the unlabeled control, and circular dichroism spectra confirm B-form helical DNA structure in solution.     

Self-assembled microspheres from f-block elements and nucleoamphiphiles

Hollow microspheres featuring a hybrid lipid-cation multilamellar shell are prepared by hydration of a nucleoside based amphiphile with an aqueous solution containing either actinide or lanthanide salts. The physico-chemical data collected clearly indicate that the formation of these microspheres is a consequence of the following concomitant stabilizing factors: (i) hydrophobic interactions, (ii) nucleobase dimer formation and (iii) phosphate/f-block element salt binding.     

Synthesis and properties of supramolecular ionic networks

The synthesis of a supramolecular ionic network, its physical properties, and the use of this network property to form macroscopic porphyrin fibers are described. These ionic networks are compared to ionic liquids. Current ionic liquid compositions have a charge and molar ratio of 1:1 where an anionic species is matched with a cationic species; however, alteration of this molar ratio while maintaining the charge ratio of 1:1 by using multivalent cationic/anionic molecular pairs affords new ionically cross-linked networks with interesting properties.     

Anionic amphiphilic dendrimers as antibacterial agents

An anionic amphiphilic dendrimer is reported that possesses increased cytotoxicological potency against prokaryotic cells compared to eukaryotic cells. The half-maximal effective concentration (EC50) for the dendrimer against Bacillus subtilis, a Gram-positive bacterial strain, was measured to be 4.1 x 10(-5) M, while that against human umbilical vein endothelial cells (HUVEC) was more than 36x greater at a value of 1.5 x 10(-3) M. EC50 ratios for two commercial amphiphiles, sodium dodecyl sulfate (SDS) and Triton X-100, in addition to a similar synthesized dendritic structure were at most only 3.8x greater. Furthermore, the observed EC50 values appear to be correlated to the critical aggregation constant (CAC) in solution suggesting a mechanism of action for these anionic amphiphilic dendrimers related to their supramolecular structures.     

Stretch‐Induced Drug Delivery from Superhydrophobic Polymer Composites: Use of Crack Propagation Failure Modes for Controlling Release Rates

The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly‐textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate‐co‐caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain‐dependent delivery of the anticancer agents cisplatin and 7‐ethyl‐10‐hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus.     

Selective Homogeneous Palladium(0)-Catalyzed Hydrogenation of Alkynes to (Z)-Alkenes

Zero-valent palladium precatalysts containing rigid bidentate bis(arylimino)acenaphthene ligands (shown schematically) facilitate the highly stereoselective homogeneous catalytic hydrogenation of alkynes to (Z)-alkenes. Internal, terminal, aryl-substituted, and cyclic alkynes are suitable substrates, as are some enynes, which are chemoselectively hydrogenated to dienes. E=CO(2)Me; R(1), R(2)=4-OCH(3), 4-CH(3), 2,6-(CH(3))(2).     

DNA-PEG-DNA triblock macromolecules for reagentless DNA detection

The sandwich assay is the most common design for electrochemical DNA sensors. This assay consists of three individual DNA components: an immobilized capture strand, a target strand, and a probe strand containing a redox-active reporter group. We report a simplified DNA assay where two strands of ssDNA, the capture and probe strands, are linked together via a flexible poly(ethylene glycol) (PEG) spacer forming an ABA triblock macromolecule. We have developed an electrochemical assay where the detection signal arises as a consequence of a large structural change induced upon hybridization with target DNA. In this system, the DNA-PEG-DNA macromolecule folds or wraps around the target DNA, bringing the ferrocene probe in close proximity to the electrode, affording an electrochemical response.