Heteroleptic copper switches.

Heteroleptic copper compounds have been designed and synthesized on solid supports. Chemical redox agents were used to change the oxidation state of the SiO(2)-immobilized heteroleptic copper compounds from Cu(I) to Cu(II) and then back to Cu(I). Optical spectroscopy of a dimethyl sulfoxide suspension demonstrated the reversibility of the Cu(I)/Cu(II) SiO(2)-immobilized compounds by monitoring the metal-to-ligand charge transfer peak at about 450 nm. Electron paramagnetic resonance spectroscopy was used to monitor the isomerization of Cu(I) tetrahedral to Cu(II) square planar. This conformational change corresponds to a 90° rotation of one ligand with respect to the other. Conductive atomic force microscopy and macroscopic gold electrodes were used to study the electrical properties of a p(+) Si-immobilized heteroleptic copper compound where switching between the Cu(I)/Cu(II) states occurred at -0.8 and +2.3 V.

pH-operated nanopistons on the surfaces of mesoporous silica nanoparticles.

The development of drug delivery systems for the targeted and on-demand release of pharmaceutical products has risen rapidly to become a contemporary challenge in the field of nanobiotechnology. Biocompatible mechanized phosphonate-clothed silica nanoparticles have been designed and fabricated in which the supramolecular machinery, which covers the surfaces of the nanoparticles, behaves like nanopistons, releasing encapsulated guest molecules in a controlled fashion under acidic conditions. The mechanized nanoparticles consist of a monolayer of ß-cyclodextrin (ß-CD) rings positioned selectively around the orifices of the nanopores of the mesoporous nanoparticles. A rhodamine B/benzidine conjugate was prepared for use as the nanopistons for movement in and out of the cylindrical cavities provided by the ß-CD rings on the surfaces of the nanoparticles. Luminescence experiments indicated that the mechanized nanoparticles were able to store small cargo molecules (e.g., 2,6-naphthalenedisulfonic acid disodium) within their nanopores at neutral pH and then release them by passage through the cavities of the ß-CD rings as soon as the pH was lowered to ∼5. In further investigations, the phosphonate-covered silica nanoparticles were functionalized selectively with the ß-CD rings, but on this occasion, the seven linkers attaching the rings to the orifices surrounding the nanopores contained cleavable imine double bonds. The ß-CD rings on the surface of the nanoparticles served as gates for the storage of large cargo molecules (e.g., rhodamine B) inside the nanopores of the nanoparticles under neutral conditions. Since imine bonds can be hydrolyzed under acidic conditions, the ß-CD rings could be severed from the surface of the nanoparticles when the pH was decreased to 6, releasing the large cargo molecules. The results described here present a significant step toward the development of pH-responsive nanoparticle-based dual drug delivery vehicles that are potentially capable of being interfaced with biological systems.

Influence of ligand substitution on excited state structural dynamics in Cu(I) bisphenanthroline complexes.

This study explores the influences of steric hindrance and excited state solvent ligation on the excited state dynamics of Cu(I) diimine complexes. Ultrafast excited state dynamics of Cu(I)bis(3,8-di(ethynyltrityl)-1,10-phenanthroline) [Cu(I)(detp)(2)](+) are measured using femtosecond transient absorption spectroscopy. The steady state electronic absorption spectra and measured lifetimes are compared to those of Cu(I)bis(1,10-phenanthroline), [Cu(I)(phen)(2)](+), and Cu(I)bis(2-9-dimethyl-1,10-phenanthroline), [Cu(I)(dmp)(2)](+), model complexes to determine the influence of different substitution patterns of the phenanthroline ligand on the structural dynamics associated with the metal to ligand charge transfer excited states. Similarities between the [Cu(I)(detp)(2)](+) and [Cu(I)(phen)(2)](+) excited state lifetimes were observed in both coordinating and noncoordinating solvents and attributed to the lack of steric hindrance from substitution at the 2- and 9-positions. The solution-phase X-ray absorption spectra of [Cu(I)(detp)(2)](+), [Cu(I)(phen)(2)](+), and [Cu(I)(dmp)(2)](+) are reported along with finite difference method calculations that are used to determine the degree of ground state dihedral angle distortion in solution and to account for the pre-edge features observed in the XANES region.

Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs.

Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 kD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 kD PEI polymer were particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in >70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the nontoxic cationic MSNP enhances the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.