Biomedical subjects
Publications and source records attributed to Vincent M Rotello.
Electrochemically tuneable hydrogen bonding interactions are described between a phenyl-urea terminated dendrimer and phenanthrenequinone.
Nanoparticles provide key tools for bridging the gap between "bottom-up" synthetic methods and "top-down" fabrication. In this Account we describe some of the unique structural aspects of nanoparticles and the use of these attributes to the creation of devices with tunable specificity and environmental response. We also explore the use of nanoparticles as "building blocks" for the creation of nanocomposite materials that feature structural control from the molecular to the micron scale.
We have explored the interactions of mono- and multivalent guests with Recognition-Induced Polymersomes (RIPs) formed from complementary random copolymers featuring diamidopyridine and thymine functionality. Addition of monovalent guests featuring imide functionality to these RIPs induced a temporary swelling of the vesicles, followed by dissociation of the vesicles due to competitive binding of the guest. Conversely, multivalent thymine-functionalized nanoparticle guests were rapidly incorporated into the RIPs, inducing a contraction of RIP diameter over time. These mono- and multivalent interactions were extremely specific: highly analogous control systems showed no interaction with the RIP structures. Taken together, these studies demonstrate highly selective molecular "lock and key" control over higher-order assembly and recognition processes.
Control of particle-particle spacing is a key determinant of optical, electronic, and magnetic properties of nanocomposite materials. We have used poly(amidoamine) (PAMAM) dendrimers to assemble carboxylic acid-functionalized mixed monolayer protected clusters (MMPCs) through acid/base chemistry between the particle and dendrimer. Small angle X-ray scattering was then used to establish average inter-MMPC distances. Five generations of PAMAM dendrimer (0, 1, 2, 4, 6) were investigated, with a monotonic increase in interparticle spacing from 4.1 to 6.1 nm observed with increasing generation.
Electrochemically controlled interactions have been shown to occur between TTF containing dendrimers 1 and 2 and the electron-rich oligomer 3.
Diaminopyridine-functionalized polyhedral oligomeric silsequioxanes (POSS-DAP) self-assemble with complementary thymine-functionalized Au nanoparticles (Thy-Au) into well-defined spherical aggregates, providing highly structured nanocomposites.
Hydrogen/deuterium exchange rates in amide-functionalized monolayer protected gold clusters (MPCs) are controlled by the radial nature of the surface, with inhibition and catalysis observed at different chain lengths.
Molecules capable of complementary hydrogen bonding were used to control the noncovalent self-assembly and electronic properties of a chemically well-defined surface mesostructure. In this work, we patterned a footprint region for molecular assembly on a surface and used moieties featuring complementary recognition to tune the current-voltage properties of the patterned region. With the appropriate functionalities on the complementary moieties, we were able to increase and decrease the observed conductance in surface-bound mesoscale structures imaged by scanning tunneling microscopy (STM).
Diaminopyridine (DAP) functionalized POSS derivatives self-assemble on thymine functionalized monolayers on gold surfaces affording hybrid inorganic/organic surfaces.
A model system for the characterization of molecular recognition events in molecularly imprinted polymers (MIPs) is presented. The use of a biologically inspired, three-point hydrogen-bonding motif and a thin film polymeric matrix allows for pre- and post-polymerization binding properties to be characterized by infrared spectroscopy. A method to determine binding constants was developed and utilized before and after cross-linking. These values showed a 10-fold decrease in binding after polymerization, which was attributed to an increase in molecular confinement after polymerization and a change in the local structural environment of the binding cavity. Transport of the guest molecule was shown to be reversible.
Polymer-mediated self-assembly of functionalized Pd and SiO2 nanoparticles provides highly active hydrogenation and Heck coupling catalysts.
Mixed Monolayer Protected Gold Clusters (MMPCs) featuring both hydrogen bonding and aromatic stacking molecular recognition functionalities have been used to create multivalent hosts for flavins. Multitopic binding of these hosts to flavin was shown to have a strong radial dependence: when the recognition site was brought closer to the MMPC surface, recognition was enhanced approximately 3-fold due to increased preorganization. The effect of preorganization is reversed upon reduction of flavin, where the MMPC with longer side chains bind the flavin guest approximately 7-fold stronger than the short chain counterpart due to unfavorable dipolar interactions between the electron-rich aromatic stacking units of the host and the anionic flavin guest. This fine-tuning of recognition and redox processes provides both a model for enzymatic systems and a tool for the fabrication of devices.
Efficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as scaffolds for the binding and inhibition of chymotrypsin. In these studies anionically functionalized amphiphilic MMPCs were shown to inhibit chymotrypsin through a two-stage mechanism featuring fast reversible inhibition followed by a slower irreversible process. This interaction is very efficient, with a K(i)(app) = 10.4 +/- 1.3 nM. The MMPC-protein complex was characterized by CD, demonstrating an almost complete denaturation of the enzyme over time. Dynamic light scattering studies confirm that inhibition proceeds without substantial MMPC aggregation. The electrostatic nature of the engineered interactions provides a level of selectivity: little or no inhibition of function was observed with elastase, beta-galactosidase, or cellular retinoic acid binding protein.
Polystyrene-based diblock copolymers, featuring diaminotriazine functionality on one of the blocks were used to assemble complementary uracil-functionalized nanoparticles into micellar aggregates. The size of these self-assembled aggregates was controlled by block length, as determined in solution (using dynamic light scattering), and in thin films (using transmission electron microscopy).
Hydrogen bonded interactions are among the most important non-covalent interactions in supramolecular chemistry. The strength, selectivity and directionality inherent in hydrogen bonding processes have allowed the creation of complex and efficient molecular hosts capable of selective binding to a wide variety of complementary guests. Major advances in controlling host-guest complexation have occurred in the last decade, principally through systematic modification of the electrostatic properties and/or geometry of the hosts, thereby fine-tuning the molecular recognition event. More recently, systems have been developed which allow the effectiveness and selectively of hydrogen bonding interactions to be reversibly modulated by an external stimulus, more accurately mimicking biological systems and providing building blocks for the construction of novel advanced materials, sensors and devices. In this review, we highlight some of the methods available for modulating the strength and selectivity of hydrogen bonded interactions in synthetic host-guest systems.
Mixed monolayer protected gold clusters (MMPCs) functionalized with quaternary ammonium chains efficiently transfect mammalian cell cultures, as determined through beta-galactosidase transfer and activity. The success of these transfection assemblies depended on several variables, including the ratio of DNA to nanoparticle during the incubation period, the number of charged substituents in the monolayer core, and the hydrophobic packing surrounding these amines. Complexes of MMPCs and plasmid DNA formed at w/w ratios of 30 were most effective in promoting transfection of 293T cells in the presence of 10% serum and 100 microM chloroquine. The most efficient nanoparticle studied (MMPC 7) was approximately 8-fold more effective than 60 kDa polyethylenimine, a widely used transfection agent.
The structure and properties of gold nanoparticles make them useful for a wide array of biological application. Toxicity, however, has been observed at high concentrations using these systems. MTT, hemolysis, and bacterial viability assays were used to explore differential toxicity among the cell types used, using 2 nm core particles. These studies show that cationic particles are moderately toxic, whereas anionic particles are quite nontoxic. Concentration-dependent lysis mediated by initial electrostatic binding was observed in dye release studies using lipid vesicles, providing the probable mechanism for observed toxicity with the cationic MMPCs.
Positively charged trimethylammonium-functionalized mixed monolayer protected clusters (MMPCs) bind DNA through complementary electrostatic interactions, resulting in complete inhibition of DNA transcription of T7 RNA polymerase. DNA was released from the nanoparticle by intracellular concentrations of glutathione, resulting in efficient transcription. The restoration of RNA production was dose-dependent in terms of GSH, with considerable control of the release process possible through variation in monolayer structure. This work presents a new approach to controlled release of DNA, with potential applications in the creation of transfection vectors and gene regulation systems.