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research Recent Highlights: I. Modular Generation of Structurally Switchable 3D- DNA Assemblies J. Am. Chem. Soc., 2007, 13376-13377 Highlighted in the Journal " Nature" : "Gene Boxes", Nov. 15, 2007 Faisal Aldaye, Hanadi F. Sleiman
This contribution describes a new method that allows ready access to a large number of three-dimensional DNA assemblies, and demonstrates, for the first time, their structural switching in response to external stimuli. 3D-construction is a current challenge in DNA nanotechnology. DNA polyhedra present tremendous potential in a number of areas, including drug encapsulation and release, regulation of the folding and activity of encaged proteins, as host molecules for nanomaterials and as building blocks for 3D-networks for catalysis and biomolecule crystallization. However, 3D-DNA assemblies have typicallly been difficult to access. Moreover, no reports have described structurally dynamic or stimuli responsive systems, which is a requirement for the potential of such DNA objects for encapsulation and selective release to be realized. This manuscript describes the pre-assembly of single stranded and cyclic DNA triangles, squares, pentagons and hexagons with rigid organic vertices, and their use as building blocks for modular access to a large number of three-dimensional objects. A triangular prism, a cube, pentameric and hexameric prisms, as well as more complex structures such as a heteroprism and biprism were readily and quantitatively accessed through the modular combination of these primary building blocks. In principle, any structure that can be retrosynthetically broken down to such DNA cycles can be readily accessed using this approach, and as such, this represents a highly economical method to build diversity in three-dimensional DNA assembly. In addition, we show the addressability of these assemblies, by constructing a dynamic triangular prism capable of real-time structural oscillation between three predefined lengths, and demonstrating the dynamic transformation of this capsule by fluorescence energy transfer (FRET) studies. A number of applications can be anticipated for these switchable capsules, including molecule-triggered drug delivery, modulation of the properties of encaged molecules or materials with cavity size, and dynamic three-dimensional DNA crystals. II. Guest-Mediated Access to a Single DNA Nanostructure from a Library of Multiple Assemblies Faisal Aldaye, Hanadi F. Sleiman
This contribution describes the first use of a small molecule guest to control the outcome and significantly increase selectivity in DNA self-assembly. There has been increased interest in the use of DNA as a component in nanoscience. However, as the complexity of DNA nanosystems increases, so will the number of different DNA sequences that need to be incorporated. This inevitably leads to the inclusion of degenerate sequences which can assemble into undesirable secondary structures. The process of error control and correction is currently a real bottleneck towards the creation of more complex DNA systems. In this manuscript, we show that the addition of a small molecule can template the formation of a single DNA nanostructure, from building blocks which otherwise assemble into a large number of possible structures. We then use this simple method to template the formation of well-defined, one-dimensional DNA fibers which are nanometers in diameter and tens of microns in length, from trifunctional building blocks that would form ill-defined networks without the template. Considering the wealth of DNA-binding molecules that can be used to refine, correct and modify DNA self-assembly, this approach promises to lead to significant advances in the area of DNA nanotechnology.
III. Platinum Phenanthroimidazole Complexes as G-Quadruplex DNA Selective Binders Roxanne Kieltyka, Johans Fakhoury, Nicolas Moitessier and Hanadi F. Sleiman Stuck on G-quadruplexes: Complexes that bind and stabilize G-quadruplex DNA structures are of significant interest due to their potential to inhibit telomerase and halt cancer cell proliferation. A series of p-extended phenanthroimidazole PtII complexes were synthesized. Their relative binding affinities to duplex and quadruplex DNA were studied through UV-vis, CD and competitive equilibrium dialysis. Significant binding affinity and selectivity to quadruplex DNA was observed.
IV. Dynamic DNA Templates for Gold Nanoparticle Discrete Structures: Control of Geometry, Particle Identity, Write /Erase and Structural Switching Highlighted in “Nature Nanotechnology”: “Gold nanoparticles: DNA builds bridges”, 30/3/2007 Faisal Aldaye, Hanadi F. Sleiman
This contribution describes a new method to selectively organize gold nanoparticles into libraries of discrete and well-defined structures, using a small set of DNA templates. Moreover, these structures are addressable post-assembly, and can undergo structural switching and write/erase functions withspecific external agents. Gold nanoparticle assemblies hold promise as new materials for catalysis, sensing, as well as nanoelectronic and nanophotonic applications. Many of their properties depend on the relative arrangement of the particles within the assembly. For example, their ability for single electron transport may lead to the design of nanoparticle-based alternatives to traditional silicon-based electronic components. As well, they can significantly enhance the electromagnetic field in particular locations, and can potentially be used for the design of plasmon superemitters and surface-enhanced Raman (SERS) substrates. However, fundamental studies of these properties have been hampered by the lack of systematic methods to assemble them into well-defined discrete model structures. As a result, many of these properties (e.g., SERS “hot spots”) have been generated in an empirical fashion using extended two- or three-dimensional assemblies. In the present method, single stranded, cyclic DNA templates that possess rigid organic vertices are used to precisely position gold nanoparticles that are singly labeled with DNA into discrete structures. Control of geometry is shown by the ready creation of triangles and squares of nanoparticles. Modularity is shown by the precise assembly of large and small particles into triangles of all combinations. Structural switching is demontrated by the use of a square DNA template to assemble nanoparticles into squares, trapezoids and rectangles. Finally, write/erase function is established by the assembly of a triangle of three gold nanoparticles, the selective removal of one of these particles, and the re-writing of a different nanoparticle within this assemblies. Overall, this represents what is, to our knowledge, the highest level of control over the assembly of nanoparticles.
V. Luminescent Vesicles, Tubules, Bowls and Star Micelles from Ruthenium Bipyridine Block Copolymers
We report the first detailed study on the self-assembly of diblock copolymers containing the luminescent metal complex Ru(bpy)32+, which were constructed by ring-opening metathesis polymerization. Control over the block length, overall polymer length, polymer concentration and solution conditions has led to the reproducible formation of a number of solution morphologies including vesicles, tubules, large compound micelles, star micelles, and bowls, which all contain Ru(bpy)32+ within the micellar core/vesicle wall. These morphologies hold interesting potential for the facile organization of architectures useful in catalysis and light harvesting.
VI. DNA-Protein Non-Covalent Crosslinking: Ruthenium Dipyridophenazine Biotin Complex for the Assembly of Proteins and Gold Nanoparticles on DNA Templates We report the first example of a small molecule which can non-covalently crosslink DNA with streptavidin and streptavidin-labeled materials. The crosslinking ability of molecule 1 was used to template the assembly of streptavidin molecules on a plasmid circular DNA, as visualized by atomic force microscopy. In addition, we show the organization of discrete groupings of gold nanoparticles labeled with streptavidin on a linear DNA template of finite size, using 1 (transmission electron microscopy), with the DNA template acting as a “molecular ruler” to dictate the number of particles in the assembly. Overall, this work allows the facile, modular and potentially selective assembly of a large number of readily obtainable streptavidin- or biotin-labeled materials on DNA templates.
VII. Molecule-Responsive Block Copolymer Micelles
This manuscript describes the first example of a block copolymer micelle, which can selectively recognize a complementary small molecule, with concomitant opening and complete deaggregation of this micelle. Environmentally responsive block copolymer micelles have been extensively investigated as selective drug delivery vehicles, as well as templates for nanopatterning of materials. Stimuli that have been used in the literature have been pH, ionic strength, temperature, oxidation and light irradiation. However, to the best of our knowledge, this is the first example of a block copolymer micelle which shows a dramatic macroscopic response to the addition of a specific small molecule, with high selectivity. Many applications can be anticipated for these polymeric micelles, including selective drug delivery in a biological environment where a specific molecule is overexpressed, molecular sensors, which translate a molecular recognition event into a large change in light scattering properties, as well as materials for the orthogonal patterning of surfaces using specific small molecules.
VIII. Sequential Self-Assembly of a DNA Hexagon as a Template for the Organization of Gold Nanoparticles A cyclic hexamer of six gold nanoparticles was sequentially and selectively self-assembled by labeling each particle (red sphere) with a DNA-containing molecule (colored block), which serves to dictate their ultimate location within the final construct. This method may be used to construct any discrete well-defined pattern of nanoparticles. This contribution was selected by the editors as a ‘hot paper’ and received its own cover page.
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