DNA's remarkable molecular recognition properties and structural features make it one of the ... more DNA's remarkable molecular recognition properties and structural features make it one of the most promising templates to pattern materials with nanoscale precision. The emerging field of DNA nanotechnology strips this molecule from any preconceived biological role and exploits its simple code to generate addressable nanostructures in one, two, and three dimensions. These structures have been used to precisely position proteins, nanoparticles, transition metals, and other functional components into deliberately designed patterns. They can also act as templates for the growth of nanowires, aid in the structural determination of proteins, and provide new platforms for genomics applications. The field of DNA nanotechnology is growing in a number of directions, carrying with it the promise to substantially affect materials science and biology.
Bioactive RNA nanoparticles with gene silencing activity have been synthesized in high yield usin... more Bioactive RNA nanoparticles with gene silencing activity have been synthesized in high yield using a complementary spherical DNA nanoparticle.
Journal of the American Chemical Society, Nov 22, 2017
We present a rapid and efficient method to generate a family of platinum supramolecular square co... more We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt(en)(N∩N)][CFSO](en= ethylenediamine, N∩N = 4,4'-bipyridine derivatives) from commercially available precursor KPtClin good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and ...
Six cyclometalated iridium(III) phenanthroimidazole complexes with different modifications to the... more Six cyclometalated iridium(III) phenanthroimidazole complexes with different modifications to the imidazole phenanthroline ligand exhibit enhanced luminescence when bound to guanine (G-) quadruplex DNA sequences. The complexes bind with low micromolar affinity to human telomeric and c-myc sequences in a 1:1 complex:quadruplex stoichiometry. Due to the luminescence enhancement upon binding to G-quadruplex DNA, the complexes can be used as selective quadruplex indicators. In addition, the electrogenerated chemiluminescence of all complexes increases in the presence of specific G-quadruplex sequences, demonstrating potential for the development of an ECL-based G-quadruplex assay.
Luminescent polymers containing Ir(ppy) 2 (bpy) PF 6 complexes, biocompatible poly(ethylene glyco... more Luminescent polymers containing Ir(ppy) 2 (bpy) PF 6 complexes, biocompatible poly(ethylene glycol) (PEG) chains, and biotin moieties were synthesized via ring-opening metathesis polymerization (ROMP). Their self-assembly in water into micelles resulted in an increased quantum yield compared to open polymer chains in acetonitrile, which is likely due to core rigidity and desolvation. Streptavidin coated magnetic beads were employed to analyze the binding ability of these micelles. The positioning of the molecular recognition moiety biotin within the polymer chain had a very significant effect on the availability of biotin on the micelle surface and the ability of the micelles to bind to streptavidin. Simply attaching biotin to the end of the ROMP polymer yielded micelles in which the biotin units were shielded by the PEG chains, whereas the synthesis of a new ROMP monomer containing biotin at the end of the PEG chains resulted in improved surface availability of the biotin group. Preliminary experiments in which streptavidin was microcontact-printed onto functionalized glass coverslips also indicated specific binding between the micelles and streptavidin and further demonstrated the potential of these micelle systems to function as luminescent probes in solid-phase biodetection assays.
DNA has recently emerged as a useful building block for higher order nanostructures, such as exte... more DNA has recently emerged as a useful building block for higher order nanostructures, such as extended two-dimensional surfaces and discrete two-and three-dimensional structures. Transition metal complexes can introduce functionality to these otherwise passive ...
DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled as... more DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled assembly of hierarchically complex linear arrays. It is highly desirable to control the positioning of rungs along the backbone of the nanotubes, minimize the polydispersity in their manufacture and reduce the building costs. We report here a solid-phase synthesis methodology in which, through a cyclic scheme starting from a 'foundation rung' specifically bound to the surface, distinct rungs can be incorporated in a predetermined manner. Each rung is orthogonally addressable. Using fluorescently tagged rungs, single-molecule fluorescence studies demonstrated the robustness and structural fidelity of the constructs and confirmed the incorporation of the rungs in quantitative yield (>95%) at each step of the cycle. Prototype structures that consisted of up to 20 repeat units, about 450 nm in contour length, were constructed. Combined, the solid-phase synthesis strategy described a...
The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with co... more The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with copper(I) ions to generate the series of rigid-rack inorganic pseudorotaxanes 3a-g. These complexes have been characterized by analytical and spectroscopic methods. Their architecture has been confirmed by determination of the crystal structures of 3e,f. The complex [Cu(2)(1e)(2)(2)](PF(6))(2) (3e) crystallizes in the space group C2/c, whereas complex [Cu(2)(1f)(2)(2)](PF(6))(2) (3f) gives crystals containing a single enantiomer in the chiral space group P2(1)2(1)2(1). The synthesis and solution structures of 3a-g and the solid-state structures of 3e,f are discussed in relation to the viability of multicomponent self-assembly as an approach to linear metal-ion arrays.
Metal–nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cage... more Metal–nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cages, these systems can use their metals for redox, photochemical, magnetic and catalytic control over encapsulated cargo. However, using DNA provides the potential to program pore size, geometry, chemistry and addressability, and the ability to symmetrically and asymmetrically position transition metals within the three-dimensional framework. Here we report
... Paul N. W. Baxter, Hanadi Sleiman, Jean-Marie Lehn* und Kari Rissanen Der Aufbau ineinander v... more ... Paul N. W. Baxter, Hanadi Sleiman, Jean-Marie Lehn* und Kari Rissanen Der Aufbau ineinander verschlungener molekularer Einhei-ZUSCHRIFTEN ... Muter. 1996, 8, 37. J.-C. Chambron, C. 0. Dietrich-Buchecker, J.-F. Nierengarten, J.-P. Sauvage, J. Chem. SOC. Chem. ...
Nanotubes hold promise for a number of biological and materials applications because of their hig... more Nanotubes hold promise for a number of biological and materials applications because of their high aspect ratio and encapsulation potential. A particularly attractive goal is to access nanotubes that exert well-defined control over their cargo, such as selective encapsulation, precise positioning of the guests along the nanotube length and triggered release of this cargo in response to specific external stimuli. Here, we report the construction of DNA nanotubes with longitudinal variation and alternating larger and smaller capsules along the tube length. Size-selective encapsulation of gold nanoparticles into the large capsules of these tubes leads to 'nanopeapod' particle lines with positioning of the particles 65 nm apart. These nanotubes can then be opened when specific DNA strands are added to release their particle cargo spontaneously. This approach could lead to new applications of self-assembled nanotubes, such as in the precise organization of one-dimensional nanomaterials, gene-triggered selective delivery of drugs and biological sensing.
Conjugated polymers synthesized by step polymerization mechanisms typically suffer from poor mole... more Conjugated polymers synthesized by step polymerization mechanisms typically suffer from poor molecular weight control and broad molecular weight distributions. We report a new method which uses nucleobase recognition to read out and efficiently copy the controlled chain length and narrow molecular weight distribution of a polymer template generated by living polymerization, into a daughter conjugated polymer. Aligning nucleobase-containing monomers on their complementary parent template using hydrogen-bonding interactions, and subsequently carrying out a Sonogashira polymerization, leads to the templated synthesis of a conjugated polymer. Remarkably, this daughter strand is found to possess a narrow molecular weight distribution and a chain length nearly equivalent to that of the parent template. On the other hand, nontemplated polymerization or polymerization with the incorrect template generates a short conjugated oligomer with a significantly broader molecular weight distribution. Hence, nucleobase-templated polymerization is a useful tool in polymer synthesis, in this case allowing the use of a large number of polymers generated by living methods, such as anionic polymerization, controlled radical polymerizations (NMP, ATRP, and RAFT) and other mechanisms to program the structure, length, and molecular weight distribution of polymers normally generated by step polymerization methods and significantly enhance their properties.
In this contribution, we report that a self-assembled platinum molecular square [Pt(en)(4,4&a... more In this contribution, we report that a self-assembled platinum molecular square [Pt(en)(4,4'-dipyridyl)]4 can act as an efficient G-quadruplex binder and telomerase inhibitor. Molecular modeling studies show that the square arrangement of the four bipyridyl ligands, the highly electropositive nature of the overall complex, as well as hydrogen bonding interactions between the ethylenediamine ligands and phosphates of the DNA backbone all contribute to the observed strong binding affinity to the G-quadruplex. Through thermal denaturation studies with duplex and quadruplex FRET probes and enzymatic assays, we demonstrate that this platinum square strongly binds to G-quadruplexes and can act as an inhibitor of telomerase. This study thus shows the potential of supramolecular self-assembly to readily generate scaffolds of unique geometries for effective targeting of G-quadruplexes and for the ultimate development of selective antitumor therapies.
We report a DNA-templated approach to construct nanotubes with controlled lengths and narrow mole... more We report a DNA-templated approach to construct nanotubes with controlled lengths and narrow molecular weight distribution, allowing the deliberate variation of this length. This approach relies on the facile and modular assembly of a DNA guide strand of precise length that contains single-stranded gaps repeating at every 50 nm. This is followed by positioning triangular DNA "rungs" on each of these single-stranded gaps and adding identical linking strands to the two other sides of the triangles to close the DNA nanotubes. The length of the guide strand can be deliberately changed. We show the use of this approach to produce nanotubes with lengths of 1 microm or 500 nm and narrow length distributions. This is in contrast to nontemplated approaches, which lead to long and polydisperse nanotubes. We also demonstrate the encapsulation of 20 nm gold nanoparticles within these well-defined nanotubes to form finite lines of gold nanoparticles with longitudinal plasmon coupling, with a number of potential nanophotonic applications. This guiding strand approach is a useful tool in the creation of DNA nanostructures, in this case allowing the use of a simple template generated by a minimal number of DNA strands to program the length and molecular weight distribution of assemblies, as well as to organize any number of DNA-labeled nano-objects into finite structures.
The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with co... more The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with copper(I) ions to generate the series of rigid-rack inorganic pseudorotaxanes 3a-g. These complexes have been characterized by analytical and spectroscopic methods. Their architecture has been confirmed by determination of the crystal structures of 3e,f. The complex [Cu(2)(1e)(2)(2)](PF(6))(2) (3e) crystallizes in the space group C2/c, whereas complex [Cu(2)(1f)(2)(2)](PF(6))(2) (3f) gives crystals containing a single enantiomer in the chiral space group P2(1)2(1)2(1). The synthesis and solution structures of 3a-g and the solid-state structures of 3e,f are discussed in relation to the viability of multicomponent self-assembly as an approach to linear metal-ion arrays.
DNA's remarkable molecular recognition properties and structural features make it one of the ... more DNA's remarkable molecular recognition properties and structural features make it one of the most promising templates to pattern materials with nanoscale precision. The emerging field of DNA nanotechnology strips this molecule from any preconceived biological role and exploits its simple code to generate addressable nanostructures in one, two, and three dimensions. These structures have been used to precisely position proteins, nanoparticles, transition metals, and other functional components into deliberately designed patterns. They can also act as templates for the growth of nanowires, aid in the structural determination of proteins, and provide new platforms for genomics applications. The field of DNA nanotechnology is growing in a number of directions, carrying with it the promise to substantially affect materials science and biology.
Bioactive RNA nanoparticles with gene silencing activity have been synthesized in high yield usin... more Bioactive RNA nanoparticles with gene silencing activity have been synthesized in high yield using a complementary spherical DNA nanoparticle.
Journal of the American Chemical Society, Nov 22, 2017
We present a rapid and efficient method to generate a family of platinum supramolecular square co... more We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt(en)(N∩N)][CFSO](en= ethylenediamine, N∩N = 4,4'-bipyridine derivatives) from commercially available precursor KPtClin good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and ...
Six cyclometalated iridium(III) phenanthroimidazole complexes with different modifications to the... more Six cyclometalated iridium(III) phenanthroimidazole complexes with different modifications to the imidazole phenanthroline ligand exhibit enhanced luminescence when bound to guanine (G-) quadruplex DNA sequences. The complexes bind with low micromolar affinity to human telomeric and c-myc sequences in a 1:1 complex:quadruplex stoichiometry. Due to the luminescence enhancement upon binding to G-quadruplex DNA, the complexes can be used as selective quadruplex indicators. In addition, the electrogenerated chemiluminescence of all complexes increases in the presence of specific G-quadruplex sequences, demonstrating potential for the development of an ECL-based G-quadruplex assay.
Luminescent polymers containing Ir(ppy) 2 (bpy) PF 6 complexes, biocompatible poly(ethylene glyco... more Luminescent polymers containing Ir(ppy) 2 (bpy) PF 6 complexes, biocompatible poly(ethylene glycol) (PEG) chains, and biotin moieties were synthesized via ring-opening metathesis polymerization (ROMP). Their self-assembly in water into micelles resulted in an increased quantum yield compared to open polymer chains in acetonitrile, which is likely due to core rigidity and desolvation. Streptavidin coated magnetic beads were employed to analyze the binding ability of these micelles. The positioning of the molecular recognition moiety biotin within the polymer chain had a very significant effect on the availability of biotin on the micelle surface and the ability of the micelles to bind to streptavidin. Simply attaching biotin to the end of the ROMP polymer yielded micelles in which the biotin units were shielded by the PEG chains, whereas the synthesis of a new ROMP monomer containing biotin at the end of the PEG chains resulted in improved surface availability of the biotin group. Preliminary experiments in which streptavidin was microcontact-printed onto functionalized glass coverslips also indicated specific binding between the micelles and streptavidin and further demonstrated the potential of these micelle systems to function as luminescent probes in solid-phase biodetection assays.
DNA has recently emerged as a useful building block for higher order nanostructures, such as exte... more DNA has recently emerged as a useful building block for higher order nanostructures, such as extended two-dimensional surfaces and discrete two-and three-dimensional structures. Transition metal complexes can introduce functionality to these otherwise passive ...
DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled as... more DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled assembly of hierarchically complex linear arrays. It is highly desirable to control the positioning of rungs along the backbone of the nanotubes, minimize the polydispersity in their manufacture and reduce the building costs. We report here a solid-phase synthesis methodology in which, through a cyclic scheme starting from a 'foundation rung' specifically bound to the surface, distinct rungs can be incorporated in a predetermined manner. Each rung is orthogonally addressable. Using fluorescently tagged rungs, single-molecule fluorescence studies demonstrated the robustness and structural fidelity of the constructs and confirmed the incorporation of the rungs in quantitative yield (>95%) at each step of the cycle. Prototype structures that consisted of up to 20 repeat units, about 450 nm in contour length, were constructed. Combined, the solid-phase synthesis strategy described a...
The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with co... more The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with copper(I) ions to generate the series of rigid-rack inorganic pseudorotaxanes 3a-g. These complexes have been characterized by analytical and spectroscopic methods. Their architecture has been confirmed by determination of the crystal structures of 3e,f. The complex [Cu(2)(1e)(2)(2)](PF(6))(2) (3e) crystallizes in the space group C2/c, whereas complex [Cu(2)(1f)(2)(2)](PF(6))(2) (3f) gives crystals containing a single enantiomer in the chiral space group P2(1)2(1)2(1). The synthesis and solution structures of 3a-g and the solid-state structures of 3e,f are discussed in relation to the viability of multicomponent self-assembly as an approach to linear metal-ion arrays.
Metal–nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cage... more Metal–nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cages, these systems can use their metals for redox, photochemical, magnetic and catalytic control over encapsulated cargo. However, using DNA provides the potential to program pore size, geometry, chemistry and addressability, and the ability to symmetrically and asymmetrically position transition metals within the three-dimensional framework. Here we report
... Paul N. W. Baxter, Hanadi Sleiman, Jean-Marie Lehn* und Kari Rissanen Der Aufbau ineinander v... more ... Paul N. W. Baxter, Hanadi Sleiman, Jean-Marie Lehn* und Kari Rissanen Der Aufbau ineinander verschlungener molekularer Einhei-ZUSCHRIFTEN ... Muter. 1996, 8, 37. J.-C. Chambron, C. 0. Dietrich-Buchecker, J.-F. Nierengarten, J.-P. Sauvage, J. Chem. SOC. Chem. ...
Nanotubes hold promise for a number of biological and materials applications because of their hig... more Nanotubes hold promise for a number of biological and materials applications because of their high aspect ratio and encapsulation potential. A particularly attractive goal is to access nanotubes that exert well-defined control over their cargo, such as selective encapsulation, precise positioning of the guests along the nanotube length and triggered release of this cargo in response to specific external stimuli. Here, we report the construction of DNA nanotubes with longitudinal variation and alternating larger and smaller capsules along the tube length. Size-selective encapsulation of gold nanoparticles into the large capsules of these tubes leads to 'nanopeapod' particle lines with positioning of the particles 65 nm apart. These nanotubes can then be opened when specific DNA strands are added to release their particle cargo spontaneously. This approach could lead to new applications of self-assembled nanotubes, such as in the precise organization of one-dimensional nanomaterials, gene-triggered selective delivery of drugs and biological sensing.
Conjugated polymers synthesized by step polymerization mechanisms typically suffer from poor mole... more Conjugated polymers synthesized by step polymerization mechanisms typically suffer from poor molecular weight control and broad molecular weight distributions. We report a new method which uses nucleobase recognition to read out and efficiently copy the controlled chain length and narrow molecular weight distribution of a polymer template generated by living polymerization, into a daughter conjugated polymer. Aligning nucleobase-containing monomers on their complementary parent template using hydrogen-bonding interactions, and subsequently carrying out a Sonogashira polymerization, leads to the templated synthesis of a conjugated polymer. Remarkably, this daughter strand is found to possess a narrow molecular weight distribution and a chain length nearly equivalent to that of the parent template. On the other hand, nontemplated polymerization or polymerization with the incorrect template generates a short conjugated oligomer with a significantly broader molecular weight distribution. Hence, nucleobase-templated polymerization is a useful tool in polymer synthesis, in this case allowing the use of a large number of polymers generated by living methods, such as anionic polymerization, controlled radical polymerizations (NMP, ATRP, and RAFT) and other mechanisms to program the structure, length, and molecular weight distribution of polymers normally generated by step polymerization methods and significantly enhance their properties.
In this contribution, we report that a self-assembled platinum molecular square [Pt(en)(4,4&a... more In this contribution, we report that a self-assembled platinum molecular square [Pt(en)(4,4'-dipyridyl)]4 can act as an efficient G-quadruplex binder and telomerase inhibitor. Molecular modeling studies show that the square arrangement of the four bipyridyl ligands, the highly electropositive nature of the overall complex, as well as hydrogen bonding interactions between the ethylenediamine ligands and phosphates of the DNA backbone all contribute to the observed strong binding affinity to the G-quadruplex. Through thermal denaturation studies with duplex and quadruplex FRET probes and enzymatic assays, we demonstrate that this platinum square strongly binds to G-quadruplexes and can act as an inhibitor of telomerase. This study thus shows the potential of supramolecular self-assembly to readily generate scaffolds of unique geometries for effective targeting of G-quadruplexes and for the ultimate development of selective antitumor therapies.
We report a DNA-templated approach to construct nanotubes with controlled lengths and narrow mole... more We report a DNA-templated approach to construct nanotubes with controlled lengths and narrow molecular weight distribution, allowing the deliberate variation of this length. This approach relies on the facile and modular assembly of a DNA guide strand of precise length that contains single-stranded gaps repeating at every 50 nm. This is followed by positioning triangular DNA "rungs" on each of these single-stranded gaps and adding identical linking strands to the two other sides of the triangles to close the DNA nanotubes. The length of the guide strand can be deliberately changed. We show the use of this approach to produce nanotubes with lengths of 1 microm or 500 nm and narrow length distributions. This is in contrast to nontemplated approaches, which lead to long and polydisperse nanotubes. We also demonstrate the encapsulation of 20 nm gold nanoparticles within these well-defined nanotubes to form finite lines of gold nanoparticles with longitudinal plasmon coupling, with a number of potential nanophotonic applications. This guiding strand approach is a useful tool in the creation of DNA nanostructures, in this case allowing the use of a simple template generated by a minimal number of DNA strands to program the length and molecular weight distribution of assemblies, as well as to organize any number of DNA-labeled nano-objects into finite structures.
The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with co... more The rigid linear ligands 1a-g and the macrocycle 2 undergo self-assembly via coordination with copper(I) ions to generate the series of rigid-rack inorganic pseudorotaxanes 3a-g. These complexes have been characterized by analytical and spectroscopic methods. Their architecture has been confirmed by determination of the crystal structures of 3e,f. The complex [Cu(2)(1e)(2)(2)](PF(6))(2) (3e) crystallizes in the space group C2/c, whereas complex [Cu(2)(1f)(2)(2)](PF(6))(2) (3f) gives crystals containing a single enantiomer in the chiral space group P2(1)2(1)2(1). The synthesis and solution structures of 3a-g and the solid-state structures of 3e,f are discussed in relation to the viability of multicomponent self-assembly as an approach to linear metal-ion arrays.
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Papers by Hanadi Sleiman