Mitsuhiko Shionoya

Programmable self-assembly of metal ions inside artificial DNA duplexes

The ultimate bottom-up approach for the construction of functional nanosystems requires the precise arrangement of atoms and molecules in three dimensions. DNA is currently one of the most prominent molecules able to self-assemble into complex networks1,2 and is therefore regarded as the ‘silicon of the nano-world’3. Metals and metal ions, in contrast, are the atomic building-blocks needed in such materials to establish functions such as electrical conductivity or magnetism. Here we report a new concept, which efficiently combines metal ions and DNA. The DNA structure is used as a matrix to program robustly the complexation of different metal ions under precise control with regard to element, number and composition.

Metal-mediated DNA base pairing: alternatives to hydrogen-bonded Watson-Crick base pairs.

With its capacity to store and transfer the genetic information within a sequence of monomers, DNA forms its central role in chemical evolution through replication and amplification. This elegant behavior is largely based on highly specific molecular recognition between nucleobases through the specific hydrogen bonds in the Watson-Crick base pairing system. While the native base pairs have been amazingly sophisticated through the long history of evolution, synthetic chemists have devoted considerable efforts to create alternative base pairing systems in recent decades. Most of these new systems were designed based on the shape complementarity of the pairs or the rearrangement of hydrogen-bonding patterns. We wondered whether metal coordination could serve as an alternative driving force for DNA base pairing and why hydrogen bonding was selected on Earth in the course of molecular evolution. Therefore, we envisioned an alternative design strategy: we replaced hydrogen bonding with another important scheme in biological systems, metal-coordination bonding. In this Account, we provide an overview of the chemistry of metal-mediated base pairing including basic concepts, molecular design, characteristic structures and properties, and possible applications of DNA-based molecular systems. We describe several examples of artificial metal-mediated base pairs, such as Cu(2+)-mediated hydroxypyridone base pair, H-Cu(2+)-H (where H denotes a hydroxypyridone-bearing nucleoside), developed by us and other researchers. To design the metallo-base pairs we carefully chose appropriate combinations of ligand-bearing nucleosides and metal ions. As expected from their stronger bonding through metal coordination, DNA duplexes possessing metallo-base pairs exhibited higher thermal stability than natural hydrogen-bonded DNAs. Furthermore, we could also use metal-mediated base pairs to construct or induce other high-order structures. These features could lead to metal-responsive functional DNA molecules such as artificial DNAzymes and DNA machines. In addition, the metallo-base pairing system is a powerful tool for the construction of homogeneous and heterogeneous metal arrays, which can lead to DNA-based nanomaterials such as electronic wires and magnetic devices. Recently researchers have investigated these systems as enzyme replacements, which may offer an additional contribution to chemical biology and synthetic biology through the expansion of the genetic alphabet.

Flexiblemeso-Bis(sulfinyl) Ligands as Building Blocks for Copper(II) Coordination Polymers: Cavity Control by Varying the Chain Length of Ligands

Fillings and cavities: Three novel pseudo-octahedral metal-organic frameworks, 1-3, consisting of macrometallacyclic noninterpenetrating meso networks and exhibiting weak antiferromagnetic interactions, have been constructed from CuII centers and structurally flexible R,S-bis(sulfinyl) ligands. Varying the chain length of ligands is found to control the cavity sizes of the networks.

Direct conductance measurement of individual metallo-DNA duplexes within single-molecule break junctions.

DNA, as the product of million years of evolution, possesses the maximal density of functionalities embedded in its framework and superior sequence-specific self-assembly properties that make it a useful scaffold for the organization of molecules into higher-order nanostructures for the development of functional nanoscale devices and materials. In this context, one major effort is to transform DNA into a conductive material that would make a significant contribution to the development of the vibrant field of DNA-based molecular electronics. It turns out that unmodified DNA lacks sufficient electrical conductance, thus making it unsuitable for application in nanoelectronics. To address this issue, a fascinating alternative solution of recent years is to exchange some or all of the Watson–Crick base pairs in DNA by metal complexes in a programmable fashion pioneered by Shionoya, Schultz, Carell, M ller, and others. The combination of DNA and functional metal complexes can introduce significant advantages for both the metals and the DNA structures, thus representing an important step for their potential application as nanomagnets, as self-assembling molecular wires, or as catalysts in chemical reactions. With a focus on DNA-based molecular electronics, it is currently urgent to unambiguously characterize the electrical conductance of these metal-containing DNA strands. Herein we demonstrate the first direct charge transport (CT) measurement of individual metallo-DNA duplexes using singlemolecule break junctions (Figure 1). These findings provide a foundation for DNA-based hybrid materials as conductive biocompatible bridges that may interface electronic circuits with biological systems.

Ti(IV)-Centered Dynamic Interconversion between Pd(II), Ti(IV)-Containing Ring and Cage Molecules

Heteronuclear, supramolecular ring and cage complexes have been constructed from a pyridyl catechol ligand, TiO(acac)2, and PdCl2(CH3CN)2. These two complexes are quantitatively interconvertible, in which Ti4+-centered coordination changes take place between a well-known Ti(catecholato)3 and a newly established TiH(catecholato)2(acetylacetonato) structures. The Ti4+-centered structural changes arise from the changes in the component fraction and basicity condition.

Ranging Correlated Motion (1.5 nm) of Two Coaxially Arranged Rotors Mediated by Helix Inversion of a Supramolecular Transmitter

For a long-range transmission of motion between two movable parts apart from each other, transmitters that can precisely correlate these two motions should be properly incorporated into the system. However, such a motional relay is yet to be realized in artificial systems because of the lack of reliable methodologies for arranging a discrete number of motional parts. Herein, we report a correlated motion of two rotor molecules, which are coaxially arranged at a distance of 1.5 nm, through either Ag (+)- or Hg (2+)-assembled helical transmitters, leading to different frequencies of synchronized motion. A helix inversion in the transmitter was proven to strongly correlate the motions of both terminals. The X-ray analysis of the entity determined a quadruple-decker nonanuclear structure of the metal complex comprising two terminal rotor-like ligands closely attached to a central transmitter moiety. (1)H NMR analysis fully demonstrated the synchronized motion of the two rotors coaxially stacked and connected through the transmitter. Since the transmitter is composed of simple helical repeating units, the principle of helix inversion would be an efficient and widely applicable strategy for the long-range transmission of molecular motion.

Template-Directed Synthesis of a Covalent Organic Capsule Based on a 3 nm-Sized Metallocapsule

A 4 nm-sized covalent organic capsule having 24 pyridyl groups was synthesized in extremely high yield (43% in three steps) using an octahedron-shaped metallocapsule as a template molecule. The entity was fully characterized by NMR and MALDI-TOF MS measurements. N-Methylation of the 24 pyridyl groups of the organic capsule produced a 5 nm-sized polycationic capsule, which is larger than the neutral precursory capsule because of the electrostatic repulsion between the positive charges on the pyridinium groups of the capsule.

Encapsulation versus Aggregation of Metal–Organic Cages Controlled by Guest Size Variation

The strength and mode of binding (inside vs outside) of bisanionic guest molecules to a cationic, self-assembled metal-organic cage depend on their size and the stoichiometry of the addition. Herein we show that the composition of the solid/liquid phase of a heterogeneous system can be kinetically controlled by the order of the addition of two different guest compounds.

A self-assembled organic capsule formed from the union of six hexagram-shaped amphiphile molecules.

A discrete 2-nm-sized self-assembled organic capsule was formed from the union of six hexagram-shaped amphiphile molecules in aqueous methanol due to the hydrophobic effect, van der Waals forces, and CH-pi interactions between the chemical components. A couple of hexa-substituted benzene molecules were encapsulated inside the capsule in both solution and the solid state, as was evidenced by 1H NMR spectroscopy and single-crystal X-ray analysis.

A C60-templated tetrameric porphyrin barrel complex via zinc-mediated self-assembly utilizing labile capping ligands.

Coordination-driven self-assembly utilizing labile capping ligands has been exploited as a novel strategy for metallo-cage containers. Herein, we report a tetrameric porphyrin barrel complex [C60⊂Zn814(H2O)4(OTs)12](OTs)4 (2) (OTs = p-CH3C6H4SO3) formed from a tetrakis(bipyridyl)porphyrin ligand 1, Zn(OTs)2, and a template guest, C60 fullerene. The tetrameric-barrel 2 contains two kinds of bis(bpy) Zn(II) centers coordinated by TsO(-) anions which serve as labile capping ligands in the formation of the finite structure of 2.