Divergent Polymer Superstructures from Protonated Poly(adenine) DNA and RNA.

Studies have shown that poly(adenine) DNA and RNA strands protonate at a low pH to form self-associating duplexes; however, the nanoscopic morphology of these structures is unclear. Here, we use Transition Electron Microscopy (TEM), Atomic Force Microscopy (AFM), dynamic light scattering (DLS), and fluorescence spectroscopy to show that both ribose identity (DNA or RNA) and assembly conditions (thermal or room-temperature annealing) dictate unique hierarchical structures for poly(adenine) sequences at a low pH. We show that while the thermodynamic product of protonating poly(adenine) DNA is a discrete dimer of two DNA strands, the kinetic product is a supramolecular polymer that branches and aggregates to form micron-diameter superstructures. In contrast, we find that protonated poly(A) RNA polymerizes into micrometer-length, twisted fibers under the same conditions. These divergent hierarchical morphologies highlight the amplification of subtle chemical differences between RNA and DNA into unique nanoscale behaviors. With the use of poly(adenine) strands spanning vaccine technologies, sensing, and dynamic biotechnology, understanding and controlling the underlying assembly pathways of these structures are critical to developing robust, programmable nanotechnologies.

Modulating the Lifetime of DNA Motifs Using Visible Light and Small Molecules.

Here we regulate the formation of dissipative assemblies built from DNA using a merocyanine photoacid that responds to visible light. The operation of our system and the relative distribution of species within it are controlled by irradiation time, initial pH value, and the concentration of a small-molecule binder that inhibits the reaction cycle. This approach is modular, does not require DNA modification, and can be used for several DNA sequences and lengths. Our system design allows for waste-free control of dissipative DNA nanotechnology, toward the generation of nonequilibrium, life-like nanodevices.

Light-Activated Assembly of DNA Origami into Dissipative Fibrils.

Hierarchical DNA nanostructures offer programmable functions at scale, but making these structures dynamic, while keeping individual components intact, is challenging. Here we show that the DNA A-motif-protonated, self-complementary poly(adenine) sequences-can propagate DNA origami into one-dimensional, micron-length fibrils. When coupled to a small molecule pH regulator, visible light can activate the hierarchical assembly of our DNA origami into dissipative fibrils. This system is recyclable and does not require DNA modification. By employing a modular and waste-free strategy to assemble and disassemble hierarchical structures built from DNA origami, we offer a facile and accessible route to developing well-defined, dynamic, and large DNA assemblies with temporal control. As a general tool, we envision that coupling the A-motif to cycles of dissipative protonation will allow the transient construction of diverse DNA nanostructures, finding broad applications in dynamic and non-equilibrium nanotechnology.

Incorporation of a Phosphino(pyridine) Subcomponent Enables the Formation of Cages with Homobimetallic and Heterobimetallic Vertices.

Biological systems employ multimetallic assemblies to achieve a range of functions. Here we demonstrate the preparation of metal-organic cages that contain either homobimetallic or heterobimetallic vertices. These vertices are constructed using 2-formyl-6-diphenylphosphinopyridine, which forms ligands that readily bridge between a pair of metal centers, thus enforcing the formation of bimetallic coordination motifs. Two pseudo-octahedral homometallic MI12L4 cages (MI = CuI or AgI) were prepared, with a head-to-head configuration of their vertices confirmed by X-ray crystallography and multinuclear NMR for AgI. The phosphino-pyridine subcomponent also enabled the formation of a class of octanuclear CdII4CuI4L4 tetrahedral cages, representing an initial example of self-assembled cages containing well-defined heterobimetallic vertices.

DNA Sequence and Length Dictate the Assembly of Nucleic Acid Block Copolymers.

The self-assembly of block copolymers is often rationalized by structure and microphase separation; pathways that diverge from this parameter space may provide new mechanisms of polymer assembly. Here, we show that the sequence and length of single-stranded DNA directly influence the self-assembly of sequence-defined DNA block copolymers. While increasing the length of DNA led to predictable changes in self-assembly, changing only the sequence of DNA produced three distinct structures: spherical micelles (spherical nucleic acids, SNAs) from flexible poly(thymine) DNA, fibers from semirigid mixed-sequence DNA, and networked superstructures from rigid poly(adenine) DNA. The secondary structure of poly(adenine) DNA strands drives a temperature-dependent polymerization and assembly mechanism: copolymers stored in an SNA reservoir form fibers after thermal activation, which then aggregate upon cooling to form interwoven networks. DNA is often used as a programming code that aids in nanostructure addressability and function. Here, we show that the inherent physical and chemical properties of single-stranded DNA sequences also make them an ideal material to direct self-assembled morphologies and select for new methods of supramolecular polymerization.

A poly(thymine)-melamine duplex for the assembly of DNA nanomaterials.

The diversity of DNA duplex structures is limited by a binary pair of hydrogen-bonded motifs. Here we show that poly(thymine) self-associates into antiparallel, right-handed duplexes in the presence of melamine, a small molecule that presents a triplicate set of the hydrogen-bonding face of adenine. X-ray crystallography shows that in the complex two poly(thymine) strands wrap around a helical column of melamine, which hydrogen bonds to thymine residues on two of its three faces. The mechanical strength of the thymine-melamine-thymine triplet surpasses that of adenine-thymine base pairs, which enables a sensitive detection of melamine at 3 pM. The poly(thymine)-melamine duplex is orthogonal to native DNA base pairing and can undergo strand displacement without the need for overhangs. Its incorporation into two-dimensional grids and hybrid DNA-small-molecule polymers highlights the poly(thymine)-melamine duplex as an additional tool for DNA nanotechnology.

Single-molecule methods in structural DNA nanotechnology.

Single molecules can now be visualised with unprecedented precision. As the resolution of single-molecule experiments improves, so too does the breadth, quantity and quality of information that can be extracted using these methodologies. In the field of DNA nanotechnology, we use programmable interactions between nucleic acids to generate complex, multidimensional structures. We can use single-molecule techniques - ranging from electron and fluorescence microscopies to electrical and force spectroscopies - to report on the structure, morphology, robustness, sample heterogeneity and other properties of these DNA nanoconstructs. In this Tutorial Review, we will detail how complementarity between static and dynamic single-molecule techniques can provide a unified image of DNA nanoarchitectures. The single-molecule methods that we discuss provide unprecedented insight into chemical and structural behaviour, yielding not just an average outcome but reporting on the distribution of values, ultimately showing how bulk properties arise from the collective behaviour of individual structures. As the fields of both DNA nanotechnology and single-molecule characterisation intertwine, a feedback loop is generated between disciplines, providing new opportunities for the development and operation of DNA-based materials as sensors, delivery vehicles, machinery and structural scaffolds.

Narcissistic, Integrative, and Kinetic Self-Sorting within a System of Coordination Cages.

Many useful principles of self-assembly have been elucidated through studies of systems where multiple components combine to create a single structure. More complex systems, where multiple product structures self-assemble in parallel from a shared set of precursors, are also of great interest, as biological systems exhibit this behavior. The greater complexity of such systems leads to an increased likelihood that discrete species will not be formed, however. Here we show how the kinetics of self-assembly govern the formation of multiple metal-organic architectures from a mixture of five building blocks, preventing the formation of a discrete structure of intermediate size. By varying ligand symmetry, denticity, and orientation, we explore how five distinct polyhedra-a tetrahedron, an octahedron, a cube, a cuboctahedron, and a triangular prism-assemble in concert around CoII template ions. The underlying rules dictating the organization of assemblies into specific shapes are deciphered, explaining the formation of only three discrete entities when five could form in principle.

Conformational Control in Main Group Phosphazane Anion Receptors and Transporters.

Anion binding by receptor molecules is a central field of modern chemistry which impacts areas of catalysis as well as biological and materials chemistry. As binding often requires high chemical stability under aerobic and aqueous conditions for practical applications, carbon-based anion receptors have dominated this field, with main group element analogues receiving far less attention. The recent observation that the air- and moisture-stable amino-cyclophosph(V)azanes of the type [RN(E)P(µ-NR)]2 (E = O, S, Se) can exhibit halide binding that is competitive with topologically related organic receptors (such as squaramides and thioureas) has motivated us here to explore how the binding properties of phosphazane receptors can be enhanced further. Coordination of transition metals by the two P,N metal coordination sites of the phosph(III)azane dimer [(2-py)NHP(µ-NtBu)]2 not only activates the receptor for anion binding (by fixing the optimum exo-exo conformation and polarizing the endocyclic N-H substituents) but also stabilizes the P2N2 ring to hydrolysis and oxidation. We show how the binding properties of these receptors can be modulated by the coordinated metal fragments and that they can bind chloride 1 to 2 orders of magnitude stronger than the related squaramides and thioureas. These features can be utilized in anion transport through phospholipid bilayers under aqueous conditions for which transport can be improved by 1 order of magnitude compared to the previous best phosphazane and thiourea transporters. This study demonstrates how careful design of inorganic systems can result in potent supramolecular functionality, beyond that observed for organic counterparts.

Transition-Metal-Functionalized DNA Double-Crossover Tiles: Enhanced Stability and Chirality Transfer to Metal Centers.

The double crossover junction (DX) is a fundamental building block for generating complex and varied structures from DNA. However, its implementation in functional devices is limited to the inherent properties of DNA itself. Here, we developed design strategies to generate the first metal-DX DNA tiles (DXM ) by site-specifically functionalizing the tile crossovers with tetrahedral binding pockets that coordinate CuI . These DX junctions bind two CuI ions independently at distinct sites, display greater thermal stability than native DX tiles upon metalation, and melt in a cooperative fashion. In addition, the right-handed helical chirality of DNA is transferred to the metal centers. Our tiles display high metal ion selectivity, such that CuII is spontaneously reduced to CuI in situ. By modifying our design over three generations of tiles, we elucidated the thermodynamic and geometric requirements for the successful assembly of DXM tiles, which have direct applicability in developing robust, stable DNA-based materials with electroactive, photoactive, and catalytic properties.

Multisite Binding of Drugs and Natural Products in an Entropically Favorable, Heteroleptic Receptor.

The cavities of artificial receptors are defined by how their components fit together. The encapsulation of specific molecules can thus be engineered by considering geometric principles; however, intermolecular interactions and steric fit scale with receptor size, such that the ability to bind multiple guests from a specific class of compounds remains a current challenge. By employing metal-organic self-assembly, we have prepared a triangular prism from two different ligands that is capable of binding more than 20 different natural products, drugs, and steroid derivatives within its prolate cavity. Encapsulation inflates the host, enhancing its ability to bind other guests in peripheral pockets and thus enabling our system to bind combinations of different drug and natural product cargoes in different locations simultaneously. This new mode of entropically favorable self-assembly thus enables central encapsulation to amplify guest-binding events around the periphery of an artificial receptor.

Hydrogen-Bond-Assisted Symmetry Breaking in a Network of Chiral Metal-Organic Assemblies.

Herein we elucidate the interplay of chiral, chelate, solvent, and hydrogen-bonding information in the self-assembly of a series of new three-dimensional metal-organic architectures. Enantiopure ligands, each containing H-bond donors and acceptors, form different structures, depending on the ratio in which they are combined: enantiopure components form M4L4 assemblies, whereas racemic mixtures form M3L3 stacks. Chiral amplification within M3L3 enantiomers was observed when a 2:1 ratio of R and S subcomponent enantiomers was employed. Simply switching the solvent (from MeCN to MeOH) or chelating unit (from bidentate to tridentate) increased the diversity of structures that can be generated from these building blocks, leading to the selective formation of novel M2L2 and M3L2 assemblies. The addition of achiral ligand building blocks resulted in the formation of further structures: When an achiral subcomponent was combined with its R and S chiral congeners, a three-layer heteroleptic architecture was generated, with the achiral unit sitting at the top of the stack. When combined with the S enantiomer only, however, the achiral unit assembled in the center of the structure, thus demonstrating the selective placement of achiral units within chiral systems. Further sorting experiments revealed that combining R and S stereocenters within a single ligand led to diastereoselective product generation. These results show how geometric complementarity between different ligands impacts upon the degree of hydrogen-bonding within the assembly, stabilizing specific low-symmetry architectures from among many possible structural outcomes.

Fluorometric Recognition of Nucleotides within a Water-Soluble Tetrahedral Capsule.

The design of aqueous probes and binders for complex, biologically relevant anions presents a key challenge in supramolecular chemistry. Herein, a tetrahedral assembly with cationic faces and corners is reported that is capable of discriminating between anionic and neutral guests in water. Electrostatic repulsion between subcomponents can be overcome by the addition of an anionic template, or generating a robust covalent framework by incorporating tris(2-aminoethyl)amine (TREN). The resultant TREN-capped, water-soluble, fluorescent cage binds mono- and poly-phosphoric esters, including nucleotides. Its covalent skeleton renders it stable at micromolar concentrations in water, enabling the fluorometric detection of biologically relevant guests in an aqueous environment. Selective supramolecular encapsulants, such as 1, could enable new sensing applications, such as recognition of toxins and drugs, under biological conditions.

Guest Binding via N-H⋠⋠⋠π Bonding and Kinetic Entrapment by an Inorganic Macrocycle.

Modern supramolecular chemistry is overwhelmingly based on non-covalent interactions involving organic architectures. However, the question of what happens when you depart from this area to the supramolecular chemistry of structures based on non-carbon frameworks remains largely unanswered, and is an area that potentially provides new directions in molecular activation, host-guest chemistry, and biomimetic chemistry. In this work, we explore the unusual host-guest chemistry of the pentameric macrocycle [{P(µ-Nt Bu}2 NH]5 with a range of anionic and neutral guests. The polar coordination site of this host promotes new modes of guest encapsulation via hydrogen bonding with the π systems of the unsaturated C≡C and C≡N bonds of acetylenes and nitriles as well as with the PCO- anion. Halide guests can be kinetically locked within the structure by oxidation of the phosphorus periphery by oxidation to PV . Our study underscores the future promise of p-block macrocyclic chemistry.

Otherwise Unstable Structures Self-Assemble in the Cavities of Cuboctahedral Coordination Cages.

We present a method for the directed self-assembly of interlocked structures and coordination complexes in a set of metal-organic hosts. New homo- and heteroleptic metal complexes-species that cannot be prepared outside-form within the cavities of cuboctahedral coordination cages. When linear bidentate guests and macrocycles are sequentially introduced to the host, a rotaxane is threaded internally; the resulting ternary host-guest complex is a new kind of molecular gyroscope. Tetradentate guests segregate the cavities of these cages into distinct spaces, promoting new stoichiometries and modes of ligand binding to metal ions. The behaviors of bound complexes were observed to alter markedly as a result of confinement: In situ oxidations and spin transitions, neither of which occur ex situ, were both observed to proceed. By providing a tailored space for new modes of coordination-driven self-assembly, the inner phases of cuboctahedral coordination cages provide a new medium for synthetic coordination chemistry.

Flexible Bonding of the Phosph(V)azane Dianions [S(E)P(µ-NtBu)]22.

Oxidation of the PIII dianion [S-P(µ-NtBu)]22- (1) with elemental sulphur, selenium and tellurium gives the PV dianions [(S)(E)P(µ-NtBu)]22- (E = S (6 a), Se (6 b), Te (6 c)). Although 6 c proves to be too unstable, the S,S-dianion 6 a and ambidentate S,Se-dianion 6 b are readily transferred intact to main group and transition metal elements, producing a range of new cage and coordination compounds. While their coordination characteristics are in many ways similar to closely-related isoelectronic phosph(V)azane anions [(E)(RN=)P(µ-NtBu)]22- , the sterically unhindered nature of 6 introduces an expanded range of coordination modes, that is, facial S,S- and Se,Se-bonding as well as side-on S,Se-coordination. All of these bonding modes are observed for the amibidentate S,Se dianion 6 b.

How Changing the Bridgehead Can Affect the Properties of Tripodal Ligands.

Although a multitude of studies have explored the coordination chemistry of classical tripodal ligands containing a range of main-group bridgehead atoms or groups, it is not clear how periodic trends affect ligand character and reactivity within a single ligand family. A case in point is the extensive family of neutral tris-2-pyridyl ligands E(2-py)3 (E=C-R, N, P), which are closely related to archetypal tris-pyrazolyl borates. With the 6-methyl substituted ligands E(6-Me-2-py)3 (E=As, Sb, Bi) in hand, the effects of bridgehead modification alone on descending a single group in the periodic table were assessed. The primary influence on coordination behaviour is the increasing Lewis acidity (electropositivity) of the bridgehead atom as Group 15 is descended, which not only modulates the electron density on the pyridyl donor groups but also introduces the potential for anion selective coordination behaviour.

Tuning the Redox Properties of Fullerene Clusters within a Metal-Organic Capsule.

A porphyrin-edged metal-organic tetrahedron forms host-guest complexes containing 1-4 equiv of fullerene C60, depending on the solvent employed. The molecules of C60 were bound anticooperatively within well-defined pockets; an X-ray crystal structure of three fullerenes inside the tetrahedron was obtained. Electrochemical measurements revealed that the electron-accepting properties of the fullerenes inside the capsules were altered depending on the mode of encapsulation. The binding of multiple fullerenes was observed to increase the electron affinity of the overall cluster, providing a noncovalent method of tuning fullerene electronics.

Self-Assembly of Conjugated Metallopolymers with Tunable Length and Controlled Regiochemistry.

Self-assembled materials can be designed to express useful optoelectronic properties; however, achieving structural control is a necessary precondition for the optimization of desired properties. Here we report a simple, metal-templated polymerization process that generates helical metallopolymer strands over 75 repeat units long (28 kDa) from a single bifunctional monomer and CuI . The resulting polymer consists of a double helix of two identical conjugated organic strands enclosing a central column of metal ions. The length of this metallopolymer can be controlled by adding monofunctional subcomponents to end-cap the conjugated ligands. The use of ditopic and bulky monotopic subcomponents, respectively, allows a head-to-head or head-to-tail double helix to be generated. Spectroscopic measurements of different polymer lengths demonstrate how control over polymer length leads to control over the electronic and luminescent properties of the resulting material, thereby enabling tunable white-light emission.

Subtle Ligand Modification Inverts Guest Binding Hierarchy in M(II)8L6 Supramolecular Cubes.

Zinc(II), a dimolybdenum(II) paddlewheel tetramine A, and 2-formylpyridine self-assembled to generate a cubic Zn(II)8(L(A))6 assembly. The paddlewheel faces of this assembly exhibited two distinct conformations, whereas the analogous Fe(II)8(L(A))6 framework displayed no such perturbation to its structure. This variation in behavior is attributed to the subtle difference in ligand rotational freedom between the Zn(II)- and Fe(II)-cornered cubes. The incorporation of a fluorinated Mo(II)2 paddlewheel, B, into analogous Zn(II)8(L(B))6 and Fe(II)8(L(B))6 structures resulted in changes to the rotational dynamics of the ligands. These differing dynamics perturbed the energies of the frontier orbitals of these structures, as determined through spectroscopic and electrochemical methods. The result of these perturbations was an inversion of the halide binding preference of the Zn(II)8(L(B))6 host as compared to its Zn(II)8(L(A))6 congener, whereas the Fe(II)8(L(B))6 host maintained a similar binding hierarchy to Fe(II)8(L(A))6.