Ni(II)-mediated self-assembly of artificial beta-dipeptides forming a macrocyclic tetranuclear complex with interior spaces for in-line molecular arrangement

Metal-mediated self-assembly of bioinspired molecular building blocks shows promise as an excellent strategy to provide well-defined metal arrays and nanoscopic metallo-architectures in a programmable way. Herein, we report Ni(II)-mediated self-assembly of artificial beta-dipeptides (1) which were prepared from a newly designed beta-amino acid bearing a propanediamine ligand as the side chain. The beta-dipeptide (1) has thus two sets of ligands, that is, each building block serves as a tridentate ligand with a bidentate propanediamine unit and an amide carbonyl group. Both C- and N-terminal tridentate ligands in 1 bind to two Ni(II) ions independently, and consequently, four beta-dipeptides are circularly arranged in a head-to-tail fashion to form a macrocyclic tetranuclear Ni(II) complex, Ni414(ClO4)8(H2O)10. The cyclic structure was determined by X-ray analysis and ESI-TOF mass spectrometry. The resulting unique twisted-boat structure allows the formation of isolated spaces for in-line hydrogen-bonded arrangement of water and anion molecules within a hole and two grooves rich in hydrogen bonding groups.     

Zn(II)-salphen complexes as versatile building blocks for the construction of supramolecular box assemblies

Zn(II)-salphen complexes are readily accessible and interesting supramolecular building blocks with a large structural diversity. Higher-order supramolecular assemblies, such as molecular boxes based on a bis-Zn(II)-salphen building block and various ditopic bipyridine ligands, have been constructed by means of supramolecular, coordinative Zn(II)-N(pyr) interactions. The use of bipyridine ligands of differing sizes enables the construction of structures with predefined box diameters. The features of the 2:2 box assemblies were investigated in detail by (variable temperature) NMR spectroscopy, UV-visible spectroscopy, NMR titrations, and X-ray crystallographic studies. The spectroscopic studies reveal a high association constant for the Zn(II)-salphen-pyridyl motif, which lies in the range 10(5)-10(6) M(-1). The strong interaction between the Zn(II) center and pyridine donors was supported by PM3 calculations that showed a relatively high Lewis acid character of the metal center in the salphen complex. Titration curves monitored by UV-visible show a cooperative effect between the two bipyridine ligands upon complexation to the bis-Zn(II) template, suggesting the formation of 2:2 complexes. The crystal structures of two supramolecular boxes have been determined. In both examples such a 2:2 assembly is present in the solid state, and the box size is different because they consist of different building blocks. Interestingly, the box assemblies line up in the solid state to form porous channels that are potentially useful in a number of applications.     

Self-assembly of inorganic nanoparticle vesicles and tubules driven by tethered linear block copolymers

Controllable self-assembly of nanoscale building blocks into larger specific structures provides an effective route for the fabrication of new materials with unique optical, electronic, and magnetic properties. The ability of nanoparticles (NPs) to self-assemble like molecules is opening new research frontiers in nanoscience and nanotechnology. We present a new class of amphiphilic "colloidal molecules" (ACMs) composed of inorganic NPs tethered with amphiphilic linear block copolymers (BCPs). Driven by the conformational changes of tethered BCP chains, such ACMs can self-assemble into well-defined vesicular and tubular nanostructures comprising a monolayer shell of hexagonally packed NPs in selective solvents. The morphologies and geometries of these assemblies can be controlled by the size of NPs and molecular weight of BCPs. Our approach also allows us to control the interparticle distance, thus fine-tuning the plasmonic properties of the assemblies of metal NPs. This strategy provides a general means to design new building blocks for assembling novel functional materials and devices.     

Mixed-Valent Heptairon Complex with a Ground-State Spin Value of S=12/2 Constructed from a Triiron Cluster Ligand

The anionic triiron(III) cluster ligand [Fe(III)(3)(μ(3)-O)(bpca)(2)Cl(4)(EtO)(2)](-) (1; Hbpca=bis(2-pyridylcarbonyl)amine) was prepared as a building block for constructing larger metal assemblies. This "metal cluster complex ligand" was used in the synthesis of the mixed-valent heptairon complex [Fe(II)(1)(2)(EtOH)(2)], which has a ground-state spin value of S=12/2.     

Macrocyclic multicenter complexes of nickel and copper of increasing complexity

Multicenter (bi-, tri-, and tetranuclear) tetraazamacrocyclic complexes were self-assembled from Ni and Cu tetraazamacrocyclic mononuclear units and α,ω-diamines as building blocks. The structures of all compounds studied were proved by spectroscopic methods (ESI MS and NMR spectroscopy). Electrochemical experiments revealed reversible one-electron electrode processes at each of the Ni(2+) and Cu(2+) centers with formation of metal cations in oxidation state +3. Long linkers allow bi- and trinuclear complexes with noninteracting metal centers to be obtained. In the case of the short linkers (e.g. ethylenediamine) higher, trinuclear species are formed as major product. The structures of the bis- and tris-macrocyclic systems were confirmed by single-crystal X-ray diffraction. The tris-macrocyclic systems form cations in the shape of triangles partially filled with counterions and solvent molecules. The cations form positively charged layers, which interact in the crystal lattice with the neighboring negatively charged layers of anions. In solution, the trinuclear complexes exhibit strong host-guest interactions with 9,10-dimethyltriptycene due to complementarity of shape and size of this guest molecule. The association constants were determined by NMR spectroscopy and voltammetry, and very good agreement was obtained. The structural flexibility of the tetranuclear complex with long linkers allows for attractive interactions between the metal-complexing macrocycles that result in folding of the molecule. On the contrary, no folding is possible in the case of short linkers consisting of two CH(2) groups.     

The Assembly of Supramolecular Boxes and Coordination Polymers Based on Bis‐Zinc‐Salphen Building Blocks

We report the assembly of supramolecular boxes and coordination polymers based on a rigid bis‐zinc(II)‐salphen complex and various ditopic nitrogen ligands. The use of the bis‐zinc(II)‐salphen building block in combination with small ditopic nitrogen ligands gave organic coordination polymers both in solution as well as in the solid state. Molecular modeling shows that supramolecular boxes with small internal cavities can be formed. However, the inability to accommodate solvent molecules (such as toluene) in these cavities explains why coordination polymers are prevailing over well‐defined boxes, as it would lead to an energetically unfavorable vacuum. In contrast, for relatively longer ditopic nitrogen ligands, we observed the selective formation of supramolecular box assemblies in all cases studied. The approach can be easily extended to chiral analogues by using chiral ditopic nitrogen ligands.     

Design and structural extension of a supramolecular inclusion-compound host made by the formation of dimers of isonicotinic acid and thiocyanato coordinating bridges

A new host design for an inclusion compound with a preference for large planar aromatic guest molecules has been proposed. Our host design includes a rectangular cavity made using a long and a short building block based on the concept of supramolecular chemistry. The long building block facilitates the inclusion of large guests, and the short building block prevents the formation of an interpenetrated structure, which is often observed in frameworks with large void spaces. The long building block is made when dimers of 4-pyridinecarboxylic acid (isoH) form through hydrogen bonding between the two carboxylic acid moieties. This isoH dimer can link two transition metal centers using the N atoms at both ends to act as a long building block. For the short building block, the thiocyanato ion was used. This makes a bent bridge between two metal centers to form a 1D double-chain [M(SCN)2]infinity complex. From the self-assembly of isoH, SCN- and Ni2+, a 2D network of [Ni(SCN)2(isoH)2]infinity, in which the 1D [Ni(SCN)2]infinity complexes are linked by the isoH dimers, is built up. The rectangular cavity is formed as a mesh within the 2D network. The crystal of our inclusion compound has a layered structure of 2D networks, and a 1D channel-like cavity penetrating the layered 2D networks is formed where guests may be included. Moreover, our host design has the advantage of easy extension of the host structure. Replacement of isoH with another component and use of three components is possible for making the long building block. In the latter case, a linear spacer having two carboxy groups is inserted into the isoH dimer to form a long building block with a trimer structure. Based on our host design, a series of new inclusion compounds were synthesized. The crystal structures of three compounds were determined by single crystal X-ray diffraction. These were a biphenyl inclusion compound [Ni(SCN)2(isoH)2].1/2C12H10 (the basic case), a 9,10-dichloroanthracene inclusion compound [Ni(SCN)2(acrylH)2].1/2C14H8Cl2, where isoH is replaced with 3-(4-pyridinyl)-2-propenoic acid (acrylH), and a perylene inclusion compound [Ni(SCN)2(isoH)2(fumaricH2)].1/2C20H12, whose long building block is a trimer inserted with fumaric acid (fumaricH2) as a linear spacer.     

Unconventional Assembly of Bimetallic Au–Ni Janus Nanoparticles on Chemically Modified Silica Spheres

This paper reports that Janus Au?Ni nanoparticles (JANNPs) can self‐assemble onto silica spheres in a novel way, which is different from that of single‐component isotropic nanoparticles. JANNPs modified with octadecylamine (ODA) assemble onto catechol‐modified silica spheres (SiO₂?OH) to form a very special core–loop complex structure and finally the core–loop assemblies link each other to form large assemblies through capillary force and the hydrophobic interaction of the alkyl chains of ODA. The nanocomposites disassemble in the presence of vanillin and oleic acid because of the breakage of the catechol–metal link. Vanillin‐induced disassembly enables the JANNPs to reassemble into a core–loop structure upon ODA addition. The assembly of SiO₂?OH and isotropic Ni or Fe₃O₄ particles generates traditional core–satellite structures. This unconventional self‐assembly can be attributed to the synergistic effect of Janus specificity and capillary force, which is also confirmed by the assembly of thiol‐terminated silica spheres (SH?SiO₂) with anisotropic JANNPs, isotropic Au, and Ni nanoparticles. These results can guide the development of novel composite materials using Janus nanoparticles as the primary building blocks.     

Hydrophobic self-assembly of a perylenediimide-linked DNA dumbbell into supramolecular polymers

The self-assembly of DNA dumbbell conjugates possessing hydrophobic perylenediimide (PDI) linkers separated by an eight-base pair A-tract has been investigated. Cryo-TEM images obtained from dilute solutions of the dumbbell in aqueous buffer containing 100 mM NaCl show the presence of structures corresponding to linear end-to-end assemblies of 10-30 dumbbell monomers. The formation of assemblies of this size is consistent with analysis of the UV-vis and fluorescence spectra of these solutions for the content of PDI monomer and dimer chromophores. Assembly size is dependent upon the concentration of dumbbell and salt as well as the temperature. Kinetic analysis of the assembly process by means of salt-jump stopped-flow measurements shows that it occurs by a salt-triggered isodesmic mechanism in which the rate constants for association and dissociation in 100 mM NaCl are 3.2 × 10(7) M(-1)s(-1) and 1.0 s(-1), respectively, faster than the typical rate constants for DNA hybridization. TEM and AFM images of samples deposited from solutions having higher concentrations of dumbbell and NaCl display branched assemblies with linear regions >1 μm in length and diameters indicative of the formation of small bundles of dumbbell end-to-end assemblies. These observations provide the first example of the use of hydrophobic association for the assembly of small DNA duplex conjugates into supramolecular polymers and larger branched aggregates.     

Gold Nanoparticle Assemblies on Surfaces: Reactivity Tuning through Capping‐Layer and Cross‐Linker Design

The immobilization of metal nanoparticles (NPs) with molecular control over their organization is challenging. Herein, we report the formation of molecularly cross‐linked AuNP assemblies using a layer‐by‐layer approach. We observed four types of assemblies: 1) small aggregates of individual AuNPs, 2) large aggregates of individual AuNPs, 3) networks of fused AuNPs, and 4) gold islands. Interestingly, these assemblies with the different cross‐linkers and capping layers represent different stages in the complete fusion of AuNPs to afford islands of continuous gold. We demonstrate that the stability toward fusion of the nanoparticles of the on‐surface structures can be controlled by the reactivity of the cross‐linkers and the hydrophilicity/hydrophobicity of the nanoparticles.     

Biomolecule-directed assembly of nanoscale building blocks studied via lattice Monte Carlo simulation

We perform lattice Monte Carlo simulations to study the self-assembly of functionalized inorganic nanoscale building blocks using recognitive biomolecule linkers. We develop a minimal coarse-grained lattice model for the nanoscale building block (NBB) and the recognitive linkers. Using this model, we explore the influence of the size ratio of linker length to NBB diameter on the assembly process and the structural properties of the resulting aggregates, including the spatial distribution of NBBs and aggregate topology. We find the constant-kernel Smoluchowski theory of diffusion-limited cluster-cluster aggregation describes the aggregation kinetics for certain size ratios.     

Conjugates between minor groove binders and Zn(II)-tach complexes: Synthesis,characterization, and interaction with plasmid DNA

A new family of conjugates between a Zn(II)-tach complex and (indole)₂ or benzofuran-indole amide minor groove binders connected through alkyl or oxyethyl linkers of different lengths has been prepared. The conjugates bind strongly to DNA. However, the complexation to DNA to promote the Zn(II) catalyzed hydrolytic cleavage of the DNA results instead in its inhibition. This inhibition effect has been confirmed also using Cu(II). Modeling studies suggest that in the most stable complex conformation, the minor groove binder and the linker lie in the minor groove hampering the interaction between the metal complex and the phosphate backbone of DNA. Therefore, the linear arrangement of minor groove binder-linker-metal complex appears to be effective to ensure tight binding but unproductive from a hydrolytic point of view.     

Reciprocal Self‐Assembly of Peptide–DNA Conjugates into a Programmable Sub‐10‐nm Supramolecular Deoxyribonucleoprotein

To overcome the limitations of molecular assemblies, the development of novel supramolecular building blocks and self‐assembly modes is essential to create more sophisticated, complex, and controllable aggregates. The self‐assembly of peptide–DNA conjugates (PDCs), in which two orthogonal self‐assembly modes, that is, β‐sheet formation and Watson–Crick base pairing, are covalently combined in one supramolecular system, is reported. Despite extensive research, most self‐assembly studies have focused on using only one type of building block, which restricts structural and functional diversity compared to multicomponent systems. Multicomponent systems, however, suffer from poor control of self‐assembly behaviors. Covalently conjugated PDC building blocks are shown to assemble into well‐defined and controllable nanostructures. This controllability likely results from the decrease in entropy associated with the restriction of the molecular degrees of freedom by the covalent constraints. Using this strategy, the possibility to thermodynamically program nano‐assemblies to exert gene regulation activity with low cytotoxicity is demonstrated.     

Interaction with plasmid DNA of Hoechst-TACN conjugates

ABSTRACT

A new family of conjugates between the Hoechst minor groove binder and the TACN metal ion ligand connected through hydrophobic alkyl or more hydrophilic oxyethyl linkers of different length has been prepared. The linkers are connected to the convex side of the Hoechst skeleton thus forcing the TACN ligand to exit the minor groove and interact with the phosphate backbone of DNA. The conjugates preserve the binding mode of Hoechst with an affinity influenced by the nature of the linker, the more hydrophobic being the more efficient. Coordination of Cu(II) or Zn(II) poorly affect these parameters. Nevertheless, the Zn(II) complex bearing a C6 linear alkyl linker induced a modest but reproducible acceleration of the hydrolytic cleavage of DNA which can be ascribed to the ability of the conjugate to deliver the hydrolytic subunit close to the DNA phosphodiester bonds.     

Order from Chaos: Self‐Assembly of Nanoprism from a Mixture of Tetratopic Terpyridine‐Porphyrin Conformers

Porphyrins have been widely used in the self‐assembly of metallo‐supramolecules. In this study, we introduced 2,2':6,2"‐terpyridine (tpy) into a porphyrin core to synthesize a tetratopic building block with multiple conformers. During the self‐assembly with Zn(II), such a mixture of conformers was able to form a discrete nanoprism with all building blocks in one conformation. Detailed characterizations, including NMR, ESI‐MS and traveling‐wave ion mobility‐mass spectrometry (TWIM‐MS), all supported the formation of the desired assemblies. AFM and TEM further confirmed the dimensions of assembled nanoprisms. Moreover, the photophysical properties of the ligands and complexes were noticeably different depending upon size and metal ion center.     

Computational Design of Single-Peptide Nanocages with Nanoparticle Templating

Protein complexes perform a diversity of functions in natural biological systems. While computational protein design has enabled the development of symmetric protein complexes with spherical shapes and hollow interiors, the individual subunits often comprise large proteins. Peptides have also been applied to self-assembly, and it is of interest to explore such short sequences as building blocks of large, designed complexes. Coiled-coil peptides are promising subunits as they have a symmetric structure that can undergo further assembly. Here, an α-helical 29-residue peptide that forms a tetrameric coiled coil was computationally designed to assemble into a spherical cage that is approximately 9 nm in diameter and presents an interior cavity. The assembly comprises 48 copies of the designed peptide sequence. The design strategy allowed breaking the side chain conformational symmetry within the peptide dimer that formed the building block (asymmetric unit) of the cage. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques showed that one of the seven designed peptide candidates assembled into individual nanocages of the size and shape. The stability of assembled nanocages was found to be sensitive to the assembly pathway and final solution conditions (pH and ionic strength). The nanocages templated the growth of size-specific Au nanoparticles. The computational design serves to illustrate the possibility of designing target assemblies with pre-determined specific dimensions using short, modular coiled-coil forming peptide sequences.     

Coordination polymers with 4,4'-bipyrimidine. Using a combination of endo- and exodentate donors to build a one-dimensional Ag(I) ladder and a heterometallic Co(II)Ag(I)2 network

The ligand 4,4'-bipyrimidine combines a chelating bipyridine group and two terminal donor atoms into a single molecule; chelation to a single Ag(I) centre forms a square planar complex which can then form an extended planar ladder-type polymer by linking through linear Ag(I) centres whereas bis-coordination to an octahedral Co(II) centre yields a building block with four external donor nitrogen atoms which can coordinate to two distinct Ag(I) ions to form a heterometallic 2D net.     

Tris(benzimidazolyl)amine-Cu(II) coordination units bridged by carboxylates: structures and DNA-condensing property

Multinuclear multibenzimidazole metal complexes frequently exhibit novel structures and properties, and are an example of versatile compounds in bioinorganic chemistry. In this work, first, we synthesized the mononuclear complex [Cu(ntb)(H(2)O)](2+), 1, by using tris[(benzimidazol-2-yl)methyl]amine (ntb). Then, a library of multicationic ntb-Cu(II) complexes, 2-9, was prepared by replacing the labile water molecule in 1 with multifunctional carboxylates acting as a bridge linker between two or four ntb-Cu(II) units under slightly acidic or alkaline conditions. Their X-ray crystal structures reveal that these complexes contain one, two or four [Cu(ntb)](2+) units. The pH media used in preparation can control the coordination patterns of the carboxylates and the overall architecture of the complexes, although the Cu(II) centers in the complexes always maintain a five-coordinated structure regardless of the preparation conditions used. Both intra- and inter-molecular π···π interactions involved in the benzimidazoles, as well as extensive hydrogen bonding networks in the complexes were observed to occur in the crystal packing. We selected complexes 1 and the dicarboxylate-bridged 4-7 as potential DNA condensers, as they can be dissolved to the required levels for examining their DNA-binding and -condensing properties in the buffer solutions tested (pH 7.4). For these complexes, the effects of the structural variations, including the number of Cu(II) ions and positive charges, length of linkers, and overall architecture, on the DNA-binding and -condensing properties and cytotoxicity were assessed and compared by biophysical measurements. The results from absorption titration showed that the affinities of the complexes for DNA are dominated by both the electrostatic interaction between them and the π···π interactions through the intercalation of the benzimidazolyl groups in the complexes into DNA base pairs. The DNA-condensing ability was observed to be mainly controlled by the numbers of positive charges on the complexes, and less correlated with the carboxylate linkers. Moreover, no direct relationships have been found between the apparent DNA-binding affinity and DNA-condensing ability of the complexes. The ability of DNA condensation triggered by 7b that carries four ntb-Cu(II) units and six positive charges is much stronger than those by the other complexes, but it also exhibits the largest cytotoxicity. This work aids in understanding the structure-activity relationships for metal complexes likely acting as a new type of gene-delivery systems.     

Crystal-to-Crystal Transformation of Magnets Based on Heptacyanomolybdate(III) Involving Dramatic Changes in Coordination Mode and Ordering Temperature

Two for one: Two unusual magnets based on the [Mo(CN)(7) ](4-) building block with Mn(II) linkers have been prepared with different topological 3D networks. Conversion of one into the other is triggered by dehydration during a single-crystal to single-crystal event (see picture; Mn:?dark red, Mo:?pink, C:?green, N:?blue, O:?red).     

Three-dimensional DNA crystals as molecular sieves

DNA has proved to be a successful nanoscale building block because of its inherent programmability and its predictable structural features. One long-standing goal of DNA nanotechnology has been the rational design and assembly of three-dimensional (3D) DNA crystals for use as molecular scaffolds, in molecular electronics assembly, and as molecular sieves. Here we demonstrate that rationally designed 3D DNA crystals with mesoporous features can function as molecular sieves by selectively adsorbing proteins based on size.