Structure and properties of the dendron-encapsulated polyoxometalate (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], a first generation dendrizyme

Combining analytical and theoretical methods, we present a detailed study of a heteropolytungstate cluster encapsulated in a shell of dendritically branching surfactants, namely (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], 3. This novel surfactant-encapsulated cluster (SEC) self-assembles spontaneously from polyoxometalate-containing solutions treated with a stoichiometric amount of dendrons. Compound 3 exhibits a discrete supramolecular architecture in which a single polyoxometalate anion resides in a compact shell of dendrons. Our approach attempts to combine the catalytic activity of polyoxometalates with the steric properties of tailored dendritic surfactants into size-selective catalytic systems. The structural characterization of the SEC is based on analytical ultracentrifugation (AUC) and small-angle neutron scattering (SANS). The packing arrangement of dendrons at the cluster surface is gleaned from molecular dynamics (MD) simulations, which suggests a highly porous shell structure due to the dynamic formation of internal clefts and cavities. From analysis of the MD trajectory of 3, a theoretical neutron-scattering function is derived that is in good agreement with experimental SANS data. Force field parameters used in MD simulations are partially derived from a quantum mechanical geometry optimization of [(Zn(H(2)O))(3)(SbW(9)O(33))(2)](12)(-), 2b, at the density functional theory (DFT) level. DFT calculations are corroborated by X-ray structure analysis of Na(6)K(6)[(Zn(H(2)O))(3)(SbW(9)O(33))(2)].23H(2)O, which is isostructural with the catalytically active Mn derivative 2a. The combined use of theoretical and analytical methods aims at rapidly prototyping smart catalysts ("dendrizymes"), which are structurally related to naturally occurring metalloproteins.     

Effect of ionic strength on the self-assembly, morphology and gelation of pH responsive β-sheet tape-forming peptides

Molecular self-assembly is an intrinsic property of proteins central to their biological functionality. One important industrially interesting property is the ability to control and switch on and off self-assembly using a variety of external chemical and physical triggers. Model peptides have been developed with significantly reduced chemical and structural complexity compared to biological proteins. These are ideal systems for exposing the fundamental principles that drive protein-like self-assembly, as well as for establishing in a quantitative manner their structure-function relationship. We investigate simple, short model peptides that adopt a purely β-strand conformation, align in an antiparallel manner and self-assemble in one dimension in solution into long β-sheet nanotapes and higher order aggregates with no other conformation (i.e., helices, turns or random coils) present in the aggregates. These micrometre-long nanostructures gel in solutions at concentrations as low as 0.2% v/v. Their gel-fluid transition has been previously shown to be controlled by pH, temperature, or by mixing with complementary peptides. Here we show the dramatic effect of another chemical trigger, that of physiological-like salt concentration, on the self-assembly, morphology and gelation of a series of systematically designed charged self-assembling tape-forming peptides, each 11 amino acid residues in length, in the pH range of 2-14. This study provides a detailed understanding of the self-assembly of this class of peptides in aqueous solutions of biologically relevant pH and ionic strength. This insight has led to the development of injectable self-assembling peptide lubricants as potential therapeutics for the treatment of early stage knee joint osteoarthritis.     

Internal molecular disorder in the nematic and smectic phases of thermotropic liquid crystals studied by NMR SPDE experiments

The recently developed NMR SPDE experiment is shown to provide a new and particularly convenient technique for probing the conformational dynamics of mesogens in thermotropic liquid crystals. Measurements have been made in the nematic and smectic phases of the 4,4′-di-n-alkoxyazoxybenzenes. It is shown for the first time that the internal disorder of the alkyl end chains is intimately related to the molecular organization of these mesophases.     

Intramolecular disorder and its relation to mesophase structure in lyotropic liquid crystals

NMR SPDE measurements are reported for the lamellar (dispersions and multibilayer stacks) and hexagonal phases of sodium octanoate/octanol/D₂O mixtures. In the lamellar L_β and L_γ (gel) phases the octyl chains are rigid and perfectly ordered, while in the lamellar L_α and hexagonal phases they are flexible and disordered. In particular, the measurements show that in the fluid lamellar L_α phase, there is a marked discontinuity in the octyl chain flexibility at the C₅-C₆ segment; this behaviour is identical to that previously reported for the alkyl end-chains in smectic 4,4′-di-n-octyloxyazoxybenzene. In contrast, in the hexagonal phase, there is an effectively continuous flexibility gradient along the whole length of the octyl chain as in nematic 4,4′-di-n-octyloxyazoxybenzene. The behaviour in the lamellar phase is attributed to interference between cooperative conformational modes and localized random thermal fluctuations.     

2,3,7,8,12,13-Hexakis[2-(2-methoxyethoxy)ethoxy]tricycloquinazoline: a discogen which allows enhanced levels of n-doping

A synthesis has been developed for 2,3,7,8,12,13-hexakis[2-(2-methoxyethoxy)ethoxy]-tricycloquinazoline (TCQ6EO2M) in which the ethylenoxy side chains are introduced before elaboration of the heterocylic core. This discogen gives a hexagonal columnar phase (Col_h) between 77 and 233°C. n-Doping using potassium metal is facilitated firstly by the electron poor/π-deficient nature of the core and secondly by the polyethylenoxy side chains which complex the potassium K⁺ counter-ions. The conductivity of the Col_h phase of TCQ6EO2M doped with 10 mol % potassium (σ _∥ = 1.1 x 10^-3 S m^-1) is substantially higher than that previously reported for 2,3,7,8,12,13-hexa(hexylthio)tricycloquinazoline doped with 6 mol % potassium (σ _∥ = 2.9 x 10^-5 S m^-1). Photoconductivity studies of TCQ6EO2M using a time of flight sample configuration show transient photocurrents for both holes and electrons. From these an upper limit on the mobility for the electrons is estimated as ~10^-4 cm² V^-1 s^-1 at 150°C which is of the same magnitude as that for hole mobilities in other columnar discotic liquid crystals.     

Controlling the Surface Functionalization of Ultrasmall Gold Nanoparticles by Sequence-Defined Macromolecules

Ultrasmall gold nanoparticles (diameter about 2 nm) were surface-functionalized with cysteine-carrying precision macromolecules. These consisted of sequence-defined oligo(amidoamine)s (OAAs) with either two or six cysteine molecules for binding to the gold surface and either with or without a PEG chain (3400 Da). They were characterized by ¹H NMR spectroscopy, ¹H NMR diffusion-ordered spectroscopy (DOSY), small-angle X-ray scattering (SAXS), and high-resolution transmission electron microscopy. The number of precision macromolecules per nanoparticle was determined after fluorescent labeling by UV spectroscopy and also by quantitative ¹H NMR spectroscopy. Each nanoparticle carried between 40 and 100 OAA ligands, depending on the number of cysteine units per OAA. The footprint of each ligand was about 0.074 nm² per cysteine molecule. OAAs are well suited to stabilize ultrasmall gold nanoparticles by selective surface conjugation and can be used to selectively cover their surface. The presence of the PEG chain considerably increased the hydrodynamic diameter of both dissolved macromolecules and macromolecule-conjugated gold nanoparticles.     

Quadruplex–Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands

A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5′- or 3′-terminus to mimic a quadruplex–duplex (Q–D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q–D hybrids with a very high affinity in the order K_a≈10⁷ m ⁻¹ irrespective of the duplex location at the quadruplex 3′- or 5′-end. NMR chemical shift perturbations identified the tetrad face of the Q–D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3′- or 5′-terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3′-Q–D junction, whereas non-hydrophobic entropic contributions favor binding with formation of a 2:1 ligand-quadruplex complex in case of the 5′-Q–D hybrid.