Mirror symmetry breaking and chiral amplification in foldamer-based supramolecular helical aggregates

Spontaneous asymmetric generation of supramolecular chiral fibers was observed in the folding induced self-assembly of a lock-washer shaped foldamer. A secondary nucleation growth mechanism is proposed to explain the observed chiral amplification or deracemization of these supramolecular fibers.     

How Péclet number affects microstructure and transient cluster aggregation in sedimenting colloidal suspensions

We study how varying the Pe?clet number (Pe) affects the steady state sedimentation of colloidal particles that interact through short-ranged attractions. By employing a hybrid molecular dynamics simulation method we demonstrate that the average sedimentation velocity changes from a non-monotonic dependence on packing fraction φ at low Pe numbers, to a monotonic decrease with φ at higher Pe numbers. At low Pe number the pair correlation functions are close to their equilibrium values, but as the Pe number increases, important deviations from equilibrium forms are observed. Although the attractive forces we employ are not strong enough to form permanent clusters, they do induce transient clusters whose behaviour is also affected by Pe number. In particular, clusters are more likely to fragment and less likely to aggregate at larger Pe numbers, and the probability of finding larger clusters decreases with increasing Pe number. Interestingly, the lifetime of the clusters is more or less independent of Pe number in the range we study. Instead, the change in cluster distribution occurs because larger clusters are less likely to form with increasing Pe number. These results illustrate some of the subtleties that occur in the crossover from equilibrium like to purely non-equilibrium behaviour as the balance between convective and thermal forces changes.     

Structure‐Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA

The galactopeptide dendrimer GalAG2 ((β‐Gal‐OC₆H₄CO‐Lys‐Pro‐Leu)₄(Lys‐Phe‐Lys‐Ile)₂Lys‐His‐Ile‐NH₂) binds strongly to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as well as disperses already established ones. By starting with the crystal structure of the terminal tripeptide moiety GalA‐KPL in complex with LecA, a computational mutagenesis study was carried out on the galactotripeptide to optimize the peptide–lectin interactions. 25 mutants were experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal titration calorimetry, and 3 by X‐ray crystallography. Two of these tripeptides, GalA‐KPY (dissociation constant (K_D)=2.7 μM ) and GalA‐KRL (K_D=2.7 μM ), are among the most potent monovalent LecA ligands reported to date. Dendrimers based on these tripeptide ligands showed improved PA biofilm inhibition and dispersal compared to those of GalAG2 , particularly G2KPY ((β‐Gal‐OC₆H₄CO‐Lys‐Pro‐Tyr)₄(Lys‐Phe‐Lys‐Ile)₂Lys‐His‐Ile‐NH₂). The possibility to retain and even improve the biofilm inhibition in several analogues of GalAG2 suggests that it should be possible to fine‐tune this dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in addition to the biofilm inhibition through amino acid substitutions.     

Natural bond orbital analysis in the ONETEP code: Applications to large protein systems

First principles electronic structure calculations are typically performed in terms of molecular orbitals (or bands), providing a straightforward theoretical avenue for approximations of increasing sophistication, but do not usually provide any qualitative chemical information about the system. We can derive such information via post‐processing using natural bond orbital (NBO) analysis, which produces a chemical picture of bonding in terms of localized Lewis‐type bond and lone pair orbitals that we can use to understand molecular structure and interactions. We present NBO analysis of large‐scale calculations with the ONETEP linear‐scaling density functional theory package, which we have interfaced with the NBO 5 analysis program. In ONETEP calculations involving thousands of atoms, one is typically interested in particular regions of a nanosystem whilst accounting for long‐range electronic effects from the entire system. We show that by transforming the Non‐orthogonal Generalized Wannier Functions of ONETEP to natural atomic orbitals, NBO analysis can be performed within a localized region in such a way that ensures the results are identical to an analysis on the full system. We demonstrate the capabilities of this approach by performing illustrative studies of large proteins—namely, investigating changes in charge transfer between the heme group of myoglobin and its ligands with increasing system size and between a protein and its explicit solvent, estimating the contribution of electronic delocalization to the stabilization of hydrogen bonds in the binding pocket of a drug‐receptor complex, and observing, in situ, the n → π* hyperconjugative interactions between carbonyl groups that stabilize protein backbones. © 2012 Wiley Periodicals, Inc.     

Selective Synthesis of β‐Hydroxy Nitroethanol Ethers by Alcoholysis of Oxiranes

β‐Hydroxy nitroethanol ethers are prepared by selective alcoholysis of oxiranes. The best results are obtained using a clay (monmorillonite K10) or a π‐acid (TCNE) as the catalyst.     

Towards conformationally dependent redox-responsive molecular switches. New polyferrocene bis benzo crown ether receptors

New polyferrocene bis benzo-15-crown-5 ligands have been prepared and shown to form 1:1 intramolecular sandwich complexes with the potassium cation. Electrochemical investigations reveal that both receptors undergo small anodic perturbations of the respective ferrocene-ferrocenium redox couples in the presence of alkali metal cations.     

Knowledge‐based choice of the initiator type for monomer removal by postpolymerization

The mechanisms involved in monomer removal by postpolymerization were investigated to establish a criterion to select the most effective initiator systems. Three redox systems yielding radicals of different hydrophobicities were studied. Efficiency in monomer removal by postpolymerization increased with the hydrophobicity of the radical formed from the initiator system. This result was independent of the water solubility of the residual monomer. The mechanistic reasons for this finding are discussed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4245–4249, 2002     

Single molecule atomic force microscopy and force spectroscopy of chitosan

Atomic force microscopy (AFM) and AFM-based force spectroscopy was used to study the desorption of individual chitosan polymer chains from substrates with varying chemical composition. AFM images of chitosan adsorbed onto a flat mica substrate show elongated single strands or aggregated bundles. The aggregated state of the polymer is consistent with the high level of flexibility and mobility expected for a highly positively charged polymer strand. Conversely, the visualization of elongated strands indicated the presence of stabilizing interactions with the substrate. Surfaces with varying chemical composition (glass, self-assembled monolayer of mercaptoundecanoic acid/decanethiol and polytetrafluoroethylene (PTFE)) were probed with chitosan modified AFM tips and the corresponding desorption energies, calculated from plateau-like features, were attributed to the desorption of individual polymer strands. Desorption energies of 2.0±0.3×10(-20)J, 1.8±0.3×10(-20)J and 3.5±0.3×10(-20)J were obtained for glass, SAM of mercaptoundecanoic/dodecanethiol and PTFE, respectively. These single molecule level results can be used as a basis for investigating chitosan and chitosan-based materials for biomaterial applications.