Total Synthesis of Cyclocitropside A and Its Conversion to Cyclocitropsides B and C via Asparagine Deamidation

The total syntheses of three closely related cyclic peptide natural products, cyclocitropsides A–C, are described. Cyclocitropside A could be readily converted into cyclocitropsides B and C through an asparagine deamidation pathway, indicating that this is a plausible biosynthetic route to these compounds

Colorimetric and Luminescent Sensors for Chloride: Hydrogen Bonding vs Deprotonation

The synthesis and photophysical properties of four squaramide based fluorescent anion sensors (<b>1</b>–<b>4</b>) are described. These luminescent compounds showed selectivity for Cl^– over various other anions with concomitant changes in both their UV/visible and fluorescence properties upon Cl^– addition, attributed to initial H-bonding followed by NH deprotonation in the presence of excess Cl^–, signaled by a color change. The nature of the electron withdrawing aryl substituents is directly related to the H-bonding ability/acidity of the squaramide protons and can be used to tune the deprotonation behavior

Hierarchical Assembly of Branched Supramolecular Polymers from (Cyclic Peptide)–Polymer Conjugates

We report the synthesis and assembly of (<i>N</i>-methylated cyclic peptide)–polymer conjugates for which the cyclic peptide is attached to either the α- or both α- and ω- end groups of a polymer. A combination of chromatographic, spectroscopic, and scattering techniques reveals that the assembly of the conjugates follows a two-level hierarchy, initially driven by H-bond formation between two <i>N</i>-methylated cyclic peptides, followed by unspecific, noncovalent aggregation of this peptide into small domains that behave as branching points and lead to the formation of branched supramolecular polymers

Investigating the effects of structure on sulfate recognition by neutral dipeptide receptors

<p>A small library of neutral peptide-based anion receptors was synthesised, where changes were made to the scaffold structure to investigate the effect these structural features have on the anion binding ability of these receptors. These changes included shortening the peptide side chain lengths, increasing the number of electron withdrawing substituents present on the squaramide phenyl substituents and increasing the length and flexibility of the peptide backbone. An effort was also made to increase the aqueous solubility of these receptors by functionalising the <i>N</i>-terminus of the peptide with a hydrophilic moiety. All the receptors displayed strong affinity and selectivity for sulfate in 20% <i>v</i>/<i>v</i> H₂O/DMSO-<i>d</i>₆ and a 5-fold increase in the affinity of the thiourea receptors was observed upon shortening the side chains by one methylene unit. Overall, the squaramide derivatives displayed much stronger association, in this competitive media, than the thiourea based receptors.</p

Total Synthesis and Reassignment of the Structures of the Antimicrobial Lipodepsipeptides Circulocin γ and δ

The structures of the naturally occurring antimicrobial lipodepsipeptides circulocin γ and circulocin δ have been reported to comprise a common cyclic depsipeptide core attached to 3-hydroxy,ω-guanidino fatty acid chains differing in length by two methylene units, but analysis of the reported data suggested that the originally reported structures had incorrect side chain lengths. The total synthesis of both side chain epimers of the originally reported structure of circulocin γ bearing a 19-guanidino-3-hydroxynonadecanoyl (GHND) side chain has been accomplished using a modular approach involving synthesis of the cyclic depsipeptide and side chain fragments followed by a late stage coupling reaction. This revealed that the originally reported structure for circulocin γ bearing the GHND side chain is incorrect and that this structure is actually that of circulocin δ. It has also enabled the absolute configuration of the side chain hydroxy group of the natural product to be assigned as (<i>R</i>). Subsequent synthesis of the analogue bearing a 17-guanidino-3-(<i>R</i>)-hydroxyheptadecanoyl (GHHD) side chain provided confirmation that this revised structure is that of circulocin γ

Selective Sorption of Actinides by Titania Nanoparticles Covalently Functionalized with Simple Organic Ligands

Although current and proposed reprocessing of used nuclear fuel is performed predominantly by solvent extraction processes, solid phase sorbent materials have many advantages including the ability to avoid production of large volumes of organic waste. Therefore, three titania nanoparticle based sorbent materials have been developed, functionalized with organic ligands designed to impart selectivity for elements relevant to important separations at the back end of the nuclear fuel cycle. A novel, simplified method of covalent functionalization to the titania surface has been utilized, and the resulting materials have been shown to be hydrolytically stable at pH 2. The sorption behavior of these organofunctionalized titania materials was investigated over a wide pH range with a selection of elements including fission products and actinides. Titania nanoparticles functionalized with an amine or phosphate moiety were able to demonstrate exclusive extraction of uranium under optimized conditions. Titania nanoparticles functionalized with a picolinamide moiety exhibited superior minor actinide sorption properties, in terms of both efficiency and selectivity, to solvent extraction processes using similar organic moieties. As such, organo-functionalized titania materials as solid phase sorbents show promise as a future alternative to solvent extraction processes for nuclear separations

Colorimetric and Luminescent Sensors for Chloride: Hydrogen Bonding vs Deprotonation

The synthesis and photophysical properties of four squaramide based fluorescent anion sensors (<b>1</b>–<b>4</b>) are described. These luminescent compounds showed selectivity for Cl^– over various other anions with concomitant changes in both their UV/visible and fluorescence properties upon Cl^– addition, attributed to initial H-bonding followed by NH deprotonation in the presence of excess Cl^–, signaled by a color change. The nature of the electron withdrawing aryl substituents is directly related to the H-bonding ability/acidity of the squaramide protons and can be used to tune the deprotonation behavior

pH-Responsive, Amphiphilic Core–Shell Supramolecular Polymer Brushes from Cyclic Peptide–Polymer Conjugates

The synthesis and self-assembly of pH-responsive, amphiphilic cyclic peptide–polymer conjugates are described. The design relies on the introduction of a poly­(2-(diisopropylamino)­ethyl methacrylate) (pDPA) block between the cyclic peptide and a hydrophilic block. These conjugates are disassembled and protonated at low pH but assemble into core–shell nanotubes at physiological pH, as determined by a combination of titration experiments and scattering techniques

Triazole–containing zinc(II)dipicolylamine-functionalised peptides as highly selective pyrophosphate sensors in physiological media

<p>A small family of linear bis[zinc(II)dipicolylamine] (bis[Zn(II)-DPA])-functionalised peptidic anion receptors has been prepared where the Zn(II)-DPA binding sites have been installed via either a reductive amination reaction or a copper(I)-catalysed azide-alkyne cycloaddition reaction. The latter reaction connects the Zn(II)-DPA binding site and the peptide backbone through a 1,2,3-triazole linkage. Subsequent anion binding studies using indicator displacement assays were conducted to elucidate the effect of the triazole linker on the anion-binding properties of these novel receptors and it was found that the triazole-containing receptors exhibited stronger affinity and slightly improved selectivity for pyrophosphate over adenosine triphosphate and adenosine diphosphate compared to the analogous receptors which did not bear the triazole linker.</p

Thermal Gating in Lipid Membranes Using Thermoresponsive Cyclic Peptide–Polymer Conjugates

The partition and self-assembly of a new generation of cyclic peptide–polymer conjugates into well-defined phospholipid trans-bilayer channels is presented. By varying the structural parameters of the cyclic peptide–polymer conjugates through the ligation of hydrophobic and hydrophilic polymers, both the structure of the artificial channels using large unilamellar vesicle assays and the structural parameters required for phospholipid bilayer partitioning are elucidated. In addition, temperature was used as an external stimulus for the modulation of transbilayer channel formation without requiring the redesign and synthesis of the cyclic peptide core. The thermoresponsive character of the cyclic peptide–polymer conjugates lays the foundation for on-demand control over phospholipid transmembrane transport, which could lead to viable alternatives to current transport systems that traditionally rely on endocytic pathways