N,O-isopropylidenated threonines as tools for peptide cyclization: application to the synthesis of mahafacyclin B

[structure: see text] The influence of a single N,O-isopropylidenated threonine turn-inducer on the cyclization of a linear heptapeptide precursor to mahafacyclin B has been investigated. Incorporation of an N,O-isopropylidenated threonine more than doubles the head-to-tail cyclization yield. The N,O-isopropylidene grouping is then readily disassembled to give the antimalarial cyclic peptide in high yield.     

Synthesis of backbone modified cyclic peptides bearing dipicolylamino sidearms

Three analogues of the Lissoclinum class of cyclic peptides, bearing dipicolylamino functionalised side chains, have been synthesised using a stepwise approach followed by macrocyclisation. Attempts to incorporate dipicolylamino functionalised side chains prior to peptide synthesis resulted in epimerisation, but this was overcome by functionalising the ornithine side chains with dipicolylamino groups after the macrocyclisation reaction.     

Effect of Swirling Desolvation Gas Flow in an Atmospheric Pressure Ion Source

A numerical study is performed to examine the effect of introducing a swirling desolvation gas flow on the flow transport characteristics in an electrospray and an atmospheric pressure chemical ionization (APCI) system. An ion source having three coaxial tubes is considered: (1) an inner capillary tube to inject the liquid sample, (2) a center coaxial tube to provide a room temperature gas flow to nebulize the liquid, referred to as the nebulizing gas flow, and (3) an outer coaxial tube having a converging exit to supply a high temperature gas for droplet desolvation, referred to as the desolvation gas flow. The results show that a swirling desolvation gas flow reduces the dispersion of the nebulizing gas and suppresses turbulent diffusion. The effect of swirling desolvation flow on the trajectory of a range of droplet sizes emitted from a source is also considered. Figure

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Synthetic, structural, electrochemical and solvent extraction studies of neutral trinuclear Co(II), Ni(II), Cu(II) and Zn(II) metallocycles and tetrahedral tetranuclear Fe(III) species incorporating 1,4-aryl-linked bis-beta-diketonato ligands

Uncharged complexes, formulated as trimeric metallocycles of type [M3(L(1))3(Py)6] (where M = cobalt(II), nickel(II) and zinc(II) and L(1) is the doubly deprotonated form of a 1,4-phenylene linked bis-beta-diketone ligand of type 1,4-bis(RC(O)CH2C(O))C6H4 (R = t-Bu)) have been synthesised, adding to related, previously reported complexes of these metals with L(1) (R = Ph) and copper(ii) with L(1) (R = Me, Et, Pr, t-Bu, Ph). New lipophilic ligand derivatives with R = hexyl, octyl or nonyl were also prepared for use in solvent extraction experiments. The X-ray structures of H2L(1) (R = t-Bu) and of its trinuclear (triangular) nickel(II) complex [Ni3(L(1))3(Py)6].3.5Py (R = t-Bu) are also presented. Electrochemical studies of H2L(1), [Co3(L(1))3(Py)6], [Ni3(L(1))3(Py)6], [Cu3(L(1))3], [Zn3(L(1))3(Py)6] and [Fe4(L(1))6] (all with R = t-Bu) show that oxidative processes for the complexes are predominantly irreversible, but several examples of quasireversible behaviour also occur and support the assignment of an anodic process, seen between +1.0 and +1.6 V, as involving metal-centred oxidations. The reduction behaviour for the respective metal complexes is not simple, being irreversible in most cases. Solvent extraction studies (water/chloroform) involving the systematic variation of the metal, bis-beta-diketone and heterocyclic base concentrations have been performed for cobalt(II) and zinc(II) using a radiotracer technique in order to probe the stoichiometries of the respective extracted species. Significant extraction synergism was observed when 4-ethylpyridine was also present with the bis-beta-diketone ligand in the chloroform phase. Competitive extraction studies demonstrated a clear uptake preference for copper(II) over cobalt(II), nickel(II), zinc(II) and cadmium(II).     

Selective recognition of sulfate ions by tripodal cyclic peptides functionalised with (thio)urea binding sites

A tripodal urea and tripodal thiourea with the same cyclic peptide core have been synthesised and their anion binding ability investigated. In CDCl(3), the tripodal urea self-associates whereas the thiourea does not. Neither compound shows self-association in the more polar 10% v/v DMSO-d(6)/CDCl(3). Both compounds bind strongly and selectively to sulfate ions in CDCl(3) and 10% v/v DMSO-d(6)/CDCl(3). This selectivity is attributed to a unique binding mode for sulfate, in which this tetrahedral anion forms nine hydrogen bonds to the receptors, with three of these coming from the amide protons of the cyclic peptide.     

Design and properties of functional nanotubes from the self-assembly of cyclic peptide templates

β-Sheet forming self assembling cyclic peptides offer a versatile scaffold for the construction and control of hydrogen-bonded nanotube assemblies. These structures have major advantages over other nanoscale tubular structures, including sub-nanometer control over the internal diameter, and the ability to control internal and external chemical functionality. This Tutorial Review presents an overview of nanotubes derived from this class of cyclic peptides. The design rationale for functional nanotubes based on cyclic peptide ring size and chemical functionality is discussed. Additionally, we highlight the recent expansion of the nanotube toolbox through conjugation of (macro)molecules to the cyclic peptides. These provide additional functionality and control nanotube dimensions that could potentially prove beneficial in future applications.