Microwave Assisted Rupture of Furoxans to Nitrile Oxides and Intermolecular Capture by Dipolarophiles

3,4-Diaroylfuroxans 1 react with various dipolarophiles 3 under microwave activation to afford the cycloadduct 4 instead of the expected isoxazole 5 in good yields in the absence of solvent.     

Collagen-like peptides and peptide–polymer conjugates in the design of assembled materials

Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs) or collagen-related peptides (CRPs), have thus been widely used to elucidate collagen triple helix structure as well as to produce higher-order structures that mimic natural collagen fibers. This mini-review provides an overview of recent progress on these topics, in three broad topical areas. The first focuses on reported developments in deciphering the chemical basis for collagen triple helix stabilization, which we review not with the intent of describing the basic structure and biological function of collagen, but to summarize different pathways for designing collagen-like peptides with high thermostability. Various approaches for producing higher-order structures via CLP self-assembly, via various types of intermolecular interaction, are then discussed. Finally, recent developments in a new area, the production of polymer–CLP bioconjugates, are summarized. Biological applications of collagen contained hydrogels are also included in this section. The topics may serve as a guide for the design of collagen-like peptides and their bioconjugates for targeted application in the biomedical arena.     

Collagen and collagen mimetic peptide conjugates in polymer science

Collagen, the most abundant protein in animal kingdom, has attracted scientists in supramolecular chemistry, biomedical and materials science. This review describes the recent developments and progress of collagen mimetic peptide based materials. Research on collagen mimetic peptides was initially developed by biochemists to elucidate the structure and stability of collagen, followed by biologists and polymer chemists to produce nanostructured fibrous scaffolds with collagen mimetic peptides as the building blocks. Modern synthesis methods have been developed and particular ligation chemistries basing on activated ester, click chemistry, carbodiimide chemistry or other ligation chemistries provide versatile methods to prepare collagen–polymer conjugates. These conjugates with collagen mimetic peptides as the building blocks show exciting stimuli responsive or spontaneously assembly behavior. The corresponding synthetic techniques of well-defined collagen architectures and assembly behaviors are discussed in detail in the present review.     

Hydrogen-bonding interactions in ferrocene-peptide conjugates containing valine

The synthesis and characterization of a series of ferrocene (Fc) peptide conjugates containing the amino acid valine is reported, where the peptide substituents are part of the hydrophobic sequence of the amyloid β-peptide. The hydrogen-bonding (H-bonding) interaction in these compounds is studied by variable temperature ¹H NMR spectroscopy. The solid-state structures, determined by single crystal X-ray crystallography, of two of the conjugates (Fc[CO-Leu-Val-OMe]₂1 and Fc[CO-Gly-Val-OH]₂6) are reported. Both structures are stabilized by intramolecular H-bonds exhibiting the familiar “Herrick motif” involving the proximal amide NH and the amide CO of the adjacent amino acid. This motif is sufficiently rigid and is maintained in solution as suggested by CD studies. However, the intermolecular H-bonding patterns observed on conjugates 1 and 6 are significantly different resulting in very different supramolecular architectures. For conjugate 1, a more conventional set of head-to-tail stacking interactions which is stabilized by β-sheet-like H-bonding interactions between the individual molecules is observed. However, for conjugate 6, the presence of the C-terminal acid group and presumably the flexibility of the Gly linker enables the formation of a more open structure that contains hydrophobic channels occupied by solvent molecules.     

Synthesis of coumarin-nucleoside conjugates via Huisgen 1,3-dipolar cycloaddition

An efficient synthesis of fluorescent coumarin-nucleoside conjugates via Cu(I) catalysed Huisgen 1,3-dipolar cycloaddition is described. Starting from azidonucleosides and coumarin derivatives, products are obtained in good yields. The fluorescent properties of the newly prepared coumarin-nucleoside conjugates are determined.     

A Tamao–Fleming oxidation route to dipeptides bearing N,O-acetal functionality

Tamao–Fleming oxidation of the N-dimethylphenylsilylmethyl group linked to the nitrogen of a peptide bond enables access to dipeptide N,O-acetal functionality. The N-silylmethyl functionality serves as a latent form of the N,O-acetal which is revealed after peptide bond construction.     

Ferrocenoyl-amino acids: redox response towards di- and trivalent metal ions

The interaction of six ferrocene-amino acid conjugates (Fc-CO-Gly-OH (2a), Fc-CO-Asp-OH (3a), Fc-CO-Glu-OH (4a), 1,1′-Fc(CO-Gly-OH) (2b), 1,1′-Fc(CO-Asp-OH) (3b), and 1,1′-Fc(CO-Glu-OH) (4b)) with Mg²⁺, Ca²⁺, Zn²⁺, La³⁺, and Tb³⁺ was investigated in aqueous solutions using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Addition of metal ions to solutions caused, in some cases, large changes in the half-wave potential, E_1/2. Our electrochemical results show that the Gly systems, 2a and 2b, show a preference for binding Mg²⁺, whereas the Asp and Glu conjugates prefer binding Ln³⁺.     

Microgravimetric flow analysis of nucleic acid based on adsorption of nanoparticle-bioconjugate

A novel nanoparticle-bioconjugate has been prepared by specific hybridization of the target with complementary thiol-labeled and nanoparticle-labeled probes. The rapid adsorption of the nanoparticle-bioconjugate onto a gold surface via a thiol-gold reaction was monitored in real-time using a quartz crystal microbalance, and used to perform microgravimetric flow analysis of nucleic acid for the first time. This innovative assay is highly reproducible and sensitive, and shows great promise for clinical applications.     

pH-labile sheddable block copolymers by RAFT polymerization: Synthesis and potential use as siRNA conjugates

Well-defined amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks linked through an acid-labile acetal bond were synthesized directly by RAFT polymerization using a new poly(ethylene glycol) (PEG) macroRAFT agent modified with an acid-labile group at its R-terminal. The new macroRAFT agent was used for polymerization of poly(t-butyl methacrylate) (PtBMA) or poly(cholesterol-methacrylate) (PCMA) to synthesize well-defined block copolymers with a PEG block sheddable under acidic conditions. The chain extension polymerization kinetics showed known traits of RAFT polymerization. The molecular weight distributions of the copolymers prepared using the new macroRAFT agent remained below 1.2 during the polymerizations and the molecular weight of the copolymers was linearly proportional to monomer conversions. The acid-catalyzed hydrolysis behavior of the PEG-macroRAFT agent and the PEG-b-PtBMA (Mn = 13,600 by GPC, PDI = 1.10) was studied by GPC, ¹H NMR and UV–vis spectroscopy. The half-life of acid-hydrolysis was 70 min at pH 2.2 and 92 h at pH 4.0. The potential use of the pH-labile shedding behavior of the copolymers was demonstrated by conjugating a thiol-modified siRNA to ω-pyridyldisulfide modified PEG-b-PCMA. The resultant PEG-b-PCMA-b-siRNA triblock modular polymer released PCMA-b-siRNA segment in acidic and siRNA segment in reductive conditions, as confirmed by polyacrylamide gel electrophoresis.     

A Practical Manufacturing Synthesis of 1-(R)-Hydroxymethyl-Dtpa: An Important Intermediate in the Synthesis of MRI Contrast Agents

An efficient synthesis of alcohol 2 is described from L-Serine (OMe) in four synthetic steps. The process uses readily available reagents and is suitable for manufacturing.