The pyrene nucleus is a valuable component for materials, supramolecular and biological chemistry, due to its photophysical/electronic properties and extended rigid structure. However, its exploitation is hindered by the limited range of methods and outcomes for the direct substitution of pyrene itself. In response to this problem, a variety of indirect methods have been developed for preparing pyrenes with less usual substitution patterns. Herein we review these approaches, covering methods which involve reduced pyrenes, transannular ring closures and cyclisations of biphenyl intermediates. We also showcase the diverse range of substituted pyrenes which have been reported in the literature, and can serve as building blocks for new molecular architectures.

[structure: see text] We report two methods for the attachment of mono- and disaccharides to one or both of the cyclopentadienyl rings in ferrocene. The first strategy involves the reaction in acidic media of thioglycosides with ferrocenemethanol or 1,1'-ferrocenedimethanol. The second method consists of the regiospecific catalytic cycloaddition of propargyl glycoside and azidomethyl and bis(azidomethyl)ferrocene leading to the 1,2,3-triazole derivatives. The inverse strategy was also explored. The electrochemical behavior of the synthesized ferrocene-containing glycoconjugates was investigated.

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms A threading receptor for polysaccharides Polysaccharides are the dominant organic molecules in the biosphere 1 , and thus key renewable resources 2,3 . However the most abundant, including cellulose and chitin, are generally the most difficult to utilise due to extreme insolubility. At present there is no method for mobilising these materials in water under mild conditions, so that modifications involve chemical transformations in aggressive media [4][5][6] or the slow action of enzymes on undissolved solids 7 . Dissolution in aqueous media at biological pH would allow new paths to exploitation. In particular, the polysaccharides could be exposed to enzymes, either natural or engineered, to which they would be far more vulnerable. The rapid conversion of cellulose to glucose is just one prospective outcome.Here we adumbrate a strategy for the dissolution of cellulose, and related polysaccharides, through the application of synthetic receptors. The approach employs cage molecules with amphiphilic interiors, complementary to the carbohydrate targets. Critically the receptors are able to thread onto the polysaccharides, forming polypseudorotaxanes 8,9 . Because of the threaded topology, many receptor molecules can bind to one polysaccharide chain, surrounding the polymer with hydrophilic groups. If binding is sufficiently strong to counteract crystal packing forces, dissolution should be feasible. We report the design and synthesis of a threading receptor for polysaccharides, and show that it forms pseudorotaxanes with water-soluble oligosaccharides.We also describe evidence for polypseudorotaxane formation from polysaccharides under certain conditions. The results demonstrate the feasibility of polysaccharide threading in water, and could point the way to systems capable of solubilisation.A defining feature of cellulose 1 and chitin 2 (Fig. 1a) is the all-equatorial disposition of intra-chain linkages and polar substituents and (consequently) the axial positioning of apolar CH groups. In the extended conformation of the polymer, this creates two parallel strips of hydrophobic surface separated by lines of hydrogen-bonding functional groups. Our strategy for complementing these supramolecular valencies is illustrated in Fig. 1b. We sought a cage-like receptor structure in which two aromatic surfaces would be held parallel to each other, separated by rigid, polar spacers. The portals of the cage would be large enough to allow threading by the polysaccharide substrates. The aromatic surfaces would be capable of forming hydrophobic and CH-π interactions with axial CH groups in the substrates, while polar groups would hydrogen bond to equatorial substituents.We had previously used a related approach to bind all-equatorial mono-and di-saccharides in water 10-13 .However, these earlier designs e...

Ferrocene with a beta-cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face were conveniently synthesized by regiospecific copper(I)-catalyzed cycloaddition of 2-O-propargyl-beta-cyclodextrin to azidomethyl or bis(azidomethyl)ferrocene. The supramolecular behavior of the synthesized conjugates in both the absence and presence of bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) was studied by using electrochemical methods (cyclic and differential pulse voltammetry), isothermal titration calorimetry, and NMR spectroscopy (PGSE, CPMG, and 2D-ROESY). These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates. It was found that the ferrocenyl conjugate with one beta-cyclodextrin unit forms a redox-controllable head-to-head homodimer in aqueous solution. The ferrocene-bis(beta-cyclodextrin) conjugate is present in two distinguishable forms in aqueous solution, each one having a different half-wave oxidation potential for the oxidation of the ferrocene. By contrast, only one distinguishable form for the oxidized state of the ferrocene-beta-cyclodextrin conjugate is detectable. The redox-sensing abilities of the synthesized conjugates towards the bile salts were evaluated based on the observed guest-induced changes in both the half-wave potential and the current peak intensity of the electroactive moiety.

We report two methods that have allowed the attachment of glucose, mannose and lactose to one or both of the cyclopentadienyl rings of ferrocene. The resulting ferrocene-carbohydrate conjugates were synthesised by the reaction of thioglycosides with ferrocenemethanol and 1,1'-ferrocenedimethanol in acidic media. A second method based on the regiospecific copper(I)-catalysed cycloaddition of propargyl glycoside, azidomethyl and bis(azidomethyl)ferrocene as well as azidoethyl glycoside and ethynylferrocene was also used and led to the synthesis of 1,2,3-triazole-containing glycoconjugates. The electrochemical behaviour of the synthesised glycoconjugates was investigated. In addition, their binding interactions with beta-cyclodextrin were studied by means of NMR spectroscopy, isothermal titration calorimetry, and cyclic and differential pulse voltammetric experiments. These techniques allowed the determination of the thermodynamic parameters of the complexes, the stability constants for the complexes formed with both the neutral and the oxidised states of the ferrocenyl glycoconjugates, the mode of inclusion and the diffusion coefficients for both the glycoconjugates and the complexes.

Three novel gold nanoparticles containing multiple long, flexible linkers decorated with lactose, β-cyclodextrin, and both simultaneously have been prepared. The interaction of such nanoparticles with β-d-galactose-recognizing lectins peanut agglutinin (PNA) and human galectin-3 (Gal-3) was demonstrated by UV-vis studies. Gal-3 is well-known to be overexpressed in several human tumors and can act as a biorecognizable target. This technique also allowed us to estimate their loading capability toward the anticancer drug methotrexate (MTX). Both results make these glyconanoparticles potential site-specific delivery systems for anticancer drugs.

Nanoparticles made of metal-organic frameworks (nanoMOFs) are becoming of increasing interest as drug carriers. However, preventing nanoMOFs recognition and clearance by the innate immune system, a prerequisite for biomedical applications, presents an important challenge. In this study we provide a proof of concept that the outer surface of biocompatible iron-based nanoMOFs can be functionalized in a rapid, organic solvent-free and non-covalent manner using a novel family of comb-like copolymers made of dextran (DEX) grafted with both poly(ethylene glycol) (PEG) and alendronate (ALN) moieties. We describe the synthesis and full characterization of DEX-PEG-ALN copolymers by click chemistry, with control of both the amount of grafted PEG and ALN moieties. The copolymers, freely soluble in aqueous media, were used to directly coat the nanoMOFs in water by simple incubation at room temperature. The coating procedure did not affect the nanoMOFs' morphology nor their crystalline structure. As strong iron complexing groups, the ALN moieties ensured multiple cooperative anchoring of the copolymers to the nanoMOFs surface, resulting in stable coatings that substantially decreased their internalization by macrophages in vitro, providing new perspectives for biomedical applications.

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