Synthesis of Poly(Methyl Methacrylate)-Based Polyrotaxane via Reversible Addition-Fragmentation Chain Transfer Polymerization.

A polyrotaxane (PR) with poly(methyl methacrylate) (PMMA) as the main chain polymer was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Because of the special mechanism of RAFT, the suprastructure of a PMMA-based PR is established by synthesizing inclusion complexes of methyl methacrylate and gamma-cyclodextrin (γCD) into the middle of the poly-N-(3-dimethylamino) propyl methacrylamide segments. The presence of threaded γCD was determined via diffusion ordered spectroscopy from the alignment of the mobility of γCD and the main chain polymer.

Synthesis and in vitro evaluation of cyclodextrin hyaluronic acid conjugates as a new candidate for intestinal drug carrier for steroid hormones.

Steroid hormones became increasingly interesting as active pharmaceutical ingredients for the treatment of endocrine disorders. However, medical applications of many steroidal drugs are inhibited by their very low aqueous solubilities giving rise to low bioavailabilities. Therefore, the prioritized oral administration of steroidal drugs remains problematic.

Reversible immobilization of a protein to a gold surface through multiple host-guest interactions.

Monolayers were formed by specific interactions between adamantylated proteins (transferrin, lysozyme) and a β-cyclodextrin (β-CD) monolayer on a gold surface. Very high stabilities could be reached by multiple interactions of 3-6 adamantyl moieties linked through triethylene glycol spacers to the protein with β-CD rings attached to the surface. Furthermore, bound proteins could be completely removed from the surface through competitive binding of an excess of free adamantane.

Synthesis of the Anionic Hydroxypropyl-β-cyclodextrin:Poly(decamethylenephosphate) Polyrotaxane and Evaluation of its Cholesterol Efflux Potential in Niemann-Pick C1 Cells.

Niemann-Pick type C disease (NPC) is a lysosomal storage disease that is characterized by a progressive accumulation of unesterified cholesterol in the lysosomes leading to organ damage from cell dysfunction. Hydroxypropyl-β-cyclodextrin (HP-β-CD) is an attractive drug candidate for treating NPC, as it diminishes cholesterol accumulation in NPC cells. Systemic HP-β-CD treatment, however, is limited by rapid renal clearance.

Molecular kinetics and cooperative effects in friction and adhesion of fast reversible bonds.

Molecular mechanisms of adhesion and friction include the rupture of single and multiple bonds. The strength of adhesion and friction thus depends on the molecular kinetics and cooperative effects in the lifetime of bonds under stress. We measured the rate dependence of friction and adhesion mediated by supramolecular guest-host bonds using atomic force microscopy (AFM).

Hyperaging Tuning of a Carbon Molecular-Sieve Hollow Fiber Membrane with Extraordinary Gas-Separation Performance and Stability.

This study reports 6FDA:BPDA-DAM polyimide-derived hollow fiber carbon molecular-sieve (CMS) membranes for hydrogen and ethylene separation. Since H /C H selectivity is the lowest among H /(C -C ) hydrocarbons, an optimized CMS fiber for this gas pair is useful for removing hydrogen from all-cracked gas mixtures. A process we term hyperaging provides highly selective CMS fiber membranes by tuning CMS ultramicropores to favor H over larger molecules to give a H /C H selectivity of over 250.

One-pot synthesis of block-copolyrotaxanes through controlled -polymerization.

The aqueous reversible addition fragmentation chain-transfer (RAFT) copolymerization of isoprene and bulky comonomers, an acrylate and an acrylamide in the presence of methylated β-cyclodextrin was employed for the first time to synthesize block-copolyrotaxanes. RAFT polymerizations started from a symmetrical bifunctional trithiocarbonate and gave rise to triblock-copolymers where the outer polyacrylate/polyacrylamide blocks act as stoppers for the cyclodextrin rings threaded onto the inner polyisoprene block. Statistical copolyrotaxanes were synthesized by RAFT polymerization as well.

Solubilizing steroidal drugs by β-cyclodextrin derivatives.

Administration of steroidal drugs is hampered by their very low solubilities in water. β-Cyclodextrin and β-cyclodextrin derivatives can solubilize steroids and improve bio-availability of these hydrophobic APIs. A systematic overview of the achievable solubility enhancements of various steroids, testosterone, estradiol, progesterone, hydrocortisone, prednisone, dexamethasone, and finasteride, is provided.

Interactions between shape-persistent macromolecules as probed by AFM.

Water-soluble shape-persistent cyclodextrin (CD) polymers with amino-functionalized end groups were prepared starting from diacetylene-modified cyclodextrin monomers by a combined Glaser coupling/click chemistry approach. Structural perfection of the neutral CD polymers and inclusion complex formation with ditopic and monotopic guest molecules were proven by MALDI-TOF and UV-vis measurements. Small-angle neutron and X-ray (SANS/SAXS) scattering experiments confirm the stiffness of the polymer chains with an apparent contour length of about 130 Å.

Single-molecule force spectroscopy of fast reversible bonds.

In single-molecule force spectroscopy, the unbinding force is often used to quantify the interaction strength of single molecular bonds. We analyze force spectroscopy of fast reversible bonds probed in thermodynamic equilibrium by considering the dynamics of force probe and molecular linker. The effect of cantilever and linker dynamics is systematically addressed by measuring the unbinding force of single cyclodextrin inclusion complexes by atomic force spectroscopy for a variety of molecular linkers and varying force probe stiffness.

One Pot Synthesis of a Polyisoprene Polyrotaxane and Conversion to a Slide-Ring Gel.

Synthesis of a cyclodextrin (CD) polyrotaxane is achieved for the first time by simultaneous free radical polymerization of isoprene, threading by CD, and stoppering by copolymerization of styrene. This reaction is performed in an eco-friendly manner in an aqueous medium similar to classical emulsion polymerization. Threaded CD rings of the polyrotaxane are cross-linked by hexamethylene diisocyanate, leading to highly elastic slide-ring gels.

Friction mediated by redox-active supramolecular connector molecules.

We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules.

Site-specific conjugation of 8-ethynyl-BODIPY to a protein by [2 + 3] cycloaddition.

We report a straightforward synthesis of 8-ethynyl-BODIPY derivatives and their potential as fluorescent labeling compounds using an alkyne-azide click chemistry approach. The ethynyl substituted BODIPY dyes at the meso-position were reacted under Cu(+) catalysis and mild physiological conditions in organic and biological model systems using benzyl azide and a Barstar protein which was selectively modified by a single amino acid substituted methionine at the N-terminus (Met1) → azidohomoalanine (Aha). Conjugation with the protein and the model azide was indicated by a significant blue shift upon formation of the triazole moiety system, which allowed easy distinction between free and coupled dyes.

Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane.

Ideal cationic polymers for siRNA delivery could result in its enhanced cellular internalization, escape from endosomal degradation, and rapid release in cell cytoplasm, to facilitate knockdown of the target gene. In this study, we have investigated the ability of an in-house synthesized cationic polyrotaxane to bind siRNA into nanometric complexes. This polymer, which had earlier shown improved transfection of model siRNA (luciferase), was used to improve the cellular internalization of the siRNA molecule with therapeutic implications.

Dynamic effects in friction and adhesion through cooperative rupture and formation of supramolecular bonds.

We introduce a molecular toolkit for studying the dynamics in friction and adhesion from the single molecule level to effects of multivalency. As experimental model system we use supramolecular bonds established by the inclusion of ditopic adamantane connector molecules into two surface-bound cyclodextrin molecules, attached to a tip of an atomic force microscope (AFM) and to a flat silicon surface. The rupture force of a single bond does not depend on the pulling rate, indicating that the fast complexation kinetics of adamantane and cyclodextrin are probed in thermal equilibrium.

Cyclodextrin-based star polymers as a versatile platform for nanochemotherapeutics: Enhanced entrapment and uptake of idarubicin.

A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives.

The mono-6-deoxy-6-azides of 2,6-di-O-methyl-β-cyclodextrin (DIMEB) and randomly methylated-β-cyclodextrin (RAMEB) were conjugated to propargylated hydroxyethyl starch (HES) by Cu(+)-catalysed [2 + 3] cycloaddition. The resulting water soluble polymers showed lower critical solution temperatures (LCST) at 52.5 °C (DIMEB-HES) and 84.

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs.

Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials towards the anaesthetic drugs sevoflurane and halothane.

Switching adhesion and friction by light using photosensitive guest-host interactions.

Friction and adhesion between two β-cyclodextrin functionalized surfaces can be switched reversibly by external light stimuli. The interaction between the cyclodextrin molecules attached to the tip of an atomic force microscope and a silicon wafer surface is mediated by complexation of ditopic azobenzene guest molecules. At the single molecule level, the rupture force of an individual complex is 61 ± 10 pN.

Polyester-idarubicin nanoparticles and a polymer-photosensitizer complex as potential drug formulations for cell-mediated drug delivery.

Cell-mediated transport of therapeutics has emerged as promising alternative to classical drug delivery approaches. To preserve viability and functions of carrier cells, encapsulation of active drugs in protective nanoparticles or the use of inducible therapeutics has been proposed. Here, we compared the effects of novel polymeric formulations of an active and a stimulus-sensitive anti-cancer drug on human T lymphocytes to identify suitable drug preparations for cell-mediated drug delivery.

Topochemical control of the photodimerization of aromatic compounds by γ-cyclodextrin thioethers in aqueous solution.

The formation of soluble 1:2 complexes within hydrophilic γ-cyclodextrin (γ-CD) thioethers allows to perform photodimerizations of aromatic guests under controlled, homogenous reaction conditions. The quantum yields for unsubstituted anthracene, acenaphthylene, and coumarin complexed in these γ-CD thioethers were found to be up to 10 times higher than in the non-complexed state. The configuration of the photoproduct reflected the configuration of the dimeric inclusion complex of the guest.

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests.

The inclusion of volatile derivatives of benzene and cyclohexane in β-cyclodextrin (β-CD), hydroxypropyl-β-CD, and hydrophilic β-CD-thioethers was investigated by static headspace gas chromatography (HS-GC) and molecular modelling. The obtained binding constants strongly increase with the amount of space filling of the CD cavity and the salt concentration. β-CD thioethers show a 3-10 times higher binding potential than native β-CD.