Cyclodextrin polyrotaxanes as a highly modular platform for the development of imaging agents.

Selectively functionalized cyclodextrins with a bodipy fluorescent tag or Gd(3+) complex were synthetized and threaded onto a polyammonium chain to form polyrotaxanes. This modular supramolecular assembly makes an ideal platform for bimodal (fluorescent and MRI) imaging applications.

Size-dependent compression of threaded alkyldiphosphate in head to head cyclodextrin [3]pseudorotaxanes.

The encapsulation of guests in a confined space enables unusual conformations and reactivities. In particular, the compression of akyl chains has been obtained by self-assembled molecular capsules but such an effect has not been reported in solution for pseudorotaxane architectures. By exploiting the tendency of cyclodextrin (CD) to form head to head [3]pseudorotaxanes and the hydrogen bonding abilities of phosphate groups, we have studied the effect of the CD dimer cavity on the conformation of threaded α,ω-alkyl-diphosphate axles. The formation of [2]pseudorotaxanes and [3]pseudorotaxanes was investigated by a combination of NMR, ITC and X-ray diffraction techniques. In the solid state, the [3]pseudorotaxane with a C8 axle presents a fully extended conformation with both terminal phosphate groups interacting with hydroxyl groups of the primary rim of CDs. Such hydrogen bonding interactions are also present with the C9 and C10 axles resulting in a compression of the alkyl chain with gauche conformations in the solid state. NMR studies have shown that this effect is maintained in solution resulting in a size-dependent progressive compression of the alkyl chain by the CD [3]pseudorotaxane architecture for C9, C10 and C11 axles.

Precise Rate Control of Pseudorotaxane Dethreading by pH-Responsive Selectively Functionalized Cyclodextrins.

A family of cyclodextrins functionalized with zero, one, two, or six amines was shown to control the rate of their threading and dethreading on a molecular axle depending on the pH and their substitution pattern. The originality of this system lies in the rate control of the switch by operating the stimulus directly on the macrocycle.

Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents.

A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]rotaxanes using copper-catalyzed azide-alkyne cycloaddition has been developed. Head-to-head [3]rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent.