Effect of the second coordination sphere on new contrast agents based on cyclodextrin scaffolds for MRI signals

Abstract

International audienceTwo new imaging tools using polydentate cyclodextrins were obtained using an innovative synthetic strategy. For the first time the influence of hydrogen bonding interactions of the cyclodextrin free rim was studied by MRI. The pos. second coordination sphere effect was then quantified

Anionic cyclodextrins as versatile hosts for pharmaceutical nanotechnology: Synthesis, drug delivery, enantioselectivity, contrast agents for MRI

“…As it has been mentioned before, poly-carboxylated CDs display metal ion binding properties (Idriss et al, 2013;Trotta et al, 2001), which are very important for development of materials and methods for biomedical and environmental applications. Thus anionic CDs bearing randomly substituted carboxymethyl groups (CM-β-CD) have been used as remediation agents to remove metal cation pollutants from mixed-contaminated soils, e.g.…”

“…The carboxymethylated β-CD (4) (Scheme 2) was only recently obtained from heptakis(2,3-di-O-allyl-6-t-butyldimethylsilyl)-β-CD in a rather involved synthetic sequence and together with 3b were studied as MRI contrast agents (vide infra 5.2) (Idriss et al, 2013).…”

Positive variation of the MRI signal via intramolecular inclusion complexation of a C-2 functionalized β-cyclodextrin

“…All these factors make the secondary side less reactive and harder to selectively functionalize than the primary face. 9 After saponification of 3, the contrast agent 3(Gd) was obtained by addition of gadolinium chloride hexahydrate. 26 Without any protection step, a designed spacer arm 6 † was regioselectively introduced into the native cyclodextrin in 18% yield using sodium hydride in DMSO (Scheme 1).…”

“…3 The higher molecular weight of the contrast agent so formed exerts a positive effect on the MRI signal by decreasing the rotation rate in water. 9 The cyclodextrins' host properties were also exploited to modify the MRI signal by inclusion of organic molecules inside their internal cone in aqueous medium. These properties were used to develop new MRI probes 4 based on polyrotaxanes 5 or nanoparticules.…”

“…9 Since gadolinium is noncoordinated, two water molecules fill the inner sphere. 9 Since gadolinium is noncoordinated, two water molecules fill the inner sphere.…”