Relaxivity Studies on Dinitroxide and Polynitroxyl Functionalized Dendrimers:  Effect of Electron Exchange and Structure on Paramagnetic Relaxation Enhancement

Abstract

The 1 H NMR relaxivity of o-and p-dinitroxide-substituted phthalate esters and a series of nitroxyl-functionalized poly(propylene imine) dendrimers has been measured in acetonitrile and methanol. Studies of dinitroxide relaxivity indicate that the electron exchange rate has only a small effect on relaxivity. Outer-sphere relaxivity has been measured using benzene as a probe molecule. In studies on dendritic polynitroxides, the per-nitroxidebased outer-sphere relaxivity nearly doubles for the generation 5 nitroxyl-functionalized dendrimer as compared to a mononitroxide model. This relaxivity enhancement may be due to crowding of dendrimer surface groups in higher generation dendrimers. Water relaxivity has been measured for these polynitroxides as well, and a significant inner-sphere contribution to relaxivity is found. Dendritic polynitroxides exhibit higher per-nitroxidebased water relaxivity as compared to a mononitroxide model. This relaxivity enhancement is attributed to an increase in rotational correlation time (τ c ) for the dendritic polynitroxides.

Dendritic PARACEST contrast agents for magnetic resonance imaging

“…2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) was purchased from Iris Biotech GmbH (Germany). The first and third generations of amine-terminated poly(propylene imine) dendrimers [DAB-dendr-(NH 2 ) n , n ¼ 4 and 16] were kindly provided by SyMO-Chem (Eindhoven, the Netherlands) (46). Cyclen was obtained from ABCR GmbH (Karlsruhe, Germany).…”

Nitroxide Radicals: Properties, Synthesis and Applications

“…60 Relaxivity studies on dinitroxides and dendritic nitroxide multiradicals (46, Scheme 5.15) have been performed. 61 Dendritic polynitroxides exhibit higher per-nitroxide-based water relaxivity compared to a mononitroxide model. The higher generation polynitroxide dendrimers exhibit relaxivities exceeding those for gadolinium(III) chloride.…”

“…A prefluorescent hydrophobic TEMPO derivative has been used to evaluate local reactivity of phenolic antioxidant in micellar systems 263 (Scheme 5. 61). An apparent rate constant that directly reflects the relevance of antioxidant hydrophobicity on the reaction toward the nitroxide has been defined.…”

Applications of Water‐Soluble Dendrimers

“…An interesting study of potential dendrimer-based MRI contrast agents, that was not based upon the proton relaxation enhancing properties of gadolinium, was carried out by Meijer and co-workers [46]. Proton relaxation studies were carried out on nitroxyl bearing PPI dendrimers (Figure 8.6) and revealed that as a result of an increased rotational correlation time, the dendrimer architecture conferred an enhanced proton relaxation on the nitroxyl moieties when compared to mononitroxyl species.…”

“…The nitroxyl terminated dendrimer proton relaxation enhancement agent for potential use in MRI[46]. A water-soluble functionalised tin-based metallodendrimer developed for applications in X-ray scanning[47].…”