A simple approach to a new T 8 -POSS based MRI contrast agent

A fast and simple route was developed to synthesize a new T -silsesquioxane based contrast agent for potential application in Magnetic Resonance Imaging. For this purpose the novel C -thiol-functionalized T -silsesquioxane (3) was constructed as a carrier molecule as well as the DOTA based gadolinium(iii) complex (11) equipped with allyl terminated linkers was prepared. The linkage of the complexes to the T -silsesquioxane was performed via an UV-light catalyzed thiol-ene click reaction within one hour which affords the desired product 13 in a yield of 80%. The successful transformation as well as the intactness of the cube was confirmed by spectroscopic methods and mass spectrometry. This new and simple approach offers a highly effective access to T -silsesquioxanes functionalized with eight metal complexes. Longitudinal relaxivity measurements of compound 13 (9.5 ± 0.9 mM s ) at 3 T in HEPES buffered cell culture medium (physiological conditions) show a significant enhancement of r per 1 mM gadolinium in comparison to the clinically applied contrast agent Dotarem™ (3.4 mM s ). In relation to the former reported T -silsesquioxane based contrast agent Gadoxane G (10.6 mM s ) a similar relaxivity is found. As the T -core of polyhedral oligosilsesquioxanes (POSS) based contrast agents undergoes a hydrolysis process depending on the pH, long-term r measurements in different solutions (water, cell culture medium and HEPES buffered medium) as well as H, H/ Si HSQC and PGSE diffusion H NMR spectroscopic investigations on aqueous solutions were performed. In solutions featuring an approximately neutral pH (D O, pD = 7.0; water and HEPES buffered medium, pH = 7.4-7.5) contrast agent 13 (t = 2.4 d, HEPES/medium) shows a slower decomposition of the T -cage in comparison to the previously synthesized Gadoxane G (t = 15 ± 3 h, HEPES/medium). However, under more basic conditions (medium, pH = 8.4-8.5) the decomposition process of 13 is considerably accelerated (t ∼ 55-60 min), indicating a higher sensitivity of the T -cage to pH shifts into the basic range similar to Gadoxane G.