title: A simple approach to a new T8-POSS based MRI contrast agent.
abstract: A fast and simple route was developed to synthesize a new T8-silsesquioxane based contrast agent for potential application in Magnetic Resonance Imaging. For this purpose the novel C2-thiol-functionalized T8-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 T8-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 T8-silsesquioxanes functionalized with eight metal complexes. Longitudinal relaxivity measurements of compound 13 (9.5 ± 0.9 mM-1s-1) at 3 T in HEPES buffered cell culture medium (physiological conditions) show a significant enhancement of r1per 1 mM gadolinium in comparison to the clinically applied contrast agent Dotarem™ (3.4 mM-1s-1). In relation to the former reported T8-silsesquioxane based contrast agent Gadoxane G (10.6 mM-1s-1) a similar relaxivity is found. As the T8-core of polyhedral oligosilsesquioxanes (POSS) based contrast agents undergoes a hydrolysis process depending on the pH, long-term r1measurements in different solutions (water, cell culture medium and HEPES buffered medium) as well as1H,1H/29Si HSQC and PGSE diffusion1H NMR spectroscopic investigations on aqueous solutions were performed. In solutions featuring an approximately neutral pH (D2O, pD = 7.0; water and HEPES buffered medium, pH = 7.4-7.5) contrast agent 13 (t1/2= 2.4 d, HEPES/medium) shows a slower decomposition of the T8-cage in comparison to the previously synthesized Gadoxane G (t1/2= 15 ± 3 h, HEPES/medium). However, under more basic conditions (medium, pH = 8.4-8.5) the decomposition process of 13 is considerably accelerated (t1/2∼ 55-60 min), indicating a higher sensitivity of the T8-cage to pH shifts into the basic range similar to Gadoxane G.
authors.affiliation: Institut für Anorganische Chemie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany. hermann.mayer@uni-tuebingen.de.
authors.forename: Helene
authors.initials: H
authors.lastname: Strauch
authors.affiliation: Hochfeld-Magnetresonanz-Zentrum, Max-Planck-Institut für Biologische Kybernetik, Spemannstraße 41, 72076 Tübingen, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Engelmann
authors.affiliation: Hochfeld-Magnetresonanz-Zentrum, Max-Planck-Institut für Biologische Kybernetik, Spemannstraße 41, 72076 Tübingen, Germany and Department of Biomedical Magnetic Resonance, Eberhard Karls Universität Tübingen, Hoppe-Seyler Str. 3, 72076 Tübingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Scheffler
authors.affiliation: Institut für Anorganische Chemie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany. hermann.mayer@uni-tuebingen.de.
authors.forename: Hermann A
authors.initials: HA
authors.lastname: Mayer
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006868:Hydrolysis; D008279:Magnetic Resonance Imaging; D017646:Organosilicon Compounds / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D017646:Organosilicon Compounds; C521417:polyhedraloligosilsesquioxane; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium