Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/49121

TitleBinuclear DOTA-based Gd(III) chelates: revisiting a straightforward strategy for relaxivity improvement
Author(s)Fontes, André
Karimi, Shima
Helm, Lothar
Yulikovc, Maxim
Ferreira, Paula M. T.
André, João P.
KeywordsDOTA
Gadolinium
Binuclear
DO3A
MRI
Contrast agents
Chelates
Imaging agents
Macrocycles
Dinuclear complexes
Issue dateMar-2015
PublisherWiley
JournalEuropean Journal of Inorganic Chemistry
Abstract(s)The need for MRI contrast agents with improved relaxivity maintains the development of new Gd(III) chelates an intensive and demanding field of research. In this work we introduce the new dimeric chelators bis(DOTA-AHA)adipate and bis(DOTA-AHA)1,3-phenyldiacetate (L2 = bis(1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid)adipate and L3 = bis(1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid)1,3-phenyldiacetate, respectively), based on the bifunctional ligand DOTA-AHA (L1 = 1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid). Their Gd(III) chelates were studied by variable temperature 1H NMRD and 17O NMR spectroscopy in order to measure the relaxivity and the parameters that govern it. The exchange of inner-sphere water from the monomer GdL1 and from the two binuclear chelates Gd2L2 and Gd2L3 is very similar (298kex ≈ 6.5 x106 s-1) and slightly faster than on [Gd(DOTA)H2O]- (298kex = 4.1 x 106 s-1). All three compounds form weakly bound aggregates with equilibrium constants 298K of 2.9, 15.6 and 14.6 for GdL1, Gd2L2 and Gd2L3, respectively. Even if the aggregates contain only 10 to 15% of the total amount of Gd(III) ions a marked increase in relaxivity between 30 and 100 MHz is observed. Furthermore the distance between the two Gd(III) centers in the binuclear compounds has been determined by double electron-electron resonance (DEER) experiments and by molecular modelling studies affording comparable distances. The linkers between the chelating moieties allow Gd(III)-Gd(III) distances of circa 3.0 nm for completely stretched linker conformation and ≤ 1.9 nm for the conformation with the metal centers at closer distance. These metal to metal distances by themselves cannot explain the considerably long tumbling times of chelates in solution. Only a model consistent with some level of aggregation for the binuclear chelates in aqueous solution could satisfactorily explain our results.
TypeArticle
URIhttp://hdl.handle.net/1822/49121
DOI10.1002/ejic.201403159
ISSN1434-1948
Peer-Reviewedyes
AccessOpen access
Appears in Collections:CDQuim - Artigos (Papers)

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