TY - JOUR
T1 - Towards the rational design of MRI contrast agents
T2 - δ-Substitution of lanthanide(III) NB-DOTA-tetraamide chelates influences but does not control coordination geometry
AU - Carney, Christiane E.
AU - Tran, Anh D.
AU - Wang, Jing
AU - Schabel, Matthias C.
AU - Sherry, A. Dean
AU - Woods, Mark
PY - 2011/9/5
Y1 - 2011/9/5
N2 - LnDOTA-tetraamide chelates (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) have received considerable recent attention as a result of their potential to act as PARACEST contrast agents for magnetic resonance imaging (MRI). Although PARACEST agents afford several advantages over conventional contrast agents they suffer from substantially higher detection limits; thus, improving the effectiveness of LnDOTA-tetraamide chelates is an important goal. In this study we investigate the potential to extend conformational control of LnDOTA-type ligands to those applicable to PARACEST. Furthermore, the question of whether δ- rather than α-substitution of the pendant arms could be used to control the chelate coordination geometry is addressed. Although δ-substitution does influence coordination geometry it does not afford control. However, it can play an important role in governing the conformation of the amide substituent relative to the chelate in such as way that suggests a PARACEST agent could be designed that has detection limits at least as low as a conventional MRI contrast agent.
AB - LnDOTA-tetraamide chelates (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) have received considerable recent attention as a result of their potential to act as PARACEST contrast agents for magnetic resonance imaging (MRI). Although PARACEST agents afford several advantages over conventional contrast agents they suffer from substantially higher detection limits; thus, improving the effectiveness of LnDOTA-tetraamide chelates is an important goal. In this study we investigate the potential to extend conformational control of LnDOTA-type ligands to those applicable to PARACEST. Furthermore, the question of whether δ- rather than α-substitution of the pendant arms could be used to control the chelate coordination geometry is addressed. Although δ-substitution does influence coordination geometry it does not afford control. However, it can play an important role in governing the conformation of the amide substituent relative to the chelate in such as way that suggests a PARACEST agent could be designed that has detection limits at least as low as a conventional MRI contrast agent.
KW - PARACEST agents
KW - conformational control
KW - coordination modes
KW - lanthanides
KW - water exchange
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U2 - 10.1002/chem.201101007
DO - 10.1002/chem.201101007
M3 - Article
C2 - 21837722
AN - SCOPUS:80052250106
SN - 0947-6539
VL - 17
SP - 10372
EP - 10378
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 37
ER -