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Towards the rational design of MRI contrast agents: ?-substitution of lanthanide(III) NB-DOTA-tetraamide chelates influences but does not control coordination geometry.

ABSTRACT: 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 ?- rather than ?-substitution of the pendant arms could be used to control the chelate coordination geometry is addressed. Although ?-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.

SUBMITTER: Carney CE

PROVIDER: S-EPMC3226831 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Towards the rational design of MRI contrast agents: δ-substitution of lanthanide(III) NB-DOTA-tetraamide chelates influences but does not control coordination geometry.

Carney Christiane E CE Tran Anh D AD Wang Jing J Schabel Matthias C MC Sherry A Dean AD Woods Mark M

Chemistry (Weinheim an der Bergstrasse, Germany) 20110811 37

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 p ...[more]

PMID: 21837722

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Project description:The coordination geometry adopted by the lanthanide complexes of DOTA-tetraamides is a critical factor in determining their water exchange kinetics. Controlling the water exchange kinetics of DOTA-tetraamide complexes, and by extension their coordination geometry, is of particular interest because of the potential application of this class of complex as PARACEST MRI contrast agents. To facilitate the maximum CEST effect at the lowest pre-saturation powers much slower exchange kinetics are required than are commonly observed with these types of chelates. Complexes that adopt the more slowly exchanging square antiprismatic coordination geometry are therefore preferred; however, the factors that govern which coordination geometry is preferred remain unclear. A series of DOTA-tetraamide complexes with butyl amide substituents in different regioisomeric configurations provides some insight into these factors. The population of each coordination geometry was found to vary substantially depending upon the regiochemistry of the butyl amide substituent. It was observed that the twisted square antiprism coordination geometry, usually favored in complexes with the larger lanthanide ions only, is also increasingly favored for certain DOTA-tetraamide complexes with the smaller lanthanides. This is in marked contrast to simple DOTA-tetraamide complexes such as DOTAM. The effect was more prevalent in complexes formed with more bulky and more electron donating amide butyl substituents. It is also associated with loss of an inner-sphere water molecule from the complexes of later lanthanides that adopt the twisted square antiprismatic geometry. The complexes with sec-butyl substituents are inherently more complicated because of the introduction of a stereochemical center into each pendant arm. Unlike chiral complexes with larger amide substituents there is no "locking" effect of the orientation of the pendant arms in these complexes and up to four diastereoisomeric coordination isomers can be observed.

Dataset Information

Towards the rational design of MRI contrast agents: ?-substitution of lanthanide(III) NB-DOTA-tetraamide chelates influences but does not control coordination geometry.

Publications

Towards the rational design of MRI contrast agents: δ-substitution of lanthanide(III) NB-DOTA-tetraamide chelates influences but does not control coordination geometry.

Similar Datasets

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