Published In

Inorganic Chemistry

Document Type

Post-Print

Publication Date

2009

Subjects

Lanthanide shift reagents, Ligands (Biochemistry), Contrast media (Diagnostic imaging), Magnetic resonance imaging, Isomerism

Abstract

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.

Description

This is the author’s version of a work that was accepted for publication in Inorganic Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Inorganic Chemistry, 2009 Nov 2;48(21):10338-45. doi: 10.1021/ic9017008.

Locate the Document

https://doi.org/10.1021/ic9017008

DOI

10.1021/ic9017008

Persistent Identifier

https://archives.pdx.edu/ds/psu/32396

NIHMS150638-supplement-1_si_001.pdf (126 kB)
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