Engineering lanthanide complexes with controlled water exchange rates for magnetic resonance imaging
The control of the rate of water exchange in lanthanide complexes is critical to their future development as contrast agents in magnetic resonance imaging. In traditional T/sub 1/ shortening agents an optimal water residence lifetime (/spl tau//sub M/) of around 25 ns is required if the highest relaxivities are to be achieved. In contrast the newer PARACEST agents require that water exchange is much slower with /spl tau//sub M/ on the order of microseconds. It is now possible to rationally design complexes that exhibit water exchange rates that are ideal for their intended use. The selection of appropriate ligating groups allow a broad control mechanism. Anionic ligating groups such as carboxylates favour faster exchange whereas neutral ligands such as amides favour slower exchange. By altering the steric hindrance around the water coordination site water exchange rates can be fine tuned. The steric hindrance can be altered by controlling the coordination environment of the lanthanide ion and optimal water exchanges rates so achieved.
Struktur und Dynamik von Lanthanoid-Tetraazacyclododecantetraacetat-(DOTA-)Komplexen in Lösung
Structure and Dynamics of Lanthanoid Tetraazacyclododecanetetraacetate DOTA Complexes in Solution 
 
 
 
In aqueous solution lanthanoid DOTA complexes exist as a mixture of two stereoisomers, and their structures have been determined from the dipolar parts of the observed 1H-NMR chemical shifts for EuDOTA and YbDOTA. The relative concentration of the δ(δδδδ) isomer decreases with decreasing ionic radius. For EuDOTA a 1:4 mixture is observed, and the main isomer has a δ(λλλλ) structure which is also found in the solid state. Two independent intramolecular isomerizations were detected by 1H-NMR Exchange Spectroscopy (EXSY). The faster process is the rotation of the four acetate substituents around the C–N bonds [δ(λλλλ)δ(λλλλ)isomerization]. The cyclododecane ring inversion is slower [δ(λλλλ)δ(δδδδ) isomerization]. The intramolecular racemization of the δ(λλλλ) main isomer into its δ(δδδδ) enantiomer includes two successive isomerizations in a δ(λλλλ)δ(λλλλ)δ(δδδδ) sequence and is the slowest process.
Sterol metabolism. XLI. Cholesterol A-ring autoxidations
Abstract Chromatographic and spectral evidence is adduced for the presence of cholest-5-en-3-one, cholest-4-en-3-one, and cholest-4-ene-3,6-dione in samples of cholesterol aged naturally in air or subjected to irradiation in air by 60 Co gamma radiation. These findings establish an additional mode of air oxidation of cholesterol to A-ring 3-ketones. Moreover, the oxidation by air of cholest-5-en-3-one induced by 60 Co gamma radiation yielded cholest-4-en-3-one, cholest-4-ene-3,6-dione, and the epimeric 3-oxocholest-4-ene-6-hydroperoxides. Cholest-4-en-3-one was not altered by irradiation in air, nor was cholesterol isomerized to cholest-4-en-3β-ol upon irradiation. From these observations it is deduced that the radiation-induced A-ring dehydrogenation of cholesterol yields initially cholest-5-en-3-one which upon isomerization yields cholest-4-en-3-one not further oxidized and which by a second oxidation yields the epimeric 3-oxocholest-4-ene-6-hydroperoxides which decompose to cholest-4-ene-3,6-dione.