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.
Solution dynamics and stability of lanthanide(III) (S)-2-(p-nitrobenzyl)DOTA complexes.
Addition of a benzyl substituent to the macrocyclic ring of DOTA has a substantial impact on the conformational ring flipping motion of the macrocycle in the resulting LnDOTA complexes. The p-NO2-benzyl substituent in the Ln(p-NO2-Bn-DOTA)- complexes lies in an equatorial position and effectively "locks" the conformation of the ring into the deltadeltadeltadelta configuration. The presence of the p-NO2-benzyl group also increases the population of the square antiprismatic (SAP) coordination isomer for all Ln(p-NO2-Bn-DOTA)- complexes relative to that seen for the respective LnDOTA- complexes. Despite this increase in SAP isomer population, the rate of water exchange in these complexes remains comparatively fast. The kinetic and thermodynamic stabilities of the Ln(p-NO2-Bn-DOTA)- complexes are also slightly lower than the corresponding LnDOTA- complexes but appear to be sufficiently high for in vivo use.
Interaction of Diclofop-Methyl and MCPA on Wild Oats (Avena fatua)
Diclofop-methyl {methyl 2-[4-(2,4-dichlorophenoxy)phenoxy] propanoate} loses part of its activity on wild oats (Avena fatua L.) when it is applied in combination with ester or amine formulations of MCPA {[4-chloro-o-tolyl)oxy] acetic acid.} Uptake of diclofop-methyl is reduced in the presence of commercial formulations of MCPA, particularly amine formulations, which are only partly compatible with the diclofop-methyl formulation. With added MCPA, regardless of formulation, hydrolysis of diclofop-methyl to the acid diclofop is slowed down, both in intact wild oat plants and in a crude leaf extract. At the same time, conversion of any acid formed to inactive conjugates is accelerated in the presence of MCPA. It is concluded that the loss of activity of diclofop-methyl by MCPA can be accounted for by the effects of MCPA on uptake and metabolic conversion of diclofop-methyl.