Modulation of water exchange in europium(III) DOTA-tetraamide complexes via electronic substituent effects

Abstract

The chemical exchange saturation transfer (CEST) efficiency for a series Eu3+-based tetraamide complexes bearing p-substituents on a single coordinating pendant arm is highly sensitive to water exchange rates. The CEST effect increases in the order Me < MeO < F approximately CO2tBu < CN < H. These results show that CEST contrast can be modulated by changes in electron density at a single ligating atom, and this forms the basis of creating imaging agents that respond to chemical oxidation and reduction.

Figure 1

CEST arising from the coordinated water molecules of the Eu³⁺ complexes recorded at 7 T, 296 K, B₁ = 450 Hz, concn = 20 mM (50% H₂O in CD₃CN) and irradiation time = 2 s (left). Spin echo CEST difference images of the complexes acquired at 9.4 T and 298 K (right), TR = 10 s, TE = 8.2 ms, irradiation time = 3 s, B₁ = 24 µT at −47.5 and +47.5 ppm.

Figure 2

CEST difference images showing that the oxidized and reduced forms of the complexes can be discriminated by MR imaging.

Chart 1

The EuDOTA–Tetraamide Complexes Prepared for This Work