Synthesis and characterization of Schiff Base Chelates of Tetramic Acids as NMR Contrast Agents for micro imaging

Abstract

Novel Cu(II) complexes derived from N,N′ P-ethylene-bis-(1′,5′,5′-trimethyltetramic acid-3′-acetiminato)copper(II) aCu [1] were evaluated as contrast agents for NMR microscopy and therefore tested for penetration into living cells (Xenopus laevis oocytes). By in vitro1H NMR relaxation (T1) and atomic absorption spectroscopy measurements (AAS) we confirmed, that independent of the complex isomers (Z/Z, Z/E, E/E, E/Z) compounds with alkyl substituents in R1 – R5 exclusively were able to penetrate the plasma membranes. It is noteworthy that compounds containing the tetramic acid moieties from both a penetrating and a non-penetrating complex most likely were accumulated in the plasma membrane and/or plasma membrane-associated vesicles, which was concluded from in vitro NMR measurements combined with AAS trace analyses. In this context the crystal and molecular structure of the ‘chimerical’ C17H22N4O4Cu · 3H2O kCu · 3H2O were determined by x-ray analysis. The x-ray structural parameters are discussed in detail.