Delineation of conformational and structural features of the amikacin-Cu(II) complex in water solution by C-13-NMR spectroscopy

The copper (II) complex of amikacin in water solution at pH 5.5 was investi gated by C-13-NMR. The temperature dependence of spin-lattice relaxation ra tes was measured and fast exchange conditions were shown to apply. The moti onal correlation time of the complex was approximated by the pseudo-isotrop ic rotational correlation time of free amikacin in water solution (tau(c) = 0.17 ns at 300 K). Formation of a pseudo-tetrahedral 1:1 complex was demon strated by relaxation rates analysis and also by UV-Vis spectrophotometry. Two amino nitrogens of amikacin, together with the amide nitrogen and the h ydroxyl in the hydroxyl-aminopropyl carbonyl side chain, were assigned as t he copper-binding sites and a model of the complex was built by using coppe r-carbon distances obtained by NMR analysis as input parameters. (C) 1999 E lsevier Science B.V. All rights reserved.