The First Selective and Efficient Transport of Imide-Containing Nucleosides and Nucleotides by Lipophilic Cyclen−Zinc(II) Complexes (Cyclen = 1,4,7,10-Tetraazacyclododecane)

Abstract

Zinc(II) complexes (ZnL) of macrocyclic tetramines, cyclens, bearing alkyl chains of four different lengths (propyl, octyl, dodecyl, and hexadecyl) have been tested as new carriers for highly selective extraction and transport of imide-containing nucleosides and nucleotides (L = cyclen = 1-alkyl-1,4,7,10-tetraazacyclododecane). The most lipophilic Zn2+−hexadecylcyclen was found to most effectively extract thymidine (dT) from an aqueous solution into a CHCl3 layer, while it did not extract other nucleobase derivatives (C, A, and G) at all. More lipophilic thymidine derivatives (HS) such as 3‘-azido-3‘-deoxythymidine (AZT), 1-methylthymine (1-MeT), and ftorafur (Ff) were almost quantitatively extracted by an equivalent amount of Zn2+−hexadecylcyclen. The 1H NMR spectra of the CDCl3-extracted AZT by Zn2+−hexadecylcyclen confirmed the formation of the 1:1 complex (S-−ZnL) bound through imide-N- anion and zinc(II) cation (S- denotes the deprotonated dT derivatives). While apparent 1:1 complexation constants, l...