Two short glycol nucleic acid (GNA) oligonucleotides, having either a terminal or an intrachain nucleobase replaced by the pyridine-2,6-dicarboxamide chelate of Pd2+, have been synthesized and their hybridization properties studied by melting temperature measurements. In the termini of a double-stranded oligonucleotide, the Pd2+ chelates provided dramatic stabilization of the duplex relative to its metal-free counterpart, in all likelihood owing to formation of Pd2+-mediated base pairs between pyridine-2,6-dicarboxamide and the opposing nucleobase. In contrast, no stabilization was observed when the Pd2+ chelate was placed in the middle of the chain. Furthermore, the results could not be reproduced by adding a Pd2+ salt in situ to the dilute oligonucleotide solutions but the palladated oligonucleotides had to be synthesized and purified prior to the hybridization studies. This behavior, presumably attributable to the relatively slow ligand-exchange reactions of Pd2+, differs greatly from what is usually observed with more labile metal ions. The present results offer an explanation for the failure of previous attempts to incorporate Pd2+-mediated base pairs into oligonucleotides. (C) 2015 Elsevier Inc. All rights reserved.