Herein we describe the reversible changing of DNA duplex thermal stability by exploiting transition metal complexation phenomena. A terpyridine ligand was conjugated to the N2'-atoms of 2'-amino-2'-deoxyuridine and its locked counterpart 2'-amino-LNA, and these metal-complexing monomers were incorporated into oligodeoxyribonucleotides. Upon addition of varying amounts of transition metal ions, the thermal stability of DNA duplexes containing these terpyridine-functionalized units in different constitutions was affected to different degrees (Delta T-m values = -15.5 to +49.0 degrees C, relative to the unmodified duplex). The most pronounced effects were observed when two complexing monomers were positioned in opposite strands. Addition of 1 equiv of Ni2+ to such a system induced extraordinary duplex stabilization. Molecular modeling studies suggest, as an explanation for this phenomenon, formation of nickel-mediated interstrand linkages in the minor groove. Addition of an excess of metal ions resulted in largely decreased T-m values. Alternating addition of metal ions and EDTA demonstrated reversibility of metal ion-induced changes in hybridization strength, proving that the described approach provides an efficient method for duplex stability modulation.