The changes in the annealing properties of a DNA duplex upon replacement of one phosphodiester linker by a formacetal or thioformacetal linker have been investigated using ab initio quantum mechanics. Potential energy as a function of torsional angle was evaluated using the 6-;31G* basis set. The detrimental effect of the formacetal linker on the Tm of the duplex (−3°C) is attributed primarily to a much stronger stereoelectronic effect for a COCO torsion than that for a COPO torsion. The effects of the thioformacetal linkers on Tm can be rationalized based on torsion angle potential and steric interactions. © 1993 John Wiley & Sons, Inc.