The importance of deoxyribonucleic acid (DNA) to life and medical science has made it the focus of intense research over the past 70 years. In vivo, chromosomal duplex DNA is sufficiently stable to preserve one’s genetic code. Yet, under appropriate conditions, portions of a chromosome must and do dissociate into single strands to permit, among other things, the transcription of genes. Many powerful techniques and technologies used in molecular biology and in clinical laboratories also exploit the ability to dissociate duplex DNA into its component single strands. Oligonucleotide probes that hybridize to natural single-stranded DNA are used to identify specific sequences that are diagnostic of disease or to identify a unique person of interest in a criminal investigation. Oligonucleotide primers are used in a wide range of applications which includes the initiation of complementary strand synthesis for sequencing or PCR-based amplification. The development and successful application of these techniques typically requires knowledge of how the stability or melting temperature, Tm, of a given duplex depends on its length, sequence and concentration. Solvent composition (e.g., salt concentration, pH, added metal ions or organic solvents, etc.) is also known to affect the stability of a duplex at a given temperature [1-3]. A longstanding goal of researchers studying structures, dynamics and energetics of nucleic

acids has, therefore, been to understand, predict and control the properties and functions of natural nucleic acids and modifications to them.