AbstractThe neighbor–neighbor interactions in the small ribotrinucleotide ApApCp were investigated with the aid of optical rotatory dispersion measurements. This trinucleotide shows a Cotton effect between 220 and 325 mμ, in the region of its maximum ultraviolet absorption. The specific rotation of the trinucleotide is independent of concentration while the magnitude of the Cotton effect (levorotation) decreases markedly with increasing temperature. Such effects were not observed with the component nucleotides alone, in a simulated hydrolysis mixture, nor with the hydrolyzed trinucleotide. The Cotton effect is attributed to perturbation of the nucleotide base chromophores by neighbor–neighborintramolecular interaction (stacking), without any hydrogen bonding being involved; this interaction decreases with increasing temperature because of increased internal rotational freedom about the single bonds of the backbone chain with an accompanying disruption of the neighbor–neighbor interaction between the bases. This explanation is supported by a statistical mechanical theory of neighbor‐neighbor interactions in polynucleotides, involving the forces between the bases. Application of this technique to further studies of polynucleotides and polypeptides is d