The origin of fluorescence in DNA thio-analogues

Abstract

Fluorescent probes are vital molecular tools for DNA biognostics – often aiding in the detection of malignant tumors. Biomimetic nucleobase analogues are amongst the most widely used probes due to their versatility and biocompatibility. Thieno[3,4-d]pyrimidin-4-amine (TPA) and isothiazolo[4,3-d]pyrimidin-7-amine (iTPA) are two recently developed sulphur-containing heteroaromatic fluorescent nucleobase analogues. Their inherent structures give rise to superior biomimetic properties that ensure their optimal interaction with double-helix DNA. Using high-level electronic structure methods, we simulate the absorption and emission spectra in order to better understand the origins of the strong absorption and emission profiles observed experimentally. Radiationless decay pathways are also computed and compared with those of the canonical DNA nucleobases, in order to unravel the geometric and electronic properties that make the thio-analogues fluorescent.