Detection of Guanine Quadruplexes by Raman Optical Activity and Quantum‐Chemical Interpretation of the Spectra

Quadruplexes formed by guanine derivatives or guanine-rich nucleic acids are involved in metabolism and genetic storage of many living organisms, they are used in DNA nanotechnologies or as biosensors. Since many quadruplex geometries are possible the determination of their structures in aqueous solutions is difficult. Raman optical activity (ROA) can make it easier: For guanosine monophosphate (GMP), we observed a distinct change of the spectra upon its condensation and quadruplex formation. The vibrational bands become more numerous, stronger, and narrower. In particular, a huge ROA signal appears below 200 cm^-1. The aggregation can be induced by high concentration, low temperature, or by a metal ion. We focused on well-defined quadruplexes stabilized by potassium, where using molecular dynamics and density functional theory the spectra and particular features related to GMP geometric parameters could be understood. The simulations explain the main experimental trends and confirm that the ROA spectroscopy is sensitive to fine structural details, including guanine base twist in the quadruplex helix.