The researchers aimed to solve a key problem in molecular biology: detecting chirality, the “handedness” of molecules at very low frequencies, where traditional techniques often fail. They focused on mononucleotides, the basic units of DNA, which can form complex G-quadruplex structures. Understanding chirality in such simple systems helps decode how biological organization arises naturally.

This study is the first to use Terahertz Raman Optical Activity (ROA) to detect supramolecular chirality in mononucleotide-based G-quadruplexes, revealing that even the simplest DNA building blocks can self-organize into chiral structures. By preparing aqueous guanosine solutions and allowing them to self-assemble, the researchers employed ROA, an optical technique that measures differences in how chiral structures scatter left- and right-circularly polarized light. The resulting terahertz ROA spectra unveiled distinct vibrational patterns associated with chirality, highlighting low-energy collective motions that underpin supramolecular chirality in flexible biomolecular assemblies. These structures exhibited a clear chiral signature detectable in the terahertz range. The observed chirality didn’t stem from the individual guanosine molecules but from how they assembled. This spontaneous chirality arose from non-covalent interactions, including hydrogen bonding and π-stacking, without the need for external chiral agents.

This groundbreaking work suggests that chirality can emerge spontaneously in simple biological systems, offering significant implications across multiple disciplines. In the context of the origins of life, it points to the possibility that chiral structures may have naturally arisen under prebiotic conditions on early Earth, potentially influencing the course of biological evolution. From a pharmaceutical perspective, understanding supramolecular chirality could enhance drug design by enabling more precise targeting and effectiveness of therapeutics. Additionally, the use of ROA introduces a promising analytical tool for probing soft, dynamic biological assemblies, providing a non-invasive means to explore molecular behavior with remarkable sensitivity.