Supramolecular chemistry is the chemistry of molecular aggregates assembled by intermolecular forces of different nature such as electrostatic (hydrogen and halogen bonds) and dispersive forces. Concerning the main components of DNA and RNA (cytosine, guanine, adenine, thymine and uracil), nucleobases are held together by non-covalent interactions determining highly specific functions, i.e. molecular recognition. Hydrogen bonds (and halogen bonds in non-canonical nucleobases), and dispersive interactions all need to be accurately described in order to explain and control RNA and DNA sequence, structure and flexibility which are still only partially understood. Moreover, unusual (epigenetic) DNA nucleobases, identified as 5-substituted cytosines, have been detected in brain cells very recently leading to a new research field that has only very little published literature as yet. In this project, we aim to combine single-crystal and powder X-ray diffraction (XRD), atomic force microscopy (AFM), molecular modeling and thermodynamic measurements to fully describe DNA/RNA old and newly-detected nucleobases (in homomers and heteromers association) in 2D and 3D aggregates. 2D systems are formed by immobilizing molecules on a substrate and the combined interactions among the adsorbates and the surface lead to molecular networks. 3D aggregates are obtained by growing single crystals or crystal powders. The detailed molecular-level investigation of these interactions is of significant importance in the study of the DNA/RNA structure and properties: a change in the interactions between nucleobases can lead to genetic mutation and tumor formation. Hence the investigation of these systems is critically relevant in a large and varied range of fields, such as medicine, genetics, biochemistry, bioengineering of nano-systems and material chemistry.
This project forms a balanced interplay between modeling and experimental approaches in these complex systems. The novelty of our approach consists of the combination of highly accurate hybrid ab initio simulations, including dispersion energies, based on structural informations obtained experimentally, to describe the structures of biologically relevant systems. The ab initio method, with an essential correction for the dispersive interactions, is based on periodic Density Functional Theory (DFT-D3) and AIM approach for both 3D and 2D systems. Moreover, since the ab initio approach is well known to describe accurately only the electrostatic forces, whereas until very recently it lacked completely the dispersive interactions, the ultimate goal is to enhance the use of this improved first principles computational description - thus far in use only for small organic molecules - to more realistic and critically important macromolecular crystals and assemblies on surfaces. The importance of the modelling in this project is its ability to pinpoint the relevant structures/processes out of the many chemical scenarios that are often compatible with experimental data (by XRD and AFM) and that need to be illustrated and explained at the molecular level by the molecular modelling. However, the calculations need to describe accurately the important contributions from electrostatic attraction and donor-acceptor orbital interactions as well as the dispersion interactions that are so important in these biological systems. Our approach permits the detailed description of the structures. Moreover we can calculate data directly comparable with other experimental results such as X-ray diffraction (XRD), atomic force microscopy (AFM), NMR, Infrared (IR), Raman and photoelectron spectroscopy spectra.