1. We have improved our ultrafast spectroscopy setups to unprecedented time resolution, and made important steps towards 2D UV spectroscopy, an as of yet undeveloped technique. These developments will facilitate the elucidation of the complex spectral signals of MCA.
2. We made important advances in the development of computational methods, improving both our ability in very accurately describing what happens in medium size molecules on an ultrafast time-scale and what happens on a longer time-scale for systems containing many chromophores.
3. The progress in points 1 and 2 allowed a much better understanding of the photophysical processes occurring in the DNA building blocks, the nucleobases, the Watson-Crick hydrogen bonded dimer, and polynucleotides with different arrangements. In particular, we characterized the photophysics of pyrimidines and of several epigenetic derivatives of cytosine, an important achievement in the field of epigenetics.
4. We characterized the primary species (electrons and radicals) resulting by absorption of low energy UV photons by guanine-quadruplexes (GQs), i.e guanine rich regions of DNA that form four stranded quadruple helices, involved in key biological processes. Based on the numerous results collected during the project, we proposed a mechanism explaining this phenomenon. We have also characterized the photoactivated processes in GQs in the presence of binders, either organic or organometallic species. We obtained new insights on the structural dynamics of another DNA arrangement, the Holliday Junction, a key intermediate in many genetic processes. Our studies brought an important insight into the mechanism of oxidative damage to the genetic code, responsible for carcinogenesis and ageing. We hope that they will also benefit the therapeutic efforts in these fields.
5. We have synthesised and studied the mechanism of potential drug scaffolds and a variety of fluorescent probes, likely to be of significant diagnostic and therapeutic use.
6. We started obtaining new information on the interaction between DNA and proteins, i.e. Taq polymerase and two CRISPR associated proteins. These proteins are relevant for two key fields for the research and technological activities of EU. Taq polymerase is indeed frequently used in the polymerase chain reaction (PCR), while CRISPR-Cas system is exploited for genome editing both in the preclinical and clinical settings.
7. The strong expertise the ESRs and the beneficiaries have developed in working on oligonucleotides, as well as in click-chemistry, can have a tremendous impact on the health and medical needs of UE. Two beneficiaries have actively worked in response to the COVID-19 crisis. LMUM has started to use the synthetic oligonucleotide technologies developed in the ETN to design synthetic RNAs that can block virus proliferation, with promising therapeutic potentialities. BAS worked on the production of a lipid nanoparticle-free SARS-CoV-2 vaccine, planned to entry in clinical trials in 2023.
8. Besides their relevance for DNA, the methodological developments attained, together with the insights gained on some ubiquitarian reactions excitation energy transfer (charge transfer, electron ejection), will positively impact the study of the many key biological and technological processes which are driven by the interaction with light.
