Dr. hab. Lukasz Cwiklik, PhD J. Heyrovsky Institute of Physical Chemistry Academy of Sciences of the Czech Republic Dolejškova 2155/3, 182 23 Prague, Czech Republic phone: +420-266053496 email: [email protected] Prague, February 22, 2017 Review report on PhD thesis of MSc Rafal Szabla Thesis title: “Origin of Life Theory: Study of Prebiotically Plausible Photochemical Reactions”. The PhD dissertation of MSc. Rafal Szabla aims at theoretical description of selected prebiotic photochemical reactions. Understanding of abiogenesis, the origin of life, is still one of fundamental questions in science. Most of research in this field uses experimental methods, therefore, the theoretical approach employed by the candidate is particularly valuable. On note, photochemical phenomena involving excited states of molecules are particularly difficult for current quantum chemistry methods, hence state-of-the-art advanced computational techniques must be used. At the beginning of my evaluation, I have to emphasize an excellent scientific level of the dissertation. The thesis is based on nine very strong papers published in high-impact journals, including one paper in the Nature Chemistry. All papers follow the topic of the thesis demonstrating that the candidate is very consistent in his scientific interests. It should be also noted that Mr. Szabla served as a corresponding author in seven of these contributions. There are three additional papers on abiogenesis subject, co-authored by Mr. Szabla, not directly included in the dissertation. This all is well above the usual criteria for PhD candidates. The research presented in the thesis focuses not only on general photochemical properties of the investigated molecular systems but also includes such specific aspects as photostability and involvement of water molecules in the studied processes; both of crucial importance for abiogenesis. First, small precursors of RNA nucleobases and nucleosides were studied in the gas phase at CASPT2/CASSCF and MRCISD levels of theory. DAMN to DAFN gas phase photoisomerization was investigated, and different roles of singlet and triplet excited states were revealed. Gas phase photorelaxation of AMOX to AICN was another issue under study; the candidate demonstrated here that only one of the molecules (AICN) is photochemically stable. Second, by employing nonadiabatic MD simulations in water clusters, the author investigated the role of solvation for the same molecules and processes that he has previously explored in the gas phase. Here, a particularly interesting general deactivation channel is proposed, involving electron-driven proton transfer along water wires. Third, a pioneering study on an alternative nucleobase, isocysteine, is presented. ADC(2)-based surface hopping nonadiabatic MD simulations were employed in this work. The molecule is shown to be less photostable and more photoreactive than its biological analog. It demonstrates that isocysteine was not suitable to be involved in creation of efficient 1 informational polymer in abiogenesis. In the last part, a new pyrimidine nucleosides synthesis mechanism is proposed based on ADC(2) and CASPT2 calculations. This mechanism involves photoanomerization under UV radiation conditions. Of note, this latter work is based on extensive joint experimental and theoretical effort. The thesis consists of four main parts. It opens with a brief but informative introduction. Next, theoretical methods are presented and followed by the synopsis of the results. A short summary and conclusions close the thesis. The dissertation is well structured and clearly presented. There is a very good balance between the theoretical part and the description of the results. The language is clear, there is very few typographic errors. I have some minor comments regarding the Theoretical Introduction. As typical in theoretical chemistry dissertations, the description of theory begins with Born-Oppenheimer approximation. However, in my opinion, this handbook knowledge seems too basic here, as the author himself notes that “the BO approximation often fails for photochemical processes which involve higher electronic states and crossings between them.” Similarly, the Methods of Quantum Chemistry chapter opens with a long description of Hartree-Fock method which is of limited use in the work presented in the thesis. Instead of these general topics, a short chapter describing more technical details of calculations performed by the candidate would be valuable, in particular, for younger students. These are, however, very minor deficiencies, which do not change my overall very positive opinion about the thesis. I suggest the following points to be discussed during the defense: 1. The role of water is particularly interesting in abiogenesis. In the thesis, for instance, AICN clusters with up to six waters were studied. How the picture would change in the water bulk? 2. The lipid world theory is not mentioned in the dissertation. Could photochemical processes be important for amphiphilic long-chain molecules present in early Earth? Conclusion This is a very solid and interesting PhD dissertation covering large body of work on prebiotical photochemical reactions with a very strong publication record. The candidate clearly demonstrated ability for creative and independent work in the field of biomolecular chemistry. Therefore, in my opinion, the dissertation of MSc Rafal Szabla fulfills all conditions for PhD dissertation if his field of study. Based on my evaluation of the presented dissertation, I recommend this thesis for a public defense. Dr. hab. Lukasz Cwiklik, PhD 2 .