Towards excited state dynamics in nucleosides

The objective of this proposal is to study ultrafast UV-laser-induced dynamics in the DNA bases adenine and guanine as a stepping stone towards the nucleosides adenosine and guanosine. Funding will enable the PI to implement laser desorption into his laboratory so that these nucleosides can be brought into vacuum without decomposition and hence their ultrafast photochemistry studied in the gas-phase for the first time. Complementary high level calculations will provide critical guidance to interpreting the experimental results whilst posing new challenges to theoreticians as these studies will explore the complex interplay between multiple reaction paths and the ways these paths are coupled with one another with increasing molecular complexity. The PI, CoI and RCoI are ideally placed to undertake this exciting and ambitious research, which will begin to bridge the gap between the photochemistry of the DNA bases and that of nucleosides, and ultimately help elucidate the 'molecular mechanisms of the photostability of life'.

The research proposed here will impact the following: Experimentalists working in the field. Whilst understanding the photochemistry of these important biomolecules has received considerable interest since the seminal paper of Kim et al., (JCP, 113 (2000) 10051), advances in extending these investigations to larger, more realistic systems has been hindered due to experimental limitations. This works aims to facilitate this transition through the incorporation of laser desorption to the PI's setup; Theoretical Chemists. These measurements will go some way to validating calculations but will also pose new challenges to theoreticians as these studies will explore the complex interplay between multiple reaction pathways and the ways these paths are coupled with one another with increasing molecular size; Experimentalists working in related areas. The potential for knowledge transfer from these experiments is particularly extensive and interdisciplinary, spanning across chemistry, physics and biology. For example, the work may prove invaluable to experimentalists working in related areas of molecular dynamics such as energy transfer processes in larger biomolecules and light harvesting in cell biology, thus bridging the gap between chemical physics with biochemistry and biophysics; The RCoI employed on this grant. The RCoI will be extending his training in a highly interdisciplinary area which spans experimental chemical physics with high level ab initio calculations. These sets of skills are in high demand, especially in an academic environment to which the RCoI aspires towards. The ability to perform experiments and compliment these with such detailed calculations will undoubtedly provide the RCoI with an invaluable toolbox that potential academic Departments hiring will value highly.

The proposed research will trigger new collaborations in related areas involving both experiment and theory: The experiments on adenosine and guanosine proposed here will aim to validate previous speculation by de Vries's group (e.g. Int. J. Mass Spec., 219 (2002) 133). As a result, links will undoubtedly be forged between the complimentary areas of high resolution spectroscopy and ultrafast spectroscopy; The CoI is extending his expertise in non-adiabatic dynamics to the field of ultrafast dynamics in DNA bases and nucleosides, giving him an invaluable opportunity to contribute to the field and diversify his research interests, igniting further collaborations with other experimental groups world-wide; The RCoI intends to pursue an academic career following this project and successful funding of this proposal will undoubtedly help spring-board his career.

There is potential for immediate exploitation of these results by both experimentalists and theoreticians. Thus far, the ability to bridge the gap between studying small subunits of biomolecules (e.g. adenine) and larger units (e.g. adenosine) in the time domain has been hindered by experimental complications. The successful merger of time-resolved velocity map ion imaging with laser desorption has the potential to trigger a vast plethora of new experiments, which ultimately seeks to connect the micro and macro in such molecular studies. Similarly, extending the application of theoretical methodologies to larger scale molecular systems will also spark interest to theorists world-wide, for example in the use of quantum mechanics/molecular mechanics methods for excited states one encounters several new challenges compared to the ground state, and at present such applications are in their relative infancy. One specific application of this research will be ascertaining the extent to which pisigma* states potentially contribute to larger polymeric forms of the units to be studied. The result of this can have a major impact on general studies on dynamics of small gas-phase molecules and the extension of knowledge gained from these isolated molecules to more realistic systems such as those in vivo.