Computational exploration of optical and functional properties of biorelevant photoswitches

Developing molecular photoswitches for applications in material science and biology is a very active research in chemistry. Photoswitches are a class of small molecular machines whose structures and properties can be switched between two states with light. In this dissertation, we contribute to better understand three biorelevant photoswitches using computational means. In Chapter 3, we develop a new class of wave functions within the accurate quantum Monte Carlo framework to explore the excited-state potential energy surfaces (PES). In constructing these wave functions, we employ multiple sets of localized active orbitals corresponding to the different Lewis resonance structures of the molecule. We also adopt the concept of orbitals domains of local coupled-cluster methods to select orbitals to correlate within an active space. Using retinal models as examples, we find that our novel and compact wave functions can be flexibly and accurately applied to very different parts of a PES. In Chapter 4, we embark on a journey to understand the complex photoswitching mechanism of donor-acceptor Stenhouse adducts (DASAs). At the density functional theory level, we are able to explain the available experimental data of photoswitching of two representative DASA molecules as regards the reversibility, the relative reaction rate on different solvents and the structure of the final products. Additionally, our multiconfigurational wave-function study shows that accounting for both static and dynamical electron correlation is necessary for an accurate excited-state PES. In Chapter 5, we focus our attention on understanding the very recent use of spiropyran photoswitch for drug-delivery applications. Photoswitching spiropyran covalently connected to subdomain IA of the human serum albumin protein was found to induce ligand release in the adjacent subdomain IB. Our molecular dynamics simulations demonstrate the allosteric nature of the interaction between the two subdomains induced by the photoswitch and provide an explanation of the factors regulating the ligand release.