Seminarium "Modeling of Complex Systems"

Polyene retinoids are an important class of biologically active molecules involved in many facets of human physiology. The geometric configurations of retinoids have enormous impact on their chemical and biological properties. For example the Z-isomeric form of retinal plays an important role as a chromophore of rod and cone photoreceptor cells in the visual cycle. Genetic or environmental factors affecting chromophore production can lead to diseases of the retina and eventually blindness. Pharmacological interventions by means of Z-isomers of retinal and retinyl acetate are used to maintain vision in inherited retinal degenerative disease [1].We recently developed three paths to access such biologically relevant 9-cis and 13-cis retinoid derivatives: (a) palladium-based catalytic approach [2], (b) direct monochromatic photoisomerisation [3] and (c) photocatalytic isomerization using iridium catalyst [3]. The single-step protocols are easily scalable and allows for gram-scale synthesis of the Z-isomers. However, depending on the method and the nature of all-trans substrate various distributions of Z-isomers were observed. To understand the distribution of the products we carried out extensive quantum chemical calculations [2,3]. Our multi-level approach include geometry optimizations at the density functional theory (DFT) level, single-point energy refinements at the local coupled-cluster level and excitation energies calculations at the (simplified) time-dependent DFT level. In the case of catalytic reaction we showed that the active catalyst exists in a dimeric form and the reaction proceeds via six-membered chair-like chloropalladate intermediate. We related the distribution of photochemical products with the relative energy ordering of the intermediates at the excited potential energy surface. In addition, we developed the “local polarization change” (LPC) model that explains photoisomerisation product distribution using only HOMO and LUMO atomic populations.[1] P. D. Kiser, K. Palczewski, Annu. Rev. Vis. Sci. 2, 197-234 (2016).space[2] S. Kahremany, A. Kubas, G. P. Tochtrop, K. Palczewski, Dalton Trans. 48, 10581 (2019).[3] S. Kahremany, C. L. Sander, G. P. Tochtrop, A. Kubas, K. Palczewski, Org. Biomol. Chem. accepted, DOI: 10.1039/C9OB01645G (2019).