The optical properties of biophysical probes can be very dependent on the conformation of the molecule and its environment. In order to optimize a probe for biomedical imaging in e.g. cancer therapy and to interpret the results, it is therefore of primordial importance to understand the different influences on the location and orientation of the probes in the biological environment and on the absorption spectra.
One of the most well-known lipid bilayer markers is the red fluorescent DiI-C18:5 probe (shortly denoted as DiI). It is centrosymmetric and has a cyanine backbone. In literature, the molecule is mostly considered to be in its all trans conformation. In the current work, the properties of the probe are investigated when the dihedral angle of the backbone is changed. This issue becomes more involved when the length of the backbone is increased and when many different conformations appear.
Since fluorescence is considered, one the first tasks is the investigation of the excited state potential energy surfaces along the dihedral angles of the backbone in vacuum. Afterwards, different implicit solvent models can be employed. For this work, time dependent density functional theory has to be used in the interest of computational time. However, benchmarking with ab initio methods is needed. Cyanine molecules are interesting but not trivial as the first excited state is one-photon allowed while the second excited state is one-photon forbidden and is found considerably higher in energy, which makes them important for non-linear optical applications. The benchmarking will therefore focus on transition state dipole moments as well. The behavior of the various DiI probes in a lipid bilayer is then investigated through molecular dynamics calculations. Since the affinity of the probes for the biological environments are partly governed by the hydrophobic lipid tails, it can be investigated what happens when they are manipulated.
The project has been designed to be performed by 3 groups of students (in total 5 people): one person is responsible for the benchmarking of the applied computational methods, two collaborators focus on the ground and excited state potential energy surfaces of the various conformers of DiI, and two other people work towards MD simulations of various conformers in lipid bilayers.