Modeling and analysis of nonlinear optical properties of dyes embedded in increasingly complex environments, up to the lipid bilayer

: A quantum mechanics and molecular dynamics study

Abstract

Most biomolecules possess few natural moieties with exploitable optical properties for bioimaging. The use of exogenous dyes can improve the contrast in tissues for being detected by commercially available microscopes. AminoNaphtylEthenylPyridinium (ANEP) dyes constitute a family of broadly employed fluorescent dyes. Moreover, in the last few years, these compounds have gained interest in the field of Second Harmonic Generation (SHG) imaging. Indeed, SHG is a nonlinear optical (NLO) phenomenon, which possesses the advantage, with respect to fluorescence, that only non-centrosymmetric compounds and structures can produce a signal, leading to stronger contrasts. This work focuses on the characterization of the SHG properties of ANEP-like dyes, the first hyperpolarizability () at the molecular scale, by employing methods of theoretical chemistry. In particular, a two-step procedure has been elaborated and tuned in order to describe these chromophores in increasingly complex environments, from the diluted gas phase, to the solution, and finally, to lipid bilayers (here built from dipalmitoylphosphatidylcholine, DPPC). The first step of the method employs Molecular Dynamics (MD) to account for the dynamical behavior of the target chromophores, as well as of their environment. For those simulations the force fields are either validated with respect to experimental data or re-parameterized with respect to density functional theory calculations. Then, for selected snapshots extracted from the MD simulations, the NLO responses of the chromophore with its nearest environment are computed using time-dependent density functional theory. Simulations have revealed a strong increase of the SHG response when accounting for geometrical fluctuations, as well as when going for aqueous solutions to the lipid bilayer environment. In all cases, these variations have been traced back by analyzing the corresponding
geometrical changes (bond length alternation and dihedral angles). Complementary studies have investigated the structure- property relationships in ANEP-derivatives, analyzing the impact of the size of the substituents and of the -conjugated linker as well as of the position of donor/acceptor substituents, with the aim of designing efficient SHG dyes.

Date of Award	2019
Original language	English
Awarding Institution	University of Namur
Supervisor	Benoit Champagne (Supervisor)