DFT-aided stereo-structural and electronic structure studies of poly-hydroxyl substituted chlorophyllous molecules

Abstract

Numerous chlorophyll-based derivatives have found applications in the dye and pharmaceutical industries. Here, we report the synthesis of a poly-hydroxyl substituted chlorophyll molecule (THM) and its absolute configuration determination using experimental electron circular dichroism (ECD), nuclear magnetic resonance (NMR) spectroscopy, and density functional theory (DFT) calculations. Furthermore, the photoreaction types of THM (type I and type II) were investigated through theoretical calculations and validated by biological experiments. We provide a detailed analysis of electron transfer and excitation processes in THM through theoretical calculation of hole-electron distribution, as well as study intramolecular weak interactions and conjugation effects using Reduced Density Gradient (RDG), Interaction Region Indicator (IRI), and Natural Bond Orbital Analysis (NBO). The photoreaction types (type I, type II) of THM in tumor cells have also been investigated by biological experimental measures and theoretical calculation of the single-triplet state energy gap and hole-electron distribution. Molecular electrostatic potential has also been investigated by DFT methods to give insight into the molecular structure. This study provides useful guidance for the structural and photochemical studies of the chlorophyll-derived photodynamic therapeutic drugs.