Intramolecular hydrogen bonds interactions in the isomers of the bilirubin molecule: DFT and QTAIM analysis

Bilirubin is an important molecule, used as a marker of some liver diseases, and it can also be toxic and cause jaundice, especially in newborns. The main treatment for neonatal jaundice is phototherapy with blue light, which is still widely studied because the photophysical processes involved are not fully understood.

Calculations based on the density functional theory (DFT) at M062X/6-31G(d,p) level were performed in order to evaluate the structural, electronic, and topological properties of bilirubin isomers. It was found that the ZZ conformation can form a greater number of hydrogen bonds, which gives the isomer greater energy stabilization compared to the other ZE, EZ, and EE isomers, and that the EE isomer is the conformer with the lowest energy of stabilization. The hydrogen bonds were characterized by the quantum theory of atoms in molecules (QTAIM) and for the ZZ isomer four hydrogen bonds (HBs) were found classified as intermediate, ∇²ρ(r) > 0, H(r) > 0. The ZE, EZ, and EE isomers show weak HBs, ∇²ρ(r) > 0, H(r) > 0.