Bilirubin and its congeners: conformational analysis and chirality from metadynamics and related computational methods

Solvent Effects and Aggregation Phenomena Studied by Vibrational Optical Activity and Molecular Dynamics: The Case of Pantolactone

“…In the present cases we adopted statistical cluster analysis based on significant collective variables adapted to the considered system, an idea borrowed from metadynamics protocols. 54 , 55 Here, we have relied on ring puckering coordinates also in the case of intermolecular ring comprising H-bonds. After the snapshot selection, the DFT optimization method has to be chosen: how much extended the solvent shell, which approximation to adopt for the solute and the shell, and so on.…”

“…The choice is to go for either a large number of snapshots at fixed time intervals (in the hypothesis that the simulation is long enough and there are no high barriers among different conformational basins) or for representative structures at conformational minima identified by previous analysis of the most significant dihedral angles or, finally, for representative structures chosen with a cluster analysis usually referred to rmsd calculation. In the present cases we adopted statistical cluster analysis based on significant collective variables adapted to the considered system, an idea borrowed from metadynamics protocols. , Here, we have relied on ring puckering coordinates also in the case of intermolecular ring comprising H-bonds. After the snapshot selection, the DFT optimization method has to be chosen: how much extended the solvent shell, which approximation to adopt for the solute and the shell, and so on.…”

Insights into the Structures of Bilirubin and Biliverdin from Vibrational and Electronic Circular Dichroism: History and Perspectives

“…Two rapidly interconverting enantiomeric conformations prevail in solution with an activation barrier ( Figure 3 ) of ΔG ‡ 74.9 kJ/mol at 53 °C and an interconversion rate of 7.2 ± 0.4 s −1 [ 42 ] or 3–95 s −1 at 50–95 °C, according to [ 43 ]. Recent metadynamics studies on BR, in accord with earlier MM–Sybyl studies [ 44 , 45 ], allow one to graphically follow the interconversion paths between different conformers bearing chiral character and to evaluate the energetics thereof (see Figure 4 ).…”

“…A most intriguing aspect of the 3D structure of intramolecularly hydrogen-bonded BR is its ability to fold into either of two interconverting enantiomeric conformations ( Figure 3 ) [ 44 ]. It is this conformation of BR that has attracted considerable attention and that has been studied spectroscopically and by theoretical calculations in recent years [ 2 , 45 ].…”

Conformational Control of the Photodynamics of a Bilirubin Dipyrrinone Subunit: Femtosecond Spectroscopy Combined with Nonadiabatic Simulations

“…The chemistry and photophysics of bilirubin-related compounds were widely studied with static ab initio methods. The conformational sampling of bilirubin was studied several times in both the gas phase and solution. − A time-dependent DFT (TDDFT) method was used for the characterization of bilirubin excited states, absorption spectra, and the character of the photochemical intermediates. , Particular attention was paid to the excitonic coupling in these systems. − , Zietz and Blomngren have briefly analyzed the topography of the potential energy surface of a dipyrrinone model system finding a conical intersection attributed to the photoisomerization . Later, Garcı́a-Iriepa and co-workers calculated the analogous topography for a similar bilirubin model, benzalpyrrolinone, connecting it with the lifetimes from fs-TA spectroscopy mentioned above .…”