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

Abstract

In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds.

Testing the Simplified Molecular Dynamics Approach to Improve the Reproduction of ECD Spectra and Monitor Aggregation

“…The herein-tested simplified MD-based ECD method applies explicit solvent molecules only in the MD simulation, the next TDDFT step is already performed on the solute molecules, where the effect of the solvents is preserved via the unoptimized structures. In case one would like to further enhance the match of the experimental and calculated spectra, QM/MM or pure QM treatment of solute–solvent complexes gained from normal MD or methadynamics simulations could be considered for the TDDFT step, proper parametrization of the solute and solvent molecules could be applied instead of the automatic one, or other approaches for the generation of solute aggregates can be attempted as described in the literature, e.g., for the chiroptical studies of pantolactone or bilirubin and biliverdin analogs [ 76 , 77 , 78 , 79 ].…”

Bilirubin and its crystal forms

“…the apparent isomeric regioselectivity and drive towards lipophilicity) probe the functional significance of bilirubin, garnering renewed interest in its structure. 9,10 Bilirubin is insoluble in aqueous media and is precipitated from the biliary tract as pigmented gall stones. Crystals also form in the urine indicating poor hepatic function, as bilirubin is usually processed by the liver before being excreted.…”

Pfeiffer effect on configurationally labile dyes within ternary complexes with metal ions and enantiopure macrocycles

“…Chiral configurationally-labile molecules are abundant in chemistry, from simple moieties such as 1,2-difluoroethane 1 or o , o ′-disubstituted biaryls, 2 to dynamic (coordination) complexes, 3 biomolecules, 4 and (supramolecular) polymers. 5 These derivatives that interconvert readily at room temperature between two enantiomeric geometries are most often found as racemic mixtures.…”