Studies of the conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide solutions by nuclear magnetic resonance

Abstract

The conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide (DMSO) was investigated by n.m.r. spectroscopy. The chemical shifts of the pyrrole NH and Lactam protons of bilirubin and its dimethyl ester in DMSO indicate a strong interaction with the solvent. Inter-proton distances were calculated from nuclear Overhauser effects (NOE), selective and non-selective relaxation times (T1) and rotational correlation times taken from 13C relaxation times. The interproton distances indicate that the conformation of the skeleton of bilirubin and its dimethyl ester in DMSO is similar to that of bilirubin and mesobilirubin in the crystalline state and in chloroform solutions, except for a possible slight twist of the pyrrolenone rings about the methine bonds, which may be a consequence of solvation of the NH groups by DMSO. Unlike in chloroform solutions, no direct hydrogen-bonding occurs between the carboxylic acid and the lactam groups of bilirubin in DMSO, as shown by the absence of an NOE between these groups. The fast exchange of the pyrrole NH protons with 2H shows that no hydrogen-bonding occurs between these protons and the propionic residues, in line with their solvation by DMSO. From the above results, and from the slowness of the internal motion of the propionic residues of bilirubin and its dimethyl ester, it is concluded that these residues are tied to the skeleton via bound solvent molecules.

The Importance of Free Bilirubin Acid Salt in Bilirubin Uptake by Erythrocytes and Mitochondria

“…The conformation of the bilirubin acid salt is probably folded about the central methylene bridge, forming a hydrophobic exterior with internal hydrogen bonding of the propionic acid side chains (26,27). In the fo ed, largely hydrophobic conformation, the acid salt would h s" ve a single ionized carboxyl group at one pole, resembling a deteb-Thus, it might readily interact with chloroform at the interface, with the hydrophobic portion buried in the chloroform and the ionized carboxylic acid group in the aqueous medium.…”

An Intramolecularly Hydrogen Bonded Dihydrotripyrrinone

“…2A), is constrained to adopt a ®xed staggered geometry. In (CD 3 ) 2 SO, however, the less complicated A 2 B 2 pattern ( 3 J AB 7.3 Hz) observed signi®es more motional freedom in the propionic acid chain, whose COOH group is thought to be linked to the dipyrrinone via bound solvent molecules [12].…”

Synthesis of water-soluble bile pigments bound to amine-ended monomethoxypolyethyleneglycol: thiol addition and attempted enzymatic reduction of a bilindione derivative

“…This behaviour does not parallel that of any previously reported dipyrrinone. Indeed, in intermolecularly hydrogen-bonded dipyrrinones a planar dimeric form is characterized by a sharper lactam NH near 11.2 ppm and a broader pyrrole NH near 10.3 ppm [21][22][23][24]. Small deviations from this behaviour have not been considered significant and a planar dimeric form has been proposed for them as well.…”