Formation and Stabilities of Free Bilirubin and Bilirubin Complexes with Transition and Rare-Earth Elements

Abstract

We investigated complexes formed between bilirubin and transition or rare-earth elements, and their relative stabilities. Relative rates of complex formation were analogous to metalloporphyrin and metal complex stabilities, according to the Irving—Williams series. Transition metals that formed strong, square planar complexes caused rapid bilirubin degradation. Iron(II) was oxidized to iron(III) in the bilirubin complex. Of the lanthanide complexes, only samarium(III) showed covalent bonding tendencies. Comparative molar absorptivities were calculated for several of the metal— bilirubin complexes. The stability of bilirubin in several solvents and under various experimental conditions is reported. At room temperature, bilirubin photooxidizes to biliverdin on exposure to laboratory light.

Biliary excretion in Sprague-Dawley and Gunn rats during manganese-bilirubin-induced cholestasis

“…This suggests that the putative cholestatic intermediate involves the unconjugated form of bilirubin. UCB is known to form complexes with various metal ions (33). An unexpected finding was that in Gunn rats, diminished bile flow did not occur following the administration of the Mn-UCB combination; only the Mn-BDT combination induced cholestasis in this strain.…”

A proposed novel structure for the metal chelates of bilirubin

“…Ever since their original description (O Carra, 1962), these have been tacitly assumed to have structures analogous to the metalloporphyrins. However, conclusive evidence in support of this notion has never been forwarded (Fog & Bugge-Asperheim, 1964;Van Roy & Heirwegh, 1965;Nichol & Morell, 1969;Velapoldi & Menis, 1971). Moreover, steric considerations must raise serious doubts as to the correctness of this assumption.…”

The Photoreactivity of Bilirubin and Related Pyrroles

“…at room temperature (Gray et aL, 1972). In that work and earlier work (Ostrow et al, 1961;Velapoldi and Menis, 1971;Ostrow, 1972b) it was deduced that BV is also a photooxidation product from BR. Subsequently, Lightner et al (1973) isolated BV (as its dimethyl ester) in high yield, and Bonnett and Stewart (1972~) detected BV (as BVDME) and two other minor verdins by TLC.…”

“…The mechanism appears to involve radical intermediates (Bonnett and Stewart, 1972c;Bonnett, 1976;Stevens and Small, 1976;Lightner and Cu, 1977). It is generally promoted by radical quenchers or electron ttansfer acceptors (Lightner and Cu, 1977); it is much more efficient with UV than with visible light excitation (Lightner and Cu, 1977); and it is promoted by aprotic solvents (Velapoldi and Menis, 1971;Bonnett and Stewart, 1972c;Bonnett, 1973Bonnett, , 1976Lightner et al, 1973;Lightner and Cu, 1977).…”

“…Albumin has been shown to be important in inhibiting BR IXa P XIIIct P lllct isomeiization McDonagh, 1975aMcDonagh, , 1976a, and it is apparently important in BR photochemistry leading to the "443", "430" or other pigment(s) (Kapitulnik et al, 1973(Kapitulnik et al, , 1976McDonagh, 1974;McDonagh and Palma, 1976;Pedersen et al, 1977) EDTA added to pH 8.5 buffered BR solution has a marked protective influence against BR photodisappearance (Ostrow and Branham, 1970), but Zni2 or Fe+2 ions accelerate BR photo-decay (Ostrow, 1972b). Such divalent metals could be important in altering the conformation (hence reactivity) of BR (Velapoldi and Menis, 1971;Hutchinson et al, 1973).…”