Synthetic analogs of bilirubin: Syntheses, conformational analysis, circular dichroism, and metabolism and novel fluorescent probes: Xanthoglow syntheses and optical properties

The catabolism of bilirubin from heme is important to human biology. Yellow-orange in color, bilirubin is an insoluble pigment in water, but its excretion from the body is essential for life. The liver is vital in the metabolism of bilirubin and its subsequent excretion into bile.; Bilirubin physiology was studied as early as 400 B.C., and its structure was not elucidated until the early 20th century. Due in large part to the contributions made by the Lightner research group, the role of bilirubin's structure and conformation in its biological behavior has been thoroughly recognized.; In a continuing effort to explore perturbations of bilirubin's structure and its affect on metabolism, several new bilirubin analogs have been synthesized. These analogs have vinyl groups replaced by n-butyl, phenyl, and o-fluorophenyl groups. The n-butyl groups increases the lipophilicity of the pigment, and the presence of the phenyl groups introduces an unsaturated moiety, analogous to the vinyl groups of the natural pigment. The complete synthesis, characterization, conformational analysis and circular dichroism (CD) of these new pigments have been extensively investigated. The presence of such groups did not alter bilirubins three-dimensional shape, as proven by NMR. As well, the new pigments form complexes with human serum albumin (HSA), as determined by CD. The influence of a tertiary substance, chloroform, on the Cotton effects of the pigment-HSA complexes was also investigated. As determined by Prof. Antony McDonagh, at the Univ. of California, San Francisco, the metabolism of some of these bilirubin analogs was altered, despite their structural similarities with bilirubin.; During the course of the research detailed above, a new class of fluorescent molecules was discovered and developed. These novel fluorophores are based upon one half of a bilirubin molecule, and may prove to be useful as fluorescent probes. The complete characterization, including fluorescence spectroscopy and X-ray crystallography (performed by Prof. Vincent Catalano at the Univ. of Nevada, Reno) was achieved.