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Bilirubin oxidation products (BOXes): synthesis, stability and chemical characteristics

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Cerebral Vasospasm

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 104))

Abstract

Bilirubin oxidation products (BOXes) have been a subject of interest in neurosurgery because they are purported to be involved in subarachnoid hemorrhage induced cerebral vasospasm. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes. A clearer understanding of the synthesis, stability and characteristics of BOXes will be important for a better understanding of the role of BOXes post subarachnoid hemorrhage.

We used hydrogen peroxide to oxidize bilirubin and produce BOXes. BOXes were extracted and analyzed using conventional methods such as HPLC and mass spectrometry. Characterization of the stability of BOXes demonstrates that light can photodegrade BOXes with a t1/2 of up to 10 h depending upon conditions. Mixed isomers of BOXes have an apparent extinction coefficient of ε = 6985, and a λ max of 310 nm.

BOXes are produced by the oxidation of bilirubin, yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene) acetamide (BOX B). The BOXes are photodegraded by ambient light and can be analyzed spectrophotometrically with their extinction coefficient as well as with HPLC or mass spectrometry. Their small molecular weight and photodegradation may have made them difficult to characterize in previous studies.

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Authors and Affiliations

  1. Department of Neurology, University of Cincinnati, Cincinnati, OH, 45267-0536, USA

    W. L. Wurster, G. J. Pyne-Geithman & Joseph F. Clark

  2. Department of Chemistry, University of Miami, Oxford, Ohio, USA

    I. R. Peat

Authors
  1. W. L. Wurster
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  2. G. J. Pyne-Geithman
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  3. I. R. Peat
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  4. Joseph F. Clark
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Correspondence to Joseph F. Clark .

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Editors and Affiliations

  1. Department of Neurosurgery, Medical Faculty of Istanbul, University of Istanbul, Istanbul, Turkey

    Talat Kırış

  2. Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, USA

    John H. Zhang

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© 2008 Springer-Verlag

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Wurster, W.L., Pyne-Geithman, G.J., Peat, I.R., Clark, J.F. (2008). Bilirubin oxidation products (BOXes): synthesis, stability and chemical characteristics. In: Kırış, T., Zhang, J.H. (eds) Cerebral Vasospasm. Acta Neurochirurgica Supplement, vol 104. Springer, Vienna. https://doi.org/10.1007/978-3-211-75718-5_8

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  • DOI: https://doi.org/10.1007/978-3-211-75718-5_8

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