Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin

Abstract Unconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physi...

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Autores principales:	Adam Čepa, Veronika Dejmková, Ladislav Lešetický, Ivan Jelínek, Stanislav Smrček, Martin Štícha, Jana Jašprová, Marie Urbanová, Iryna Goncharova, Martin Dračínský, Eliška Procházková, Donald J. Ostrow, Libor Vítek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76e84440156a41a0b3afe937582ade16
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spelling	oai:doaj.org-article:76e84440156a41a0b3afe937582ade162021-12-02T17:39:53ZPhysico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin10.1038/s41598-021-92377-82045-2322https://doaj.org/article/76e84440156a41a0b3afe937582ade162021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92377-8https://doaj.org/toc/2045-2322Abstract Unconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pK a ). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pK a values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pK a * values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pK a values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pK a * values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pK a * values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.Adam ČepaVeronika DejmkováLadislav LešetickýIvan JelínekStanislav SmrčekMartin ŠtíchaJana JašprováMarie UrbanováIryna GoncharovaMartin DračínskýEliška ProcházkováDonald J. OstrowLibor VítekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam Čepa Veronika Dejmková Ladislav Lešetický Ivan Jelínek Stanislav Smrček Martin Štícha Jana Jašprová Marie Urbanová Iryna Goncharova Martin Dračínský Eliška Procházková Donald J. Ostrow Libor Vítek Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
description	Abstract Unconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pK a ). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pK a values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pK a * values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pK a values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pK a * values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pK a * values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.
format	article
author	Adam Čepa Veronika Dejmková Ladislav Lešetický Ivan Jelínek Stanislav Smrček Martin Štícha Jana Jašprová Marie Urbanová Iryna Goncharova Martin Dračínský Eliška Procházková Donald J. Ostrow Libor Vítek
author_facet	Adam Čepa Veronika Dejmková Ladislav Lešetický Ivan Jelínek Stanislav Smrček Martin Štícha Jana Jašprová Marie Urbanová Iryna Goncharova Martin Dračínský Eliška Procházková Donald J. Ostrow Libor Vítek
author_sort	Adam Čepa
title	Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title_short	Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title_full	Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title_fullStr	Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title_full_unstemmed	Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title_sort	physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/76e84440156a41a0b3afe937582ade16
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Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin

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