Cargando…

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

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-chemic...

Descripción completa

Detalles Bibliográficos
Autores principales: Čepa, Adam, Dejmková, Veronika, Lešetický, Ladislav, Jelínek, Ivan, Smrček, Stanislav, Štícha, Martin, Jašprová, Jana, Urbanová, Marie, Goncharova, Iryna, Dračínský, Martin, Procházková, Eliška, Ostrow, Donald J., Vítek, Libor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213708/
https://www.ncbi.nlm.nih.gov/pubmed/34145377
http://dx.doi.org/10.1038/s41598-021-92377-8
_version_ 1783709908830519296
author Čepa, Adam
Dejmková, Veronika
Lešetický, Ladislav
Jelínek, Ivan
Smrček, Stanislav
Štícha, Martin
Jašprová, Jana
Urbanová, Marie
Goncharova, Iryna
Dračínský, Martin
Procházková, Eliška
Ostrow, Donald J.
Vítek, Libor
author_facet Čepa, Adam
Dejmková, Veronika
Lešetický, Ladislav
Jelínek, Ivan
Smrček, Stanislav
Štícha, Martin
Jašprová, Jana
Urbanová, Marie
Goncharova, Iryna
Dračínský, Martin
Procházková, Eliška
Ostrow, Donald J.
Vítek, Libor
author_sort Čepa, Adam
collection PubMed
description 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 Online
Article
Text
id pubmed-8213708
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-82137082021-06-21 Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin Čepa, Adam Dejmková, Veronika Lešetický, Ladislav Jelínek, Ivan Smrček, Stanislav Štícha, Martin Jašprová, Jana Urbanová, Marie Goncharova, Iryna Dračínský, Martin Procházková, Eliška Ostrow, Donald J. Vítek, Libor Sci Rep Article 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. Nature Publishing Group UK 2021-06-18 /pmc/articles/PMC8213708/ /pubmed/34145377 http://dx.doi.org/10.1038/s41598-021-92377-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Čepa, Adam
Dejmková, Veronika
Lešetický, Ladislav
Jelínek, Ivan
Smrček, Stanislav
Štícha, Martin
Jašprová, Jana
Urbanová, Marie
Goncharova, Iryna
Dračínský, Martin
Procházková, Eliška
Ostrow, Donald J.
Vítek, Libor
Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213708/
https://www.ncbi.nlm.nih.gov/pubmed/34145377
http://dx.doi.org/10.1038/s41598-021-92377-8
work_keys_str_mv AT cepaadam physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT dejmkovaveronika physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT lesetickyladislav physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT jelinekivan physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT smrcekstanislav physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT stichamartin physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT jasprovajana physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT urbanovamarie physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT goncharovairyna physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT dracinskymartin physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT prochazkovaeliska physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT ostrowdonaldj physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin
AT viteklibor physicochemicalcharacterizationofbilirubin10sulfonateandcomparisonofitsacidbasebehaviorwithunconjugatedbilirubin