Linked Life Data

15581375

Source:http://linkedlifedata.com/resource/pubmed/id/15581375

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2004-12-7
pubmed:abstractText
A water-soluble conjugate (1) with intact carboxyl groups was prepared by addition of poly(ethylene glycol) thiol (MPEG-SH) regiospecifically to the exo vinyl group of bilirubin. (1)H and (13)C NMR and absorbance spectroscopy in CDCl(3) and DMSO-d(6) confirmed the assigned structure and showed that pegylation did not disrupt the hydrogen-bonded ridge-tile conformation of the pigment moiety. Aqueous solutions of 1 were optically clear, but NMR signals were seen only from the MPEG portion and none from the tetrapyrrole, consistent with dissolved assemblies containing aggregated bilirubin cores within mobile polyether chains. On alkalinization (pH >12), signals from the pigment moiety reappeared. Titrimetric measurements on 1 in water showed the pK(a)'s of the two carboxyl groups to be similar (average 6.42). Control studies with pegylated half-esters of succinic, suberic, brassylic, thapsic, and 1,20-eicosanedioic acid showed that pegylation per se has little, if any, effect on carboxyl ionization. However, aggregation increases the apparent pK(a) by approximately 1-2 units. The molecularity of bilirubin in solution was further characterized by ultracentrifugation. Over the pH range 8.5-10 in buffer, bilirubin formed multimers with aggregation numbers ranging from approximately 2-7. Bilirubin is monomeric in DMSO or CHCl(3) at approximately 2 x 10(-)(5) M, but aggregation occurred when the CHCl(3) was contaminated with trace adventitious (perhaps lipoidal) impurities. These observations show that aggregation increases the pK(a)'s of aliphatic carboxylic acids relative to their monomer values in water. They are consistent with earlier (13)C NMR-based estimates of approximately 4.2 and approximately 4.9 for the aqueous pK(a)'s of bilirubin and similar studies of bilirubin in micellar bile-salt solutions. Together with earlier work, they confirm that the pK(a)'s of bilirubin are about normal for aliphatic carboxyls and suggest that the high (>7.5) values occasionally reported, including those based on CHCl(3) partitioning, are artifacts of aggregation or technique.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15617-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15581375-Bilirubin, pubmed-meshheading:15581375-Buffers, pubmed-meshheading:15581375-Carbon Isotopes, pubmed-meshheading:15581375-Fatty Acids, pubmed-meshheading:15581375-Hydrogen Bonding, pubmed-meshheading:15581375-Hydrogen-Ion Concentration, pubmed-meshheading:15581375-Models, Chemical, pubmed-meshheading:15581375-Models, Molecular, pubmed-meshheading:15581375-Nuclear Magnetic Resonance, Biomolecular, pubmed-meshheading:15581375-Polyethylene Glycols, pubmed-meshheading:15581375-Potentiometry, pubmed-meshheading:15581375-Protein Subunits, pubmed-meshheading:15581375-Protons, pubmed-meshheading:15581375-Solubility, pubmed-meshheading:15581375-Solutions, pubmed-meshheading:15581375-Solvents, pubmed-meshheading:15581375-Spectrophotometry, Ultraviolet, pubmed-meshheading:15581375-Thermodynamics, pubmed-meshheading:15581375-Ultracentrifugation, pubmed-meshheading:15581375-Water
pubmed:year
2004
pubmed:articleTitle
pKa and aggregation of bilirubin: titrimetric and ultracentrifugation studies on water-soluble pegylated conjugates of bilirubin and fatty acids.
pubmed:affiliation
Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Validation Studies