Coordination modes between copper(II) and N-acetylneuraminic (Sialic) acid from a 2D-simulation analysis of EPR spectra. Implications for copper mediation of sialoglycoconjugate chemistry relevant to human biology

Marina Fainerman-Melnikova, Terézia Szabó-Plánka, Antal Rockenbauer, Rachel Codd

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The equilibrium distribution of species formed between Cu(II) and N-acetylneuraminic (sialic) acid (I, LH) at 298 K has been determined using a two-dimensional (2D) simulation analysis of electron paramagnetic resonance (EPR) spectra. In acidic solutions (pH values < 4), the major species present are Cu2+, [CuL]+ [logβ = 1.64(4)], and [CuL 2] [logβ = 2.77(5)]. At intermediate pH values (4.0 < pH < 7.5), [CuL2H-1]- [logβ = -2.72(7)] and two isomers of [CuLH-1] [logβ (overall) = -3.37(2)] are present. At alkaline pH values (7.5 < pH < 11), the major species present is [CuL2H-2]2-, modeled as three isomers with unique giso and Aiso values [logβ (overall) = -8.68(3)]. Two further species ([CuLH-3]2- and [CuL 2H-3]3-) appear at pH values > 11. It is proposed that [CuL]+ most likely features I coordinated via the deprotonated carboxylic acid group (O1) and the endocyclic oxygen atom (OR) forming a five-membered chelate ring. Select Cu(II)-I species of the form [CuLH-1] may feature I acting as a dianionic tridentate chelate, via oxygen atoms derived from O1, OR, and one deprotonated hydroxy group (O7 or O8) from the glycerol tail. Alternatively, I may coordinate Cu(II) in a bidentate fashion as the tert-2-hydroxycarboxylato (O1,O2) dianion. Spectra predicted for Cu(II)-I complexes in which I is coordinated in either a O 1,OR {I(1-)} or O1,O2{I(2-)} bidentate fashion {e.g., [CuL]+ (O1,OR), [CuL2] (bis-O1,OR), [CuLH-1] (isomer: O1,O2), [CuL2H-1] - (O1,OR; O1,O2), and [CuL2H-2]2- (isomer: bis-O1,O 2)} have "irregular" EPR spectra that are ascribed to the existence of Cu(II)-I(monomer) ⇌ Cu(II)-I(polymer) equilibria. The formation of polymeric Cu(II)-I species will be favored in these complexes because the glycerol-derived hydroxyl groups at the complex periphery (O 7,O8O9) are available for further Cu(II) binding. The presence of polymeric Cu(II)-I species is supported by EPR spectral data from solutions of Cu(II) and the homopolymer of I, colominic acid (I poly). Conversely, spectra predicted for Cu(II)-I complexes where I is coordinated in a {I(2-)} tridentate {e.g., [CuLH-1] (isomer: O1,OR,O7, or O8) and [CuL 2H-2]2- (isomer: bis-O1,O R,O7, or O8)} or tetradentate fashion {I(3-)} {e.g., [CuLH-3]2- (O1,OR,O 8,O9)} are typical for mononuclear tetragonally elongated Cu(II) octahedra. In this latter series of complexes, the tendency toward the formation of polymeric Cu(II)-I analogues is small because the polydentate I effectively wraps up the mononuclear Cu(II) center. This work shows that Cu(II) could potentially mediate the chemistry of sialoglycoconjugate-containing proteins in human biology, such as the sialylated amyloid precursor protein of relevance to Alzheimer's disease.

Original languageEnglish
Pages (from-to)2531-2543
Number of pages13
JournalInorganic Chemistry
Issue number7
Publication statusPublished - Apr 7 2005


ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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