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 Relev
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- 作者：Marina Fainerman-Melnikova ; Teré ; zia Szabó ; -Plá ; nka ; Antal Rockenbauer ; and Rachel Codd
- 刊名：Inorganic Chemistry
- 出版年：2005
- 出版时间：April 4, 2005
- 年：2005
- 卷：44
- 期：7
- 页码：2531 - 2543
- 全文大小：266K
- 年卷期：v.44,no.7(April 4, 2005)
- ISSN：1520-510X
文摘
The equilibrium distribution of species formed between Cu(II) and N-acetylneuraminic (sialic) acid (I, LH) at 298 Khas 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]+ [log
= 1.64(4)], and[CuL2] [log = 2.77(5)]. At intermediate pH values (4.0 < pH < 7.5), [CuL2H-1]- [log = -2.72(7)] and twoisomers of [CuLH-1] [log (overall) = -3.37(2)] are present. At alkaline pH values (7.5 < pH < 11), themajor species present is [CuL2H-2]2-, modeled as three isomers with unique giso and Aiso values [log (overall) =-8.68(3)]. Two further species ([CuLH-3]2- and [CuL2H-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 asa dianionic tridentate chelate, via oxygen atoms derived from O1, OR, and one deprotonated hydroxy group (O7 orO8) 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 O1,OR {I(1-)} orO1,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,O2)} have "irregular" EPR spectra that are ascribed to the existenceof Cu(II)-I(monomer) 
Cu(II)-I(polymer) equilibria. The formation of polymeric Cu(II)-I species will be favored inthese complexes because the glycerol-derived hydroxyl groups at the complex periphery (O,7O,8O9) are availablefor further Cu(II) binding. The presence of polymeric Cu(II)-I species is supported by EPR spectral data fromsolutions of Cu(II) and the homopolymer of I, colominic acid (Ipoly). Conversely, spectra predicted for Cu(II)-I complexeswhere I is coordinated in a {I(2-)} tridentate {e.g., [CuLH-1] (isomer: O1,OR,O7, or O8) and [CuL2H-2]2- (isomer:bis-O1,OR,O7, or O8)} or tetradentate fashion {I(3-)} {e.g., [CuLH-3]2- (O1,OR,O,8O9)} are typical for mononucleartetragonally elongated Cu(II) octahedra. In this latter series of complexes, the tendency toward the formation ofpolymeric 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 inhuman biology, such as the sialylated amyloid precursor protein of relevance to Alzheimer's disease.
= 1.64(4)], and[CuL2] [log = 2.77(5)]. At intermediate pH values (4.0 < pH < 7.5), [CuL2H-1]- [log = -2.72(7)] and twoisomers of [CuLH-1] [log (overall) = -3.37(2)] are present. At alkaline pH values (7.5 < pH < 11), themajor species present is [CuL2H-2]2-, modeled as three isomers with unique giso and Aiso values [log (overall) =-8.68(3)]. Two further species ([CuLH-3]2- and [CuL2H-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 asa dianionic tridentate chelate, via oxygen atoms derived from O1, OR, and one deprotonated hydroxy group (O7 orO8) 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 O1,OR {I(1-)} orO1,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,O2)} have "irregular" EPR spectra that are ascribed to the existenceof Cu(II)-I(monomer) Cu(II)-I(polymer) equilibria. The formation of polymeric Cu(II)-I species will be favored inthese complexes because the glycerol-derived hydroxyl groups at the complex periphery (O,7O,8O9) are availablefor further Cu(II) binding. The presence of polymeric Cu(II)-I species is supported by EPR spectral data fromsolutions of Cu(II) and the homopolymer of I, colominic acid (Ipoly). Conversely, spectra predicted for Cu(II)-I complexeswhere I is coordinated in a {I(2-)} tridentate {e.g., [CuLH-1] (isomer: O1,OR,O7, or O8) and [CuL2H-2]2- (isomer:bis-O1,OR,O7, or O8)} or tetradentate fashion {I(3-)} {e.g., [CuLH-3]2- (O1,OR,O,8O9)} are typical for mononucleartetragonally elongated Cu(II) octahedra. In this latter series of complexes, the tendency toward the formation ofpolymeric 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 inhuman biology, such as the sialylated amyloid precursor protein of relevance to Alzheimer's disease.