Carbohydrates as ligands: coordination equilibria and structure of the metal complexes

Publisher Summary This chapter describes the complexes (briefly designated as metal-sugar complexes) that are formed, in detectable proportions, in aqueous solution from cations and unionized carbohydrates. Complex formation between cations and carbohydrates can be readily detected by paper electrophoresis. Thin-layer ligand-exchange chromatography makes the use of commercially available, thin-layer plates coated with a cation-exchange resin in the sodium form; the sodium ions can readily be exchanged for other cations by immersing the plate in an appropriate salt solution. Complex-formation causes the changes of the chemical shifts in the nuclear magnetic resonance spectra of sugars and polyols. Complex-formation with a cation does not, in itself, affect the optical rotatory power of a carbohydrate. However, complex-formation is often accompanied by a change of conformation that causes a change in the optical rotation. The proposal that strong complexing occurs between cations and a contiguous a,e,a sequence of hydroxyl groups in carbohydrates was first based simply on the observation that many compounds having such an arrangement complex well and many others lacking such an arrangement complex poorly, as shown by electrophoretic mobilities. The nature of complex- formation between cations and monosaccharides is now well understood; this knowledge should form a firm basis for the study of cation-polysaccharide interactions.

Complexes of Metal Cations with Carbohydrates in Solution

Metal coordination to carbohydrates. Structures and function

The major features of N.M.R. transverse water proton relaxation in solutions of native bovine serum albumin can be quantitatively interpreted in terms of fast chemical exchange between water and protein protons. Transverse proton relaxation dispersions are observed as a function of CPMG pulse spacing and spectrometer frequency and are shown to be consistent with the fast exchange of water with NH and OH protons of the amino acid side chains in the protein. The mean first order exchange rate is about 5 × 103 s-1. Although there is evidence that proteins influence the state of the water around them (the so called ‘bound’ water concept) the results obtained suggest that this influences the proton relaxation in a minor way compared to the potent effect of the chemical exchange mechanism.

The effects of proteins on the proton N.M.R. transverse relaxation times of water: I. Native bovine serum albumin

Physiological concentration of Mg2+, Cu2+, and Zn2+ accelerated AGE formation only in glucose-mediated conditions, which was effectively inhibited by chelating ligands. Only quercetin (10) inhibited MGO-mediated AGE formation as well as glucose- and ribose-mediated AGE formation among 10 polyphenols (1-10) tested. We performed an additional structure-activity relationship (SAR) study on flavanols (10, 11, 12, 13, and 14). Morin (12) and kaempherol (14) showed inhibitory activity against MGO-mediated AGE formation, whereas rutin (11) and fisetin (13) did not. These observations indicate that 3,5,7,4'-tetrahydroxy and 4-keto groups of 10 are important to yield newly revised mono-MGO adducts (16 and 17) and di-MGO adduct (18) having cyclic hemiacetals, while 3'-hydroxy group is not essential. We propose here a comprehensive inhibitory mechanism of 10 against AGE formation including chelation effect, trapping of MGO, and trapping of reactive oxygen species (ROS), which leads to oxidative degradation of 18 to 3,4-dihydroxybenzoic acid (15) and other fragments.

Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species

At low temperatures in a small pH range, well resolved hydroxy-resonance features have been detected for dilute aqueous solutions of sugars. Shifts in these resonances on the addition of calcium chloride have been followed for the major forms of a range of monosaccharides. These trends take three forms: (i) normal, linear, up-field shifts, comparable to that for the water-proton resonance, indicating no preferential interaction, (ii) reduced up-field or weak down-field shifts, which remain almost linear, assigned to weak binding of two OH groups to Ca2+ ions, either adjacent axial + equatorial groups or two cis axial groups separated by one —CHX— group, and (iii) down-field shifts becoming normal up-field shifts at high salt concentrations, assigned to strong binding of Ca2+ ions to three adjacent OH groups in the axial–equatorial–axial configuration. Only in the case of strong complexing (iii) is there clear evidence for cation-induced conformational changes.These assignments apply to the pyranose forms of the sugars. Our more limited results for the furanose forms strongly support the suggestion that three cis OH groups are required for strong bonding. When the anomeric (O1H) proton in α- or β-D-glucose is replaced by a methyl group the weak binding to Ca2+ ions observed for the O1H and O2H groups is lost, since the down-field shift for the O2H-proton resonance changes to a normal up-field shift. This means that the —OMe group fails to coordinate to the Ca2+ ions. Reasons for this result are proposed.

Interactions between calcium ions and a range of monosaccharides studied by hydroxy-proton resonance spectroscopy

Resolved hydroxy-proton resonance features for various forms of D-ribose in dilute aqueous solutions shift markedly on the addition of calcium chloride. Down-field shifts are assigned to OH groups which bind to Ca2+ ions. These shifts level off in the 1.0–1.5 mol dm–3 region when complexing is complete. Resonances for OH groups which are not involved in complex formation shift linearly to high-field, the shift being greater than that expected for the sum of general Ca2+ and Cl– ionic effects. This is because the Ca2+ ions are removed by complex formation, the up-field shift being largely due to the effect of chloride ions. When chloride is replaced by perchlorate, this up-field shift is greatly enhanced. Approximate equilibrium constants for complex formation have been derived, and the influence of conformational changes is discussed.

Study of calcium ion binding to D-ribose in aqueous solutions using hydroxy-proton resonance shifts

The major tautomers of D-fructose in water are the β-pyranose and β-furanose forms, the former predominating. NMR studies have shown that when aqueous DNA is added, there is a shift in the β-pyranose ⇌β-furanose equilibrium, the latter form being favoured. It is suggested that this is caused by weak, preferential binding of the β-furanose form to DNA. This is supported by computer modelling, which shows that for the former, only two hydrogen bonds can be formed between sugar O–H groups and phosphate units, whereas three good bonds can be formed with the latter.Studies of the O–1H resonances of the anomeric groups of the two forms confirm this change in equilibrium. In addition this feature for the β-furanose form shifts to low-field without significant broadening. This indicates that strong hydrogen bonding to DNA occurs, but that the equilibrium is very rapid giving fast averaging of the NMR signals.

Heather Pelmore

Papers

Interactions between calcium ions and a range of monosaccharides studied by hydroxy-proton resonance spectroscopy

Study of calcium ion binding to D-ribose in aqueous solutions using hydroxy-proton resonance shifts

Binding of sugars to DNA. An NMR study of D-fructose

Binding of Sugars to DNA. An NMR Study of D-Fructose