title: Acid-base and metal-ion-binding properties of xanthosine 5'-monophosphate (XMP) in aqueous solution: complex stabilities, isomeric equilibria, and extent of macrochelation.
abstract: The four acidity constants of threefold protonated xanthosine 5'-monophosphate, H3(XMP)+, reveal that at the physiological pH of 7.5 (XMP-H)(3-) strongly dominates (and not XMP(2-) as given in textbooks); this is in contrast to the related inosine (IMP(2-)) and guanosine 5'-monophosphate (GMP(2-)) and it means that XMP should better be named as xanthosinate 5'-monophosphate. In addition, evidence is provided for a tautomeric (XMP-HN1)(3-)/(XMP-HN3)(3-) equilibrium. The stability constants of the M(H;XMP)+ species were estimated and those of the M(XMP) and M(XMP-H)- complexes (M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+) measured potentiometrically in aqueous solution. The primary M2+ binding site in M(XMP) is (mostly) N7 of the monodeprotonated xanthine residue, the proton being at the phosphate group. The corresponding macrochelates involving P(O)2(OH)- (most likely outer-sphere) are formed to approximately 65% for nearly all M2+. In M(XMP-H)- the primary M2+ binding site is (mostly) the phosphate group; here the formation degree of the N7 macrochelates varies widely from close to zero for the alkaline earth ions, to approximately 50% for Mn2+, and approximately 90% or more for Co2+, Ni2+, Cu2+, Zn2+, and Cd2+. Because for (XMP-H)(3-) the micro stability constants quantifying the M2+ affinity of the xanthosinate and PO3(2-) residues are known, one may apply a recently developed quantification method for the chelate effect to the corresponding macrochelates; this chelate effect is close to zero for the alkaline earth ions and it amounts to about one log unit for Co2+, Ni2+, Cu2+. This method also allows calculation of the formation degrees of the monodentatally coordinated isomers; this information is of relevance for biological systems because it demonstrates how metal ions can switch from one site to another through macrochelate formation. These insights are meaningful for metal-ion-dependent reactions of XMP in metabolic pathways; previous mechanistic proposals based on XMP(2-) need revision.
authors.affiliation: Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, 4056 Basel, Switzerland. helmut.sigel@unibas.ch
authors.forename: Helmut
authors.initials: H
authors.lastname: Sigel
authors.forename: Salah S
authors.initials: SS
authors.lastname: Massoud
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Rolf
authors.initials: R
authors.lastname: Griesser
authors.forename: Bernd
authors.initials: B
authors.lastname: Knobloch
authors.forename: Bert P
authors.initials: BP
authors.lastname: Operschall
mesh_terms: D000143:Acids / Q000737:chemistry; D000468:Alkalies / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D011199:Potentiometry; D012265:Ribonucleotides / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry; D019820:Xanthine
chemical_list: D000143:Acids; D000468:Alkalies; D002614:Chelating Agents; D007477:Ions; D008670:Metals; D012265:Ribonucleotides; D012996:Solutions; D014867:Water; D019820:Xanthine; C011141:xanthosine monophosphate