Acid-base and metal-ion-binding properties of xanthosine 5′-monophosphate (XMP) in aqueous solution:: Complex stabilities, isomeric equilibria, and extent of macrochelation

The four acidity constants of threefold protonated xanthosine 5'-monophosphate, H-3(XMP)(+), reveal that at the physiological pH of 7.5 (XMP-H)(3-) strongly dominates (and not XMP2- as given in textbooks); this is in contrast to the related inosine (IMP2-) 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-H.N1)(3-)/(XMP-H.N3)(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 approximate to 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 1widely from close to zero for the alkaline earth ions, to approximate to 50% for Mn2+, and approximate to 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 pO(3)(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 XMP2- need revision.