title: Acid-base properties of xanthosine 5'-monophosphate (XMP) and of some related nucleobase derivatives in aqueous solution: micro acidity constant evaluations of the (N1)H versus the (N3)H deprotonation ambiguity.
abstract: The first acidity constant of fully protonated xanthosine 5'-monophosphate, that is, of H3(XMP)+, was estimated by means of a micro acidity constant scheme and the following three deprotonations of the H2(XMP)+/- (pKa=0.97), H(XMP)- (5.30), and XMP2- (6.45) species were determined by potentiometric pH titrations; further deprotonation of (XMP-H)3- is possible only with pKa>12. The most important results are that the xanthine residue is deprotonated before the P(O)2(OH)- group loses its final proton; that is, twofold negatively charged XMP carries one negative charge in the pyrimidine ring and one at the phosphate group. Micro acidity constant evaluations reveal that this latter mentioned species occurs with a formation degree of 88 %, whereas its tautomer with a neutral xanthine moiety and a PO3(2-) group is formed only to 12 %; this distinguishes XMP from its related nucleoside 5'-monophosphates, like guanosine 5'-monophosphate. At the physiological pH of about 7.5 mainly (XMP-H)3- exists. The question, which of the purine sites, (N1)H or (N3)H, is deprotonated in this species cannot be answered unequivocally, though it appears that the (N3)H site is more acidic. By application of several methylated xanthine species intrinsic micro acidity constants are calculated and it is shown that, for example, for 7-methylxanthine the N1-deprotonated tautomer occurs with a formation degree of about 5 %; a small but significant amount that, as is discussed, may possibly be enhanced by metal ion coordination to N7, which is known to occur preferably to this site.
authors.affiliation: Departement Chemie, Anorganische Chemie, Universität Basel, Spitalstrasse 51, 4056 Basel, Switzerland.
authors.forename: Salah S
authors.initials: SS
authors.lastname: Massoud
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Corfù
authors.forename: Rolf
authors.initials: R
authors.lastname: Griesser
authors.forename: Helmut
authors.initials: H
authors.lastname: Sigel
mesh_terms: D000143:Acids / Q000737:chemistry*; D000468:Alkalies / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D011522:Protons; D012265:Ribonucleotides / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D019820:Xanthine / Q000737:chemistry
chemical_list: D000143:Acids; D000468:Alkalies; D011522:Protons; D012265:Ribonucleotides; D012996:Solutions; D019820:Xanthine; C011141:xanthosine monophosphate; D006859:Hydrogen; D009584:Nitrogen