STABILITIES AND STRUCTURES OF METAL-ION COMPLEXES OF ADENOSINE 5'-O-THIOMONOPHOSPHATE (AMPS(2-)) IN COMPARISON WITH THOSE OF ITS PARENT NUCLEOTIDE (AMP(2-)) IN AQUEOUS-SOLUTION

The stability constants of the 1:1 complexes formed between Mg2+, Ca2, Ba2+, Mn2+, Co2+, Ni2+, Zn2+, or Cd2+ and AMPS(2-), i.e., of the M(A MPS) complexes, were determined by potentiometric pH titrations (25 de grees C; I = 0.1 M, NaNO3). For the Mn2+/AMPS, Co2+/AMPS, Ni2+/AMPS, a nd Cd2+/AMPS systems also the protonated species M(H;AMPS)(+) were qua ntified, and for the Zn2+/AMPS system, the stability of the hydroxo sp ecies Zn(AMPS)(OH)(-), which results from the Zn2+-thio coordination, could be determined. On the basis of previously established log K-M(R- MP(M)) versus pK(H(R-MP)(H)) straight-line plots (R-MP(2-) = simple mo nophosphate ester ligands without further coordinating groups; Sigel, H.; et al. Helv. Chim. Acta 1992, 75, 2634), it is concluded that the alkaline earth ions in the M(AMPS) complexes are coordinated to the th iophosphate group with the same intensity as to a normal phosphate gro up. For the M(AMPS) complexes of Mn2+, Co2+, Ni2+, Zn2+, and Cd2+, it is shown by comparison with the corresponding M(AMP) complexes and by employing the mentioned straight-line plots that the stability increas e is larger than may be expected due to macrochelate formation, which means that the metal ions also bind to the sulfur atom of the thiophos phate group. The stability increases amount for Mn(AMPS), Zn(AMPS), an d Cd(AMPS) to about 0.2, 0.7, and 2.4 log units, respectively, and the estimated approximate percentages of the sulfur-coordinated species a re about 30, 80, and 100%, respectively. Furthermore, comparisons betw een these stability increases and the solubility products for the corr esponding metal ion sulfides, M(Pi)S, as well as with the stability in creases due to the M(2+) - thioether interaction observed for the comp lexes of tetrahydrothiophene-2-carboxylate, which also result in strai ght-line plots, further support the conclusions about metal ion-sulfur binding in the mentioned M(AMPS) complexes. The indicated correlation s allow also an estimate for the extent of the M(2+)-sulfur interactio n in Pb(AMPS) and Cu(AMPS). The various isomers of the M(H;AMPS)(+) sp ecies are analyzed in a microconstant scheme, and estimations about th eir formation degrees are presented; for example, for the Cd2+ system, (H;AMPS . Cd)(+) is the dominating isomer, which has the proton at N1 and Cd2+ at the thiophosphate group. It is evident that for metal ion s like (Mn2+), Zn2+, or Cd2+ the metal ion binding properties of the p arent compound AMP(2-) and its thio analogue AMPS(2-) differ considera bly, and therefore, great care should be exercised in enzymatic studie s where AMPS(2-) is employed as a probe for AMP(2-) in the presence of metal ions. Regarding studies of ribozymes, it is of interest that pl ots are presented (pseudo-first-order rate constants versus complex st abilities) which suggest that on top of a sulfur-metal ion interaction during the transition state of the rate-determining step of the hydro lytic cleavage of an oligonucleotide containing a bridged internucleot ide 5'-phosphorothioate RNA linkage also an oxygen-metal ion interacti on occurs and that the two effects are ''additive''.