Metal ion-binding properties of 9-[(2-phosphonomethoxy)ethyl]-2-aminopurine (PME2AP), an isomer of the antiviral nucleotide analogue 9-[(2-phosphonomethoxy)ethyl]adenine (PMEA). Steric guiding of metal ion-coordination by the purine-amino group.
ABSTRACT The acidity constants of 3-fold protonated 9-[(2-phosphonomethoxy)ethyl]-2-aminopurine, H(3)(PME2AP)(+), and the stability constants of the M(H;PME2AP)(+) and M(PME2AP) complexes with M(2+) = Ca(2+), Mg(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+) or Cd(2+) have been determined by potentiometric pH titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO(3)). It is concluded that in the M(H;PME2AP)(+) species, the proton is at the phosphonate group and the metal ion at N7 of the purine residue. This "open" form allows macrochelate formation of M(2+) with the monoprotonated phosphonate residue. The formation degree of this macrochelate amounts on average to 64 +/- 13% (3sigma) for those metal ions for which an evaluation was possible (Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+)). The identity of this formation degree indicates that the M(2+)/P(O)(2)(-)(OH) interaction occurs in an outersphere manner. The application of previously determined straight-line plots of log K(M)(M(R-PO(3)))versus pK(H)(H(R-PO(3))) for simple phosph(on)ate ligands, R-PO(3)(2-), where R represents a residue that does not affect metal ion binding, proves that all the M(PME2AP) complexes have larger stabilities than is expected for a sole phosphonate coordination of M(2+). Combination with previous results allows the following conclusions: (i) The increased stability of the M(PME2AP) complexes of Ca(2+), Mg(2+) and Mn(2+) is due to the formation of 5-membered chelates involving the ether-oxygen atom of the -CH(2)-O-CH(2)-PO(3)(2-) residue; the formation degrees of these M(PME2AP)(cl/O) chelates for the mentioned metal ions vary between about 25% (Ca(2+)) to 40% (Mn(2+)). (ii) For the M(PME2AP) complexes of Co(2+), Ni(2+), Cu(2+), Zn(2+) or Cd(2+) next to the mentioned 5-membered chelates a further isomer is formed, namely a macrochelate involving N7, M(PME2AP)(cl/N7). The formation degrees of these macrochelates vary between about 30% (Cd(2+)) and 85% (Ni(2+)). (iii) The most remarkable observation of this study is that the shift of the NH(2) group from C6 to C2 facilitates very significantly macrochelate formation of a PO(3)(2-)-coordinated M(2+) with N7 due to the removal of steric hindrance in the M(PME2AP) complexes. However, any M(2+) interaction with N3 is completely suppressed, thus leading to significantly different coordination patterns than those observed previously with the antivirally active PMEA(2-) species.
- SourceAvailable from: Larisa E. KapinosInorganic Chemistry - INORG CHEM. 01/2001; 40(11):2500-2508.
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ABSTRACT: It is emphasized and shown that the concept of pH is more complicated than might be thought (and to some extent also unsatisfactory); there are (at least) three pH scales in general use and it is the aim to make this fact recognized. These scales are: (1) an activity scale, where the hydrogen ion activity is measured based on NBS or similar standards by carefully eliminating the liquid-junction potentials of the electrode system via experimental determinations; (2) a practical scale, which has unintentionally developed by convenience over the past ca. 30 years, is based on now generally available combined glass electrodes together with NBS (or related) buffers used for calibration; and (3) a concentration scale which uses strong acids and/or bases for calibration and defines the pH-meter reading in terms of −log[H+]. Scale (2) is clearly the one least well defined, yet it is also the one most widely used. If a ‘pH’ is measured for a given constant H+ concentration in the three scales, its value decreases in the order (1) > (2) > (3). Scales (1) and (3) may be converted into each other by using the single ion activity coefficient of H+, e.g., at 25°C and at ionic strengths of 0.1 and 0.5 M the differences correspond to 0.11 and 0.15 log unit, respectively. The conversion term from scale (2) to (3) corresponds at 25°C and an ionic strength between 0.1 and 0.5 M to about 0.03 log unit. It is evident that any acidity constant, i.e. pKa value, determined for a given system (HA ⇌| A − + H+) is affected to the same extent; hence, the mentioned conversion factors have to be applied if PKa values determined in different scales are to be compared or used. It may be added that many workers believe that combined glass electrodes measure the hydrogen ion activity and that they are working in sale (1), yet this is not the case, they are actually working in scale (2). Moreover it is also barely (or not at all) recognized that the values in scale (2) are in fact closer to those of scale (3) and not to those of scale (1), as is often assumed. Some general comments regarding potentiometric pH titrations and the determination of equilibrium constants (i.e., pKa values and stability constants of metal ion complexes) are also made, and the advantages of different titration procedures are discussed and pitfalls are pointed out.Analytica Chimica Acta. 01/1991;
- ChemInform 01/1991; 22(17):317-317.