Metal Ion-Binding Properties of (1H-Benzimidazol-2-yl-methyl)phosphonate (Bimp^2-) in Aqueous Solution. Isomeric Equilibria, Extent of Chelation, and a New Quantification Method for the Chelate Effect

Abstract

The acidity constants of the 2-fold protonated (1H-benzimidazol-2-yl-methyl)phosphonate, H2(Bimp)(+/-), are given, and the stability constants of the M(H;Bimp)+ and M(Bimp) complexes with the metal ions M2+ = Mg2+, Ca2+, Ba2+, Mn2+, Co2+, Cu2+, Zn2+, or Cd2+ have been determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 degrees C. Application of previously determined straight-line plots of log KM(M(Bi-R)) versus pKH(H(Bi-R)) for benzimidazole-type ligands, Bi-R, where R represents a residue which does not affect metal ion binding, proves that the primary binding site in the M(H;Bimp)+ complexes is (mostly) N3 and that the proton is located at the phosphonate group; outersphere interactions seem to be important, and the degree of chelate formation is above 60% for all metal ion complexes studied, except for Zn(H;Bimp)+. A similar evaluation based on log KM(M(R-PO3)) versus pKH(H(R-PO3)) straight-line plots for simple phosph(on)ate ligands, R-, where R represents a residue which cannot participate in the coordination process, reveals that the primary binding site in the M(Bimp) complexes is (mostly) the phosphonate group with all metal ions studied. In this case, the formation degree of the chelates varies more widely in dependence on the kind of metal ion involved, i.e., from 17 +/- 11% to nearly 100% for Ba(Bimp) and Cu(Bimp), respectively. For all the M(H;Bimp)+ and M(Bimp) systems, the intramolecular equilibria between the isomeric complexes are evaluated in a quantitative manner. The fact that for Bimp2- the metal ion affinity of the two binding sites, N3 and PO3(2-), can be calculated independently, i.e., the corresponding micro stability constants become known, allows us to present for the first time a method for the quantification of the chelate effect solely based on comparisons of stability constants which carry the same dimensions. This effect is often ill defined in textbooks because equilibrium constants of different dimensions are compared, which is avoided in the present case. For the M(Bimp) complexes, it is shown that the chelate effect is close to zero for Ba(Bimp) whereas for Cu(Bimp) it amounts to about four log units. This method is also applicable to other chelating systems. Finally, considering that benzimidazole as well as phosphonate derivatives are employed as therapeutic agents, the potential biological properties of Bimp, especially regarding nucleic acid polymerases, are briefly discussed.

Acid–Base and Metal‐Ion‐Binding Properties of Xanthosine 5′‐Monophosphate (XMP) in Aqueous Solution: Complex Stabilities, Isomeric Equilibria, and Extent of Macrochelation

“…[21,60,61] 2) All the other log D M/XMP values are very similar; in fact, they are within the error limits identical with the average of the remaining nine values (i.e., ignoring the one for Ni 2 + ), which equals 0.46 AE 0.11(3s) log units. This similarity indicates [55] that the interaction of the N7-coordinated metal ions with the P(O) 2 …”

“…Such an observation involving a P(O) 2 (OH) À group has been made before; [55] the extent of this macrochelate formation will be considered in Section 2.9.…”

“…À complexes without chelate formation but based on the M 2 + affinity of the two binding sites are known, and therefore we can define the chelate effect [55] according to Equation (31) by comparing the expected stability constant with the one actually measured [Eq. (10)]: [69] log Chelate ¼ log K The values for the three terms which appear in Equation (31) are listed in columns 9, 7, and 8, respectively, in Table 7.…”

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

“…It may be added that by a different evaluation method [164], in which the various binding sites were considered independently [97], it was concluded that the total amount of Cd(XMP -H) [= (XH·MP·Cd) ] (eq. 22) equals 87 ± 4% (which agrees within the error limits with the above result of 93 ± 3%), but that there are two open isomers, one in which Cd 2+ is coordinated to the phosphate group of (XMP -H) 3-and one where it is at the xanthinate residue (Figure 13), the formation degrees being 9 and 14%, respectively [97].…”

Acid–base and metal ion binding properties of 2-thiocytidine in aqueous solution

“…20 is the one experimentally measured for the M (C2S However, as far as the extent of (C2)S-M 2+ binding is concerned, some conclusions are possible. The following reasoning is closely related to a new evaluation method which was recently introduced to quantify the chelate [54] or macrochelate [55] …”