Beda E. Fischer

Binary and ternary complexes of metal ions, nucleoside 5′-monophosphates, and amino acids

The aromatic-ring stacking interactions between the indole moiety of L-tryptophan and the purine or pyrimidine moieties of AMP2− or CMP2+, respectively, were studied by 1H NMR spectroscopy. Under the influence of increasing concentrations of L-trytophan the resonance of H-2, H-8 and H-1′ of AMP2− of a H-5 and H-6 of CMP2− are shifted upfield. Computer curve fitting of the shift data gave the stability constants K(AMP)(H·Trp)(AMP) = 6.83 ± 0.81 M−1 and K(CMP)(H·Trp)CMP = 0.77 ± 0.35 M−1 (in D2O; 27°C; I = 0.1 M) which show that the purine moiety forms the more stable stacks. Repetition of the experiments under conditions where the amino acid exists as the anion, i.e. as tryptophanate, gave K(AMP)(Trp)(AMP) = 2.24 ± 0.29 M−1 and K(CMP)(Trp)(CMP) = 0.14 ± 0.05 M−1 (in D2O; 27°C; I = 0.1–0.15 M). Hence, it is evident that the formation of an ionic bridge between the negatively charged phosphate moiety of the nucleotides and the positively charged ammonium group of L-tryptophan favors the formation of the stack between the nucleic bases and the indole residue. In the case with AMP2− the stability constant of this ion pair formation could be estimated, i.e. KIP ≅ 0.6 M−1 (in D2O; 27°C; I = 0.1–0.15 M), a value which compares well with KIP = 1.35 ± 0.76 M−1 for the (CH3)4N+/Trp− interaction. Intramolecular equilibrium constants for the ion pair interaction within the stacked complex and for the stacking interaction within the ion pair complex are also estimated and discussed. Stability constant of metal ion complexes could only be determined with Ni2+ as a precipitate formed with Cu2+ and Zn2+. The stability constants of the binary systems, Ni2+/AMP2−, Ni2+/CMP2−, Ni2+/Trp−, and Ni2+/Ala−, were determined by potentiometric pH-titrations. The somewhat enhanced stability of Ni(Trp)2 compared with Ni(Ala)2, and of Ni(AMP)22− compared with Ni(CMP)22− (for which no evidence of formation was observed) is explained by self-stacking within these binary 1:2 complexes. Based on the data of the binary systems, the following ternary systems were studied and the corresponding stability constants determined: Ni2+/AMP2−/Trp−, Ni2+/AMP2−/Ala−, Ni2+/CMP2−/Trp−, and Ni2+/CMP2−/Ala−. A most likely intramolecular purine/indole stack in the ternary Ni(AMP)(Trp)− complex is not significantly reflected in the measured stability constants. This observation and the implications of stacking with regard to the stability of ternary complexes, as well as the general importance of “bridged” stacking adducts for biological systems are briefly discussed.

Hydration, protonation and metal ion-coordination of di-2-pyridyl ketone

Abstract The qualities of di-2-pyridyl ketone (DPK) in aqueous solution (I = 0·1, NaClO4; 25°) were studied by potentiometry and spectrophotometry in the absence and presence of metal ions. The acidity constants of DPKH+ ( p K A 1 = 3·06 ) and of the geminal diol, formed by the addition of H2O to the carbonyl group ( p K A 2 = 13·61 ), were measured. The log stability constants for the metal ion-DPK 1 : 1 complexes are for Mn2+ 1·03, Co2+ 2·56, Ni2+ 3·98, Cu2+ 5·13 and for Zn2+ 2·12. In these complexes the metal ion is N,N-coordinated, and the keto group is present in form of the geminal diol. This latter group is ionized in the pH range 5–8 leading to an N,O-coordination of the metal ion; the negative log acidity constants for the complexes with Mn2+ are 7·8, Co2+ 5·7, Ni2+ 6·34, Cu2+ 5·2, and with Zn2+ 5·3. From these and the other preceding data the stability constants of the N,O-coordinated complexes may be calculated.

Ternary Complexes in Solution, XX

The stability constants of the ternary Cu2+ complexes containing 1,2-diaminobenzene and oxalate or salicylate have been calculated from potentiometric titration curves published by G. K. CHATURVEDI and J. P. TANDON (Z. Naturforsch. 23b, 303 [1968]; 25b, 26 [1970]). A comparison of the results with data of the literature reveals that the qualities of 1,2-diaminobenzene in ternary complexes correspond to those of ethylenediamine, while the qualities of both amines differ considerably from those of 2,2′-bipyridyl, which has a stability-enhancing effect.

Comparison of the ligating properties of disulphides and thioethers: dimethyl disulphide, dimethyl sulphide, and related ligands

The stability constants of 1 : 1 complexes between dimethyl disulphide (dmds) or dimethyl thioether (dms) and Ca2+, Zn2+, Cd2+, Pb2+, or Ag+(KML for Mn++ L ⇌[ML]n+) have been determined in aqueous solution by 1H n.m.r. shift measurements. The results [e.g. log KCa(dmds)ca.–1.4, log KCd(dmds)ca.–1.4, log KAg(dmds)= 2.01 ± 0.09; log KCa(dms)ca.–1.6, log KCd(dms)=–0.3 ± 0.2, and log KAg(dms)= 3.7 ± 0.3] show that the complexes with soft metal ions are stronger than those with borderline or hard metal ions. It is also evident that the ligating properties of the thioether moiety are somewhat more pronounced towards borderline and soft metal ions than those of the disulphide group. Spectrophotometrically determined stability constants (in 50% aqueous ethanol) for the complexes between Mn2+, Cu2+, or one of the above metal ions and dmds, diethyl sulphide, or tetrahydrothiophen accord with this. In addition, for several complexes of tetrahydrothiophen-2-carboxylate (thtc–) and 1,2-dithiolan-3-carboxylate [= tetranorlipoate (tnl–)], the dimensionless constants for the intramolecular equilibrium between the chelated isomer (which is bonded to the metal by the sulphur atom and the carboxylate group) and the simple carboxylate-co-ordinated isomer have been calculated, together with the percentages of the chelated isomer {e.g. 93 ± 1 for [Cu(thtc)]+ and 41 ± 7 for [Cu(tnl)]+; 55 ± 5 for [Cd(thtc)]+ and ⩽20% for [Cd(tnl)]+; ⩽20% for both [Mn(thtc)]+ and [Mn(tnl)]+}. Possible biological implications of such weak interactions and the resulting intramolecular equilibria are briefly discussed.

Ternary Complexes in Solution, XXX Increased Stability Through Intramolecular Stacking in Mixed-Ligand Cu 2+ and Zn 2+ Complexes of 2,2′ -Bipyridyl and Carboxymethyl Aryl Derivatives

Abstract The stability constants of ternary Cu 2+ and Zn 2+ complexes, each of which contains 2,2′-bipyridyl and a carboxymethyl aryl sulfide, were determined in 50% aqueous dioxane. A comparison of the stability of these ternary complexes with those formed with simple carboxylates demonstrates an enhanced stability of the carboxymethyl aryl sulfide containing mixed ligand complexes. This enhanced stability is not due to a thioether-metal ion interaction, but due to an intramolecular aromatic stacking interaction between the aryl moiety of the carboxymethyl aryl sulfide and 2,2′-bipyridyl. Indeed, by UV difference spectra and by PMR measurements it is possible to show that a binary (metal ion-free) stacked adduct between the aromatic moieties of the two mentioned ligands is formed. Furthermore, by studying the binary and ternary systems of Zn 2+ or Cu 2+ , 2,2′-bipyridyl and hydrocinnamate, i.e. 3-phenylpropionate (-S-of carboxymethyl phenyl sulfide is replaced by -CH2-), it becomes obvious that the thioether moiety is not essential for the observation of an enhanced stability of the ternary complexes. PMR shift studies of 2,2′-bipyridyl/Zn 2+ /carboxymethyl aryl sulfide systems confirm the presence of stacking in the corresponding ternary complexes. Depending on the kind of the ternary metal ion complex the stability enhancement, due to the intramolecular stacking between the aromatic parts of the coordinated ligands, is between about 0.2 to 0.5 log unit.