| With recent advances demonstrating that pH measurement by potentiometric methods in alcohol can be as simple as that in water, we endeavoured to exploit this in our own studies of metal ion-promoted acyl and phosphoryl transfer reactions in alcohols. The potentiometric titration of these metal ions can give valuable information as to the relative acidity of the metal-bound solvent molecules, and in favourable cases where corroborative information exists from kinetic studies, spectroscopy and mass spectrometry, the speciation of the metal ions in solution can be determined. The potentiometric titrations of nine Ln3+ triflates, Zn2+ and Cu2+ triflate, and the Ni2+, Co2+, Mg 2+ and Ti4+ perchlorates were obtained in methanol, and that for Zn2+, Cu2+ and twelve Ln 3+ triflates were obtained in ethanol to determine the titration constants (defined as the pssH at which the [-OR]/[Mx+]t ratios are 0.5, 1.5 and 2.5) as well as the apparent pssKa values for deprotonation of the metal ion-bound solvent molecules. The titrations were performed under various conditions with and without added salts as electrolytes, and the variations in the titration constants are discussed. Trends in the titration constants in passing from water to the lower polarity alcohol media are also discussed which indicate a profound effect on pssKa values that may help explain the excellent catalysis observed for metal ions in these media and in enzyme active sites. In selected cases the titration profiles were analyzed using the computer fitting program Hyperquad 2000 to obtain information about the species present in solution. In the case of La3+, a dinuclear model is presented where the species La 3+2(-OR)n (where n = 1 to 4, 5 or 6) spontaneously form over a range of pssH values. The speciation of this metal ion was related to kinetic studies for the La3+-catalyzed methanolysis of the activated phosphate diester methyl (p-nitrophenyl) phosphate and the beta-lactam nitrocefin and two simple beta-lactams, as well as for the ethanolysis of the phosphate triester paraoxon. In these cases, the kinetics for second order rate constants vs. pssH showed unconventional non-linear curves on log/log plots which were difficult to explain unless one takes into account the variation in speciation of the catalyst as a function of pssH . These kinetics, which demonstrate cases of strong substrate binding to the metal ion and no strong binding, were analyzed in detail and individual rate constants for the active species are presented. In the case of Zn 2+ and Cu2+, which are most active in a mononuclear state but spontaneously form dimers in alcohol solution, immobilization on polymer- and silica-based supports was attempted to enforce monomeric speciation on the metal ions. The kinetics of unactivated amide methanolysis promoted by metal ions were also explored to see if speciation analysis was required, ultimately revealing that these substrates were not amenable to catalysis by the metal ions studied. |
