A GENERAL-METHOD FOR THE DETERMINATION OF THE KINETIC STABILITY OF MACROCYCLIC ALKALI-METAL COMPLEXES WITH RATES OF DECOMPLEXATION BELOW 10(-3) S(-1)

A general method has been developed for the determination of kinetic stabilities of macrocyclic alkali-metal complexes with rates of decomplexation (k(d)) below 10(-3) s-1, by use of radioactive isotopes. This method offers the possibility to study the influence of the solvent polarity and of the salt concentration in solution on the rate of decomplexation of macrocyclic metal complexes. Further advantages are the small amounts of ligand required for these determinations and the simplicity of the method. Furthermore, it is possible by this method to study the 'degenerate' exchange of sodium for sodium and of rubidium for rubidium. By this method the kinetic stabilities of the sodium and rubidium complexes of calixspherands 1-4 were determined. Calixspherand 3 forms kinetically very stable complexes with sodium and rubidium cations in acetone and Me2SO in the presence of high concentrations of sodium cations in solution; half-life times of exchange are 855 (Na+) and 528 (Rb+) h in acetone and 352 (Na+) and 845 (Rb+) h in Me2SO, respectively. The results of this method were verified by an independent H-1 NMR spectroscopic method

FUNCTIONALIZED CALIXSPHERANDS - SYNTHESIS AND PEPTIDE COUPLING

Calixspherands, like 1, form kinetically stable complexes with alkali metal cations. For practical in vivo applications coupling of these complexes with carrier molecules is mandatory, Therefore, a general method for the synthesis of functionalized calixspherand 17 was developed starting from functionalized m-terphenyl 10 and p-tert-butylcalix[4]arene (14). The functionalized m-terphenyl was synthesized by a Suzuki-cross-coupling reaction. Functionalized calixspherand 17 has been coupled to a low molecular weight protein

KINETICALLY STABLE COMPLEXES OF ALKALI CATIONS WITH CALIXSPHERANDS - AN EVALUATION OF SHIELDING

Three new calixspherands (2-4) were synthesized in good yields (>60%) via a new method; p-tert-butylcalix[4]arene (6) is bridged with a m-terphenyl (7-9) and subsequently alkylated. H-1 NMR spectroscopy and X-ray crystallography showed that all the complexes are in a partial cone conformation. All the calixspherands form kinetically stable complexes with Na+, K+, and Rb+. The kinetic stability was determined both by H-1 NMR spectroscopy, in CDCl3 saturated with D2O, and by a new method based on the exchange of radioactive rubidium or sodium in the complexes for nonradioactive sodium in different solvents. Both methods showed that the kinetic stability of the different complexes is strongly increased when the size of the group on the central aromatic ring of the m-terphenyl is increased. This effect is most pronounced for the rubidium complexes. The half-life times for decomplexation, in CDCl3 saturated with D2O, increased from 2.8 h for [1.Rb]+ to 139 h and 180 days for [2.Rb]+ and [3.Rb]+, respectively. The ''exchange method'' shows that the rate of decomplexation is the rate-limiting step in the exchange of rubidium in the complex for sodium present in solution. These results can be explained in terms of increased shielding of the cavity from solvent molecules. The kinetic stabilities of the complex of 3 with Na+, K+, and Rb+ are the highest ever reported