The unusual protonation constants of cyclam. A potentiometric, crystallographic and molecular mechanics study

The protonation constants for cyclam (1,4,8,11-tetraazacyclotetradecane) have been determined by glass electrode potentiometry in 0.10 M KCI at 25 degrees C and yield values of 11.29(2), 10.19(1), 1.61(1) and 1.91(1) for the logarithms of the first, second, third and fourth protonation constants. This result supports previous studies (Micheloni 1978, Them 1985) which show the unusual sequence of protonation constants where the third protonation constant of cyclam is smaller than the fourth, in contrast with a large number of other workers who report the third to be larger than the fourth protonation constant. The crystal structure of cyclam . 4HClO(4) . 2H(2)O is reported: monoclinic, P2(1)/n, a = 8.409(2), b = 15.81(3), c = 9.221(1) Angstrom, beta = 105.99(1)degrees, Z = 2, R = 0.0374. A molecular mechanics (MM) analysis of the conformations of cyclam . H-n(n+), and of trien . H-n(n+) (trien = 1,4,7,10-tetraazadecane) with differing numbers of protons (n) present, is reported. It is shown that the structures cyclam . H-4(4+) that have been determined crystallographically correspond to the two lowest energy conformers identified in the MM analysis. The strain energies of the series trien . H-n(n+) rise smoothly as n increases from 0 to 4 mainly due to increasing electrostatic repulsion between the protons on the nitrogens of the ligand. In contrast, for the cyclam . H-n(n+) series, there is a sudden large increase in strain energy at n = 3, with a change in conformation to having some of the nitrogens of the ligand exo. For n = 4 the rise in strain energy is again not large. These results are discussed in relation to the inversion in order of protonation constants for the cyclam . H-n(n+) series from n = 3 to n = 4.