The entire series of 14-membered macrocyclic ligands containing the N(x)S4-x donor set (where x = 1, 2, 3) with alternating ethylene and propylene bridging groups and two related 15-membered macrocycles with the N(x)S5-x donor set (where x = 1, 2) containing only ethylene bridging groups have been characterized in terms of their protonation constants, Cu(II) complex stability constants, and complex formation kinetics with aquocopper(II) ion in aqueous solution at 25-degrees-C. These data are compared to the properties of the corresponding homoleptic ligands [14]aneS4, [14]aneN4 (i.e., cyclam), [15]aneS5, and [15]aneN5 in an attempt to shed further light on the effects of ligand cyclization upon the thermodynamics and the mechanism of metal complex formation. The logarithmic values of the aqueous mixed-mode protonation constants (defined as K(Hn)m = [H(n)L(n+)]/a(H)[H(n-1)L(n-1)+]) at 25-degrees-C, mu = 0.10 M, are as follows (listed in the order log K(H1)m and, where applicable, log K(H2)m, log K(H3)m; values in parentheses represent standard deviations within a single determination, while italicized values in braces represent standard deviations among several replicate determinations): [14]aneNS3, 8.75 (+/- 0.02); [14]aneN2S2, 9.41 {+/- 0.23}, 5.69 {+/- 0.34}; [14]aneNSSN, 9.71 {+/- 0.17}, 6.60 {+/- 0.14}; [14]aneNSNS, 9.78 (+/- 0.12), 8.16 (+/- 0.08); [14]aneN3S, 9.66 (+/- 0.08), 8.24 (+/- 0.12), 2.53 (+/- 0.02); [15]aneNS4, 8.14 (+/- 0.07); [15]aneN2S3, 8.70 (+/- 0.01), 5.16 (+/- 0.01). The corresponding logarithmic stability constants for the Cu(II)L complexes (log K(Cu)(II)L) are as follows: [14]aneNS3, 9.25; [14]aneN2S2, 15.26; [14]aneNSSN, 15.72; [14]aneNSNS, 15.15; [14]aneN3S, > 18; [15]aneNS4, 9.80; [15]aneN2S3, 16.02. The specific rate constants for the reaction of aquocopper(II) ion with the various protonated ligand species were resolved as follows (listed in the order k(Cu)L, k(Cu)HL, and, where applicable, k(Cu)H2L, the superscript indicating the degree of protonation of the ligand; all values in M-1 s-1): [14]aneNS3, (3.2 +/- 0.2) x 10(6), (1.4 +/- 0.3) x 10(2); [14]aneN2S2, (1.6 +/- 0.1) x 10(8), (1.3 +/- 0.6) x 10(3); [14]aneNSSN, (8.2 +/- 0.6) x 10(7), (5 +/- 2) x 10(3); [14]aneNSNS, (2.0 +/- 0.4) x 10(9), (2.9 +/- 0.7) x 10(5); [14]aneN3S, k(Cu)L not evaluated, (3.1 +/- 0.1) x 10(5), 51 +/- 13; [15]aneNS4, (8.4 +/- 0.4) x 10(6), (1.4 +/- 0.3) x 10(3); [15]aneN2S3, (8 +/- 2) x 10(7), (2.5 +/- 0.1) x 10(5). For unprotonated ligands containing a single nitrogen donor atom, the rate-determining step in the complex formation with aquocopper(II) ion comes at the point of the first coordinate bond formation involving a nitrogen donor atom, with the values being essentially identical with those for corresponding open-chain ligands. This implies that the increased stability constants commonly observed for macrocyclic ligand complexes arise directly from a reduction of the dissociation rate constants. In the case of monoprotonated ligand species, the complex formation rate constants are generally much smaller than corresponding open-chain species, although this effect varies by several orders of magnitude for ligands with the same donor set, depending upon the specific arrangement of the donor atoms within the macrocyclic ring. The results of the current studies indicate that the reaction kinetics of the unprotonated, mono- and diprotonated species of macrocyclic ligands yield differing information about the fundamental mechanistic consequences of simple ligand cyclization.
