Zinc thiolate complexes [ZnLn(SR)]+ with azamacrocyclic ligands, part III:: The influence of the ligand Ln on the reactivity of zinc-bound thiolate

In this study, we focus on the structure-re activity relationship of cationic zinc thiolate complexes with the general formula [Zn(L-n)(SR)]ClO4 (L-n: n-dentate azamacrocyclic ligand; R = phenylmethyl). The complexes feature macrocyclic ligands with ring sizes varying from 11 to 16 atoms and possess three or four nitrogen donors (three of them containing one tertiary nitrogen). Thiol methylations with methyl iodide have been performed in order to determine the relative reactivities, because this reaction has been used before to investigate zinc thiolate reactivity and therefore allows comparison of our results with literature data. The kinetic behaviour was investigated in nitromethane and dichloromethane and was found to be second order in all cases. The observed rate constants vary in the range of k(2) = 2.46-55.28 x 10(-3) m(-1)s(-1) in nitromethane and k(2) = 0.23-7.35 x 10(-3) M(-1)s(-1) in dichloromethane at 300 K. Furthermore, the structures of all thiolate complexes were optimised at the B3LYP/6-311+G(d) level of theory. Natural bond orbital (NBO) analyses were performed to obtain information on partial charges of the heteroatoms and energies of a lone pair in a p-type orbital at the zinc-bound sulfur. In order to elucidate which parameters determine reactivity, selected structural and electronic parameters were correlated with the experimental rate constants. As a result, we found that the reaction is controlled predominantly by frontier orbital energy in dichloromethane and by charge in nitromethane. However, we observed that electronic reactivity control can be overridden by the degree of steric obstruction of the zinc ion, which directly depends on ring size and configuration of the ring nitrogens. The complex [Zn(cyclen)(SR)]ClO4 (5) can therefore not be included in any of the correlations; steric constraint imposed by the comparably small ring system causes an extraordinarily increased reactivity. In turn, this finding provides a new rationale for the high reactivity reported for the cyclen complex [Zn(cyclen)(OH)](+), which has been used as a model for carbonic anhydrase in previous studies. (c) Wiley-VCH Verlag GmbH & Co. KGaA.