Methylation of tethered thiolates in [(bme-daco)Zn]2 and [(bme-daco)Cd]2 as a model of zinc sulfur-methylation proteins

The dimeric dithiolate complex [1,5-bis(mercaptoethyl)-1,5-diazacyclooctanato]zinc(II), [(bme-daco)Zn](2) or Zn-1. and its cadmium analogue, Cd-1, were investigated as models for the active site of zinc-dependent methylation proteins. The key issue addressed was whether alkylation of a thiolate in a relatively rigid tetradentate ligand would result in coordination of the thioether product to the metal. On the basis of H-1 and C-13 NMR spectroscopy and similar reactivity toward alkylating agents, the newly synthesized cadmium complex, Cd-1, is proposed to be isostructural with the previously reported Zn-1 complex, which is known from X-ray crystallography to be dimeric in the solid state (Tuntulani, T.; Reibenspies, J. H.; Farmer, P. J.; Darensbourg, M. Y. Inorg. Chem. 1992, 31, 3497). Iodomethane reacts with Zn-1 in hot CH3OH/CH3CN to produce a thioether which dissociates, replaced by coordination of iodide in the pseudotetrahedral complex, (Me(2)bme-daco)ZnI2 or Zn-2. Complex Zn-2 crystallizes in the triclinic P (1) over bar space group with a = 7.911(2) Angstrom, b = 10.675(2) Angstrom, c = 12.394(2) Angstrom, alpha = 75.270(10)degrees, beta = 75.270(10)degrees, gamma = X2.12(2)degrees, V = 998.270 Angstrom(3), and Z = 2. An analogous reaction was observed for the cadmium derivative, Cd-1, which displays a H-1 NMR spectrum identical to that of Zn-2. In attempts to promote thioether binding, the iodide was displaced by addition of AgBF4 to solutions of Zn-2 or the BF4- analogue was synthesized directly from Zn(BF4)(2) and methylated ligand, Me(2)bme-daco, to yield Zn-3. Similar reactions with the cadmium analogue yielded a product identified as Cd-3 that was indistinguishable from Zn-3 by H-1 NMR. The Cd-113 NMR spectra of Cd-3 displayed a single resonance at 88 ppm consistent with a hard donor environment and inconsistent with sulfur binding. As a further attempt to induce thioether binding to zinc, the macrocyclization reagent 1,3-dibromopropane was added to Zn-1. The resulting product, [BrZn(macrocycle)](+), was only slightly soluble in pyridine and identified by +FAB/MS as the desired macrocyclic product with a large amount of free macrocycle ligand. Recrystallization from pyridine/ether resulted in loss of the zinc as Zn(py)(2)Br-2, which was obtained as colorless crystals and characterized by X-ray crystallography. Complex Zn(py)(2)Br-2 crystallizes in the monoclinic P2(1)/c space group with a = 8.534(2) Angstrom, b = 18.316(4) Angstrom, c = 8.461(2) Angstrom, beta = 101.07(3)degrees, V = 1297.9(5) Angstrom(3), and Z = 4.