Zinc−Thiolate Complexes of the Bis(pyrazolyl)(thioimidazolyl)hydroborate Tripods for the Modeling of Thiolate Alkylating Enzymes

Abstract

The new tripod ligands bis(pyrazolyl)(3-tert-butyl-2-thioimidazol-1-yl)hydroborate (L(1)) and bis(pyrazolyl)(3-isopropyl-2-thioimidazol-1-yl)hydroborate (L(2)), together with zinc nitrate or zinc chloride and the corresponding thiolates, have yielded a total of 17 zinc-thiolate complexes. These comprise aliphatic as well as aromatic thiolates and a cysteine derivative. Structure determinations have confirmed the tetrahedral ZnN(2)S(2) coordination in the complexes. Upon reaction with methyl iodide, the species L(1).Zn-SR are slowly converted to L(1).Zn-I and the free thioethers CH(3)SR. A kinetic analysis has shown these alkylations to be about 1 order of magnitude slower than those of the tris(pyrazolyl)borate complexes Tp(Ph,Me)Zn-SR. Alkylations with trimethyl phosphate were found to proceed very slowly even in DMSO at 80 degrees C.

Zinc Thiolate Complexes [ZnLn(SR)]+ with Azamacrocyclic Ligands, Part III: The Influence of the Ligand Ln on the Reactivity of Zinc‐Bound Thiolate

“…Investigation of the kinetics provided strong evidence that these reactions occur intramolecularly, featuring a four-centre transition structure. [11][12][13] A similar conclusion has been drawn by Carrano et al, who investigated the methylation of a series of scorpionate zinc thiolates. [14][15][16] Darensbourg et al studied alkylations of a zinc complex with a bis-thiolate [N 2 S 2 ]…”

“…[12][13][14][15]26,27] In this case, the methylation (as well as any other reaction) is restricted to occur at the thiolate side of the complex cation. As the coordination of the reacting molecules to Zn II implicates a steric demand, the degree of obstruction of the zinc(II) ion by the macrocycle should have a pivotal influence on the geometry of the transition state.…”

Zinc Thiolate Complexes [ZnLn(SR)]+ with Azamacrocyclic Ligands: Synthesis and Structural Properties

“…Vahrenkamp et al have studied the methylation of [tris(pyrazolyl)borato]zinc thiolates (Tp R,R ZnSR) and have provided strong evidence (gained from kinetic measurements) that these reactions occur intramolecularly and feature a four-center transition structure. [8][9][10] A similar interpretation has been provided by Carrano et al, who have investigated the methylation of a series of (scorpionato)zinc thiol-1444 2.2259(5) to 2.2492(9) Å and the pentacoordinate N 4 S systems from 2.266(2) to 2.3200(7) Å. In addition, two complexes with the very rare N 5 S coordination environment for zinc have been found.…”

Biomimetic Thiolate Alkylation with Zinc Pyrazolylbis(thioimidazolyl)borate Complexes

“…[18] Following our introductory study on the alkylation of tris(pyrazolyl)boratozinc thiolates, [13] in the second part of the investigation we used the bis(pyrazolyl)(thioimidzolyl)-boratozinc thiolates. [19] The major, and unexpected, observation of this study was that the thiolate alkylations are slower than those of the tris(pyrazolyl)boratozinc thiolates, despite the increased electron density of the complexes. It remained to be demonstrated, however, that the trend continued for the (pyrazolyl)bis(thioimidazolyl)boratozinc thiolates.…”