Thiolate Alkylation in Tripod Zinc Complexes:  A Comparative Kinetic Study

Abstract

The biologically relevant alkylations of the thiolate ligands in tripod zinc thiolates by methyl iodide were studied kinetically. Five tripod ligands of the pyrazolyl/thioimidazolyl borate type were employed, offering N3, N2S, NS2, and S3 donor sets. For each of them, the ethyl-, benzyl-, phenyl-, and p-nitrophenylthiolate zinc complexes were investigated, yielding a total of 20 second-order rate constants. The comparison of these rate constants shows three effects: (1) the electronic effect among the thiolates, i.e., the ethanethiolates react about 3 orders of magnitude faster than the p-nitrophenylthiolates; (2) the steric effect among the pyrazolylborates, i.e., the phenyl-substituted ones react about 2 orders of magnitude faster than the tert-butyl-substituted ones; and (3) the strong acceleration by the sulfur donors in the tripods, reaching 4 orders of magnitude between the reaction times of the (N3)Zn-SR and (S3)Zn-SR complexes.

Nucleophilicity of zinc-bound thiolates

“…It should be noticed that a counter-example of the previous rule has already been mentioned. [19] These results indicate that the alkylthiolate nucleophilicity in a given complex stands in the same range as the one observed for the phenylthiolate in the same complex. Furthermore, the alkylthiolate reactivity may be either higher (in 11, 12 and 13) or smaller (in 5 and 6) than the reactivity of the phenylthiolate.…”

“…ZnS 4 cores. This shows that the conclusion obtained in previous studies [17,19] that ZnS 4 complexes are more reactives than ZnNS 3 and ZnN 2 S 2 complexes cannot be generalized to a broader series. It should be noticed that a counter-example of the previous rule has already been mentioned.…”

“…It has been postulated that the Zn-S bond lengths [19] or the HOMO energy of the complex [18] could correlate with the complex reactivity. Figure 4B) shows a clear disruption of the previous trend, as observed by others.…”

“…[15] The influence of the nature of the metal cation on the nucleophilicity of p-toluenethiolate has been studied both experimentally and by DFT computation, revealing that nickel-and zinc-thiolate complexes are more reactive than ironand cobalt-thiolate complexes. [16] In the case of zinc complexes, both the composition of the ligand set, [17][18][19][20] in terms of donating capability and steric hindrance, and the presence of hydrogen bonding towards the reactive thiolate [21][22][23][24] have been shown to modulate the reactivity against electrophiles.…”

“…In the case of zinc-bound thiolates, several studies provide the rate constants of their reaction against electrophile but it is difficult from these data to have a general view of their relative nucleophilicities as the experimental conditions are not the same. [19,21,23,24,29] Such a determination would however be of great significance in order to evaluate the relative reactivity of enzymes and to determine which thiolate is reactive in zinc active sites including more than one cysteinate.…”