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

Abstract

In this study, we focus on the structure-reactivity relationship of cationic zinc thiolate complexes with the general formula [Zn(L n )(SR)]ClO 4 (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 = 2.46-55.28ϫ10 -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

Nucleophilicity of zinc-bound thiolates

“…Figure 4B) shows a clear disruption of the previous trend, as observed by others. [20] This means that the reactivity of various zinc-bound thiolates cannot be deduced from the zinc-thiolate bond length.…”

“…[18,20] This however does not allow to determine the most reactive site of a zinc complex if several thiolate ligands are bound to the metal.…”

“…[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.…”

Synthetic Bioinorganic Chemistry: Scorpionates Turn 50

“…The Ada DNA repair protein, which restores damaged DNA by abstracting a methyl group from a methylated nucleic base residue or phosphate group and transfers it to one of its own cysteine thiolate groups, also has a Zn(Cys) 4 core [134,135]. In this regard, the alkylation of well-defined zinc thiolate complexes has been studied by a number of researchers, including Lippard [136,137], Darensbourg [138], Vahrenkamp [139][140][141][142][143][144][145][146], Parkin [130,[147][148][149], Riordan [111,150], Carrano [151][152][153][154], Anders [155,156], and Ibrahim [157,158]. There appears to be mounting evidence that the methylation of zinc thiolates occurs by two distinct mechanisms: dissociative, in which a zinc-bound thiolate is released and then reacts with the electrophile, a pathway taking place in anionic complexes such as [Zn(SPh) 4 ] 2À [137], and associative, in which the methylating agent directly attacks the thiolate ligand still bound to the metal [112,159,160].…”

(Phenylmethanethiolato)(1,5,9-triazacyclododecane)zinc(II) thiocyanate

“…A series of related complexes has been prepared and characterized structurally . The complexes react with carbon disulfide to give trithiocarbonates (Notni, Schenk et al, 2006;Schenk et al, 2006), and with methyl iodide to give thioethers (Notni et al, 2007). The complexes are of importance as biomimetics for a sulfur analogue of carbonic anhydrase (Schenk et al, 2006).…”