Sulfur-Rich Zinc Chemistry:  New Tris(thioimidazolyl)hydroborate Ligands and Their Zinc Complex Chemistry Related to the Structure and Function of Alcohol Dehydrogenase

Abstract

The 1-substituted tris(2-thioimidazolyl)hydroborate ligands Tt(R) were prepared as the potassium salts from KBH(4) and the corresponding 1-R-2-thioimidazole for R = t-Bu and C(6)H(4)-p-CH(CH(3))(2) (Cum). Their reactions with zinc salts yielded the tetrahedral complexes Tt(R)Zn-X with X = F, Cl, ONO(2) and (Tt(t)()(-)(Bu))(2)Zn. With zinc perchlorate the labile perchlorate complexes Tt(R)Zn-OClO(3) were obtained. They served as starting materials for the incorporation of substrates which are relevant for the chemistry of horse liver alcohol dehydrogenase: Ethanol led to [Tt(t)()(-Bu)Zn.EtOH] ClO(4).EtOH, p-nitrophenol (NitOH) yielded Tt(Cum)Zn-ONit. Pyridine-2-carbaldehyde and salicylic aldehyde were incorporated as N(pyridine) and O(phenolate) coligands with possible additional O(aldehyde) coordination. Substituted pyridyl methanols (R-PyCH(2)OH) yielded the trinuclear complexes [(Tt(t)()(-Bu))(2)Zn(3)(R-PyCH(2)O)(2)] (ClO(4))(2) with bridging Tt and pyridylmethoxide ligands. Preliminary experiments on the functional modeling of alcohol dehydrogenase have shown that TtZn complexes promote both the dehydrogenation of 2-propanol and the hydrogenation of pentafluorobenzaldehyde.

New Tris(thioimidazolyl)borate Ligands and Some Zinc Complexes Thereof

“…It was already known [3,5,11] that zinc in the sulfur-rich ligand environment of the tris(thioimidazolyl)borate ligands is complemented favourably by oxygen-containing coligands and by the halides. This was verified here for ligands L1, L3 and L5 in combination with zinc and simple anionic coligands.…”

“…The existence of a Zn-OClO 3 connection has already been proved by us by the structure determination of tris(N-tert-butylthioimidazolyl)boratozinc perchlorate. [3] The ease of isolation of 10-14 has made it clear now that these complexes are much less labile than originally assumed.…”

“…In our previous studies of zinc complexes of tris(thioimidazolyl)borate ligands, which were aimed predominantly at modelling alcohol dehydrogenase, [3] alkoxide complexes had evaded us. We now found that they are accessible with the new ligands L. In trying to make mononuclear L·Zn-OR complexes we learnt that these are still inaccessible with aliphatic alkoxides or with benzylate, but the more electronegative p-nitrobenzylate and p-(trifluoromethyl)benzylate could be introduced as terminal ligands in complexes 15 and 16.…”

“…We [3,4] and others [5][6][7][8][9] have tried to model the structure and function of these enzymes by applying tripodal scorpionate [10] ligands bearing one to three sulfur donors. During these studies Parkin's [5,8,11,12] and our own research group [3,13] have found that the sulfur-rich environment of the tris(thioimidazolyl)borate ligands (Tti R ) enables the attachment of quite unusual and biologically relevant coligands X at the zinc ion in an S 3 ZnX environment.…”

“…[14] Remarkably little metal complex chemistry has been done with them in the eight years since, either by Reglinski himself [15][16][17][18][19][20] or by other research groups. [3,5,8,[11][12][13][14][15][16][21][22][23][24][25] So far only methyl, [14] tert-butyl, [3] benzyl, [22] phenyl, [5] p-tolyl, [22] [ mesityl [5] and p-cumenyl substituents [3] have been attached at the N 1 nitrogens of the thioimidazolyl moieties, of which only tert-butyl and mesityl can be considered as sterically demanding.…”