Tris(thioimidazolyl)borate-Zinc-Thiolate Complexes for the Modeling of Biological Thiolate Alkylations

The S3Zn−SR coordination of thiolate-alkylating enzymes such as the Ada DNA repair protein was reproduced in tris(thioimidazolyl)borate-zinc-thiolate complexes TtiRZn−SR‘. Four different TtiR ligands and nine different thiolates were employed, yielding a total of 12 new complexes. In addition, one TtiRZn−SH complex and two thiolate-bridged [TtiR-SEt-TtiR]+ complexes were obtained. A selection of six thiolate complexes was converted with methyl iodide to the corresponding methyl thioethers and TtiRZn−I. According to a kinetic analysis these reactions are second-order processes, which implies that the alkylations are likely to occur at the zinc-bound thiolates. They are much faster than the alkylations of zinc thiolates with N3 or N2S tripod ligands. The most reactive thiolate, TtiXylZn−SEt, reacts slowly with trimethyl phosphate in a nonpolar medium at room temperature, yielding methyl-ethyl-thioether and TtiXylZn−OPO(OMe)2 which can be converted back to the thiolate complex with NaSEt. This is the closest reproduction of the Ada repair process so far.