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 Tti(R)Zn-SR'. Four different Tti(R) ligands and nine different thiolates were employed, yielding a total of 12 new complexes. In addition, one Tti(R)Zn-SH complex and two thiolate-bridged [Tti(R)-SEt-Tti(R)]+ complexes were obtained. A selection of six thiolate complexes was converted with methyl iodide to the corresponding methyl thioethers and Tti(R)Zn-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, Tti(Xyl)Zn-SEt, reacts slowly with trimethyl phosphate in a nonpolar medium at room temperature, yielding methyl-ethyl-thioether and Tti(Xyl)Zn-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.
Ibrahim
Mohamed M
MM
Institut für Anorganische und Analytische Chemie der Universität Freiburg, Albertstrasse 21, D-79104 Freiburg, Germany.
Seebacher
Jan
J
Steinfeld
Gunther
G
Vahrenkamp
Heinrich
H
D000478:Alkylation; D001881:Borates / Q000138:chemical synthesis* / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D001881:Borates; D007093:Imidazoles; D013438:Sulfhydryl Compounds; D015032:Zinc