Zinc Complexes of Amino Acids and Peptides, 9[]. Coordination of Cysteine and Histidine Derivatives to the Pyrazolylborate‐Zinc Unit

Abstract

Highly substituted pyrazolylborate ligands TpRrMe were used to limit the coordination number of zinc towards cysteineand histidine-derived coligands. Monodentate thiolate attachment (-+ la-f) was achieved with N-and C-protected cysteine, monodentate carboxylate attachment (-+ 3) with Nprotected histidine. C-protected cysteine was found to form a five-membered N,S-chelate ring (2). While imidazole coordination with N-and C-protected histidine could not be achieved, cationic pyrazolylborate-zinc-coligand complexes [TpZn-L]+ (4a, b) were obtained for L = 2-methylimidazole. The new complexes were characterized by their spectra and three structure determinations.Zinc exercises its biological functions in a chemical environment consisting mainly of the thiolate groups of cysteine and the imidazole groups of histidine in the protein [2]. Accordingly, the investigation of its coordination chemistry with these two amino acids as well as simple derivatives and small peptides thereof is an important aspect of the bioinorganic chemistry of z i n~ [~,~] .We are contributing to this by the determination of stabilities and structures of cysteine-and histidine-containing zinc complexe~[~~.It is a general problem of model studies of this kind that the two amino acids are polyfunctional, even in the form of their derivatives. Therefore, in contrast to the situation in a protein, they normally occupy more than one coordination position on zinc, which often results in the formation of coordination polymers. This problem can be avoided in model compounds only in a signular case, namely by providing the most advantageous electronic situation in the form of i1 ZnN2S2 coordination. The problem does not exist in the case of the protein because the functionality of cysteine and hstidine is reduced to that of their side chain donors thiolate and imidazole, and because a favorable geometrical situation is preformed. This paper reports on our attempts to imitate the natural case by controlling the geometrical situation and by reducing the donor abilities of cysteine and histidine derivatives to monodentate coordination. Our approach was based on the use of highly substituted pyrazolylborate ligands. The target compounds were the complexes of type A in which the substituents R at the 3-positions of the pyrazole units encapsulate the zinc ion and its coligands. The coligands X were meant to be cysleine and histidine derivatives bound in a monodentate fashion via their thiolate or imidazolr: functions. The neutral complexes with X = OH were used as starting compounds, based on our experien~e[~,~I that the OH-group is the most efficient leaving group in this class of complexes.

On the Ligating Properties of Sulfonate and Perchlorate Anions Towards Zinc

“…The aromatic resonances of the cumenyl groups are shifted upfield by 0.3-0.6 ppm compared to those of TpCUm,MeZn-OH, and likewise the pyridine resonances are shifted upfield by 0.5-1.5 ppm compared to those of free pyridine. In both cases the mutual ring-current effect is responsible for the shifts which we have observed in similar cases before [8,26]. These data indicate a location of the pyridine sing between the cumenyl substituents and hence its coordination to the zinc ion.…”

Hydrolytic Cleavage of Diphosphates, Sulfonatophosphates, and Disulfonates by (Pyrazolylborate)zinc Hydroxide Complexes

“…The Tp*ZnϪOH complexes [8] [10] [22] , the diphosphate [23] 1 H-and 31 P-NMR spectra showed that the starting materials had and the sulfonatophosphate [24] were prepared according to the disappeared and the solution contained an equimolar mixture of published procedures. All other reagents were obtained commer3c and 4c.…”

Pyrazolylboratozinc Complexes of Nucleosides and Nucleoside Analogues

“…The TpZn-OH complexes were prepared as described. [48,49] All other starting materials were obtained commercially. The analytical equipment was as described previously.…”