Saha Manas K, Mukhopadhyay Uday, Bernal Ivan
Department of Chemistry, University of Houston, Houston, Texas 77204, USA.
Dalton Trans. 2004 May 7(9):1466-73. doi: 10.1039/b402571g. Epub 2004 Mar 31.
Cleavage of the peptide bond occurs when beta]-alanyl-L-histidine (carnosine) reacts with [Co(tren)Cl2]+ (tren = tris(2-aminoethyl)amine) to give Co(tren)(histidine) 1 and Co(tren)(beta-alanine) 2. Co(tren)(histidine) 1 crystallizes in the enantiomorphic space group P2(1)2(1)2(1) and 2 crystallizes in the P2(1)/c space group. The mechanism of the cleavage reactions were studied in detail for the precursor [Co(tren)Cl2]+ and [Co(trien)Cl2]+, which convert into [Co(tren)(OH)2]+/[Co(tren)(OH)(OH2)]2+ and [Co(trien)(OH)2]+/[Co(trien)(OH)(OH2)]2+ in water at basic pH (trien = 1,4,7,10-tetraazadecane). At a slightly basic pH, the initial coordination of the substrate (beta-alanyl-L-histidine) is by the carboxylate group for the reaction with [Co(tren)Cl2]+. This is followed by a rate-limiting nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. In a strongly basic reaction medium substrate, binding of the metal was through carboxylate and amine terminals. On the other hand, for the reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine, the initial coordination of the substrate takes place via an imidazole ring nitrogen, independently, and followed by a nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. The circular dichroism spectrum for 1 suggests that a very small extent of racemization of the amino acid (L-histidine) takes place during the cleavage reaction between [Co(tren)Cl2]+ and beta-alanyl-L-histidine. Reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine also causes cleavage of the peptide bond, producing a free beta-alanyl molecule and a cationic fragment cis-alpha-Co(trien)(histidine) 3 that crystallizes in the optically active space group P2(1)2(1)2(1). Unlike the previous case an appreciable degree of racemization of the L-histidine takes place during the reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine. Crystals containing L-histidine and D-histidine fragments in the [cis-alpha-Co(trien)(histidine)]2+ moiety were crystallographically documented by mounting a number of randomly selected crystals.
当β-丙氨酰-L-组氨酸（肌肽）与[Co(tren)Cl₂]⁺（tren = 三（2-氨基乙基）胺）反应生成[Co(tren)(组氨酸)]²⁺ 1和[Co(tren)(β-丙氨酸)]²⁺ 2时，肽键发生断裂。[Co(tren)(组氨酸)]²⁺ 1结晶于对映异构空间群P2(1)2(1)2(1)，2结晶于P2(1)/c空间群。对前体[Co(tren)Cl₂]⁺和[Co(trien)Cl₂]⁺的裂解反应机理进行了详细研究，它们在碱性pH值的水中转化为[Co(tren)(OH)₂]⁺/[Co(tren)(OH)(OH₂)]²⁺和[Co(trien)(OH)₂]⁺/[Co(trien)(OH)(OH₂)]²⁺（trien = 1,4,7,10-四氮杂癸烷）。在略碱性pH值下，底物（β-丙氨酰-L-组氨酸）与[Co(tren)Cl₂]⁺反应时，最初是通过羧酸根基团配位。随后是氢氧根对β-丙氨酰-L-组氨酸羰基的限速亲核进攻。在强碱性反应介质中，底物通过羧酸根和胺端基与金属结合。另一方面，对于[顺-β-Co(trien)Cl₂]⁺与β-丙氨酰-L-组氨酸之间的反应，底物最初通过咪唑环氮独立配位，随后是氢氧根对β-丙氨酰-L-组氨酸羰基的亲核进攻。1的圆二色光谱表明，在[Co(tren)Cl₂]⁺与β-丙氨酰-L-组氨酸的裂解反应过程中，氨基酸（L-组氨酸）发生了非常少量的消旋。[顺-β-Co(trien)Cl₂]⁺与β-丙氨酰-L-组氨酸之间的反应也会导致肽键断裂，生成一个游离的β-丙氨酰分子和一个阳离子片段[顺-α-Co(trien)(组氨酸)]²⁺ 3，它结晶于旋光空间群P2(1)2(1)2(1)。与前一种情况不同，在[顺-β-Co(trien)Cl₂]⁺与β-丙氨酰-L-组氨酸的反应过程中，L-组氨酸发生了明显程度的消旋。通过安装多个随机选择的晶体，对[顺-α-Co(trien)(组氨酸)]²⁺部分含有L-组氨酸和D-组氨酸片段的晶体进行了晶体学记录。
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