Kállay Csilla, Várnagy Katalin, Malandrinos Gerasimos, Hadjiliadis Nick, Sanna Daniele, Sóvágó Imre
Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010, Debrecen, Hungary.
Dalton Trans. 2006 Oct 14(38):4545-52. doi: 10.1039/b608190h. Epub 2006 Aug 8.
Copper(II) complexes of the pentapeptides Ac-HisAlaHisValHis-NH2, Ac-HisValHisAlaHis-NH2, Ac-HisProHisAlaHis-NH2, Ac-HisAlaHisProHis-NH2, Ac-HisGlyHisValHis-NH2 and Ac-HisValHisGlyHis-NH2 have been studied by potentiometric, UV-Vis, CD and EPR spectroscopic methods. It has been found that the pentapeptides are efficient ligands for the complexation with copper(II) and exhibit an outstanding versatility in the co-ordination geometry of complexes. The presence of three histidyl residues provides a high possibility for the formation of macrochelates via the exclusive binding of imidazole-N donor atoms. The macrochelation suppresses, but cannot preclude the deprotonation and metal ion co-ordination of amide functions and the species [CuH(-2)L] and [Cu2H(-4)L] predominate at physiological pH in equimolar solutions and in the presence of excess metal ions, respectively. It is also clear from the data that both C-terminal and internal histidyl residues can work as the anchoring sites for metal binding and subsequent amide deprotonation resulting in the formation of co-ordination isomers and dinuclear species in equimolar solutions and in the presence of excess metal ions, respectively. In more alkaline solutions (pH approximately 10) a third amide function can be deprotonated and co-ordinated in the species [CuH(-3)L]- with (N-,N-,N-,N(im)) co-ordination. The dinuclear species [Cu2H(-5)L]- and Cu2H(-6)L containing hydroxide ions and/or imidazolato bridges are formed at high pH in the presence of excess of metal ions. The insertion of one proline into the sequence preceding histidyl residues hinders the deprotonation of amide functions at that site and the formation of only mononuclear complexes was observed with these peptides.
通过电位滴定、紫外可见光谱、圆二色光谱和电子顺磁共振光谱方法研究了五肽Ac-HisAlaHisValHis-NH2、Ac-HisValHisAlaHis-NH2、Ac-HisProHisAlaHis-NH2、Ac-HisAlaHisProHis-NH2、Ac-HisGlyHisValHis-NH2和Ac-HisValHisGlyHis-NH2的铜（II）配合物。已发现这些五肽是与铜（II）络合的有效配体，并且在配合物的配位几何结构中表现出出色的多样性。三个组氨酸残基的存在使得通过咪唑-N供体原子的专一性结合形成大环螯合物的可能性很高。大环螯合作用抑制了但不能排除酰胺官能团的去质子化和金属离子配位，并且在生理pH下，等摩尔溶液中主要存在物种[CuH(-2)L]，在存在过量金属离子时主要存在物种[Cu2H(-4)L]。从数据中还可以清楚地看出，C末端和内部组氨酸残基都可以作为金属结合的锚定位点，随后酰胺去质子化，分别在等摩尔溶液中和存在过量金属离子时导致形成配位异构体和双核物种。在更强碱性的溶液（pH约为10）中，第三个酰胺官能团可以去质子化并以（N-，N-，N-，N(im)）配位存在于物种[CuH(-3)L]-中。在高pH下，存在过量金属离子时会形成含有氢氧根离子和/或咪唑桥的双核物种[Cu2H(-5)L]-和Cu2H(-6)L。在组氨酸残基之前的序列中插入一个脯氨酸会阻碍该位点酰胺官能团的去质子化，并且用这些肽仅观察到单核配合物的形成。
