Kaminskaia N V, Ullmann G M, Fulton D B, Kostic N M
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
Inorg Chem. 2000 Oct 30;39(22):5004-13. doi: 10.1021/ic000254l.
Binding of tryptophan residue to intrinsic metal ions in proteins is unknown, and very little is known about the coordinating abilities of indole. Indole-3-acetamide displaces the solvent ligands from cis-[Pt(en)(sol)2]2+, in which sol is acetone or H2O, in acetone solution and forms the complex cis-[Pt(en)(indole-3-acetamide)]2+ (3) of spiro structure, in which the new bidentate ligand coordinates to the Pt(II) atom via the C(3) atom of the indolyl group and the amide oxygen atom. This structure is supported by 1H, 13C, 15N, and 195Pt NMR spectra and by UV, IR, and mass spectra. Molecular mechanical simulations by Hyperchem and CHARMM methods give consistent structural models; the latter is optimized by density-functional quantum chemical calculations. Dipeptide-like molecules N-(3-indolylacetyl)-L-amino acid in which amino acid is alanine, leucine, isoleucine, valine, aspartic acid, or phenylalanine also displace the solvent ligands in acetone solution and form complexes cis-[Pt(en) N-(3-indolylacetyl)-L-amino acid)]2+ (6), which structurally resemble 3 but exist as two diastereomers, detected by 1H NMR spectroscopy. The bulkier the amino acid moiety, the slower the coordination of these dipeptide-like ligands to the Pt(II) atom. The indolyl group does not coordinate as a unidentate ligand; a second donor atom is necessary for bidentate coordination of this atom and the indolyl C(3) atom. The solvent-displacement reaction is of first and zeroth orders with respect to indole-3-acetamide and cis-[Pt(en)(sol)2]2+, respectively. A mechanism consisting of initial unidentate coordination of the ligand via the amide oxygen atom followed by closing of the spiro ring is supported by 1H NMR data, the kinetic effects of acid and water, and the activation parameters for the displacement reaction. In the case of N-(3-indolylacetyl)-L-phenylalanine, the bulkiest of the entering ligands, the reaction is of first order with respect to both reactants. The bidentate indole-3-acetamide ligand in 3 is readily displaced by (CH3)2SO and 2-methylimidazole, but not by CNO-, CH3COO-, and CH3CN. Complexes cis-[Pd(en)(sol)2]2+ and cis-[Pd(dtco)(sol)2]2+ react with indole-3-acetamide more rapidly than their Pt(II) analogues do and yield complexes similar to 3. This study augments our recent discovery of selective, hydrolytic cleavage of tryptophan-containing peptides by Pd(II) and Pt(II) complexes.
色氨酸残基与蛋白质中固有金属离子的结合情况尚不清楚，而且关于吲哚的配位能力也知之甚少。在丙酮溶液中，吲哚 - 3 - 乙酰胺能取代顺式 - [Pt(en)(sol)₂]²⁺（其中sol为丙酮或H₂O）中的溶剂配体，形成具有螺环结构的配合物顺式 - [Pt(en)(吲哚 - 3 - 乙酰胺)]²⁺（3），其中新的双齿配体通过吲哚基的C(3)原子和酰胺氧原子与Pt(II)原子配位。¹H、¹³C、¹⁵N和¹⁹⁵Pt核磁共振谱以及紫外、红外和质谱都证实了这种结构。通过Hyperchem和CHARMM方法进行的分子力学模拟给出了一致的结构模型；后者通过密度泛函量子化学计算进行了优化。氨基酸为丙氨酸、亮氨酸、异亮氨酸、缬氨酸、天冬氨酸或苯丙氨酸的二肽样分子N - (3 - 吲哚基乙酰基) - L - 氨基酸在丙酮溶液中也能取代溶剂配体，形成配合物顺式 - [Pt(en) N - (3 - 吲哚基乙酰基) - L - 氨基酸)]²⁺（6），其结构与3相似，但以两种非对映异构体形式存在，通过¹H核磁共振光谱检测到。氨基酸部分体积越大，这些二肽样配体与Pt(II)原子的配位速度越慢。吲哚基不作为单齿配体配位；该原子与吲哚基C(3)原子进行双齿配位需要第二个供体原子。溶剂取代反应对吲哚 - 3 - 乙酰胺和顺式 - [Pt(en)(sol)₂]²⁺分别为一级和零级反应。¹H核磁共振数据、酸和水的动力学效应以及取代反应的活化参数支持了一种机制，即配体首先通过酰胺氧原子进行单齿配位，然后螺环闭合。对于进入的配体中体积最大的N - (3 - 吲哚基乙酰基) - L - 苯丙氨酸，反应对两种反应物均为一级反应。3中的双齿吲哚 - 3 - 乙酰胺配体很容易被(CH₃)₂SO和2 - 甲基咪唑取代，但不被CNO⁻、CH₃COO⁻和CH₃CN取代。配合物顺式 - [Pd(en)(sol)₂]²⁺和顺式 - [Pd(dtco)(sol)₂]²⁺与吲哚 - 3 - 乙酰胺的反应比它们的Pt(II)类似物更快，并生成与3类似的配合物。这项研究扩展了我们最近关于Pd(II)和Pt(II)配合物对含色氨酸肽进行选择性水解裂解的发现。
