Helically chiral ferrocene peptides containing 1′-aminoferrocene-1-carboxylic acid subunits as turn inducers
Helically chiral ferrocene peptides containing 1′-aminoferrocene-1-carboxylic acid subunits as turn inducers
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DOI：
10.1002/chem.200600156
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发表时间：
2006-06-23
影响因子：
4.3
通讯作者：
Rapic, Vladimir
中科院分区：
文献类型：
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作者：
Barisic, Lidija;Cakic, Mojca;Rapic, Vladimir
1‘-氨基二茂铁-1-羧酸(FCA)是最简单的有机金属氨基酸之一，我们对它的多肽衍生物进行了详细的结构研究。FCA被掺入二至五肽中，D-和L-丙氨酸残基连接到羧基或氨基上，或两者都连接上。用结晶学和光谱学(圆二色谱(CD)、红外光谱和核磁共振)研究了大约24个化合物在固体和溶液中的结构。用单晶X-射线衍射法对四个化合物进行了结构表征，分别为Boc-FCA-Ala-ome(16)、Boc-FCA-D-Ala-ome(17)、Boc-FCA-Pala-ome(18)和Boc-Ala-FCA-Ala-ome(21)(Boc=叔丁氧基氨基甲酰)。圆二色谱是一种非常有用的工具，可以用来解释茂金属核心的螺旋手性。与所有其他已知的二茂铁肽不同，二茂铁的螺旋手性仅由FCA N端连接的氨基酸的手性决定。根据两个环戊二烯(CP)环的取代度，实现了不同的氢键模式。H-1核磁共振和红外光谱与X射线结晶学的结果相结合，不仅提供了关于化合物的氢键模式的详细信息，而且提供了关于溶液中不同构象之间的平衡的详细信息。本文首次用二甲基亚砜([D，]DMSO)和氯化镉(CDCl3)中NH质子的化学位移之差，即变异比(Vr)作为衡量[Cohn]-[DMSO]-[CdCl3]-[DMSO]-[DMSO]-[CdCl3]-[DMSO]-[CdCl3]体系氢键强度的一种新方法.二茂铁酰基多肽中的键。在侧链之间有一个分子内氢键的二肽中，例如在二肽16中，观察到氢键形式和开放形式之间的平衡，VR值约为0.5。更高级的多肽，如四肽21，能够在CDCl3溶液中形成两个分子内氢键，稳定一个单一构象(VR接近O)。由于CP环旋转的低势垒，新的和非自然的氢键模式正在出现。本文的系统工作为合理设计具有特殊结构和性质的茂金属多肽奠定了坚实的基础。
We present a detailed structural study of peptide derivatives of 1'aminoferrocene-1-carboxylic acid (ferrocene amino acid, Fca), one of the simplest organometallic amino acids. Fca was incorporated into di- to penta-peptides with D- and L-alanine residues attached to either the carboxy or amino group, or to both. Crystallographic and spectroscopic studies (circular dicroism (CD), IR, and NMR) of about two dozen compounds were used to gain a detailed insight into their structures in the solid state as well as in solution. Four derivatives were characterized by single-crystal X-ray analysis, namely Boc-Fca-Ala-OMe (16), Boc-Fca-D-Ala-OMe (17), Boc-Fca-pAla-OMe (18), and Boc-Ala-Fca-AlaAla-OMe (21) (Boc=tert-butyloxycarbamyl). CD spectroscopy is an extremely useful tool to elucidate the helical chirality of the metallocene core. Unlike in all other known ferrocene peptides, the helical chirality of the ferrocene is governed solely by the chirality of the amino acid attached to the N terminus of Fca. Depending on the degree of substitution of both cyclopentadiene (Cp) rings, different hydrogen-bonding patterns are realized. H-1 NMR and IR spectroscopy, together with the results from X-ray crystallography, give detailed information regarding not only the hydrogen-bonding patterns of the compounds, but also the equilibria between different conformers in solution. Differences in chemical shifts of NH protons in dimethyl sulfoxide ([D,]DMSO) and CDCl3, that is, the variation ratio (vr), is used for the first time as a measure of the hydrogen-bonding strength of individual (COHN)-H-... bonds in ferrocenoyl peptides. In dipeptides with one intramolecular hydrogen bond between the pendant chains, for example, in dipeptide 16, an equilibrium between hydrogenbonded and open forms is observed, as testified by a vr value of around 0.5. Higher peptides, such as tetrapeptide 21, are able to form two intramolecular hydrogen bonds stabilizing one single conformation in CDCl3 solution (vr approximate to O). Due to the low barrier of Cp-ring rotation, new and unnatural hydrogenbonding patterns are emerging. The systematic work described herein lays a solid foundation for the rational design of metallocene peptides with unusual structures and properties.