Controlled self-assembling structures of ferrocene-dipeptide conjugates composed of Ala-Pro-NHCH2CH2SH chain
Graphical abstract
Bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH2CH2SH and Fc-L-Ala-D-Pro-NHCH2CH2SH (Fc = ferrocenoyl), were designed to demonstrate the chirality controlled hydrogen-bonded molecular assembling structures.
Introduction
The design of structurally organized molecular arrangement has attracted great attention for the development of functional materials [1], [2], [3], [4], [5], [6], [7] because of that the chemical and/or physical properties are related to molecular arrangement of component molecules. Hydrogen bond, which has the virtue of directionality, specificity, reversibility, and tunability, is regarded as a powerful tool in the creation of supramolecular assemblies [8]. Well-organized structures are constructed in proteins, in which skillful intra- and intermolecular hydrogen bonds between amino acids are formed in protein secondary structures [9], [10], to exhibit the unique functional properties. The utilization of chiral self-assembling properties of amino acids based on hydrogen bonding sites and chiral centers is regarded as one of convenient strategies to construct structurally organized chiral self-assemblies. It has drawn considerable attention to ferrocene, which has two rotatory coplanar cyclopentadienyl (Cp) rings and redox properties, in application to a variety of materials [11]. In the last two decades, much attention has been given to bioorganometallic chemistry, which is a hybrid area between biology and organometallic chemistry [12], [13], [14], [15], [16], [17]. Great efforts have been made to conjugate organometallic ferrocenes and self-assembling amino acids to design bioorganometallic conjugates for design of protein secondary structures and application to a variety of materials [18], [19], [20], [21], [22], [23], [24], [25]. Ferrocene-peptide conjugates have been utilized as self-assembled monolayers on a gold surface, wherein controlled molecular arrangement plays an important role in electron transfer processes [26], [27], [28], [29], [30], [31], [32], [33], [34]. Thiol derivatives are also known to play a crucial role in biological systems based on the redox properties, metal binding ability, and nucleophilicity [35], [36]. The introduction of thiol moiety into chirality-organized peptides is envisioned to afford additional functional properties. However, self-assembly properties of the ferrocene-peptide conjugate bearing thiol moiety in a solid state have not been investigated so far. From these points of view, we herein report the controlled self-assembling structures of ferrocene-dipeptide conjugates composed of the Ala-Pro-NHCH2CH2SH chain to gain insight into the effect of the chirality of amino acids on the self-assembly properties.
Section snippets
Results and discussion
The alanylproline consisting of a hydrogen bonding alanine and a sterically constrained proline as a well-known turn inducer in proteins was used as a dipeptide chain. Cystamine (H2NCH2CH2S-SCH2CH2NH2) was focused on as a precursor of cysteamine (H2NCH2CH2SH). The reaction of (chlorocarbonyl)ferrocene with H-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-H dihydrochloride, which was obtained by the N-Boc deprotection of Boc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Boc, in the presence of 4-(dimethylamino)pyridine
Conclusions
In conclusion, the self-assembly properties of the bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH2CH2SH (2) and Fc-L-Ala-D-Pro-NHCH2CH2SH (4), which were prepared by the reduction of the ferrocene-dipeptide conjugates, Fc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Fc (1) or Fc-L-Ala-D-Pro-cystamine-D-Pro-L-Ala-Fc (3), respectively, were structurally elucidated by single-crystal X-ray structure determination to gain insight into the effect of the
General materials and experimental procedures
All reagents and solvents were purchased from commercial sources and were further purified by the standard methods, if necessary. (Chlorocarbonyl)ferrocene was prepared according to the literature method [37]. The dipeptide derivatives were prepared according to the method reported in a previous paper [38]. 1H and 13C NMR spectra were recorded on a JNM-ECS 400 (1H NMR, 400 MHz; 13C NMR, 100 MHz) spectrometer. For 1H NMR spectra, chemical shifts were determined relative to the solvent residual
Acknowledgment
This work was supported in part by “JSPS KAKENHI Grant Number JP16H01024 in Precisely Designed Catalysts with Customized Scaffolding”. The authors thank Dr. Hideki Sugimoto and Prof. Shinobu Itoh for the single-crystal X-ray structure determination. Thanks are due to the Analytical Center, Graduate School of Engineering, Osaka University.
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