Hierarchical Organization of Ferrocene–Peptides

Abstract

Hierarchical self-assembly of disubstituted ferrocene (Fc)-peptide conjugates that possess Gly-Val-Phe and Gly-Val-Phe-Phe peptide substituents leads to the formation of nano- and micro-sized assemblies. Hydrogen-bonding and hydrophobic interactions provide directionality to the assembly patterns. The self-assembling behavior of these compounds was studied in solution by using (1)H NMR and circular dichroism (CD) spectroscopies. In the solid state, attenuated total reflectance (ATR) FTIR spectroscopy, single-crystal X-ray diffraction (XRD), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) methods were used. Spontaneous self-assembly of Fc-peptides through intra- and intermolecular hydrogen-bonding interactions induces supramolecular assemblies, which further associate and give rise to fibers, large fibrous crystals, and twisted ropes. In the case of Fc[CO-Gly-Val-Phe-OMe](2) (1), molecules initially interact to form pleated sheets that undergo association into long fibers that form bundles and rectangular crystalline cuboids. Molecular offsets and defects, such as screw dislocations and solvent effects that occur during crystal growth, induce the formation of helical arrangements, ultimately leading to large twisted ropes. By contrast, the Fc-tetrapeptide conjugate Fc[CO-Gly-Val-Phe-Phe-OMe](2) (2) forms a network of nanofibers at the supramolecular level, presumably due to the additional hydrogen-bonding and hydrophobic interactions that stem from the additional Phe residues.

Redox-triggered changes in the self-assembly of a ferrocene–peptide conjugate

“…S6, ESI † for details). These values are significantly higher than that of other H-bonded Fc-peptide previously reported, 13 suggesting the formation of very strong intermolecular hydrogen bonding interactions. Upon heating the ultrasound-induced gel-phase material all amide protons gradually shift downfield, up to the gel melting temperature of 60 1C (Fig.…”

“…Ferrocene (Fc)-peptide conjugates have received significant attention due to their interesting structural properties and their potential bioanalytical applications. [11][12][13] Organogels and hydrogels of Fc-peptide are not common. 14 Recently, the simple conjugate FcCO-Phe-OH has been reported to form a hydrogel.…”

Oxalamide-Bridged Ferrocenes: Conformational and Gelation Properties and In Vitro Antitumor Activity

“…The self-assembly of small molecules in water or in organic solvents could lead to the formation of a gel consisting of a large amount of a solvent entrapped in a three-dimensional (3D) network of nanosized gelator aggregates. − Since the aggregates are stabilized by weak noncovalent interactions, various internal or external stimuli (light, sound, pH, solvent, temperature, ions, enzymes) can be used to tune the molecular assembly behavior required for functional expression. − It is very difficult to predict the gelling ability of a potential gelator as it is closely related to the 3D intermolecular nature of the gel. Therefore, the design and development of simple and effective gelators that exhibit a sharp and rapidly reversible response to one or more stimuli are rather challenging tasks. − Numerous studies on ferrocene-containing peptides have revealed not only the interesting structural properties resulting from the ability of ferrocene scaffolds to undergo turn nucleation − but also a potential bioanalytical application. , Recent work on two ferrocene-modified peptides Phe–Phe (FF) and Phe–Tyr (FY) demonstrated that Fc–FF and Fc–FY (Fc = ferrocenoyl) effectively inhibit insulin fibrillation and thus represent an available strategy for the treatment of amyloid aggregation disease …”

“…8−11 Numerous studies on ferrocene-containing peptides have revealed not only the interesting structural properties resulting from the ability of ferrocene scaffolds to undergo turn nucleation 12−19 but also a potential bioanalytical application. 20,21 Recent work on two ferrocene-modified peptides Phe−Phe (FF) and Phe−Tyr (FY) demonstrated that Fc−FF and Fc−FY (Fc = ferrocenoyl) effectively inhibit insulin fibrillation and thus represent an available strategy for the treatment of amyloid aggregation disease. 22 Research on ferrocene-containing gelators began with the study of the role of ferrocene in aromatic-mediated intermolecular π interactions in an organogelator consisting of a ferrocene unit linked to a cholesterol group via a short peptide linkage.…”

Synthesis and biological evaluation of hydroxyl-substituted Schiff-bases containing ferrocenyl moieties

“…9 Ferrocene and its derivatives, because of their lipophilicity, 10,11 excellent electrochemical activity 12,13 and high stability in aqueous solution, 11,14 have received tremendous interest in pharmaceutical chemistry. [15][16][17][18][19][20][21] When incorporated into a drug, the ferrocene moiety could yield interesting results.…”