Ferrocene–Tryptophan Conjugate: An Example of a Redox-Controlled

Article pubs.acs.org/Organometallics

Ferrocene−Tryptophan Conjugate: An Example of a RedoxControlled Reversible Supramolecular Nanofiber Network Bimalendu Adhikari, Rouzbeh Afrasiabi, and Heinz-Bernhard Kraatz* Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada S Supporting Information *

ABSTRACT: In this study, the tryptophan derivative of ferrocene-1,1′-dicarboxylic acid self-assembles in toluene to form a supramolecular nanofibrillar network structure. The ferrocene bioconjugate based nanofibers are responsive toward oxidation/reduction and show thermo and redox reversibility. Interestingly, redox-induced reversible morphological transformations between nanofiber and spheroid were observed. The self-assembly was characterized by 1H NMR spectroscopy, FT-IR spectroscopy, UV−vis spectroscopy, circular dichroism (CD), and transmission electron microscopy (TEM).

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materials.34−39 Commonly exploited stimuli include pH,27 temperature,27 light,40−42 and more recently a few redoxresponsive36,43−46 examples have been reported. The construction of redox-active nanomaterials that efficiently produce redox-induced morphological features is an attractive goal in the design of functional stimuli-responsive materials. Though there are some examples in the literature for polymer-based redox-active nanostructures,36,44,47 redox-responsive materials that are constructed from small molecules possessing a supramolecular nanoarchitecture are rare.45,48,49 Here, we explore the properties of ferrocene-1,1′-dicarboxylic acid derivatives of L-and D-tryptophan, Fc[CO-L-Trp-OMe]2 (1) and Fc[CO-D-Trp-OMe]2 (2), which both self-assemble in toluene to form a supramolecular nanofibrillar network structure. These nanofibers are responsive toward oxidation/ reduction and show thermo and redox reversibility. The redox state change of the Fc bioconjugate leads to structural changes in the assembly.

INTRODUCTION Bioorganometallic ferrocene (Fc) amino acid and peptide conjugates have received significant attention in recent years due to their interesting structural properties1−3 and potential bioanalytical applications.4 The versatility and reversible redox behavior of ferrocene are key features.2,4 A number of Fc bioconjugates of amino acids,1,2,5−12 peptides,1−4,13−20 nucleic acids,2,21 peptide nucleic acids,2 and carbohydrates2,21−23 have been studied for applications in peptide foldamers,14 as enzyme mimics,4,16,24 in electrochemical detection,2,4 and in biomedical applications.2,25 However, materials applications have not been well explored and represent a significant knowledge gap in our understanding of these interesting systems. In particular, nanostructures based on Fc bioconjugates, where the supramolecular system displays some properties that are redoxtriggered, have not been reported in the literature. Biomimetic self-assembly is a motivating approach to construct functional soft nanomaterials.26,27 Life is built by the association of simple building blocks, namely amino acids, nucleic acids, fatty acids, and sugars, which collectively form larger molecules such as proteins, carbohydrates, and lipid structures. Amino acids possess a variety of attractive features, including chirality, hydrogen-bond donor and acceptor sites, electrostatic dipoles, hydrophobic domains, ionizable groups, and metal binding sites that make them attracting building blocks for the formation of supramolecular assemblies.28 Amino acids and peptides can self-assemble into ordered nanostructures under suitable conditions through various noncovalent interactions, including hydrogen bonding, hydrophobic, π−π stacking, electrostatic, metal−ligand, and van der Waals interactions.28,29 Self-assembling amino acids/peptides form a range of nanostructures, including nanofibers, nanotubes, and nanovesicles.26−33 In this context, the development of stimuliresponsive soft materials is important for making functional © 2013 American Chemical Society

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EXPERIMENTAL SECTION

General Considerations. Ferrocene and toluene were purchased from Aldrich. Methyl esters of amino acids were purchased from Advanced ChemTech. We used the chemicals as received without further purification. Ferrocene-1,1′-dicarboxylic acid was synthesized according to a modified literature procedure,50 and the experimental procedure can be found in the Supporting Information. General Synthesis of Ferrocene Bioconjugate. Amino acid derivatives of ferrocene-1,1′-dicarboxylic acid were synthesized by using the standard EDC/HOBt method. Fc[COOH]2 (0.548 g, 2 mmol) was dissolved in dry CH2Cl2 (70 mL) with stirring, and when Special Issue: Ferrocene - Beauty and Function Received: May 27, 2013 Published: August 12, 2013 5899

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wet viscous sample was prepared by dissolving Fc bioconjugate 1 in toluene at a concentration of 0.5% w/v, and dried material was obtained by drying the wet sample. Transmission Electron Microscopy (TEM) Study. The morphologies of the assemblies of bioconjugates 1 and 2 were studied using TEM. The samples were prepared by depositing a small amount of assembling viscous solution (concentration 0.1% w/v) of ferrocene bioconjugates in toluene on a TEM grid (300 mesh size Cu grid) coated with Formvar and a carbon film. The grid was allowed to dry by slow evaporation in air and then allowed to dry separately in a vacuum for a few hours. Images were taken using a Hitachi 7500 transmission electron microscope. Circular Dichroism (CD) Study. Circular dichroism spectroscopy was used for determining the conformation of Fc bioconjugates and chiral molecular arrangement of the supramolecular assemblies obtained from conjugates 1 and 2. CD spectra were recorded between 300 and 600 nm using a JASCO J-810 spectrometer. Experiments were carried out by placing the gel-like viscous material into a quartz plate having 0.1 mm path length. CD experiments were performed using gel-like viscous samples obtained from Fc bioconjugates 1 and 2 at a constant concentration of 1% w/v.

Et3N (0.61 mL, 4.4 mmol) was added, a clear solution was obtained. HOBt (1.22 g, 8 mmol) and EDC (1.54 g, 8 mmol) were added into the reaction mixture at 0 °C, and the reaction mixture was stirred for 15 min. HCl·NH2-(L)Trp-OCH3 (2.032 g, 8 mmol) was dissolved in 15 mL of CH2Cl2 and 1.4 mL of Et3N was added to neutralize it with stirring. The resulting clear solution was added to the initial mixture, and this mixture was stirred overnight. After a standard aqueous workup (saturated aqueous NaHCO3, 10% citric acid solution, saturated NaHCO3, followed by distilled water, collection, and drying of the organic layer), the crude material was purified by column chromatography. Yield: 0.539 g (0.8 mmol, 40%). Compounds were characterized by 1H NMR, 13C NMR, mass spectrometry, and CHN analysis. These data have been given below for ferrocene bioconjugates 1 and 2, and others can be found in the Supporting Information. Spectroscopic Characterization of Fc[CO-L-Trp-OMe]2. 1H NMR (500 MHz, CDCl3, 22 °C): δ 8.33−8.32 (s, 2H; NH of Trp), 7.71− 7.69 (m, 2H), δ 7.43−7.16 (m, 10H; aromatic H of Trp), 5.12−5.08 (m, 2H; α-CH of Trp), 4.72−4.71 (m, 2H; aromatic H of ferrocene), 4.66−4.65 (m, 2H; aromatic H of ferrocene), 4.29−4.28 (m, 2H; aromatic H of ferrocene), 4.20−4.19 (m, 2H; aromatic H of ferrocene), δ 3.83 (s, 6H; OCH3), 3.48−3.44 (m, 2H; β-CH2 of Trp), 3.21−3.16 (m, 2H; β-CH2 of Trp). 13C NMR (125 MHz, CDCl3, 22 °C): δ 175.6 (2C of CONH), 170.6 (2C of COOMe), 136.3 (2C, aromatic indole ring), 127.0 (2C, aromatic indole ring), 122.6 (2C, aromatic indole ring), 122.2 (2C, aromatic indole ring), 119.6 (2C, aromatic indole ring), 118.2 (2C, aromatic indole ring), 111.4 (2C, aromatic indole ring), 110.9 (2C, aromatic indole ring), 77.5−76.7 (C of CDCl3), 71.8 (2C, aromatic ferrocene), 71.3 (2C, aromatic ferrocene), 70.1 (2C, aromatic ferrocene), 70.0 (2C, aromatic ferrocene), 53.4 (2C, α-C), δ 52.7 (C of OCH3), δ 26.9 (C of β-CH2). MS: m/z 675.18 [M + H]+, 697.17 [M + Na]+, 713.14 [M + K]+. Anal. Calcd for C36H34FeN4O6: C, 64.10; H, 5.08; N, 8.31. Found: C, 63.98; H, 5.19; N, 8.40. Spectroscopic Characterization of Fc[CO-D-Trp-OMe]2. 1H NMR (500 MHz, CDCl3, 22 °C): δ 8.38−8.36 (s, 2H; NH of Trp), 7.71− 7.67 (m, 2H), δ 7.43−7.16 (m, 10H; aromatic H of Trp), 5.11−5.07 (m, 2H; α-CH of Trp), 4.71−4.70 (m, 2H; aromatic H of ferrocene), 4.66−4.64 (m, 2H; aromatic H of ferrocene), 4.25−4.24 (m, 2H; aromatic H of ferrocene), 4.19−4.17 (m, 2H; aromatic H of ferrocene), 3.83 (s, 6H; OCH3), 3.48−3.44 (m, 2H; β-CH2 of Trp), 3.21−3.16 (m, 2H; β-CH2 of Trp). 13C NMR (125 MHz, CDCl3, 22 °C): δ 175.7 (2C of CONH), 170.6 (2C of COOMe), 136.4 (2C, aromatic indole ring), 127.1 (2C, aromatic indole ring), 122.7 (2C, aromatic indole ring), 122.2 (2C, aromatic indole ring), 119.5 (2C, aromatic indole ring), 118.1 (2C, aromatic indole ring), 111.6 (2C, aromatic indole ring), 110.6 (2C, aromatic indole ring), 77.5−76.7 (C of CDCl3), 71.7 (2C, aromatic ferrocene), 71.4 (2C, aromatic ferrocene), 70.0 (2C, aromatic ferrocene), 70.0 (2C, aromatic ferrocene), 53.5 (2C, α-C), 52.7 (C of OCH3), 26.8 (C of β-CH2). MS: m/z 675.18 [M + H]+, 697.17 [M + Na]+, 713.14 [M + K]+. Anal. Calcd for C36H34FeN4O6: C, 64.10; H, 5.08; N, 8.31. Found: C, 63.94; H, 5.22; N, 8.19. UV/Vis Spectroscopic Study. UV−visible experiments were performed to probe the oxidation/reduction reaction of ferrocene by dissolving Fc bioconjugate 1 in acetone. UV/vis absorption spectra of the Fc bioconjugates were recorded in the wavelength range 300−900 nm using a UV/vis spectrophotometer (Agilent 8453). A sample was prepared by dissolving bioconjugate 1 in acetone at a concentration of 0.45% w/v. NMR Study. All synthetic Fc bioconjugates were characterized using NMR spectroscopy (Bruker spectrometer 500 MHz). Samples were dissolved in CDCl3 at a concentration of 0.4% w/v. A variabletemperature 1H NMR was used to evaluate the conformation of ferrocene and to investigate the involvement of inter- and intramolecular hydrogen bonding in ferrocene bioconjugate. VT-NMR spectra of Fc bioconjugate 1 in toluene-[D]8 were recorded in the temperature range 30−60 °C at a concentration of 0.15% w/v. FTIR Study. FTIR spectra of wet viscous material, dried material, and toluene were recorded in the range 3400−1400 cm−1 using a Bruker ALPHA FTIR spectrometer equipped with a diamond ATR. A

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RESULTS AND DISCUSSION The tryptophan derivatives of ferrocene-1,1′-dicarboxylic acid Fc[CO-L-Trp-OMe]2 (1) and Fc[CO-D-Trp-OMe]2 (2) were synthesized, and their self-assembling behavior was studied. The Fc conjugate 1 and its enantiomer 2 are soluble in toluene with increasing temperature. When the hot solution was cooled to room temperature followed by sonication, a gel-like viscous material was obtained. The formation of a viscous material suggests the self-assembly of the bioconjugate. It was observed that, in the absence of sonication, the gel-like material was less viscous. This indicates that sonication plays a crucial role in assisting the assembly of the Fc bioconjugate into a gel-like material. Sonication-induced gel formation has been reported in the literature.51,52 Sonication-assisted dissolution of compounds with hydrogen-bonding functionality can result in their rapid aggregation under nonequilibrium conditions, and this leads to the deposition of a fibrillar network that can effectively entrap solvent molecules, giving rise to gel formation.51,52 It was found that both bioconjugates 1 and 2 can act as supramolecular building blocks that produce selfassociating viscous materials even at very low concentrations (0.5% w/v). Importantly, similar Fc bioconjugates involving other amino acid esters, including Gly-OMe, Ala-OMe, ValOMe, Phe-OMe, Asp(OMe)-OMe, and Glu(OMe)-OMe, do not form viscous assemblies under similar conditions. An equimolar mixture of 1 and 2 is incapable of producing any viscous material and forms a crystalline precipitate instead. It was found that in the presence of equimolar amount of Fc[COL-Ala-OMe]2 or Fc[CO-L-Gly-OMe]2, bioconjugate 1 produced a viscous material. This suggests that the interaction between two molecules with opposite chiralities may be responsible for preventing self-assembly. Stimuli-Responsiveness Study. The viscous gel-like material for both conjugates 1 and 2 melted upon heating to form a complete solution. This process was reversible, and cooling of the heated solutions resulted again in the formation of a viscous gel-like material. The temperature at which the gellike viscous material transforms into a solution state is called the melting temperature. It was found that the melting temperature increased with increasing concentration of the Fc bioconjugates. The melting temperature is about 60 °C for a viscous material of 0.15% w/v for bioconjugate 1. We also investigated the assembling behavior of the bioconjugate 5900

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Figure 1. (a) Chemical structure of ferrocene bioconjugate Fc[CO-L-Trp-OMe]2 (1). (b) Photograph of gel-like viscous material in toluene, obtained by self-assembly of 1 (middle), which undergoes reversible transition into solution in the presence of stimuli such as heating/cooling (left) and oxidation/reduction (right).

reversible. The photographs of the oxidized and reduced states of ferrocene conjugate 1 are shown in Figure 2. NMR Study. NMR is a useful tool to identify the conformation and H-bonding interaction of ferrocene peptides.1 A temperature-dependent 1H NMR spectroscopic measurement was performed to investigate the effects of the amide groups and NH group of the indole ring of the bioconjugate 1 of hydrogen bond formation in the assembly (see Figure 3). The experiment was carried out with selfassembled viscous material in toluene-[D]8 in the temperature range of 30−60 °C. At a concentration of 1.5 mg/1 mL the molecules remained in a nonassembled molecular state at 60 °C and a self-assembled state at 30 °C. At 60 °C, the NH proton of the amide groups and NH proton of indole appeared as doublets at 7.69 and 7.47 ppm, respectively. With a decrease in temperature the peak at 7.47 ppm gradually shifted downfield and appeared at 7.81 ppm at 30 °C. The downfield chemical shift of the NH proton of the indole ring suggests a gain of interaction and consequently formation of intermolecular hydrogen bonds at lower temperatures. This confirms the involvement of the indole NH moiety in intermolecular hydrogen bonding for the ferrocene bioconjugate. On the other hand, the peak position at 7.69 ppm remained almost constant in the temperature range 30−60 °C. The presence of amide resonances above δ 7 ppm in non-hydrogen-bonding solvents (toluene-[D]8) indicates the presence of H bonding and a “Herrick conformation” stabilized by two symmetrical intramolecular interstrand hydrogen bonds which exist in both the assembled and nonassembled states.1,7 FTIR Study. To understand the molecular interactions of the ferrocene conjugate 1 in the assembled state, FTIR experiments were performed using wet viscous material as well as the dried material (Figure 4). For wet viscous material, the NH stretching and bending bands were observed at 3266 cm−1 (as a broad peak) and 1533 cm−1, respectively. This suggests that the NH group is involved in hydrogen-bonding interactions in the assembled state.1,53 The appearance of the CO stretching band at 1634 cm−1 indicates that the hydrogen-bonded structure is present in the assembled state. Another peak at 1728 cm−1 is characteristic of the CO stretch of the ester group in the ferrocene bioconjugate.53 An FTIR study of toluene was also carried out to ensure the aforementioned bands arise from the ferrocene bioconjugate 1 rather than the solvent. Figure 4 shows three dashed lines indicating the presence of these bands in the assembled system. Moreover, in the dried sample (Figure 4a), the presence of the

toward redox as a stimulus. For this experiment, the ferrocenebased viscous gel-like material (in toluene) was treated with an equimolar amount of Fe(ClO4)3, a suitable oxidizing agent. Upon aging with the oxidizing agent, a gradual decrease in viscosity of the gel-like material was observed which transformed into a complete solution within a few minutes. The transformation was accompanied by a distinct color change from light orange-brown to blue (Figure 1). This color change is due to the fact that the Fc moiety of Fc bioconjugates was oxidized to ferrocenium. The original reduced Fc bioconjguate solution can be regenerated by the addition of ascorbic acid, which acts as a reducing agent. To probe the redox behavior of Fc bioconjugates, UV− visible experiments were performed with bioconjugate 1 in acetone, shown in Figure 2. A peak at 440 nm, characteristic of the neutral ferrocene state, was obtained for the Fc bioconjugate. After oxidation with Fe(ClO4)3, the peak at 440 nm disappeared and a new peak at 650 nm, responsible for the ferrocenium, appeared. The peak at 440 nm reappeared after reduction of the ferrocenium moiety by ascorbic acid, indicating that this oxidation and reduction process is completely

Figure 2. UV−vis study of Fc bioconjugate 1 in acetone showing reversible redox transition between ferrocene and ferrocenium: (a) Fc bioconjugate 1 before oxidation; (b) 1 after oxidation; (c) reduction of (b). Therefore, (a) and (c) represent neutral Fc bioconjugate 1 and (b) represents the oxidized state of 1. 5901

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Figure 3. Temperature-dependent 1H NMR spectra of ferrocene bioconjugate 1 in toluene-[D]8 at a concentration of 0.15% w/v, showing the downfield shift of one NH proton with decreasing temperature from (a) to (e).

almost uniform and well-ordered nanofibrillar26−29,33,52 network structure exclusively (Figure 5a−c). The width of these fibers is within the range 40−80 nm, and each fiber is a few micrometers in length, indicating a high aspect ratio. We also investigated the partially and fully oxidized ferrocene bioconjugate 1 with Fe(ClO4)3, and the results are shown in parts a and b of Figure 6, respectively. Interestingly, the coexistence of fibers and spherical morphologies were obtained for partially oxidized ferrocene bioconjugate 1, while the fully oxidized species exclusively exhibited a spherical morphology. Furthermore, after reduction, ferrocenium (Fc+) transformed into a neutral ferrocene (Fc) containing bioconjugate and regenerated its fibrillar morphology (Figure 6c). The change of the redox state can lead to obvious structural changes of the assembly, which is schematically explained by the proposed tentative model (Scheme S1 in the Supporting Information). This is a good example of the reversible transformations of nanostructures using redox reactions as stimuli. In order to check the role of chirality in the assembled structure, we also checked the assembling behavior of ferrocene bioconjugate 2 by changing its chirality. The TEM images of the ferrocene bioconjugate 2 also exhibit almost uniform and well-ordered nanofibrillar network structure (Figure 5d−f). The width of these fibers is within the range 40−80 nm, and each fiber is a few micrometers in length. Such nanofibers are not very stable in the solution state for a long time and can transform into a rod/tape-like structure with increasing time (Figure S1 in the Supporting Information). However, nanofibrillar network structures remain stable under dried conditions for a long time. Interestingly, the racemic mixture (1 + 2) of the two-component system exhibited a starlike macroscopic morphology (Figure S2 in the Supporting Information). Therefore, the presence of two opposite chiralities in a mixture of 1 and 2 inhibits the formation of their individual nanofibrillar morphology.

Figure 4. FTIR spectra of ferrocene bioconjugate 1: (a) dried sample obtained from gel-like material; (b) viscous material in toluene; (c) toluene. Peaks marked by dotted lines are due to the hydrogen-bonded amide functionality.

bands at 3266, 1630, and 1530 cm−1 suggests that a similar hydrogen-bonded structure is preserved in the dried material. Morphological Study. To investigate the morphological features of the self-assembling ferrocene conjugates 1 and 2 in toluene, transmission electron microscopic (TEM) studies were performed. For this experiment, the ferrocene conjugate was dissolved in toluene with increasing temperature and which upon cooling formed a viscous solution. This freshly prepared slightly viscous solution was placed on a carbon-coated copper grid followed by slow evaporation in air and then vacuum drying at room temperature for a few hours. The TEM images of the ferrocene bioconjugate 1 show the formation of an 5902

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Figure 5. (a−c) TEM images of self-assembled ferrocene bioconjugate Fc[CO-L-Trp-OMe]2 with increasing magnification from (a) to (c), showing the formation of a nanofibrillar network structure. (d−f) TEM images of Fc[CO-D-Trp-OMe]2 with increasing magnification from (d) to (f), showing the formation of a similar nanofibrillar network structure with respect to the enantiomer. Scale bars are 10 μm for (a) and (d), 2 μm for (b) and (e), and 200 nm for (c) and (f).

Figure 6. TEM images of self-assembled ferrocene bioconjugate Fc[CO-L-Trp-OMe]2: (a) after partial oxidation showing coexistence of nanofiber and spheroid morphology; (b) after complete oxidation showing exclusive presence of spheroid morphology; (c) after reduction of oxidized ferrocene bioconjugate showing regeneration of nanofibrous network. Scale bars are 2 μm for (a), 10 μm for (b), and 2 μm for (c).

Figure 7. (i) CD spectra of different ferrocene bioconjugates in toluene at constant concentration (1% w/v) and temperature (20 °C): (a) Fc[CO-LTrp-OMe]2; (b) Fc[CO-D-Trp-OMe]2; (c) racemic mixture Fc[CO-L-Trp-OMe]2 + Fc[CO-L-Trp-OMe]2. (ii) CD spectra of different ferrocene bioconjugates under different conditions: (a) Fc[CO-L-Trp-OMe]2 in toluene at 80 °C at a concentration of 1% w/v; (b) Fc[CO-L-Trp-OMe]2 in MeOH at 20 °C; (c) Fc[CO-L-Phe-OMe]2 in toluene at 20 °C. 5903

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Circular Dichroism. Circular dichroism (CD) is a valuable tool to determine the chiral molecular arrangement in a selfassembled state. The intermolecular interactions, in particular between chromophoric molecules, may produce remarkable chiroptical responses and show CD bands that are much stronger in the self-assembled state than in their isolated molecular state. CD is also very useful for the elucidation of metallocene chirality.1 The CD study of the reported ferrocene bioconjugate 1, Fc[CO-L-Trp-OMe]2, in the self-assembled state in toluene showed a strong positive band around 500 nm (Figure 7ia). Bands between 300 and 600 nm are characteristic of metal-centered transitions, and bands below 300 nm originate from the amino acid. The strong Cotton effect about 500 nm indicates the formation of a chiral P-helical ferrocene core as the result of intramolecular H-bonding interactions, as expected for a 1,n′-disubstituted Fc amino acid conjugate adopting a “Herrick conformation”.1,7 Individual molecules assemble into larger chiral supramolecular aggregates, which give rise to a higher ellipticity. It is important to point out that this increase is due to the formation of a supramolecular structure.54,55 In order to probe this further, temperature-dependent and solvent-dependent CD studies were performed. The ferrocene-based CD signal at 500 nm decreases significantly at higher temperature (80 °C) where molecules are isolated and not in the assembled state (Figure 7iia). In MeOH, a solvent which does not support assembly formation, the CD signal of Fc bioconjugate 1 around 500 nm is negligible (Figure 7iib). This clearly suggests the presence of supramolecular chirality in the self-assembled state in toluene, and the CD response is a consequence of the self-assembly of the chiral ferrocenyl amino acid into a supramolecular structure, rather than the inherent molecular chirality of the amino acid. We also checked the CD of Fc[CO-D-Phe-OMe]2, which does not gives any self-assembling viscous material in toluene and does not show any significant CD signal near 500 nm (Figure 7iic). The CD spectrum of Fc bioconjugate 2, Fc[CO-D-TrpOMe]2, in the assembled state exhibits a strong negative band around 500 nm, and this CD signal is the mirror image of the CD signal obtained from the Fc bioconjugate 1 (Figure 7ib). This indicates that the chirality of the assembly obtained from the self-assembly of Fc-bioconjugate 1 is opposite in nature with respect to the assembly obtained from the D isomers: i.e., Fc bioconjugate 2. The negative band about 500 nm suggests the formation of an M-helical chirality of the ferrocene group induced by intramolecular H bonding involving the two D-Trp residues.7 Interestingly, the CD spectrum of the racemic mixture containing equimolar amounts of 1 and 2 does not show any significant CD response (Figure 7ic). This suggests that the interchromophore orientation is disordered, achiral, or chiral but racemic.54,55

and spheroid were observed. This self-assembling Fc bioconjugate may open opportunities in developing new redox-active functional biomaterials in the near future.

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ASSOCIATED CONTENT

S Supporting Information *

Figures and text giving a scheme for redox-induced reversible morphological transformations, TEM images of Fc[CO-D-TrpOMe]2 in toluene with increasing time and racemic mixture of Fc bioconjugates, the synthetic procedure of 1,1′-ferrocenedicarboxylic acid, and characterization and 1H NMR and ESI-MS spectra of conjugates 1 and 2 and of other Fc bioconjugates synthesized as part of this study. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail for H.-B.K.: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the NSERC and the University of Toronto Scarborough. In addition we thank the Department of Biochemistry, Western University, for access to its bioanalytical facility. We also thank the CNS, University of Toronto Scarborough, for access to its TEM facility.

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REFERENCES

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CONCLUSION The self-assembly process is a bottom-up approach to make well-defined functional nanostructures with varying properties. The construction of supramolecular redox-active nanomaterials that efficiently produce redox-induced morphological features is an attractive goal in the design of functional stimuli-responsive materials. In this study, redox and thermo reversible supramolecular nanofibrillar network structures have been developed using the self-assembly of the tryptophan conjugate of ferrocene-1,1′-dicarboxylic acid. Moreover, redox-induced reversible morphological transformations between nanofiber 5904

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dx.doi.org/10.1021/om4004779 | Organometallics 2013, 32, 5899−5905