Next Article in Journal
Noise Attenuation Based on Wave Vector Characteristics
Previous Article in Journal
Strained Silicon Single Nanowire Gate-All-Around TFETs with Optimized Tunneling Junctions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Applied Sciences
Volume 8
Issue 5
10.3390/app8050671
applsci-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis, Characterization, and Self-Assembly of a Tetrathiafulvalene (TTF)–Triglycyl Derivative

by
Sónia Pérez-Rentero
1,2,
Ramon Eritja
1,2,*,
Marleen Häring
3,
César Saldías
4 and
David Díaz Díaz
1,3,*
1
Institute of Advanced Chemistry of Catalonia-Spanish National Research Council (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain
2
Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Jordi Girona 18-26, 08034 Barcelona, Spain
3
Institut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
4
Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 302, Correo 22, 7820436 Santiago, Chile
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2018, 8(5), 671; https://doi.org/10.3390/app8050671
Submission received: 3 April 2018 / Revised: 18 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018
(This article belongs to the Section Materials Science and Engineering)
Browse Figures
Versions Notes

Abstract

:
In this work, we describe the synthesis, characterization, and self-assembly properties of a new tetrathiafulvalene (TTF)–triglycyl low-molecular-weight (LMW) gelator. Supramolecular organogels were obtained in various solvents via a heating–cooling cycle. Critical gelation concentrations (CGC) (range ≈ 5–50 g/L) and thermal gel-to-sol transition temperatures (Tgel) (range ≈ 36–51 °C) were determined for each gel. Fourier transform infrared (FT-IR) spectroscopy suggested that the gelator is also aggregated in its solid state via a similar hydrogen-bonding pattern. The fibrillar microstructure and viscoelastic properties of selected gels were demonstrated by means of field-emission electron microscopy (FE-SEM) and rheological measurements. As expected, exposure of a model xerogel to I2 vapor caused the oxidation of the TTF unit as confirmed by UV-vis-NIR analysis. However, FT-IR spectroscopy showed that the oxidation was accompanied with concurrent alteration of the hydrogen-bonded network.

1. Introduction

Oligonucleotide conjugates carrying aromatic systems are important tools for a large number of applications due to their enhanced hybridization properties and their special fluorescence and chemical properties coming from the aromatic moieties [1,2,3,4,5,6]. Recently, tetrathiafulvalene (TTF) derivatives have been incorporated in oligonucleotides demonstrating the fluorescence-quenching properties of the DNA–TTF conjugates upon hybridization [7], the preservation of the electrochemical properties of TTF [8], an enhanced affinity to complementary sequences [9], and compatibility with the RNA interference mechanism for gene inhibition [10]. In the field of materials chemistry, TTF and its derivatives constitute electron donors that can form charge-transfer (CT) complexes and have been widely studied for the development of electrically conducting materials [11,12]. TTF moiety can be consecutively oxidized to the radical cation TTF+ and dication TTF2+ by either electrochemical or chemical processes. Due to the reversibility of these transformations [13], TTF has become a general building block for the fabrication of switchable functional materials [14,15,16,17], including supramolecular self-assembled nanostructures [18,19,20,21].
The interesting properties of the TTF-oligonucleotides prompted us to synthesize a TTF derivative carrying a biodegradable triglycyl peptide linker between the oligonucleotide and the TTF molecule. This simple peptide sequence has been demonstrated to be hydrolyzed by cathepsin B present in endosomes [22]. During the preparation of the mentioned TTF derivative we accidentally observed the formation of gels in some solvents. In general, gels have received great attention during the last decade [23,24,25,26,27,28,29,30,31,32,33,34] due to their exceptional hierarchical architectures and potential applications in many important areas such as biomedicine, health care, and catalysis, among others [35,36,37,38,39,40,41,42,43,44,45]. Chemical gels are based on covalent bonds, usually cross-linked polymers [46,47,48], whereas physical gels (also called supramolecular gels) are normally fabricated using low-molecular-weight (LMW) molecules that self-assembly via non-covalent interactions. For this reason, supramolecular gels usually show reversible stimuli-responsive gel-to-sol transitions [23,24]. Systems based on both covalent and non-covalent interactions are also known [49]. Typically, the entanglement of 1D nanofibers of gelator molecules generates a 3D-network with the solvent molecules trapped into the interstices by capillary forces. This provides a solid-like appearance and viscoelastic features to physical gels [50,51,52,53].
Within this context, Jørgensen and co-workers reported in 1994 [54] the first TTF-based LMW gelator bearing bis-arborol units, which was used to fabricate a self-assembling “molecular” nanowire [55]. Since then, a large number of electroactive TTF-based LMW gelators and their gels have been described in the literature [56]. In general, the rational design behind these examples involves the connection of the TTF unit with groups capable of H-bonding, such as urea [57] or amide groups [58,59,60,61,62,63], to form extended structures. The incorporation of other molecular building blocks commonly used to form physical gels [64,65,66,67] or the use of metal–organic interactions [68,69,70] have also been employed to form TTF-based gels. Moreover, the inclusion of hydrophobic aliphatic chains is also employed to facilitate van der Waals interactions and stabilize the supramolecular aggregates [58,59,60,61,62,63,64,65,66,67,68,69,70,71]. If formation of CT complexes takes place, the TTF unit will bear positive charge, which can alter the interaction of neighboring TTF units and influence the intermolecular interactions arising from other groups involved in the self-assembly process. Indeed, the above-mentioned studies have confirmed the possibility of tuning the gel formation by CT interaction and oxidation. In addition, conductive gels have also been fabricated by simple mixing and mechanically grinding neutral TTF and an acceptor (i.e., tetracyanoquinodimethane) in ionic liquids [72]. More recently, gels made of TTF–dipeptide and tripeptide conjugates have been reported [73,74].
In this communication we describe the synthesis, characterization, and gelation properties of a new TTF–triglycyl-based LMW organogelator (Figure 1). As far as we are aware, a triglycyl peptide has not been used to fabricate TTF-based gelators.

2. Materials and Methods

2.1. Materials

Unless otherwise noted, all reagents and dry solvents were purchased from commercial suppliers (Sigma-Aldrich, St. Louis, MO, USA, TCI Chemicals, Tokyo, Japan) and used as received.

2.2. Synthesis and Characterization of Compounds

2.2.1. General Remarks

Nuclear magnetic resonance (NMR) spectra, 1H-NMR (400 MHz), and 13C-NMR (100 MHz) were recorded using Varian Mercury 400 spectrometer at room temperature (RT). Tetramethylsilane (TMS) was used as internal reference (0 ppm) for 1H spectra recorded in CDCl3. Chemical shifts for 1H-NMR and 13C-NMR were reported as δ, parts per million (ppm), relative to the signal of the residual solvent (1H-NMR: CHCl3 = 7.26 ppm, DMSO = 2.50 ppm; 13C-NMR: CHCl3 = 77.16 ppm, DMSO = 39.5 ppm; CD3OD = 49.0 ppm). Coupling constants (J) are given in Hertz (Hz). Multiplicity notations: s = singlet, bs = broad singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet. Estimated error of reported values: 0.01 ppm (δ, 1H-NMR), 0.1 ppm (δ, 13C-NMR), 0.1 Hz (J, coupling constant). Copies of the NMR spectra are provided in the Supporting Information. Fourier transform infrared (FT-IR) spectra were recorded on a Thermo-Nicolet Avatar 380 FT-IR equipped with a SMART iTR sampling accessory. Electrospray ionization mass spectra (ESI-MS) were recorded on a Micromass ZQ instrument with single quadrupole detector coupled to an HPLC and high-resolution (HR) ESI-MS on an Agilent 1100 LC/MS-TOF instrument (Servei d’Espectrometría de Masses, Universitat de Barcelona). Flash chromatography was performed using silica gel (230–400 mesh) as stationary phase. Thin-layer chromatography (TLC) analysis were carried out on silica gel 60 F254 aluminum sheets and visualized under UV light (365 nm).

2.2.2. Synthetic Procedures and Characterization of Compounds

4,5-Bis-(butylthio)-1,3-dithiole-2-thione (3): A mixture of bis(tetrabutylammonium) bis(1,3-dithiole-2-thione-4,5-dithiolate) zinc (1, TCI chemicals) (2.18 g, 2.30 mmol) and 1-bromobutane (2, Sigma-Aldrich) (1.24 mL, 11.50 mmol) in anhydrous acetonitrile (ACN) (30 mL) was refluxed for 1 h. The initially formed reddish solution turned into a green-yellowish mixture. Once the solution was cooled to room temperature (RT), the precipitate was filtered out and the solution mixture was concentrated to dryness under reduced pressure. The residue was dissolved in dichloromethane (DCM) (50 mL) and the organic phase was washed with water (4 × 30 mL). The organic phase was dried over anhydrous MgSO4 and concentrated to dryness under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane/ethyl acetate (AcOEt) 1:1) affording the desired compound 3 as reddish oil (1.40 g, 98% yield). TLC in AcOEt/hexane 10:0.1, Rf = 0.85. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.85 (t, J = 7.3 Hz, 4H, =C-SCH2-), 1.67–1.59 (m, 4H, =C-SCH2-CH2-), 1.48–1.38 (m, 4H, =C-SCH2-CH2-CH2-), 0.91 (t, J = 7.3 Hz, 6H, CH3). 13C-NMR (100 MHz, CDCl3) δ (ppm): 211.49 (C=S), 136.34 (S-C-S), 36.42 (S-CH2-), 31.64 (S-CH2-CH2-), 21.63 (S-CH2-CH2-CH2-), 13.51 (-CH3). IR (oil): ν = 2954 m, 2925 m and 2869 w (C-H stretch), 1461 m (H-C-H bend), 1060 s (C=S stretch), 884 m (H-C-S bend), 742 w (C-S stretch) cm−1. HRMS (ESI+): m/z: calcd for C11H19S5 ([M + H]+) 311.0090; found 311.0084.
2,3-Bis(2-cyanoethylthio)-6,7-bis(butylthio)tetrathiafulvalene (5): A mixture of 4,5-bis(2-cyanoethylthio)-1,3-dithiol-2-one (4, Sigma-Aldrich) (1 g, 3.47 mmol) and compound 3 (1.3 g, 4.16 mmol) was dried by successive evaporation of dry ACN (×3) followed by storage in a desiccator. The residue was dissolved in trimethyl phosphite (40 mL) and the solution heated gradually to reach 110 °C under argon atmosphere. The solution was stirred for 2 h at 110 °C and subsequently allowed to cool RT. The mixture was concentrated to dryness and the residue was treated with toluene and evaporated (×4) in order to eliminate the excess of trimethyl phosphite. The obtained residue was purified by flash chromatography on silica gel (DCM/hexane 8:2 to pure DCM) affording the desired compound 5 as a yellow solid (1.22 g, 64% yield). TLC in DCM/hexane 10:0.1, Rf = 0.38. 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.07 (t, J = 7.2 Hz, 4H, =C-SCH2-CH2-CN), 2.81 (t, J = 7.2 Hz, 4H, =C-SCH2-CH2-CH2-CH3), 2.72 (t, J = 7.2 Hz, 4H, =C-SCH2-CH2-CN), 1.64–1.56 (m, 4H, C-SCH2-CH2-CH2-CH3), 1.47–1.38 (m, 4H, C-SCH2-CH2-CH2-CH3), 0.91 (t, J = 7.3 Hz, 6H, CH3). 13C-NMR (100 MHz, CDCl3) δ (ppm): 127.95 and 127.82 (S-C-S), 117.40 (CN), 114.75 (C=C), 106.38 (C=C), 36.02 (S-CH2-), 31.70 (S-CH2-CH2-), 31.23 (S-CH2-CH2-CN), 21.60 (S-CH2-CH2-CH2-), 18.89 (S-CH2-CH2-CN), 13.57 (-CH3). IR (solid): ν = 2954 m, 2924 m and 2869 m (C-H stretch), 2249 w (C≡N stretch), 1457 w (H-C-H bend), 1415 m-s (H-C-H bend), 889 s (H-C-S bend), 771 s (C-S stretch) cm−1. HRMS (ESI+): m/z: calcd for C20H27N2S8 ([M + H]+) 550.9940; found 550.9956.
2-(2-Cyanoethylthio)-3,6,7-tris(butylthio)tetrathiafulvalene (6): A solution of CsOH·H2O (365 mg, 2.12 mmol) in dry methanol (MeOH) (15 mL) was added dropwise over a period of 30 min to a stirred solution of TTF derivative 5 (1.13 g, 2.07 mmol) in tetrahydrofuran (THF) (40 mL). The resulting orange solution was stirred for 30 min at RT. To this solution, 1-bromobutane (2) (0.44 mL, 4.14 mmol) dissolved in THF (15 mL) was added and the resulting mixture was stirred overnight (o.n.) at RT under nitrogen atmosphere. The mixture was concentrated to dryness and the resulting oil was purified by flash chromatography on silica gel (DCM/hexane 1:1→2:1) giving the desired compound 6 as an orange solid (1.09 g, 89% yield). TLC in DCM/hexane 2:1, Rf = 0.45. 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.01 (t, J = 7.2 Hz, 2H, SCH2-CH2-CN), 2.87–2.78 (m, 6H, SCH2-CH2-CH2-CH3), 2.68 (t, J = 7.2 Hz, 2H, SCH2-CH2-CN), 1.65–1.57 (m, 6H, SCH2-CH2-CH2-CH3), 1.47–1.38 (m, 6H, SCH2-CH2-CH2-CH3), 0.93–0.89 (m, 9H, CH3). 13C-NMR (100 MHz, CDCl3) δ (ppm): 133.71, 127.92, 127.61 and 121.83 (-CH2-S-C-S-), 117.53 (CN), 112.36 and 108.27 (S2C=CS2), 36.02 and 35.98 (S-CH2-), 31.77 and 31.73 (S-CH2-CH2-), 31.24 (S-CH2-CH2-CN), 21.62 (S-CH2-CH2-CH2-), 18.69 (S-CH2-CH2-CN), 13.57 and 13.53 (-CH3). IR (solid): ν = 2954 s, 2925 s and 2870 m (C-H stretch), 2250 w (C≡N stretch), 1463 m (H-C-H bend), 1412 m (C-H stretch), 890 s (H-C-S bend), 772 m-s and 742 m-s (C-S stretch) cm−1. HRMS (ESI+): m/z: calcd for C21H31NS8 554.0300; found 554.0288.
3-{[4′,5,5′-Tris(butylsulfanyl)-2,2′-bi-1,3-dithiol-4-yl]sulfanyl}propionic acid (8): (2-Cyanoethyl)sulfanyl TTF derivative 6 (1.01 g, 1.82 mmol) was dissolved in anhydrous THF (40 mL) and a solution of CsOH·H2O (0.32 g, 1.9 mmol) in anhydrous MeOH (15 mL) was added. After stirring the reaction mixture at RT for 30 min, a suspension of 3-bromopropionic acid (7, Sigma-Aldrich) (0.56 g, 3.6 mmol) and freshly annealed K2CO3 (1.39 g, 10 mmol) in anhydrous MeOH (15 mL) was added. The reaction mixture was stirred at RT for 3 h and concentrated to dryness. The obtained residue was dissolved in Et2O (230 mL) and 1M HCl aqueous solution (150 mL) was added slowly. The organic phase was washed with water (100 mL) and brine (100 mL), dried over anhydrous MgSO4 and concentrated to dryness under reduced pressure. The obtained residue was purified by chromatography on silica gel (DCM/MeOH 100:0→90:10) affording the desired compound 8 as an orange solid (0.95 g, 91% yield). TLC in DCM/MeOH 10:0.5, Rf = 0.50. 1H NMR (400 MHz, CDCl3), δ (ppm): 3.03 (t, J = 7.2 Hz, 2H, SCH2-CH2-COOH), 2.83–2.79 (m, 6H, SCH2-CH2-CH2-CH3), 2.72 (t, J = 7.2 Hz, 2H, SCH2-CH2-COOH), 1.63–1.56 (m, 6H, C-SCH2-CH2-CH2-CH3), 1.47–1.37 (m, 6H, C-SCH2-CH2-CH2-CH3), 0.91 (t, J = 7.2 Hz, 9H, CH3). 13C-NMR (100 MHz, CDCl3) δ (ppm): 176.78 (COOH), 131.10, 127.87, 127.61 and 124.70 (-CH2-S-C-S-), 111.17 and 109.22 (S2C=CS2), 35.99 and 36.96 (S-CH2-), 34.41 (SCH2-CH2-COOH), 31.74 (S-CH2-CH2-), 30.48 (SCH2-CH2-COOH), 21.63 (S-CH2-CH2-CH2-), 13.57 and 13.54 (-CH3). IR (solid): ν = 2956 m, 2912 m and 2854 m (C-H stretch), 1704 s (C=O stretch), 1465 m (H-C-H bend), 1438 m-s (O-H bend), 1294 m (C-O stretch), 947 m, broad (O-H bend), 887 m (H-C-S bend), 788 m-s, 772 m-s and 740 m-s (C-S stretch) cm−1. HRMS (ESI-): m/z: calcd. for C21H31O2S8 571.0095; found 571.0093.
N-[N’-(Tert-butoxycarbonyl)glycylglycylglycyl]-l-threoninol (13): The N-protected tripeptide Boc-(Gly)3-OH (9, Bachem) (1.05 g, 3.54 mmol) along with 4-nitrophenol (10, Fluka) (0.59 g, 4.25 mmol) were dissolved in anhydrous pyridine (15 mL) under argon and the solution was cooled at 0 °C. Then, 1,3-dicyclohexylcarbodiimide (DCC) (0.88 g, 4.25 mmol) was added under argon and the reaction was stirred at 0 °C for 30 min and then at RT overnight. After this time, the precipitate was filtered out and the solvent was removed under vacuum. The obtained residue was dissolved in toluene and concentrated to dryness under reduced pressure (×3). The resulting 4-nitrophenyl ester 11 was used in the next step without further purification.
The activated acid and (2R, 3R)-2-aminobutane-1,3-diol (12, l-threoninol, Sigma-Aldrich) (0.41 g, 3.89 mmol) were dissolved in anhydrous DMF (15 mL) under argon and stirred at RT for 3 h. After this time, the solvent was removed under reduced pressure and the residue was dissolved in toluene and concentrated to dryness (×3). The obtained residue was purified by flash chromatography on silica gel (crude adsorbed onto the silica, DCM/MeOH 100:5→100:15) affording the desired compound 13 as a white solid (1.13 g, 87%). TLC in DCM/MeOH 100:10, Rf = 0.35. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.07–8.01 (m, 2H, NH), 7.25 (d, J = 8.0 Hz, 1H, NH), 6.95 (t, J = 6.0 Hz, 1H, NH), 4.52–4.50 (br, 2H, OH), 3.85-3.83 (m, 1H, OH-CH-CH3), 3.71–3.68 (m, 4H, NH-CH2-CO), 3.62–3.56 (m, 2H, NH-CH-CH2), 3.56 (d, J = 8.0 Hz, 2H, NH-CH2-CO), 3.44-3.37 (m, 1H, OH-CH(A)H(B)-CH), 3.31–3.26 (m, 1H, OH-CH(A)H(B)-CH), 1.35 (s, 9H, (CH3)3-C), 0.95 (d, J = 6.4 Hz, 3H, CH3-CH-CH). 13C-NMR (100 MHz, DMSO-d6) δ (ppm): 170.58 (NH-CO), 169.67 (NH-CO), 169.37 (NH-CO), 156.50 (O-CO-NH), 78.83 (CH3-C), 64.88 (CH3-CH), 61.12 (OH-CH2-CH), 56.43 (NH-CH-CH), 43.99 (NH-CH2-CO), 42.77 (NH-CH2-CO), 42.70 (NH-CH2-CO), 28.87 (CH3-C), 20.73 (CH3-CH). IR (solid): ν = 3428 w, broad, 3294 m, broad and 3094 w, broad (N-H and O-H stretch), 2963 w and 2929 w (C-H stretch), 1683 m and 1632 s (C=O stretch), 1525 s (N-H bending), 1481 w–1394 w (C-H bend), 1279 m, 1244 s, 1156 m, 1123 w, 1102 w, 1076 m, 1048 m and 1025 m (C-O stretch or C-N stretch), 947 m and 857 m (C-H bend), 654 m, broad (N-H out of plane bend). HRMS (ESI+): m/z: calcd. for C15H29N4O7([M + H]+) 377.2036 found 377.2031; m/z: calcd. for C15H28N4NaO7 ([M + Na]+) 399.1856 found 399.1856.
l-Threoninol-(Gly)3-TTF derivative (14): Compound 13 (0.87 g, 2,32 mmol) was dissolved in DCM (10 mL) and TFA (1 mL) was added slowly at RT. Stirring was continued until TLC showed no remaining starting material (ca. 1–1.5 h) and the mixture was concentrated to dryness under reduced pressure. The obtained residue was dissolved in toluene and concentrated to dryness under reduced pressure. This process was repeated three times to remove traces of TFA to yield the TFA salt of the deprotected amino compound (colorless oil). This crude TFA salt was dried in vacuo and used in the next step without purification.
{[4′,5,5′-Tris(butylsulfanyl)-2,2′-bis-1,3-dithiol-4-yl]sulfanyl}propanoic acid (8, 0.95 g, 1.66 mmol) along with N-hydroxysuccinimide (NHS) (Sigma-Aldrich) (0.21 g, 1.83 mmol) were dissolved in anhydrous THF (40 mL) under argon and the solution was cooled at 0 ºC. Then, DCC (0.38 g, 1.83 mmol) was added under argon and the reaction was stirred at 0 °C for 30 min and at RT overnight. The precipitate was filtered out and the solvent was removed under reduced pressure. The resulting N-hydroxysuccinimide ester was used in the next step without further purification. The active ester was dissolved in anhydrous DMF (30 mL). The TFA salt of the deprotected amino compound was dissolved in DMF (30 mL) and N,N-diisopropylethylamine (DIEA) (405 µL, 2.32 mmol) was added. Then, the solution of the active ester was added under argon and the mixture was allowed to react at RT for 30 min. The solvent was removed under reduced pressure and the residue was dissolved in toluene and concentrated to dryness (×3). The crude compound was washed with hexane (5 × 70 mL) and with diethyl ether (5 × 70 mL). The residue was dissolved in DCM (300 mL) and the organic phase was washed with 5% aqueous NaHCO3 (2 × 75 mL) and saturated aqueous NaCl (75 mL), dried over anhydrous MgSO4, and concentrated to dryness under reduced pressure. The crude residue was purified by chromatography on silica gel (DCM/MeOH 100:0.5→90:10) obtaining a reddish solid (868 mg, 62%). TLC (DCM/MeOH 100:1) Rf = 0.10. 1H-NMR (400 MHz, CD3OD) δ (ppm): 7.83–7.52 (NH zone), 3.98–3.95 (m, 1H, OH-CH-CH3), 3.91–3.69 (m, 6H, NH-CH2-CO), 3.82–3.79 (m, 1H, NH-CH-CH2), 3.66–3.62 (m, 1H, OH-CH(A)H(B)-CH), 3.60–3.55 (m, 1H, OH-CH(A)H(B)-CH), 3.09 (t, J = 7.2 Hz, 2H, SCH2-CH2-CONH), 2.87–2.81 (m, 6H, SCH2-CH2-CH2-CH3), 2.64 (t, J = 7.2 Hz, 2H, SCH2-CH2-CONH), 1.64–1.56 (m, 6H, C-SCH2-CH2-CH2-CH3), 1.49–1.40 (m, 6H, C-SCH2-CH2-CH2-CH3), 1.13 (d, J = 6.4 Hz, 3H, CH3-CH-CH), 0.92 (t, 9H, J = 7.2 Hz, SCH2-CH2-CH2-CH3). 13C-NMR (100 MHz, CD3OD) δ (ppm): 172.71, 171.21, 170.82 and 170.44 (NH-CO), 129.50, 127.78, 127.10 and 126.18 (-CH2-S-C-S-), 110.15 and 109.49 (S2C=CS2), 65.80 (CH3-CH), 61.35 (OH-CH2-CH), 56.34 (NH-CH-CH), 42.49, 42.43 and 42.17 (NH-CH2-CO), 35.52, 35.45, 35.40 and 35.38 (S-CH2- and SCH2-CH2-CONH), 31.59, 31.56 and 31.55 (S-CH2-CH2), 31.02 (SCH2-CH2-CONH), 21.16 and 21.14 (S-CH2-CH2-CH2-), 18.92 (CH3-CH), 12.54 and 12.51 (S-CH2-CH2-CH2-CH3). IR (solid): ν = 3280 m, broad and 3086 w, broad (O-H and N-H stretch), 2955 m-w, 2926 m-w and 2869 w (C-H stretch), 1642 s (C=O stretch), 1553 m-s (N-H bend), 1456 m-w, 1417 m-w and 1376 m-w (C-H bend or O-H bend or H-C-H bend), 1249 m, 1099 m and 1028 m (C-O stretch and N-H stretch), 886 w (H-C-S bend or C-H bend), 771 m (C-S stretch), 684 m, broad (N-H out of plane). HRMS (ESI+): m/z: calcd for C31H52N4O2S8 ([M + H]+) 831.1574 found 831.1613; m/z: calcd for C31H52N4NaO2S8 ([M + Na]+) 853.1394 found 853.1416.

2.3. Preparation and Characterization of Gel Materials

Anhydrous solvents used for gelation tests were purchased from commercial suppliers. Gelation tests were carried out in screw-capped glass vials (4 cm length × 1 cm diameter) having a specific amount of the TTF derivative 14 and the desired solvent (1 mL). The mixture was heated with a standard heat gun until complete dissolution. Then, the clear solution was allowed to cool down to RT. The material was initially classified as gel if it did not flow by turning the vial upside-down. The viscoelastic nature was further confirmed by rheology of a model system.
Critical gelation concentration (CGC) corresponds to the minimum gelator concentration required for gelation. The values were obtained by continuously adding aliquots of solvent (0.02–0.1 mL) into vials having the TTF derivative 14 and performing either the heating or cooling until no gelation was observed. The waiting time used to define the state of the material was ~12 h. Concentrations above 200 g/L were not tested.
Thermal gel-to-sol transition temperature (Tgel) values were determined using a calibrated thermoblock at 1 °C/5 min (Figure S1). The temperature at which the bulk gel started to break was defined as Tgel. Due to potential effects of thermal history and hysteresis [75], the apparatus has been previously calibrated with samples measured by differential scanning calorimetry (DSC) [76].
Rheological measurements were performed with an AR 2000 Advanced rheometer (TA Instruments, New Castle, DE, USA). Conditions: 1000 mm gap, torque = 5 × 10−4 N/m, 25 °C, plain-plate geometry (20 mm, stainless steel), sample volume = 2 mL. Dynamic strain sweep (DSS) measurements were performed between 0.01 and 100% strain. For dynamic frequency sweep (DFS) measurements, frequency was varied from 0.1 to 10 Hz at 0.1% strain. Finally, dynamic time sweep (DTS) measurements were carried out within the linear regime at 0.1% strain and 1 Hz frequency.
FT-IR spectra were obtained at RT with a Cary 630 FTIR spectrometer (Agilent Technologies, Santa Clara, CA, USA) equipped with an attenuated total reflection (ATR) accessory (32 scans, spectral resolution = 8 cm−1).
Field emission scanning electron microscopy (FE-SEM) of xerogels was carried out with a Zeiss Merlin, Field Emission Scanning Electron Microscope (accelerating voltage = 10 kV). Xerogels, prepared by freeze-drying the gels, were placed on top of a tin plate and shielded with Pt (40 mA, 30–60 s; film thickness = 5–10 nm). Images were by Servicio General de Apoyo a la Investigación-SAI (University of Zaragoza).
Images under polarized light were obtained using a Wild Makroskop M420 optical microscope equipped with a Canon Power shot A640 camera.
UV-vis spectra were obtained with an Ocean Optics, Flame spectrometer with a DH-2000-BAL light source or on a Varian Cary 50 UV spectrophotometer. Quartz-glass cuvettes of 0.5 cm thickness were used.
Iodine doping was achieved by exposing the xerogel to I2 vapor for circa 120 min in a sealed glass beaker with I2 crystals.

3. Results and Discussion

3.1. Synthesis of TTF–Triglycyl Derivative

The synthesis of the TTF–triglycyl derivative 14 was achieved by assembling the l-threoninol, and triglycine units with the TTF carboxylic derivative 8 (Scheme 1). First, compound 8 was prepared following the procedure described in the literature [10] with slight modifications. The first step consisted in the synthesis of 4,5-bis-(butylthio)-1,3-dithiole-2-thione (3) by alkylation of the zinc complex of bis(1,3-dithiole-2-thione-4,5-dithiolate) tetrabutylammonium salt (1) with 1-bromobutane (2) as described for similar compounds by Simonsen and co-workers [77]. Phosphite-induced coupling of compounds 3 and 4 [77] gave the symmetric TTF derivative 5 in good yield (64%). Selective sequential deprotection of one 2-cyanoethyl group followed by alkylation with 1-bromobutane (2) gave the TTF derivative 6 in very good yield (89%). A second round of sequential deprotection of the second 2-cyanoethyl group followed by alkylation with 3-bromopropionic acid (7) [78] gave the desired TTF carboxylic derivative 8 in 91% yield.
Then Boc-protected triglycine 9 was activated with DCC and 4-nitrophenol (10). Then, the obtained nitrophenyl active ester 11 was reacted with l-threoninol (12) yielding the t-butoxycarbonyl (Boc)-protected triglycine-l-threoninol derivative 13. This compound was treated with a TFA solution in DCM to remove the Boc-amino protecting group yielding the corresponding l-threoninol-triglycine trifluoroacetate salt that was subsequently used without purification for the coupling with compound 8 in the presence of Hünig’s base. This reaction was done via classical activation of the carboxyl group with DCC and NHS, affording the desired TTF-based gelator 14 in 24% (isolated yield).

3.2. Gelation Properties

The gelation ability of TTF–triglycyl derivative 14 was studied for a number of anhydrous solvents of different nature (i.e., apolar, polar aprotic, polar protic) using the standard heating–cooling treatment. Materials that did flow upon inversion of the vial upside-down were initially classified as gels. One of the gels was used later as a model example to demonstrate its viscoelastic nature by oscillatory rheological measurements (see below). Compound 14 was found to be soluble in methanol, ethanol, isopropanol, dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran, whereas it resulted insoluble in diethyl ether, acetonitrile, n-hexane, and cyclohexane. In contrast, opaque gels were obtained in 10 solvents at concentrations varying between 5 ± 1 and 50 ± 10 g/L (Table 1).
These gels remained stable for at least two months when stored in sealed vials at RT. Their color varied from bright orange to dark orange-brown depending on the solvent (Figure 2a). The supramolecular gels showed typical thermoreversibility (Figure 2b), and their opaque appearance suggested the presence of aggregates larger than the wavelength of visible light (λ = 380–780 nm), which was in agreement with electron microscopy (see below). Further investigations were carried out using only some selected gels as representative materials.
As mentioned in the introduction, it is well established that the redox TTF core in this type of LMW also provides both S···S and π···π interactions during molecular aggregation, whereas the peptide chain drives molecular aggregation via hydrogen bonding [73,74]. Comparison of Fourier transform infrared (FT-IR) spectra of solid TTF derivative 14 with that of the xerogel (i.e., prepared by freeze-drying the corresponding organogel) and 14 in solution (i.e., below the CGC) showed only very small frequency shifts (i.e., red-shift Δν ~ 5 cm−1) for characteristic bands such as C=O stretching (~1641 cm−1), N-H amide I (br ~ 3280 cm−1), and N-H amide II (bending vibration) (~1553 cm−1) (Figure S2). These values suggest that 14 may also be aggregated in the solid state and in solution via similar intermolecular hydrogen-bonding pattern between amide groups, most likely in the parallel β-sheet conformation [79], as well as van der Waals interactions between the alkyl chains.

3.3. Characterization of Organogels

In general, relatively low gel-to-sol transition temperatures (Tgel) were determined for all gels ranging from 36 to 51 °C (±3) (Table 1). As typically observed with most supramolecular gels, Tgel gradually increased with increasing gelator concentration due to the generation of denser networks (Figure 3). Taking the gels prepared in toluene and ethyl acetate as representative systems, a plateau region was reached before the gels collapsed into partial and inhomogeneous gels that constantly lose solvent over time. The increment of the Tgel until the plateau region was ~39 °C for toluene and ~25 °C for ethyl acetate with respect to the initial values obtained at their CGC. Linear Ln-Ln plot (Figure 3, inset) using the percentage increases of Tgel showed that the percentage increment of Tgel was ~1.1-fold higher for the gel made in ethyl acetate. Further research is necessary to understand the reasons behind such differences.
Dynamic rheological experiments (Figure 4) for the model gel made of 14 in toluene confirmed its viscoelastic nature. Within the linear regime established by dynamic frequency sweep (DFS) and dynamic strain sweep (DFS) measurements, the storage modulus G′′ was found to be one order of magnitude higher than the loss modulus G′′ with low frequency dependency (i.e., G′ ≈ 8.9 ± 0.5 kPa, G′′ ≈ 0.75 ± 0.1 kPa) (Figure 3a). Moreover, the gels were brittle in nature, which was confirmed by its destruction at low frequency and ~7% of strain (Figure 4a). Finally, dynamic time sweep (DTS) measurements at 0.1% strain and 1 Hz frequency confirmed the stability of the gel over time at RT (Figure 4b).
Morphological studies of selected organogels were conducted by field emission scanning electron microscopy (FE-SEM) of the corresponding xerogels (Figure 5). In general, fibrillar networks with high aspect ratio were observed for several organogels made of 14. As observed with other supramolecular self-assembled gels, interactions between solvent–aggregate, solvent–gelator, and gelator–gelator molecules are also regulated by the solvent nature and have a major effect on the microstructure of the materials. For instance, dense and entangled leaf-like structures were observed for the material obtained in ethyl acetate (Figure 5a), whereas the samples prepared in benzonitrile showed a smooth surface with fibrillar structures of ~0.5–1 μm in diameter (Figure 5b). A highly dense and porous network made of fibers up to ~1 μm in diameter was observed for the gel made in 1,4-dioxane (Figure 5c). Surfaces made of smaller fibers of ~50–100 nm in diameter resembling a mountainous valley were observed for the specimens prepared in toluene (Figure 5d). However, fibrillar-globular structures with diameters between ~100 and 500 nm were distinguished when the solvent used for the preparation of the gel was dichloromethane (Figure 5e). Although we systematically took pictures of the bulk samples at different magnifications and locations on the grid in order to identify possible artifacts in the microstructures, it should be considered that such artifacts can be produced during the preparation and visualization of the samples and, therefore, the conclusions derived from these images should not be oversold. Furthermore, the typical anisotropic growth in this type of materials, suggesting well-ordered molecular packing, is also evidenced by the observation of birefringent domains under polarized light (Figure 5f), which is important for optical applications [80].

3.4. Effect of Iodine-Doping

Iodine-doping of the fibrous xerogel derived from a model gel made in DCM confirmed the oxidation of the TTF moiety in the gelator preserving the self-assembled network structure. UV-vis-NIR spectrum of the xerogel after exposure to I2 vapor showed new absorption bands centered at approximately 360, 500, and 850 nm (Figure 6). The absorption bands at 360 and 500 nm are typically ascribed to intramolecular electronic transitions involving the TTF cation radical, whereas the broad band located at 850 nm indicates the formation of a full CT state between cation radicals of self-stacked TTF units (i.e., TTF+I−). The increase in the absorbance above 600 nm is in agreement with the formation of a partial mixed-valence CT state between TTF-containing neutral and cation radicals (i.e., (TTF)(I)n with n < 1) [58,73]. Unfortunately, the intermolecular hydrogen-bonded network seemed to be altered during the oxidation as shown by visible changes in the intensity and position of the IR absorption bands associated to N-H and C=O stretching vibrations of the amides (Figure S3). Unfortunately, although iodine can create the necessary unfilled states required for conduction, the instability of the fibrillar network prevented us from obtaining reproducible conductivity values. As observed with other similar gels, preliminary experiments also showed a gel-to-sol transition after exposure of the wet gel to iodine vapors.

4. Conclusions

In conclusion, TTF–triglycyl derivative 14 was synthesized and fully characterized by standard techniques. This compound was found to act as a LMW gelator for a series of organic solvents after a heating–cooling cycle. Therefore, the presence of aromatic rings on the peptide linked to the TTF unit is not a requirement for the formation of supramolecular gels using TTF-peptide conjugates. The critical gelation concentrations ranged from ~5 to 50 g/L, and the thermal gel-to-sol transition temperatures varied from ~36 to 51 °C. FE-SEM imaging of the xerogels, prepared by freeze-drying the organogels, showed fibrillar microstructures with distinctive features depending on the solvent used to prepare the gels. Moreover, the viscoelastic and brittle nature of a model gel system was also supported by dynamic rheological experiments. Finally, UV-vis-NIR analysis of a model xerogel confirmed the oxidation of the TTF unit upon exposure to I2 vapor. Nevertheless, FT-IR spectroscopy showed that the oxidation was accompanied with concurrent alteration of the intermolecular hydrogen-bonded network.

Supplementary Materials

The following are available online at https://www.mdpi.com/2076-3417/8/5/671/s1, NMR spectra, FT-IR spectra, Figure S1: Thermoblock used for Tgel determinations. (A) Front view of the set-up. (B) Top view of the set-up during a typical experiment. The set-up was previously calibrated with literature data for known compounds, Figure S2: FT-IR spectra of solid 14, 14 dissolved in DCM, and xerogel, i.e., prepared by freeze-drying the organogel made of 14 in DCM (29 g/L), Figure S3: FT-IR spectra of the xerogel, obtained from the corresponding organogel made of 14 in DCM (29 g/L), before and after iodine-doping.

Author Contributions

Pérez-Rentero Sónia carried out the synthesis and characterization of all compounds, and observed for the first time the aggregation tendency of the gelator. Häring Marleen, Saldías César, and Díaz Díaz David carried out the rest of the experiments. Díaz Díaz David and Eritja Ramon directed the project. All authors participated in writing the manuscript.

Acknowledgments

This work was supported by the Ministerio de Economía, Industria y Competitividad (CTQ2014-52588-R, CTQ2017-84415-R), Generalitat de Catalunya (2014/SGR/624), the Instituto de Salud Carlos III (ISCIII) (CB06_01_0019), and Universität Regensburg. CIBER-BBN is an initiative funded by the VI National R+D+i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER actions and financed by ISCIII with assistance from the European Regional Development Fund. We thank Ivo Starý, Jiří Janoušek, Martin Bělohradský, and Irena G. Stará (IOCB, Academy of Sciences of the Czech Republic) for their help in the synthesis of the TTF derivative; Judith Mayr (Universität Regensburg) for preliminary gelation tests; and Alex Abramov (Universität Regensburg) for assistance with UV/IR measurements. David Díaz Díaz thanks Deutsche Forschungsgemeinschaft (DFG) for the Heisenberg Professorship Award.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Hornum, M.; Kumar, P.; Podsiadly, P.; Nielsen, P. Increasing the stability of DNA:RNA duplexes by introducing stacking phenyl-substituted pyrazole, furan, and triazole moieties in the major groove. J. Org. Chem. 2015, 80, 9592–9602. [Google Scholar] [CrossRef] [PubMed]
  2. Hrdlicka, P.J.; Karmakar, S. 25 years and still going strong: 2′-O-(pyren-1-yl)methylribonucleotides—Versatile building blocks for applications in molecular biology, diagnostics and materials science. Org. Biomol. Chem. 2017, 15, 9760–9774. [Google Scholar] [CrossRef] [PubMed]
  3. Krasheninina, O.A.; Novopashina, D.S.; Apartsin, E.K.; Venyaminova, A.G. Recent advances in nucleic acid targeting probes and supramolecular constructs based on pyrene-modified oligonucleotides. Molecules 2017, 22, 2108. [Google Scholar] [CrossRef] [PubMed]
  4. Dogan, Z.; Paulini, R.; Stütz, J.A.R.; Narayanan, S.; Richert, C. 5-Tethered stilbene derivatives as fidelity- and affinity-enhancing modulators of DNA duplex stability. J. Am. Chem. Soc. 2004, 126, 4762–4763. [Google Scholar] [CrossRef] [PubMed]
  5. Zahn, A.; Leumann, C.J. Recognition properties of donor- and acceptor-modified biphenyl-DNA. Chem. Eur. J. 2008, 14, 1087–1094. [Google Scholar] [CrossRef] [PubMed]
  6. Aviñó, A.; Mazzini, S.; Ferreira, R.; Eritja, R. Synthesis and structural properties of oligonucleotides covalently linked to acridine and quindoline derivatives through a threoninol linker. Bioorg. Med. Chem. 2010, 18, 7348–7356. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Bouquin, N.; Malinovskii, V.L.; Guégano, X.; Liu, S.X.; Decurtins, S.; Häner, R. TTF-modified DNA. Chem. Eur. J. 2008, 14, 5732–5736. [Google Scholar] [CrossRef] [PubMed]
  8. Schnippering, M.; Zahn, A.; Liu, S.X.; Leumann, C.; Decurtins, S. Synthesis and electrochemical properties of TTF modified oligodeoxynucleotides. Chem. Commun. 2009, 45, 5552–5554. [Google Scholar] [CrossRef] [PubMed]
  9. Pérez-Rentero, S.; Gállego, I.; Somoza, A.; Ferreira, R.; Janoušek, J.; Bělohradský, M.; Stará, I.; Starý, I.; Eritja, R. Interstrand interactions on DNA duplexes modified by TTF units at the 3′ or 5′-ends. RSC Adv. 2012, 2, 4069–4071. [Google Scholar] [CrossRef]
  10. Pérez-Rentero, S.; Somoza, A.; Grijalvo, S.; Janoušek, J.; Bělohradský, M.; Stará, I.; Starý, I.; Eritja, R. Biophysical and RNA interference inhibitory properties of oligonucleotides carrying tetrathiafulvalene groups at terminal positions. J. Chem. 2013, 2013, 650610. [Google Scholar] [CrossRef]
  11. Yamada, J.; Akutsu, H. New trends in the synthesis of π-electron donors for molecular conductors and superconductors. Chem. Rev. 2004, 104, 5057–5083. [Google Scholar] [CrossRef] [PubMed]
  12. Fourmigué, M.; Batail, P. Activation of hydrogen- and halogen-bonding interactions in tetrathiafulvalene-based crystalline molecular conductors. Chem. Rev. 2004, 104, 5379–5418. [Google Scholar] [CrossRef] [PubMed]
  13. Jeppesen, J.O.; Nielsen, M.B.; Becher, J. Tetrathialfulvalene cyclophanes and cage molecules. Chem. Rev. 2004, 104, 5115–5131. [Google Scholar] [CrossRef] [PubMed]
  14. Moonen, N.N.P.; Flood, A.H.; Fernández, J.M.; Stoddart, J.F. Towards a racional design of molecular switches and sensors from their basic building blocks. Top. Curr. Chem. 2005, 262, 99–132. [Google Scholar]
  15. Kay, E.R.; Leigh, D.A.; Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 2007, 46, 72–191. [Google Scholar] [CrossRef] [PubMed]
  16. Balzani, V.; Credi, A.; Venturi, M. Light powered molecular machines. Chem. Soc. Rev. 2009, 38, 1542–1550. [Google Scholar] [CrossRef] [PubMed]
  17. Fang, L.; Olson, M.A.; Benítez, D.; Tkatchouk, E.; Goddard, W.A., III; Stoddart, J.F. Mechanically bonded macromolecules. Chem. Soc. Rev. 2010, 39, 17–29. [Google Scholar] [CrossRef] [PubMed]
  18. Rovira, C. Bis(ethylenethio)tetrathiafulvalene (BET-TTF) and related dissymmetrical electron donors: From the molecule to functional molecular materials and devices (OFETs). Chem. Rev. 2004, 104, 5289–5317. [Google Scholar] [CrossRef] [PubMed]
  19. Hasegawa, M.; Iyoda, M. Conducting supramolecular nanofibers and nanorods. Chem. Soc. Rev. 2010, 39, 2420–2531. [Google Scholar] [CrossRef] [PubMed]
  20. Iyoda, M.; Hasegawa, M. Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly. Beilstein J. Org. Chem. 2015, 11, 1596–1613. [Google Scholar] [CrossRef] [PubMed]
  21. Uji, H.; Kim, H.; Imai, T.; Mitani, S.; Sugiyama, J.; Kimura, S. Electronic properties of tetrathiafulvalene-modified cyclic-β-peptide nanotube. Biopolymers 2016, 106, 275–282. [Google Scholar] [CrossRef] [PubMed]
  22. Pérez-Rentero, S.; Grijalvo, S.; Peñuelas, G.; Fàbrega, C.; Eritja, R. Thioctic acid derivatives as building blocks to incorporate DNA oligonucleotides onto gold nanoparticles. Molecules 2014, 19, 10495–10523. [Google Scholar] [CrossRef] [PubMed]
  23. Estroff, L.A.; Hamilton, A.D. Water gelation by small organic molecules. Chem. Rev. 2004, 104, 1201–1218. [Google Scholar] [CrossRef] [PubMed]
  24. Liu, X.Y. Gelation with small molecules: From formation mechanism to nanostructure architecture. Top. Curr. Chem. 2005, 256, 1–37. [Google Scholar] [PubMed]
  25. George, M.; Weiss, R.G. Molecular organogels. Soft matter comprised of low-molecular-mass organic gelators and organic liquids. Acc. Chem. Res. 2006, 39, 489–497. [Google Scholar] [CrossRef] [PubMed]
  26. Weiss, R.G.; Terech, P. Molecular Gels: Materials with Self-Assembled Fibrillar Networks; Weiss, R.G., Terech, P., Eds.; Springer: Dordrecht, Netherlands, 2006. [Google Scholar]
  27. Smith, D.K. Dendritic supermolecules—Towards controllable nanomaterials. Chem. Commun. 2006, 34–44. [Google Scholar] [CrossRef] [PubMed]
  28. Zaccarelli, E. Colloidal gels: Equilibrium and non-equilibrium routes. J. Phys. Condens. Matter 2007, 19, 323101. [Google Scholar] [CrossRef]
  29. Ajayaghosh, A.; Praveen, V.K.; Vijayakumar, C. Organogels as scaffolds for excitation energy transfer and light harvesting. Chem. Soc. Rev. 2008, 37, 109–122. [Google Scholar] [CrossRef] [PubMed]
  30. Banerjee, S.; Das, R.K.; Maitra, U. Supramolecular gels ‘in action’. J. Mater. Chem. 2009, 19, 6649–6687. [Google Scholar] [CrossRef]
  31. Adams, D.J. Dipeptide and tripeptide conjugates as low-molecular-weight hydrogelators. Macromol. Biosci. 2011, 11, 160–173. [Google Scholar] [CrossRef] [PubMed]
  32. Dawn, A.; Shiraki, T.; Haraguchi, S.; Tamaru, S.; Shinkai, S. What kind of “soft materials” can we design from molecular gels? Chem. Asian J. 2011, 6, 266–282. [Google Scholar] [CrossRef] [PubMed]
  33. Yang, X.; Zhang, G.; Zhang, D. Stimuli responsive gels based on low molecular weight gelators. J. Mater. Chem. 2012, 22, 38–50. [Google Scholar] [CrossRef]
  34. Draper, E.R.; Adams, D.J. Low-molecular-weight gels: The state of the art. Chem 2017, 3, 390–410. [Google Scholar] [CrossRef]
  35. Sangeetha, N.M.; Maitra, U. Supramolecular gels: Functions and uses. Chem. Soc. Rev. 2005, 34, 821–836. [Google Scholar] [CrossRef] [PubMed]
  36. Vintiloui, A.; Leroux, J.-C. Organogels and their use in drug delivery—A review. J. Control. Release 2008, 125, 179–192. [Google Scholar] [CrossRef] [PubMed]
  37. Ulijn, R.V.; Smith, A.M. Designing peptide based nanomaterials. Chem. Soc. Rev. 2008, 37, 664–675. [Google Scholar] [CrossRef] [PubMed]
  38. Piepenbrock, M.O.M.; Lloyd, G.O.; Clarke, N.; Steed, J.W. Metal- and anion-binding supramolecular gels. Chem. Rev. 2010, 110, 1960–2004. [Google Scholar] [CrossRef] [PubMed]
  39. Du, X.; Zhou, J.; Shi, J.; Xu, B. Supramolecular hydrogelators and hydrogels: From soft matter to molecular biomaterials. Chem. Rev. 2015, 115, 13165–13307. [Google Scholar] [CrossRef] [PubMed]
  40. Li, S.; John, V.T.; Irvin, G.C.; Bachakonda, S.H.; McPherson, G.L.; O’Connor, C.J. Synthesis and magnetic properties of a novel ferrite organogel. J. Appl. Phys. 1999, 85, 5965–5967. [Google Scholar] [CrossRef]
  41. Kato, T. Self-assembly of phase-segregated liquid crystal structures. Science 2002, 295, 2414–2418. [Google Scholar] [CrossRef] [PubMed]
  42. Kubo, W.; Kambe, S.; Nakade, S.; Kitamura, T.; Hanabusa, K.; Wada, Y.; Yanagida, S. Photocurrent-determining processes in quasi-solid-state dye-sensitized solar cells using ionic gel electrolytes. J. Phys. Chem. B 2003, 107, 4374–4381. [Google Scholar] [CrossRef]
  43. Sanchez, C.; Llusar, M. Inorganic and hybrid nanofibrous materials templated with organogelators. Chem. Mater. 2008, 20, 782–820. [Google Scholar]
  44. Díaz, D.D.; Kühbeck, D.; Koopmans, R.J. Stimuli-responsive nanostructured gels as reaction vessels and reusable catalysts. Chem. Soc. Rev. 2011, 40, 427–448. [Google Scholar] [CrossRef] [PubMed]
  45. Abdallah, D.J.; Weiss, R.G. Organogels and low molecular mass organic gelators. Adv. Mater. 2000, 12, 1237–1247. [Google Scholar] [CrossRef]
  46. Tanaka, T. Gels. Sci. Am. 1981, 244, 110–123. [Google Scholar] [CrossRef]
  47. DeRossi, D.; Kajiwara, Y.; Osada, Y.; Yamauchi, A. Polymer Gels: Fundamentals and Biomedical Applications; Plenum Press: New York, NY, USA, 1991. [Google Scholar]
  48. Ahn, S.-K.; Kasi, R.M.; Kim, S.-C.; Sharma, N.; Zhou, Y. Stimuli-responsive polymer gels. Soft Matter 2008, 4, 1151–1157. [Google Scholar] [CrossRef]
  49. Zubarev, E.R.; Pralle, M.U.; Sone, E.D.; Stupp, S.I. Scaffolding of polymers by supramolecular nanoribbons. Adv. Mater. 2002, 14, 198–203. [Google Scholar] [CrossRef]
  50. Huang, X.; Terech, P.; Raghavan, S.R.; Weiss, R.G. Kinetics of 5α-cholestan-3β-yl N-(2-naphthyl)carbamate/n-alkane organogel formation and its influence on the fibrillar networks. J. Am. Chem. Soc. 2005, 127, 4336–4344. [Google Scholar] [CrossRef] [PubMed]
  51. Ihara, H.; Takafuji, M.; Sakurai, T. Encyclopedia of Nanoscience and Nanotechnology; Nalwa, H.S., Ed.; American Scientific: California, CA, USA, 2004; Volume 9, pp. 473–495. [Google Scholar]
  52. Shin, J.H.; Gardel, M.L.; Mahadeva, L.; Matsudaira, P.D.; Weitz, A. Relating microstructure to rheology of a bundled and cross-linked F-actin network in vitro. Proc. Natl. Acad. Sci. USA 2004, 101, 9636–9641. [Google Scholar] [CrossRef] [PubMed]
  53. Fages, F. Low Molecular Mass Gelators. In Topics Current Chemistry; Fages, F., Ed.; Springer: Berlin/Heidelberg, Germany, 2005; Volume 256. [Google Scholar]
  54. Jørgensen, M.; Bechgaard, K. Synthesis and structural characterization of a bis-arborol-tetrathiafulvalene gel: Toward a self-assembling “molecular” wire. J. Org. Chem. 1994, 59, 5877–5882. [Google Scholar] [CrossRef]
  55. Le Gall, T.; Pearson, C.; Bryce, M.R.; Petty, M.C.; Dahlgaard, H.; Becher, J. Arborol-functionalised tetrathiafulvalene derivatives: Synthesis and thin-film formation. Eur. J. Org. Chem. 2003, 2003, 3562–3568. [Google Scholar] [CrossRef]
  56. Yang, X.; Zhang, D.; Zhang, G.; Zhu, D. Tetrathiafulvalene (TTF)-based gelators: Stimuli responsive gels and conducting nanostructures. Sci. China Chem. 2011, 54, 596–602. [Google Scholar] [CrossRef]
  57. Wang, C.; Zhang, D.; Zhu, D. A Low-molecular-mass gelator with an electroactive tetrathiafulvalene group: Tuning the gel formation by charge-transfer interaction and oxidation. J. Am. Chem. Soc. 2005, 127, 16372–16373. [Google Scholar] [CrossRef] [PubMed]
  58. Kitamura, T.; Nakaso, S.; Mizoshita, N.; Tochigi, Y.; Shimomura, T.; Moriyama, M.; Ito, K.; Kato, T. Electroactive supramolecular self-assembled fibers comprised of doped tetrathiafulvalene-based gelators. J. Am. Chem. Soc. 2005, 127, 14769–14775. [Google Scholar] [CrossRef] [PubMed]
  59. Puigmartí-Luis, J.; Laukhin, V.; del Pino, P.A.; Vidal-Gancedo, J.; Rovira, C.; Laukhina, E.; Amabilino, D.B. Supramolecular conducting nanowires from organogels. Angew. Chem. Int. Ed. 2007, 46, 238–241. [Google Scholar] [CrossRef] [PubMed]
  60. Wang, X.-J.; Xing, L.-B.; Cao, W.-N.; Li, X.-B.; Chen, B.; Tung, C.-H.; Wu, L.-Z. Organogelators based on TTF supramolecular assemblies: Synthesis, characterization, and conductive property. Langmuir 2011, 27, 774–781. [Google Scholar] [CrossRef] [PubMed]
  61. Wang, Y.; Liu, Y.; Jin, L.; Yin, B. T-shaped monopyridazinotetrathiafulvalene-amino acid diad based chiral organogels with aggregation-induced fluorescence emission. Soft Matter 2016, 12, 6373–6384. [Google Scholar] [CrossRef] [PubMed]
  62. Liu, Y.; Dai, Y.; Yin, B. Gel properties of T-shaped tetrathiafulvalene–pyridazine conjugates and F4TCNQ-induced morphological transformation. New J. Chem. 2016, 40, 464–474. [Google Scholar] [CrossRef]
  63. Kong, D.; Xia, Y.; Li, D.; Hou, R. Super organogelator based on tetrathiafulvalene with four amide derivatives and its F TCNQ chargetransfer complex. Supramol. Chem. 2017, 29, 102–110. [Google Scholar] [CrossRef]
  64. Wang, C.; Chen, Q.; Sun, F.; Zhang, D.; Zhang, G.; Huang, Y.; Zhao, R.; Zhu, D. Multistimuli responsive organogels based on a new gelator featuring tetrathiafulvalene and azobenzene groups: Reversible tuning of the gel-sol transition by redox reactions and light irradiation. J. Am. Chem. Soc. 2010, 132, 3092–3096. [Google Scholar] [CrossRef] [PubMed]
  65. Wang, C.; Sun, F.; Zhang, D.; Zhang, G.; Daoben, Z. Cholesterol-substituted tetrathiafulvalene (TTF) compound: Formation of organogel and supramolecular chirality. Chin. J. Chem. 2010, 28, 622–626. [Google Scholar] [CrossRef]
  66. Canevet, D.; del Pino, A.P.; Amabilino, D.B.; Sallé, M. Varied nanostructures from a single multifunctional molecular material. J. Mater. Chem. 2011, 21, 1428–1437. [Google Scholar] [CrossRef]
  67. Liu, Y.; Yin, Z.; Jin, L.; Yin, B. Monopyrrolotetrathiafulvalene-based supramolecular organogels: Multi-stimuli responsiveness and formation of charge-transfer salt gels. Dyes Pigments 2017, 140, 500–511. [Google Scholar] [CrossRef]
  68. Ahn, S.; Kim, Y.; Beak, S.; Ishimoto, S.; Enozawa, H.; Isomura, E.; Hasegawa, M.; Iyoda, M.; Park, Y. Synthesis and electrical conductivity of perchlorate-doped TTF–diamide nanofibers with double and triple helix structures. J. Mater. Chem. 2010, 20, 10817–10823. [Google Scholar] [CrossRef]
  69. Ji, S.-F.; Sun, Y.-G.; Huo, P.; Shen, W.-C.; Huang, Y.-D.; Zhu, Q.-Y.; Dai, J. Effect of metal coordination on photocurrent response properties of a tetrathiafulvalene organogel film. Inorg. Chem. 2014, 53, 3611–3617. [Google Scholar] [CrossRef] [PubMed]
  70. Amacher, A.M.; Puigmartí-Luis, J.; Geng, Y.; Lebedev, V.; Laukhin, V.; Krämer, K.; Hauser, J.; Amabilino, D.B.; Decurtins, S.; Liu, S.-X. Coordination-directed self-assembly of a simple benzothiadiazole-fused tetrathiafulvalene to low-bandgap metallogels. Chem. Commun. 2015, 51, 15063–15066. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  71. Sun, X.; Lai, G.; Li, Z.; Ma, Y.; Yuan, X.; Shen, Y.; Wang, C. Urethane tetrathiafulvalene derivatives: Synthesis, selfassembly and electrochemical properities. Beilstein J. Org. Chem. 2015, 11, 2343–2349. [Google Scholar] [CrossRef] [PubMed]
  72. Mei, X.; Ouyang, J. Electronically and ionically conductive gels of ionic liquids and charge-transfer tetrathiafulvalene-tetracyanoquinodimethane. Langmuir 2011, 27, 10953–10961. [Google Scholar] [CrossRef] [PubMed]
  73. Nalluri, S.K.M.; Shivarova, N.; Kanibolotsky, A.L.; Zelzer, M.; Gupta, S.; Frederix, P.W.J.M.; Skabara, P.J.; Gleskova, H.; Ulijn, R.V. Conducting nanofibers and organogels derived from the self-assembly of tetrathiafulvalene-appended dipeptides. Langmuir 2014, 30, 12429–12437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Liu, Y.; Wang, Y.; Jin, L.; Chen, T.; Yin, B. MPTTF-containing tripeptide-based organogels: Receptor for 2, 4, 6-trinitrophenol and multiple stimuli-responsive properties. Soft Matter 2016, 12, 934–945. [Google Scholar] [CrossRef] [PubMed]
  75. Lu, L.; Cocker, T.M.; Bachman, R.E.; Weiss, R.G. Gelation of organic liquids by some 5α-cholestan-3β-yl N-(2-aryl)carbamates and 3β-cholesteryl 4-(2-anthrylamino)butanoates. How important are H-bonding interactions in the gel and neat assemblies of aza aromatic-linker-steroid gelators? Langmuir 2000, 16, 20–34. [Google Scholar] [CrossRef]
  76. Schiller, J.; Alegre-Requena, J.V.; Marqués-López, E.; Herrera, R.P.; Casanovas, J.; Alemán, C.; Díaz, D.D. Self-assembled fibrillar networks of a multifaceted chiral squaramide: Supramolecular multistimuli-responsive alcogels. Soft Matter 2016, 12, 4361–4374. [Google Scholar] [CrossRef] [PubMed]
  77. Simonsen, K.B.; Svenstrup, N.; Lau, J.; Simonsen, O.; Mork, P.; Kristensen, G.J.; Becher, J. Sequential functionalization of bis-protected tetrathiafulvalene-dithiolates. Synthesis 1996, 1996, 407–418. [Google Scholar] [CrossRef]
  78. Zhao, B.T.; Blesa, M.J.; Le Derf, F.; Canevet, D.; Benhaoua, C.; Mazari, M.; Allain, M.; Sallé, M. Carboxylic acid derivatives of tetrathiafulvalene: Key intermediates for the synthesis of redox-active calixarene-based anion receptors. Tetrahedron 2007, 63, 10768–10777. [Google Scholar] [CrossRef] [Green Version]
  79. Toniolo, C.; Palumbo, M. Solid-state infrared absorption spectra and chain arrangement in some synthetic homooligopeptides in the intermolecularly hydrogen-bonded pleated-sheet β-conformation. Biopolymers 1977, 16, 219–224. [Google Scholar] [CrossRef] [PubMed]
  80. Fischer, R.E.; Tadic-Galeb, B.; Yoder, P.R. Optical System Design, 2nd ed.; McGraw Hill: New York, NY, USA, 2008. [Google Scholar]
Applsci 08 00671 g001 550
Figure 1. Chemical structure of tetrathiafulvalene (TTF)–triglycyl derivative studied in this work.
Figure 1. Chemical structure of tetrathiafulvalene (TTF)–triglycyl derivative studied in this work.
Applsci 08 00671 g001
Applsci 08 00671 sch001 550
Scheme 1. Synthesis of TTF–triglycyl derivative 14.
Scheme 1. Synthesis of TTF–triglycyl derivative 14.
Applsci 08 00671 sch001
Applsci 08 00671 g002 550
Figure 2. (a) Photographs of upside-down vials having selected gels made of 14 in toluene, benzene, chlorobenzene (PhCl), and dichloromethane (DCM) at the CGC (see Table 1); (b) illustration of the thermal sol–gel transition of the gel made of 14 in toluene at the CGC.
Figure 2. (a) Photographs of upside-down vials having selected gels made of 14 in toluene, benzene, chlorobenzene (PhCl), and dichloromethane (DCM) at the CGC (see Table 1); (b) illustration of the thermal sol–gel transition of the gel made of 14 in toluene at the CGC.
Applsci 08 00671 g002
Applsci 08 00671 g003 550
Figure 3. Variation of Tgel with increasing gelator concentration for the gels made in toluene and ethyl acetate. Inset: Normalized Ln-Ln plot of Tgel percentage increases.
Figure 3. Variation of Tgel with increasing gelator concentration for the gels made in toluene and ethyl acetate. Inset: Normalized Ln-Ln plot of Tgel percentage increases.
Applsci 08 00671 g003
Applsci 08 00671 g004 550
Figure 4. (a) Dynamic frequency sweep (DFS), dynamic strain sweep (DSS), and (b) dynamic time sweep (DTS) measurements for the model gel made of 14 in toluene (9 g/L). The tan δ (i.e., G′′/G′, damping coefficient) was reproducible in random experiments.
Figure 4. (a) Dynamic frequency sweep (DFS), dynamic strain sweep (DSS), and (b) dynamic time sweep (DTS) measurements for the model gel made of 14 in toluene (9 g/L). The tan δ (i.e., G′′/G′, damping coefficient) was reproducible in random experiments.
Applsci 08 00671 g004
Applsci 08 00671 g005 550
Figure 5. Representative FE-SEM photographs of xerogels prepared by freeze-drying the organogels made of 14 in (a) ethyl acetate (5 g/L); (b) benzonitrile (35 g/L); (c) 1,4-dioxane (50 g/L); (d) toluene (9 g/L); (e) dichloromethane (29 g/L); (f) birefringent domains visualized under polarized light for the xerogel derived from the gel made of 14 in dichloromethane (29 g/L).
Figure 5. Representative FE-SEM photographs of xerogels prepared by freeze-drying the organogels made of 14 in (a) ethyl acetate (5 g/L); (b) benzonitrile (35 g/L); (c) 1,4-dioxane (50 g/L); (d) toluene (9 g/L); (e) dichloromethane (29 g/L); (f) birefringent domains visualized under polarized light for the xerogel derived from the gel made of 14 in dichloromethane (29 g/L).
Applsci 08 00671 g005
Applsci 08 00671 g006 550
Figure 6. UV-vis-NIR spectra before and after doping with I2 the xerogel prepared from the organogel made of 14 in DCM (29 g/L).
Figure 6. UV-vis-NIR spectra before and after doping with I2 the xerogel prepared from the organogel made of 14 in DCM (29 g/L).
Applsci 08 00671 g006
Table
Table 1. Gelation ability of TTF–triglycyl derivative 14, critical gelation concentration (CGC), gelation time, and gel-to-sol transition temperature (Tgel). 1
Table 1. Gelation ability of TTF–triglycyl derivative 14, critical gelation concentration (CGC), gelation time, and gel-to-sol transition temperature (Tgel). 1
Solvent 2CGC (g/L)Gelation Time (min)Tgel (°C)
Acetone40 ± 1060 ± 10 36 ± 3 4
Benzene6 ± 178 ± 5 37 ± 2
Benzonitrile35 ± 1055 ± 5 42 ± 2
Chlorobenzene9 ± 178 ± 5 38 ± 2
Chloroform18 ± 210 ± 250 ± 3
Dichloromethane29 ± 210 ± 249 ± 2
1,4-Dioxane50 ± 1060 ± 1051 ± 3
Ethyl acetate5 ± 110 ± 2 47 ± 2
Toluene9 ± 190 ± 10 41 ± 2
Xylene 38 ± 190 ± 10 46 ± 2
1 Gels were obtained upon a heating–cooling cycle (see Experimental Section). The use of anhydrous solvents was found to be very critical to obtain the lowest possible critical gelation concentration (CGC) values. In general, the use non-anhydrous solvents either inhibited the gelation or raised the CGC up to 3–4 times in comparison to anhydrous solvents. Error values were calculated from three randomized experiments. 2 Solvent volume = 1 mL. 3 Xylene was used as mixture of isomers. 4 Partial gel formation was observed. In this case, Tgel value corresponds to the isolated gelled portion.

Share and Cite

MDPI and ACS Style

Pérez-Rentero, S.; Eritja, R.; Häring, M.; Saldías, C.; Díaz, D.D. Synthesis, Characterization, and Self-Assembly of a Tetrathiafulvalene (TTF)–Triglycyl Derivative. Appl. Sci. 2018, 8, 671. https://doi.org/10.3390/app8050671

AMA Style

Pérez-Rentero S, Eritja R, Häring M, Saldías C, Díaz DD. Synthesis, Characterization, and Self-Assembly of a Tetrathiafulvalene (TTF)–Triglycyl Derivative. Applied Sciences. 2018; 8(5):671. https://doi.org/10.3390/app8050671

Chicago/Turabian Style

Pérez-Rentero, Sónia, Ramon Eritja, Marleen Häring, César Saldías, and David Díaz Díaz. 2018. "Synthesis, Characterization, and Self-Assembly of a Tetrathiafulvalene (TTF)–Triglycyl Derivative" Applied Sciences 8, no. 5: 671. https://doi.org/10.3390/app8050671

APA Style

Pérez-Rentero, S., Eritja, R., Häring, M., Saldías, C., & Díaz, D. D. (2018). Synthesis, Characterization, and Self-Assembly of a Tetrathiafulvalene (TTF)–Triglycyl Derivative. Applied Sciences, 8(5), 671. https://doi.org/10.3390/app8050671

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop