Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators

Abstract

The three gelators presented in this work (Boc-D-Phe-L-Oxd-OH F0, Boc-D-F₁Phe-L-Oxd-OH F1 and Boc-D-F₂Phe-L-Oxd-OH F2) share the same scaffold and differ in the number of fluorine atoms linked to the aromatic ring of phenylalanine. They have been applied to the preparation of gels in 0.5% or 1.0% w/v concentration, using three methodologies: solvent switch, pH change and calcium ions addition. The general trend is an increased tendency to form structured materials from F0 to F1 and F2. This property ends up in the formation of stronger materials when fluorine atoms are present. Some samples, generally formed by F1 or F2 in 0.5% w/v concentration, show high transparency but low mechanical properties. Two gels, both containing fluorine atoms, show increased stiffness coupled with high transparency. The biocompatibility of the gelators was assessed exposing them to fibroblast cells and demonstrated that F1 and F2 are not toxic to cells even in high concentration, while F0 is not toxic to cells only in a low concentration. In conclusion, the presence of even only one fluorine atom improves all the gelators properties: the gelation ability of the compound, the rheological properties and the transparency of the final materials and the gelator biocompatibility.

Keywords: fibers; fluorine atom; gelator; supramolecular gel; thixotropy; transparency.

Figure 1

Chemical structure of the three gelators.

Figure 2

Picture of the samples formed with gelators F0, F1 and F2 and different mixtures of solvents: (a) gelators in 0.5% w/v concentration in mixtures of ethanol/water; (b) gelators in 0.5% w/v concentration in mixtures of 2-propanol/water; (c) gelators in 1.0% w/v concentration in mixtures of ethanol/water; (d) gelators in 1.0% w/v concentration in mixtures of 2-propanol/water. The red frames indicate the gel formed. The red arrows indicate the transparent gels according to the spectrophotometric analysis reported below.

Figure 3

Picture of the samples formed with gelators F0, F1 and F2 in PBS with different triggers: (a) gelators in 0.5% w/v concentration with GdL (37–39) and CaCl₂ (40–42) in PBS; (b) gelators 1.0% w/v concentration with GdL (43–45) and CaCl₂ (46–48) in PBS. The red arrows indicate the transparent gels according to the spectrophotometric analysis (see Table 3).

Figure 4

SEM image of the xerogel of samples. The samples 19, 22 and 25 are indicated as F0_EtOH, F1_EtOH and F2_EtOH, respectively. The samples 28, 31 and 34 are indicated as F0_iPrOH, F1_ iPrOH and F2_ iPrOH, respectively. The samples 43, 44 and 45 are indicated as F0_GdL, F1_ GdL, and F2_ GdL respectively. The samples 46, 47 and 48 are indicated as F0_Ca²⁺, F1_ Ca²⁺ and F2_ Ca²⁺, respectively. Scale bar: 1 μm.

Figure 5

Summary of the stiffness of the gels (γ = 0.068%) by means of G’ (kPa). (a) Gels in 0.5 w/v concentration; (b) gels in 1% w/v concentration. The empty bars are referred to transparent gels with transmittance T ≥ 50%, solid bars are instead referred to gels with T ≤ 50%. Error bars are reported with red lines. Samples 10 and 40 did not form a gel.

Figure 6

Thixotropic behavior of gels 7 and 38 formed after vigorous shaking (left) and 16 h of recovery (right).

Figure 7

Optical micrographs of cells after 24 h (a) F0, (b) F1, (c) F2 at concentration 5 mg/mL, (d) F0 (e) F1 and (f) F2 at concentration 0.5 mg/mL.