A synthetic tripeptide as organogelator: elucidation of gelation mechanism

Abstract

A new terminally protected synthetic tripeptide with noncoded amino acids, tert-butyloxycarbonyl-β-alanyl-α-aminoisobutyryl-β-alanyl methyl ester, is synthesized. The product is characterized by ¹H NMR and DQF COSY NMR data. This tripeptide produces thermoreversible gels in 1,2-dichlorobenzene (DCB) at room temperature (30 °C). The morphology of the dried gels is studied using optical microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The micrographs show the presence of both rod like morphology and liquid–liquid phase separated morphology in the gels. Thermal study by differential scanning calorimeter (DSC-7) indicates the presence of a reversible first order phase transition during heating and cooling processes. Wide-angle X-ray scattering (WAXS) and electron diffraction experiments indicate the presence of polycrystalline materials in the gel and the crystal structure of the gel is almost the same as that of the pure tripeptide. Solvent subtracted Fourier transformed infra-red (FT-IR) study indicates that in the sol state there are free N–H and intramolecular hydrogen bonded N–H stretching vibrations at 3440 and 3375 cm⁻¹, respectively. In the gel state both these vibrations shifted to 3325 and 3309 cm⁻¹, respectively. The phase diagram of these gels, determined from both the DSC method and visually, indicates the tripeptide–DCB complexation with singular point characteristics. An attempt is made to understand the gelation mechanism of this system by measuring the gelation rate (t⁻¹_gel) using the test tube tilting method. The gelation rate (t⁻¹_gel) is expressed as t⁻¹_gel ∝ f(C)f(T) and the analysis of the concentration function f(C) at a particular temperature indicates that the gelation process obeys the three dimensional percolation mechanism. The microscopic mechanism of the gelation process is explored from the temperature function f(T) of the gelation rate at a particular concentration expressing f(T) in two different forms: (I) for fibrillar (rod like) crystallization and (II) for spinodal decomposition. A tentative structure of the tripeptide in the gel state has been proposed by molecular modeling using the MMX program.