Low-molecular-weight gelators: elucidating the principles of gelation based on gelator solubility and a cooperative self-assembly model

This paper highlights the key role played by solubility in influencing gelation and demonstrates that many facets of the gelation process depend on this vital parameter. In particular, we relate thermal stability ( T gel) and minimum gelation concentration (MGC) values of small-molecule gelation in terms of the solubility and cooperative self-assembly of gelator building blocks. By employing a van't Hoff analysis of solubility data, determined from simple NMR measurements, we are able to generate T calc values that reflect the calculated temperature for complete solubilization of the networked gelator. The concentration dependence of T calc allows the previously difficult to rationalize "plateau-region" thermal stability values to be elucidated in terms of gelator molecular design. This is demonstrated for a family of four gelators with lysine units attached to each end of an aliphatic diamine, with different peripheral groups (Z or Boc) in different locations on the periphery of the molecule. By tuning the peripheral protecting groups of the gelators, the solubility of the system is modified, which in turn controls the saturation point of the system and hence controls the concentration at which network formation takes place. We report that the critical concentration ( C crit) of gelator incorporated into the solid-phase sample-spanning network within the gel is invariant of gelator structural design. However, because some systems have higher solubilities, they are less effective gelators and require the application of higher total concentrations to achieve gelation, hence shedding light on the role of the MGC parameter in gelation. Furthermore, gelator structural design also modulates the level of cooperative self-assembly through solubility effects, as determined by applying a cooperative binding model to NMR data. Finally, the effect of gelator chemical design on the spatial organization of the networked gelator was probed by small-angle neutron and X-ray scattering (SANS/SAXS) on the native gel, and a tentative self-assembly model was proposed.     

A new urea gelator: incorporation of intra- and intermolecular hydrogen bonding for stable 1D self-assembly

A new bisurea gelator derived from 2,6-diaminopyridine has been developed. It efficiently gelates common organic and liquid crystalline (LC) solvents by forming elongated self-assembled fibres in solvents. X-Ray crystallography and 1H NMR measurements reveal that two urea groups in pyridine-based bisurea compounds form different hydrogen bonding patterns. One of two urea units is involved in intramolecular hydrogen bonding with the pyridyl nitrogen, while the other urea unit forms bifurcated intermolecular hydrogen bonding. This hydrogen-bonded structure is key for the fibrous self-assembly along with the efficient gelation. In addition, LC gels based on the pyridine-based gelator exhibit good electrooptic properties. These results indicate that the pyridine-based bisurea compound is a good gelator not only effective in gelation but also useful as a component of functional soft materials.     

一种含芘葡萄糖衍生物的合成及其胶凝行为

合成并表征了一种荧光活性小分子胶凝剂——芘磺酰基-丙二胺-葡萄糖(PSDAPG), 考察了其在36种常见溶剂中的胶凝行为. 结果发现, PSDAPG可使其中16种溶剂胶凝. 对癸醇, PSDAPG表现出罕见的超级胶凝能力, 室温下最低胶凝浓度(MGC)达7.0×10-4 g·mL-1. 此外, PSDAPG还是一种既可胶凝水又可胶凝有机溶剂的双性胶凝剂. 扫描电镜(SEM)、傅立叶变换红外光谱(FTIR)、核磁共振(1HNMR)和荧光光谱研究表明,在不同溶剂中, PSDAPG具有不同的聚集结构, 除了芘基之间的疏水π-π堆积作用外, 氢键作用是PSDAPG自发形成三维网络结构的重要驱动力. 实验研究还表明, 溶液态和凝胶态的PSDAPG荧光光谱均同时呈现芘的单体荧光和激基缔合物荧光光谱特征, 但两者的光谱形貌差异显著. 随凝胶的形成, 体系单体荧光发射增强, 激基缔合物荧光发射减弱,表明形成的三维网络结构阻碍了PSDAPG中芘单元的运动性, 使得以Birks途径形成激基缔合物的效率降低.     

Water gelation of an amino acid-based amphiphile

The water immobilization by a simple amino acid-containing cationic surfactant was investigated. A variety of techniques, such as (1)H NMR spectroscopy, circular dichroism (CD), steady-state fluorescence spectroscopy, and field-emission scanning electron microscopy (FESEM) were applied to determine the formation and architecture of the hydrogel. The new gelator with a minimum gelation concentration (MGC) of 0.3 % w/v shows prolonged stability and a low melting temperature (39 degrees C). (1)H NMR experiments revealed that intermolecular hydrogen bonding between the amide groups and pi-pi stacking of the indole rings are the two regulating parameters for gelation. Furthermore, fluorescence studies with 8-anilino-1-naphthalenesulfonic acid (ANS) as the probe indicate the participation of hydrophobicity during gelation. The luminescence study using both ANS and pyrene, along with FESEM results, indicate a critical concentration, well below the MGC, at which fibres begin to form. These cross-link further to give thicker fibers, leading to the formation of a hydrogel (0.3 % w/v). This new hydrogelator expresses high supramolecular chirality, as evidenced by the CD spectra. In addition, the gelator molecule was found to be nontoxic up to a concentration of 4 mM (0.2 % w/v). The high supramolecular chirality, prolonged stability, low melting point, and biocompatibility of the molecule make it a focus of chemical and biological interest.     

Thermal properties of the gel made by low molecular weight gelator 1,2-O-(1-ethylpropylidene)-alpha-D-glucofuranose with toluene and molecular dynamics of solvent

The studies of the gel-to-sol phase transition by the Raman, FT-IR, and 1H NMR methods of the gel made by low molecular weight organogelator 1,2-O-(1-ethylpropylidene)-alpha-D-glucofuranose with toluene as the solvent are reported. The FT-IR spectra revealed the existence of a hydrogen bond network formed by gelator molecules in the crystalline and gel phase. In both phases, the network formation is dominated by the gelator self-interaction. Upon gelation, only one stretching band of infrared absorption modes nualpha, assigned to the O(6)H hydroxyl protons of gelator, is shifted by Deltaupsilonalpha = 25 cm-1, which indicates the involvement of this proton in the interaction with the solvent molecules. The phase transition measurements performed as a function of gelator concentration allowed the calculation of the energy correlated with the transition from gel to solution phase. The obtained value of 72 kJ/mol is the largest one reported up until now for monosaccharide-based gels. The analysis of the temperature measurements of the toluene 1H NMR spectra provides evidence for a different chemical environment of toluene molecules in the gel. The toluene spin-lattice relaxation in bulk and gel indicate that the viscosity is most likely the main factor that influences the dynamics of toluene.     

一种基于胆固醇的荧光小分子胶凝剂的合成及其胶凝行为

合成并表征了一种含7-硝基苯并-2-氧杂-1,3-二唑基(7-Nitrobenzo-2-oxa-1,3-diazol-4-yl)的胆固醇衍生物(NBD-C), 考察了其在30种溶剂中的胶凝行为. 实验结果表明, NBD-C对乙腈具有很强的胶凝作用, 且该凝胶体系具有显著的剪切触变性. 对干凝胶的显微分析发现, 在不同溶剂中, NBD-C具有不同的聚集结构. 红外光谱(FTIR)、核磁共振光谱(¹H NMR)和荧光光谱研究结果表明, 除了胆固醇的范德华堆积作用之外, 分子间氢键作用也是该化合物聚集的重要驱动力.     

Organogels with Fe(III) complexes of phosphorus-containing amphiphiles as two-component isothermal gelators

The properties of thermally reversible organogels in which the gelators consist of a phosphonic acid monoester, phosphonic acid, or phosphoric acid monoester and a ferric salt are probed by IR and NMR spectroscopies, optical microscopy, X-ray diffraction, rheology, and light and small-angle neutron scattering (SANS) techniques. This is one of a small number of two-component molecular gelator systems in which gelation can be induced isothermally. The data indicate that complexation between the phosphonate moieties and Fe(III) is accompanied by their in situ polymerization to form self-assembled fibrillar networks that encapsulate and immobilize macroscopically the organic liquid component. From SANS measurements, the cross-sectional radii of the cyclindrical fibers are ca. 15 A. The efficiencies of the gelators (based on the diversity of the liquids gelated, the minimum concentration of gelator required to make a gel at room temperature, and the temporal and thermal stabilities of the gels) have been determined. With a common ferric salt and liquid component, phosphonic acid monoesters are generally more efficient than phosphinic acids or phosphoric acid esters. Of the phosphonic acid monoesters, monophosphonates are better gelator components than bisphosphonates, and introduction of an omega-hydroxy group on the alkyl chain directly attached to phosphorus reduces significantly gelation ability. Several of the gels are stable for very long periods at room temperature. When heated, they revert to sols over wide temperature ranges. The structures of the gelator complexes and the mechanism of their formation and transformation to gels in selected liquids are examined as well.     

Self-assembly of two-component peptidic dendrimers: dendritic effects on gel-phase materials

The self-assembly of diaminododecane solubilised by different dendritic peptides, possessing increasing levels of dendritic branching, was investigated. The dendritic peptides were based on l-lysine building blocks and were of first, second and third generation, containing one, three and seven amino acid repeat units respectively. By applying these structures as potential gelator units, the dendritic effect on gelation was investigated. The degree of structuring was modulated, with the dendritic peptide controlling the aggregate morphology and the ability of the self-assembled state to manifest itself macroscopically as gelation. First generation gelator units (G1) did not induce macroscopic gelation with diaminododecane under any conditions, whilst those self-assemblies based on second (G2) and third (G3) generation branches did form gel-phase materials. Furthermore, gel-phase materials based on G2 exhibited optimum gelation behaviour compared to those based on G3(in terms of the thermal strength of the materials). Circular dichroism showed that the dendritic effect, programmed in at the molecular level, is directly related to the degree of chiral organisation within the self-assembled state. The dendritic generation of the peptide controls the pattern of amide-amide hydrogen bonding in terms of binding strength and alignment as determined using NMR methods. The mode of self-assembly can be qualitatively rationalised in terms of an attractive enthalpic interaction (i.e., amide-amide hydrogen bonding), a repulsive interaction (i.e., steric interactions between dendritic peptides) and an entropic term related to the hierarchical organisation of the gelator building blocks. It is argued that the balance between these factors determines the nature of the dendritic effect.     

Studies on supramolecular gel formation using DOSY NMR

Herein, we present the results obtained from our studies on supramolecular self‐assembly and molecular mobility of low‐molecular‐weight gelators (LMWGs) in organic solvents using pulsed field gradient (PFG) diffusion ordered spectroscopy (DOSY) NMR. A series of concentration‐dependent DOSY NMR experiments were performed on selected LMWGs to determine the critical gelation concentration (CGC) as well as to understand the behaviour of the gelator molecules in the gel state. In addition, variable‐temperature DOSY NMR experiments were performed to determine the gel‐to‐sol transition. The PFG NMR experiments performed as a function of gradient strength were further analyzed using monoexponential DOSY processing, and the results were compared with the automated Bayesian DOSY transformation to obtain 2D plots. Our results provide useful information on the stepwise self‐assembly of small molecules leading to gelation. We believe that the results obtained from these experiments are applicable in determining the CGC and gel melting temperatures of supramolecular gels. Copyright © 2015 John Wiley & Sons, Ltd.     

A synthetic tripeptide as a novel organo-gelator: a structural investigation

A self-associating synthetic tripeptide [Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe (Aib: α-amino-isobutyric acid, β-Ala: β-alanine)] forms thermoreversible transparent gels in various organic solvents and this offers the first example of a peptide gelator whose molecular self-assembly afforded for gelation has been characterised by single-crystal X-ray diffraction and FT-IR and NMR spectroscopic studies. The crystal structure of an analogous synthetic non-gelator tripeptide [Boc-Ala(1)-Gly(2)-β-Ala(3)-OMe] is also discussed in light of the self-assembly of the gelator tripeptide.     

Proton NMR investigation of a hydrogen-bonded liquid crystal gel

Proton NMR is employed to determine director distributions in a hydrogen-bonded liquid crystal gel in the presence of a magnetic field. The samples consist of the mesogen 8CB mixed with small percentages of gelator, which forms a hydrogen-bonded network when the sample is cooled below the gelation point in the isotropic liquid. Since the gelation occurs above the clearing point, a non-oriented random director configuration is frozen in. The configuration of the hydrogen-bonded network is found to be isotropic. It fixes a preferential random local orientation of the nematic director, even in the presence of an external magnetic field of a few Tesla. The NMR spectra of the samples give information on orientation and order in such systems. A simple model for the director field is provided.     

Multidrug‐Containing,Salt‐Based,Injectable Supramolecular Gels for Self‐Delivery,Cell Imaging and Other Materials Applications

Both molecular and crystal‐engineering approaches were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l ‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table‐top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature‐dependent ¹H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single‐crystal X‐ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen‐bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self‐delivery) applications for future multidrug‐containing injectable delivery vehicles.     

Proton NMR investigation of a hydrogen-bonded liquid crystal gel

Proton NMR is employed to determine director distributions in a hydrogen-bonded liquid crystal gel in the presence of a magnetic field. The samples consist of the mesogen 8CB mixed with small percentages of gelator, which forms a hydrogen-bonded network when the sample is cooled below the gelation point in the isotropic liquid. Since the gelation occurs above the clearing point, a non-oriented random director configuration is frozen in. The configuration of the hydrogen-bonded network is found to be isotropic. It fixes a preferential random local orientation of the nematic director, even in the presence of an external magnetic field of a few Tesla. The NMR spectra of the samples give information on orientation and order in such systems. A simple model for the director field is provided.     

Supramolecular Synthons in Designing Low Molecular Mass Gelling Agents: L‐Amino Acid Methyl Ester Cinnamate Salts and their Anti‐Solvent‐Induced Instant Gelation

Easy access to a class of chiral gelators has been achieved by exploiting primary ammonium monocarboxylate ( PAM ), a supramolecular synthon. A combinatorial library comprising of 16 salts, derived from 5 l ‐amino acid methyl esters and 4 cinnamic acid derivatives, has been prepared and scanned for gelation. Remarkably, 14 out of 16 salts prepared (87.5 % of the salts) show moderate to good gelation abilities with various solvents, including commercial fuels, such as petrol. Anti‐solvent induced instant gelation at room temperature has been achieved in all the gelator salts, indicating that the gelation process is indeed an aborted crystallization phenomenon. Rheology, optical and scanning electron microscopy, small angle neutron scattering, and X‐ray powder diffraction have been used to characterize the gels. A structure‐property correlation has been attempted, based on these data, in addition to the single‐crystal structures of 5 gelator salts. Analysis of the FT‐IR and ¹H NMR spectroscopy data reveals that some of these salts can be used as supramolecular containers for the slow release of certain pest sex pheromones. The present study clearly demonstrates the merit of crystal engineering and the supramolecular synthon approach in designing new materials with multiple properties.     

光响应偶氮苯类小分子凝胶因子的合成及性能

合成了3个系列各6类的偶氮苯衍生物1a~6a, 1b~6b和1c~6c. 凝胶性能测试结果表明, 这些化合物均能在多种极性或非极性有机溶剂中形成凝胶. 运用扫描电子显微镜和核磁共振波谱仪对代表性化合物4b形成的凝胶结构和成胶驱动力进行了分析. 化合物4a~4c形成的凝胶在紫外光和可见光照射下, 能够发生凝胶-溶胶的相互转化. 计算了溶剂和凝胶因子的梯氏参数, 利用梯氏三角图分析了凝胶测试结果, 发现凝胶因子在溶剂中的4种行为(溶液、 半凝胶、 凝胶和沉淀)分别分布在三角图的不同区域; 在凝胶区域, 溶剂与凝胶因子之间的距离反映了凝胶的热稳定性, 距离越远表示凝胶的热稳定性越好.     

Curcumin-derived one-and two-component organogelators and their performance as template for the synthesis of silver nanoparticles

A single-component gelation system based on bis-cholesteryl appended curcumin derivative (BCC) and its corresponding two-component organogelation system with sodium stearate (SS) was proposed. As a single component gelator, BCC forms gel with ethylene diamine (ED), through hydrogen bonding between carbonyl group of BCC and amino group of ED as indicated by temperature dependent solid state NMR (SSNMR) and X-ray diffraction (XRD) profiles. As two-component gelator, BCC forms gel with a variety of solvents in the presence of sodium stearate (SS). Replacing sodium stearate by other sodium and stearate sources failed to form gel, revealing that both BCC and SS are crucial for effective gelation. The ion-dipole interactions between sodium and keto group of SS and BCC respectively, as well as π-π interactions confers better gelation abilities to BCC-SS system compared to the single component system. The morphology of the as-formed organogels exhibited entangled fibrillated structures and can be regulated by changing the composition of SS towards BCC and the type of organic solvents. Interestingly, our designed gelator, BCC-ED demonstrates potential application as an effective template for the synthesis of silver nanoparticles (AgNPs) at low temperatures as demonstrated by XRD and SEM analysis. Replacing BCC or ED failed to form AgNPs, revealing the synergistic effect of BCC-ED.     

Bile acid alkylamide derivatives as low molecular weight organogelators: systematic gelation studies and qualitative structural analysis of the systems

A series of amino- and hydroxyalkyl amides of bile acids have been synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), (1)H and (13)C nuclear magnetic resonance spectroscopy (NMR), as well as electrospray ionization mass spectrometry (ESI-MS) measurements. The ability of the synthesized molecules to promote gel formation was systematically investigated. Out of 396 combinations formed by 11 compounds and 36 different solvents, 22 gel-containing systems were obtained with 1% (w/v) gelator concentration. Apart from one exception, the gelator compounds were lithocholic acid derivatives. This challenges the general trend of bile acid-based physical gelators, according to which the gelation ability of lithocholic acid derivatives is poor. A correlation between the values of Kamlet-Taft parameters and solvent preferences for gelators was observed. The morphologies of the solid and gel structures studied with scanning electron microscopy (SEM) showed variability from fibers to spherical microscale aggregates, the latter of which are unique among bile acid-based organogels. The gels exhibited more complex behavior than was previously established with bile acid derivatives, judging by the microscale diversity present in gelating and non-gelating systems and the tendency for polymorphism. This study underlines the importance of both the molecular and colloidal scale aspects of the gelation phenomenon.     

Influence of solvent on the thermal stability and organization of self-assembling fibrillar networks in methyl-4,6-O-(p-nitrobenzylidene)-α-d-glucopyranoside gels

Sugar based low-molecular-mass organogelator (LMOG) methyl-4,6-O-(p-nitrobenzylidene)-α-d-glucopyranoside, is a unique gelator because its small and weakly-interacting molecules can form large supramolecular structures in nonpolar, but also in polar, solvents and cause their gelation. The self-assembling properties of the gelator were studied in selected nonpolar and polar solvents. It was shown that the driving forces for both types of solvent are the intermolecular hydrogen bond interaction. The effect of the nature of the solvent on the thermal stability of the gels and on the three-dimensional network organization was determined. Different solvent parameters, such as dielectric constant, one-component solubility parameter, the polarity parameter and the Kamlet-Taft parameters were considered to quantify solvent effects on the gelation. Some correlation between these parameters and the gel stability, microstructure and the enthalpy of the phase transition were established. The effort to correlate the Kamlet-Taft parameters to the thermal stability and gelation ability is also possible but applies only to the studied gelator.     

Two-component hydrogels comprising fatty acids and amines: structure, properties, and application as a template for the synthesis of metal nanoparticles

Stearic acid or eicosanoic acid mixed with di- or oligomeric amines in specific molar ratios form stable gels in water. The formation of such hydrogels depends on the hydrophobicity of the fatty acid, and also on the type of amine used. The gelation properties of these two-component systems were investigated using electron microscopy, FTIR spectroscopy, 1H NMR spectroscopy, differential scanning calorimetry (DSC), and both single-crystal and cast-film X-ray diffraction. Results of FTIR spectral analysis suggest salt formation during gelation. 1H NMR analysis of the gels indicates that the fatty acid chains are immobilized in the gel state and when the gel melts, these chains regain their mobility. Analysis of DSC data indicates that increase in the spacer length in the di-/oligomeric amine lowers the gel-melting temperature. Two of these gelator salts developed into crystals and structural details of such systems could be secured by single-crystal X-ray diffraction analysis. The structural information of the salts thus obtained was compared with the XRD data of the self-supporting films of those gels. Such analyses provided pertinent structural insight into the supramolecular interactions that prevail within these gelator assemblies. Analysis of the crystal structure confirmed that multilayered lamellar aggregates exist in the gel and it also showed that the three-dimensional ordering observed in the crystalline phase is retained in only one direction in the gel state. Finally, the hydrogel was used as a medium for the synthesis of silver nanoparticles. The nanoparticles were found to position themselves on the fibers and produced a long, ordered assembly of gel-nanoparticle composite.