Low Molecular Weight Gelators Research Articles

Versatile robust organogels based on a low molecular weight gelator of phenylquinolinylacrylonitrile

A versatile organogel based on phenylquinolinylacrylonitrile derivatives was prepared, and exhibited high mechanical strength as well as thermo-, photo-, and acid vapor stimuli responsive properties.

Electrofabrication of a low molecular weight hydrogel at high pH

We describe the electrodeposition at high pH of a low molecular weight gelator. Electrodeposition can be used to grow simultaneously two hydrogels at opposing pH extremes on different electrodes.

A novel supramolecular Zn(ii)-metallogel: an efficient microelectronic semiconducting device application.

A unique strategy for the synthesis of a supramolecular metallogel employing zinc ions and adipic acid in DMF medium has been established at room temperature. Rheological analysis was used to investigate the mechanical characteristics of the supramolecular Zn(ii)-metallogel. Field emission scanning electron microscopy and transmission electron microscopy were used to analyse the hexagonal shape morphological features of the Zn(ii)-metallogel. Interestingly, the electrical conductivity is observed in the electronic device with Zn(ii)-metallogel based metal-semiconductor (MS) junctions. All aspects of the metallogel's electrical properties were investigated. The electrical conductivity of the metallogel-based thin film device was 7.38 × 10-5 S m-1. The synthesised Zn(ii)-metallogel based device was investigated for its semi-conductive properties, such as its Schottky barrier diode nature.

Interpenetrated Biosurfactant-Biopolymer Orthogonal Hydrogels: The Biosurfactant's Phase Controls the Hydrogel's Mechanics.

Controlling the viscoelastic properties of hydrogels is a challenge for many applications. Low molecular weight gelators (LMWGs) like bile salts and glycolipids and biopolymers like chitosan and alginate are good candidates for developing fully biobased hybrid hydrogels that combine the advantages of both components. Biopolymers lead to enhanced mechanics, while LMWGs add functionality. In this work, hybrid hydrogels are composed of biopolymers (gelatin, chitosan, and alginate) and microbial glycolipid bioamphiphiles, known as biosurfactants. Besides their biocompatibility and natural origin, bioamphiphiles can present chameleonic behavior, as pH and ions control their phase diagram in water around neutrality under strongly diluted conditions (<5 wt%). The glycolipid used in this work behaves like a surfactant (micellar phase) at high pH or like a phospholipid (vesicle phase) at low pH. Moreover, at neutral-to-alkaline pH in the presence of calcium, it behaves like a gelator (fiber phase). The impact of each of these phases on the elastic properties of biopolymers is explored by means of oscillatory rheology, while the hybrid structure is studied by small angle X-ray scattering. The micellar and vesicular phases reduce the elastic properties of the hydrogels, while the fiber phase has the opposite effect; it enhances the hydrogel's strength by forming an interpenetrated biopolymer-LMWG network.

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway.

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an l-histidine methyl ester catalyst to prepare the drug-loaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.

The Effect of Branched Alkyl Chain Length on the Properties of Supramolecular Organogels from Mono-N-Alkylated Primary Oxalamides.

Mono-N-alkylated primary oxalamide derivatives with different sized branched alkyl tail-groups were excellent low molecular weight gelators for a variety of different organic solvents with different polarities and hydrogen-bonding abilities. Solvent-gelator interactions were analyzed using Hansen solubility parameters, while 1H NMR and FTIR spectroscopy were used to probe the driving forces for the supramolecular gelation. The molecular structures of the twin tail-groups did not significantly affect the supramolecular gelation behavior in different solvents. However, for select solvents, the molecular structures of the tail-groups did have a significant effect on gel properties such as the critical gelator concentration, thermal stability, gel stiffness, gel strength, network morphology, and molecular packing. Finally, metabolic activity studies showed that the primary alkyl oxalamide gelators had no effect on the metabolic activity of mouse immune cells, which suggests that the compounds are not cytotoxic and are suitable for use in biomedical applications.

A transparent self-healable multistimuli-responsive novel supramolecular Co(II)-metallogel derived from adipic acid: Effective hole transport layer for polymer solar cells

A fascinating approach for the instantaneous synthesis of adipic acid as a low molecular weight gelator and cobalt(II)-ion based metallogel through one-shot mixing in N,N-dimethyl formamide medium has been attained under ambient condition and at room temperature. The rheological study was applied to investigate the mechanical property of the synthesized Co(II)-metallogel. Through thixotropic experiments, the self-healing ability of the synthesised cobalt metallogel is established. The layered structure of the metallogel was envisaged through FESEM and the present elements were characterized through EDX mapping investigations. The potential metallogel formation approach has been examined using FT-IR, and the Powder X-ray diffraction pattern verifies the crystallinity of the Co(II)-metallogel's xerogel form. The absorption characteristics of this gel showed transparent in the visible to near infrared region of solar spectrum. The semiconducting property of the metallogel has been further confirmed and verified and with electronic device characterization and charge career mobility evaluation and found that this gel exhibits quite high hole mobility. We have used this as hole transport layer for polymer solar cells using PM6:Y6 as active layer and compared with the MoO3 as hole transport layer. The power conversion efficiency for Co(II)-metallogel (Co-AD) as hole transport layer 13.15 % which is higher than that for MoO3 counterpart (12.17 %). The higher power conversion efficiency for Co(II)-metallogel is associated with enhanced value of fill factor owing to the more efficient charge transport and suppressed charge recombination.

An organic acid consisted multiresponsive self-healing supramolecular Cu(II)-metallogel: Fabrication and analysis of semiconducting device

A remarkable strategy of a supramolecular metallogel synthesis using copper ion and succinic acid as a low molecular weight gelator (LMWG) in N,N-dimethyl formamide (DMF) medium has been developed at room temperature under ambient conditions. The mechanical property of the supramolecular copper acetate - succinic acid i.e. CuA-SA metallogel was examined by rheological study. The excellent self-healing property of CuA-SA metallogel has been recorded through thixotropic analysis. Field emission scanning electron microscopy (FESEM) and Transmission electron microscopy (TEM) were used to analyse the flake-like morphological features of CuA-SA metallogel. Further, the supramolecular structure of CuA-SA metallogel exhibits electrical conductivity on a metal-semiconductor (MS) junction electronic device. The metallogel's electrical properties were extensively investigated. The metallogel based thin film device shows the electrical conductivity as 3.24 × 10−5 S.m−1. The synthesised CuA-SA metallogel based device was explored for its semi-conductive properties, such as its Schottky barrier diode-like nature.

Anion Effects on the Supramolecular Self-Assembly of Cationic Phenylalanine Derivatives.

Supramolecular hydrogels have emerged as a class of promising biomaterials for applications such as drug delivery and tissue engineering. Self-assembling peptides have been well studied for such applications, but low molecular weight (LMW) amino acid-derived gelators have attracted interest as low-cost alternatives with similar emergent properties. Fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-Phe) is one such privileged motif often chosen due to its inherent self-assembly potential. Previously, we developed cationic Fmoc-Phe-DAP gelators that assemble into hydrogel networks in aqueous NaCl solutions of sufficient ionic strength. The chloride anions in these solutions screen the cationic charge of the gelators to enable self-assembly to occur. Herein, we report the effects of varying the anions of sodium salts on the gelation potential, nanoscale morphology, and hydrogel viscoelastic properties of Fmoc-Phe-DAP and two of its fluorinated derivatives, Fmoc-3F-Phe-DAP and Fmoc-F5-Phe-DAP. It was observed that both the anion identity and gelator structure had a significant impact on the self-assembly and gelation properties of these derivatives. Changing the anion identity resulted in significant polymorphism of the nanoscale morphology of the assembled states that was dependent on the chemical structure of the gelator. The emergent viscoelastic character of the hydrogel networks was also found to be reliant on the anion identity and gelator structure. These results demonstrate the complex interplay between the gelator and environment that have a profound and often unpredictable impact on both self-assembly properties and emergent viscoelasticity in supramolecular hydrogels formed by LMW compounds. This work also illustrates the current lack of understanding that limits the rational design of potential biomaterials that will be in contact with complex biological fluids and provides motivation for additional research to correlate the chemical structure of LMW gelators with the structure and emergent properties of the resulting supramolecular assemblies as a function of environment.

Biomimetic Approach toward Visible Light-Driven Hydrogen Generation Based on a Porphyrin-Based Coordination Polymer Gel.

There has been a widespread interest in developing self-assembled porphyrin nanostructures to mimic nature's light-harvesting processes. Herein, porphyrin-based coordination polymer gel (CPG) has been developed as a "soft" photocatalyst material for hydrogen (H2) production from water under visible light. The CPG offers a hierarchical nanofibrous network structure obtained through self-assembly of a terpyridine alkyl-amide appended porphyrin (TPY-POR)-based low molecular weight gelator with ruthenium ions (RuII) and produces H2 with a rate of 5.7 mmol g-1 h-1 in the presence of triethylamine (TEA) as a sacrificial electron donor. Further, the [Fe2(bdt)(CO)6] (dbt = 1,2-benzenedithiol) cocatalyst, which can mimic the activity of iron hydrogenase, is coassembled in the CPG and shows remarkable improvement in H2 evolution (catalytic activity; rate ∼10.6 mmol g-1 h-1 and turnover number ∼1287). The significant enhancement in catalytic activity was supported by several controlled experiments, including femtosecond transient absorption (TA) spectroscopy and also DFT calculation. The TA study supported the cascade electron transfer process from porphyrin core to [Ru(TPY)2]2+ center, and subsequently, the electron transfers to the cocatalyst [Fe2(bdt)(CO)6] for H2 production.

Self‐Healable Metallogels for Selective Dye Adsorption

AbstractThe low molecular weight gelator, disodium L‐(3,5‐di‐tert‐butyl‐2‐hydroxy‐benzyl)amino aspartic acid (Na2HL), has been used to prepare three metal‐organic hydrogels (metallogel) with the metal ions Ni2+ (MOG 1), Co2+ (MOG 2), and VO2+ (MOG 3). The gels have been prepared by mixing the aqueous solutions (0.5 mL) of the Na2HL(0.01 to 0.05 mmol) and M(CH3COO)2⋅4H2O {M=Ni or Co} or VO(SO)4⋅H2O (0.01 to 0.05 mmol). The gels have been characterized by IR spectroscopic studies, MALDI TOF spectrometry and various microscopic studies. All the gels are multi‐responsive in nature to different external stimuli, and among them, MOG 1 and MOG‐2 show the self‐healable property indicating a strong metal‐ligand interaction and hydrogen bonding interactions in the gel network. The thixotropic behavior and viscoelastic nature of the self‐healable metallogels have been confirmed by time dependent step‐strain experiment at room temperature. It was observed that MOG 1 shows rapid and more efficient selective dye adsorption of cationic dyes, rhodamine B (RhB) {61.7 mg g−1}, and malachite green (MG) {15.3 mg g−1} from mixtures of cationic, anionic dyes, and neutral dyes. MOG 2 also selectively adsorb cationic dyes from the mixture of dyes. The gel, MOG 3, selectively degrades fluorescein (FL) dye.

Process Dependent Complexity in Multicomponent Gels.

Mixing low molecular weight gelators (LMWGs) can be used to combine favorable properties of the individual components within a multifunctional gel. Such multicomponent systems are complex enough in themselves but the method of combining components is not commonly considered something to influence self-assembly. Herein, two multicomponent systems comprising of a naphthalene-based dipeptide hydrogelator and one of two modified naphthalene diimides (NDIs), one of which forms gels, and the other does not,are investigated. These systems are probed, examining the structures formed and their gel properties (when preparing a solution from either a mixed powder of both components or by mixing pre-formed solutions of each component) using rheology, small angle neutron scattering (SANS), and absorbance spectroscopy. It is found that by altering the method of preparation, it is can either induce self-sorting or co-assembly within the fibers formed that underpin the gel network.

Sucralose hydrogels: Peering into the reactivity of sucralose versus sucrose under lipase catalyzed trans-esterification

Sucralose differs from sucrose only by virtue of having three Cl groups instead of OH groups. Its intriguing features include being noncaloric, noncariogenic, ∼600 times sweeter than sucrose, stable at high temperatures/acidic pH's, and void of disagreeable aftertastes. These properties are attractive as food additive, one of which is as hydrogel obtainable via the technique of molecular gelation using a sucralose-derived low-molecular weight gelator (LMWG). Such hydrogels are highly responsive to external stimuli like temperature, because the LMWGs self-assemble via non-covalent interactions and could thus be utilized in applications like control-release. We found that sucralose to be unreactive under lipase biocatalysis, unlike sucrose. Hence, the aim of this work was (i) to use computational simulations to further understand sucralose's lack of enzymatic reactivity and (ii) to synthesize the sucralose-based amphiphiles using conventional chemical synthesis and systematically study their tendency towards hydrogelation. Sucrose and sucralose were docked with a high-resolution atomic structure of lipase B from Candida antarctica, modeling the esterification transition state with an active site serine. In extended molecular dynamics simulations, sucrose remained in the active site due to multiple sugar-protein hydrogen bonds. The oxygen-to-chlorine substitutions in sucralose disrupted this hydrogen bonding network. Consistent with observed lack of enzymatic conversion, in multiple simulations, sucralose would rapidly dissociate from the active site. The sucralose-based LMWGs were subsequently synthesized using base-catalyzed conventional chemical synthesis. Three of the sucralose-based amphiphiles (SL-5, SL-6 and SL-7) proved to be successful hydrogelators. The gelators also showed the ability to gel selected beverages. The LMWGs gelled quantities of water and beverage up to 71 and 55 times their weight, respectively, and remain thermally stable up to 144 °C.

Supramolecular Gels from Bis-amides of L-Phenylalanine: Synthesis, Structure and Material Applications.

A series of small organic molecules having a bis-amide backbone containing hydrogen-bond functionalities were rationally designed, synthesized and characterized to examine their ability to act as potential low-molecular-weight gelators (LMWGs). All the bis-amides were decorated with identical 3-pyridyl amide of L-phenylalanine moieties along with variously substituted terminal benzoyl groups. Gelation studies revealed that only 4-methylphenyl substituted bis-amide (PME) was capable of gelling both aqueous (DMSO/water) and methyl salicylate (MS) (an important solvent for topical formulation for medical applications) solvents; whereas 4-chlorophenyl and 4-bromophenyl substituted bis-amides (PCL, PBR, respectively) acted as organogelator for various organic solvents. On the contrary, 4-nitrophenyl as well as 3,5-dinitrophenyl substituted bis-amides (PNI, DNI, respectively) were unable to gel any solvents studied herein. The corresponding aqueous gel namely PME-HG and three methyl salicylate gels PME-MS, PCL-MS and PBR-MS were characterized by dynamic and table top rheology followed by electron microscopy. Single crystal X-ray diffraction (SXRD) data revealed crucial insights into the supramolecular assembly of all the gelator and nongelator bis-amides. Both PME-HG and PME-MS were rheoreversible - an important property in material applications. Interestingly, PME-MS displayed remarkable material properties such as shape-sustaining, loadbearing and self-healing. Selected MS and aqueous gels loaded with nano-molar iodine were found to possess anti-bacterial property as revealed by zone inhibition assay.

New Fmoc-Amino Acids/Peptides-Based Supramolecular Gels Obtained through Co-Assembly Process: Preparation and Characterization.

One of the methods of obtaining supramolecular gels consists of the possibility of self-assembly of low molecular weight gelators (LMWGs). However, LMWG-based gels are often difficult to handle, easy to destroy and have poor rheological performance. In order to improve the gels’ properties, the LMWGs molecules are co-assembled, which induces more cross-links with more stable structures. Starting from these aspects, the present study refers to the preparation of a bionic hydrogel stabilized with a physiologically occurring, bifunctional biomolecule, L-lysine, co-assembled with other amino acids or peptides (such as a modified amino acid (Fmoc-serine or Fmoc-glutamic acid) or a tripeptide (Fmoc-Gly-Gly-Gly)) with the potential to support the repair of injuries or the age-related impaired structures or functions of living tissues. The introduction of a copartner aims to improve hydrogel characteristics from a morphological, rheological and structural point of view. On the other hand, the process will allow the understanding of the phenomenon of specific self-association and molecular recognition. Various characterization techniques were used to assess the ability to co-assemble: DLS, FT-IR, SEM and fluorescence microscopy, rheology and thermal analysis. Studies have confirmed that the supramolecular structure occurs through the formation of inter- and intramolecular physical bonds that ensure the formation of fibrils organized into 3D networks. The rheological data, namely the G′ > G″ and tan δ approximately 0.1–0.2 gel-like behavior observed for all studied samples, demonstrate and sustain the appearance of the co-assembly processes and the ability of the samples to act as LMWG. From the studied systems, the Fmoc–Lys–Fmoc_ Fmoc–Glu sample presented the best rheological characteristics that are consistent with the observations that resulted from the dichroism, fluorescence and SEM investigations.

A Wide Bandgap Semiconducting Magnesium Hydrogel: Moisture Harvest, Iodine Sequestration, and Resistive Switching.

Water harvesting from the ubiquitous moisture is pivotal for delivering fresh water to earth's arid/semiarid regions, and sequestration of iodine from the solution is crucial for environmental safety due to its severe effect on human metabolic processes. In this context, herein, a multifunctional supramolecular metallohydrogel (Mg@TAEA) is synthesized through direct mixing of magnesium nitrate hexahydrate and the low molecular weight gelator tris(2-aminoethyl)amine. Electron microscopy reveals that Mg@TAEA is sculptured in vertically grown well-oriented micrometer-sized flakes. The porous crystalline material (52 m2/g) was found to be an efficacious host matrix for water harvesting from moisture (847 mg/g). Mg@TAEA shows effective (513 mg/g) iodine sequestration from solution and adsorption of carbon dioxide (15 mg/g). The wide bandgap semiconducting Mg@TAEA (3.6 eV) material is a potential candidate for building memory devices, and the Ion/Ioff ratio of the device based on the indium tin oxide (ITO)/Mg@TAEA/Ag heterostructure was found to be ∼62. We further extended our work by analyzing the charge transport properties of the system and found space charge limited conduction (SCLC) and trap-filled SCLC to be responsible for the nonlinear transport behavior observed in the device.

Synthesis of an ursolic acid organic salt based low-molecular-weight supramolecular hydrogel with unique thermo-responsiveness behavior

Low-molecular-weight supramolecular hydrogels (LMWSHs) are widely used in biomedical area and soft materials with desirable stimuli-responsiveness and self-healing abilities. Natural product hydrogelators (NPHGs) based LMWSHs can be synergistically used as drug matrix due to the low toxicity, good biocompatibility, biodegradability and biological activity from hydrogelator. Usually NPHGs based LMWSHs are obtained in organic reagents or following complex modifications. This work introduces a pentacyclic triterpene acid, ursolic acid, derivatives based LMWSH that formed in aqueous solution following simple preparation of 1-ethyl-3-methylimidazolium ursolic salt ([EMIM][UA]). Surprisingly, the gelator [EMIM][UA] based LMWSH showed unusual heating-induced irreversible transparent-turbid transitions in sol state at the gelator concentration lower than the minimum gelation concentration (MGC), but self-assembled to form LMWSH upon cooling like a conventional low-molecular-weight gelator (LMWG) at the gelator concentration higher than MGC. Rarely observed in the LMWSH system, a large number of crystallites were formed in both sol and gel state by increasing temperature, which was analogous to lower critical solution temperature (LCST) phase behavior in polymer systems. Moreover, the formed LMWSH displayed enormous viscoelasticity as chewing gum at room temperature with a porous honeycomb structure based supramolecular network. The good stability and injectability of the formed LMWSH, together with the in vitro drug releasing ability, demonstrated the potential of the formed LMWSH to be the drug delivery system for sustained drug releasing.

Synthesis and self-assembly of novel pH triggered smart organogelators from novel alkyl-substituted chalcone-based hydrazonotriazole derivatives

Chalcones have been known as a significant group of compounds used for treatment of parasitic infections, cardiovascular diseases, viral disorders, gastritis, pain, and stomach cancer. Additionally, they have been employed in cosmetic formulation ingredients and food additives. In the current study, a series of new 4-(1-(2-(2,4-dinitrophenyl)hydrazineylidene)ethyl)-5-methyl-1-aryl-1H-1, 2, 3-triazole derivatives with different terminal alkyl chains were synthesized to function as pH-induced and thermally reversible low molecular weight gelators (LMWG). The novel hydrazonotriazole derivatives were synthesized by a simple reaction of (2,4-dinitrophenyl)hydrazine with various derivatives of 1-(5-methyl-1-(4- alkoxyphenyl)-1H-1, 2, 3-triazol-4-yl)ethan-1-ones in absolute ethanol using hydrochloric acid as a catalyst. Elemental analysis, FTIR, and NMR spectroscopic techniques were used to prove the molecular structures of the synthesized chalcone-based gelators. The photophysical properties of the synthesized gelators were described. The chalcone-based gelators were found to efficiently gelate various organic solvents with reversible responsiveness ability to pH stimulus, demonstrating a sol–gel switching process in association with a colorimetric shift from yellow to purple. The optimum gelation activity was observed for the nonyloxy-substituted chalcone-based organogelator in various solvents with critical gel concentration (CGC) in the range of 2.05–9.28 mM, and thermal stability up to 46 °C. Various analytical techniques were utilized to examine the morphologies of xerogels, displaying nanofibrous assemblies (10–30 nm). Both cytotoxicity and antibacterial activities of the synthesized alkyl-substituted chalcone-based gelators were explored.

Tailoring co-assembly loading of doxorubicin in solvent-triggering gel

Noncovalent interactions are ubiquitous, endowing high feasibility on assembly and disassembly of gel network structure. Loading anticancer drugs in low molecular weight gelator (LMWG)-based gel through a noncovalently co-assembly process shows advantages of high efficacy, thixotropy, and controllable release. Drug-loaded fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F)/DMSO/H2O-doxorubicin (DOX) gels were fabricated by an effective solvent-triggering method dominated by solvated Fmoc-F with DMSO. Density Functional Theory (DFT) calculation results show that the noncovalent interactions between Fmoc-F and DOX drive the co-assembly of the gel. DOX can assemble with Fmoc-F and realize its co-assembly loading through the H-bonding and π-π stacking, similar to the way that gel networks form. Depending on a network dis-assembly process, sustained release of DOX was achieved along with carrier decomposition through a repetitive diffusion-surface erosion process. DOX loading and release prove the non-covalent interactions and the mechanism for controlling the assembly process. By such tailoring co-assembled loading, the administration of DOX is hoped to be optimized to improve the clinical application.

Nucleoside-Derived Low-Molecular-Weight Gelators as a Synthetic Microenvironment for 3D Cell Culture.

For the last few decades, many efforts have been made in developing cell culture methods in order to overcome the biological limitations of the conventional two-dimensional culture. This paradigm shift is driven by a large amount of new hydrogel-based systems for three-dimensional culture, among other systems, since they are known to mimic some living tissue properties. One class of hydrogel precursors has received interest in the field of biomaterials, low-molecular-weight gelators (LMWGs). In comparison to polymer gels, LMWG gels are formed by weak interactions upon an external trigger between the molecular subunits, giving them the ability to reverse the gelation, thus showing potential for many applications of practical interest. This study presents the use of the nucleoside derivative subclass of LMWGs, which are glyco-nucleo-bola-amphiphiles, as a proof of concept of a 3D cell culture scaffold. Physicochemical characterization was performed in order to reach the optimal features to fulfill the requirements of the cell culture microenvironment, in terms of the mechanical properties, architecture, molecular diffusion, porosity, and experimental practicality. The retained conditions were tested by culturing glioblastoma cells for over a month. The cell viability, proliferation, and spatial organization showed during the experiments demonstrate the proof of concept of nucleoside-derived LMWGs as a soft 3D cell culture scaffold. One of the hydrogels tested permits cell proliferation and spheroidal organization over the entire culture time. These systems offer many advantages as they consume very few matters within the optimal range of viscoelasticity for cell culture, and the thermoreversibility of these hydrogels permits their use with few instruments. The LMWG-based scaffold for the 3D cell culture presented in this study unlocked the ability to grow spheroids from patient cells to reach personalized therapies by dramatically reducing the variability of the lattice used.