Hydrophobic Chain Length Research Articles

Molecular dynamics simulation on the structure–activity relationship between the Gemini surfactant and foam properties

AbstractThe structure–activity relationship between the molecular structure of Gemini surfactants and foam properties has not yet been deeply revealed. In this study, we clarified for the first time the structure–activity relationship between foam properties and molecular structure of Gemini surfactant by discussing the variation characteristics of parameters such as free energy of interface formation, radial distribution function, and mean square displacement calculated by molecular simulation method. The research results show that (1) the Gemini surfactant with the sulfonic acid head group has the most excellent foam properties; (2) the foam properties increase monotonously with the increase of the hydrophobic tail chain length; (3) the foam properties decrease monotonously with the increase of the spacer group length. It is hoped that this article can further broaden the application range of surfactants as foaming agents in industrial fields such as oil and gas exploitation.

Effect of Gemini surfactant structure on water/oil interfacial properties: A dissipative particle dynamics study

Understanding the structural effects of Gemini surfactants on interfacial properties is pivotal towards the rational design of efficient Gemini surfactants. Herein, a series of alkylbenzene sulfonate Gemini surfactants have been constructed, and their influences on the interfacial properties of dodecane/water systems are systematically explored by using dissipative particle dynamics simulation. The Gemini surfactants are modeled as ‘π-shaped’ coarse-grained molecules, and their spacer lengths and hydrophobic chain lengths are varied for examining the properties including radial distribution functions, interfacial tension and thickness, and self-assembly morphologies. We find that when increasing the hydrophobic chain length, the critical micelle concentration decreases, and the oil molecules tend to penetrate into the space between two hydrophobic chains, causing nano-mixing phenomenon. This phenomenon is further enhanced when increasing the spacer length, and consequently, the oil–water interface gradually becomes curved and blurred due to the enhanced surfactant efficiency, and the system evolves from the lamellar interface state to micelle state. This work provides a theoretical basis for rational designing efficient Gemini surfactants.

Synthesis and Physicochemical Properties of CO2-switchable Gemini Surfactants

Conventional surfactants have excellent performance but not easily recycled and sustainable. The CO2/N2 switchable Gemini surfactants can be reused while maintaining performance and can also effectively utilize greenhouse gas CO2, thereby reducing carbon emissions. In our work, three tertiary amines N, N'-dimethyl N, N'-dialkyl ethylenediamine with different hydrophobic chain lengths (CnDEs, n = 12, 14, and 16) were fabricated by a two-step process using alkyl bromide, ethylenediamine, formic acid, and formaldehyde as raw materials. Structures of intermediates and end products were characterized by FTIR and 1H NMR. The Gemini surfactants such as N,N′-dimethyl N,N′-bis (dodecane, tetradecane, and hexadecane) alkylethylenediamine bicarbonates (CnDBs, n = 12, 14, and 16) were generated by the synthetic corresponding tertiary amines after bubbling CO2. After bubbling N2, the bicarbonate surfactants were converted into tertiary amine non-surfactants again. The reversibility of the switching of three surfactants was verified by measuring the changes in surface tension, zeta potential, particle size distribution, and foaming volume before and after CO2/N2 bubbled into the tertiary amine solutions. The physicochemical properties of CnDBs were studied by thermogravimetric analysis, surface tension measurement, cation content measurement, and dissipative particle dynamics (DPD). The results demonstrated that the synthesized CO2/N2 switchable Gemini surfactants had excellent reversibility and reproducibility. The application properties indicated that the Gemini surfactants could reduce interfacial tension of oil/water to ultra-low value; possessed good cation conversion rate and decent foaming properties. Furthermore, the surfactant performances were verified through DPD simulation experiments. With the industrialization of synthetic technology, the costs of CO2/N2 switchable Gemini surfactants will effectively decrease. Storage and utilization of considerable quantities carbon dioxide promote our green low-carbon life, which are conducive to the achievement of the national strategic goal of China's carbon peak in 2035 and carbon neutralization in 2050.

Self‐assembly of gemini amphiphiles with symmetric tails in selective solvent

AbstractGemini amphiphile is a special type of block copolymers formed by connecting two traditional diblock molecules at hydrophilic head groups through spacers. The special structure makes gemini amphiphiles potentially promising for drug delivery and gene delivery. The self‐assembly behavior of gemini amphiphiles with tails of equal length in selective solvent was investigated using the dissipative particle dynamics method. The effects of the size of the hydrophilic head group, interaction parameters, concentration and hydrophobic tail chain length on the self‐assembled morphology of gemini amphiphiles were examined. By varying these parameters, worm‐like micelles, large compound micelles, vesicles, hierarchical rod‐like micelles, cylindrical bundles, pomegranate‐like micelles and bilayers were obtained. Compared with conventional diblock copolymers, the dominant feature of gemini amphiphiles is the presence of the spacer. By analyzing the distance between two head groups, we explored in depth the influence of spacer length on the self‐assembly of gemini amphiphile molecules. Through simulation probes, we hope to improve the understanding of ordered aggregates of gemini amphiphiles in selective solvent, to reveal theoretically the pattern variation of aggregation morphology and to provide guidance for their practical application. © 2022 Society of Industrial Chemistry.

Synthesis and properties of ester functionalized cationic Gemini surfactants with amide groups

Abstract In this paper, a novel series of ester-functionalized cationic Gemini surfactants with amide groups (abbreviated as C m -(BAE)-C m (m = 12, 14, 16)) were synthesized and their surface tension as well as the thermodynamic surface parameters were determined with conductivity and fluorescence measurements, respectively. The structures of these Gemini surfactants were characterized by FT-IR, 1H NMR, and MS. The Krafft points of the three surfactants are below 0 °C, indicating better water solubility. The critical micelle concentration (CMC) of these surfactants decreases with the increase in the length of hydrophobic chain. The micellization process of these surfactants was found to be entropy-driven. The polar functional ester groups in the spacer form hydrogen bonds with water molecules, which increases the solubility of these Gemini surfactants in aqueous systems, facilitates the aggregation of their monomers and improves the stability of their micelles.

Molecular engineering of complexation between RNA and biodegradable cationic gemini surfactants: role of the hydrophobic chain length

The effects of the hydrophobic alkyl chain length of Cm-E2O-Cm gemini surfactants (m = 12, 14 and 16) on ribonucleic acid were investigated using different methods. The various calculated parameters revealed that complexation occurs via an intercalative binding mode.

Effect of Hydrophobic Chain Length on the Antioxidation Properties of Alanyl Tyrosine Dipeptide-type Surfactants.

The antioxidant (AOX) activities of alanyl tyrosine dipeptide-type surfactants with several chain lengths were investigated. The critical micelle concentration decreased exponentially with the carbon number of the hydrophobic chain of the surfactant. The antioxidative property was investigated using the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS) assay and the oxygen radical absorbance capacity (ORAC) assay. The AOX activity was found to be strongly dependent on the chain length in the monomer solution. Therefore, an increase in the molecular size negatively influenced the AOX ability of the tyrosine residue. However, it was almost independent of the chain length of the surfactant in the micellar solution. The micelle particles acted as a catalyst for the reduction of the radicals in the ORAC assay.

On the Effect of pH, Temperature, and Surfactant Structure on Bovine Serum Albumin-Cationic/Anionic/Nonionic Surfactants Interactions in Cacodylate Buffer-Fluorescence Quenching Studies Supported by UV Spectrophotometry and CD Spectroscopy.

Due to the fact that surfactant molecules are known to alter the structure (and consequently the function) of a protein, protein–surfactant interactions are very important in the biological, pharmaceutical, and cosmetic industries. Although there are numerous studies on the interactions of albumins with surfactants, the investigations are often performed at fixed environmental conditions and limited to separate surface-active agents and consequently do not present an appropriate comparison between their different types and structures. In the present paper, the interactions between selected cationic, anionic, and nonionic surfactants, namely hexadecylpyridinium chloride (CPC), hexadecyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), polyethylene glycol sorbitan monolaurate, monopalmitate, and monooleate (TWEEN 20, TWEEN 40, and TWEEN 80, respectively) with bovine serum albumin (BSA) were studied qualitatively and quantitatively in an aqueous solution (10 mM cacodylate buffer; pH 5.0 and 7.0) by steady-state fluorescence spectroscopy supported by UV spectrophotometry and CD spectroscopy. Since in the case of all studied systems, the fluorescence intensity of BSA decreased regularly and significantly under the action of the surfactants added, the fluorescence quenching mechanism was analyzed thoroughly with the use of the Stern–Volmer equation (and its modification) and attributed to the formation of BSA–surfactant complexes. The binding efficiency and mode of interactions were evaluated among others by the determination, comparison, and discussion of the values of binding (association) constants of the newly formed complexes and the corresponding thermodynamic parameters (ΔG, ΔH, ΔS). Furthermore, the influence of the structure of the chosen surfactants (charge of hydrophilic head and length of hydrophobic chain) as well as different environmental conditions (pH, temperature) on the binding mode and the strength of the interaction has been investigated and elucidated.

Two new cationic Gemini surfactants: synthesis, surface activity, and applicability as a corrosion inhibitor

Two novel cationic Gemini surfactants (2C n GeQS, n = 12, 18) was designed and prepared via amidation and quaternization reaction. The molecular structure of the 2C n GeQS was confirmed by FTIR, 1H NMR and elemental analysis. The critical micelle concentration (CMC) of aqueous solutions of these surfactants was determined by surface tension measurements, and the surface activity parameter, such as effectiveness (π CMC), efficiency (pC 20), critical micelle concentration (CMC), maximum surface excess (Г max), minimum surface area (A min), were obtained. The results showed that 2C n GeQS have a higher surface activity than conventional monomeric surfactant. The CMC decreases with an increment in hydrophobic chain length, however, the surface tension at the cmc (γ CMC) shows the opposite trend. The thermodynamic parameters indicate that both micellization and adsorption processes of 2C n GeQS were spontaneous. In addition, the results obtained from weight loss measurements show that 2C n GeQS exhibits a greater protective effect than that of DTAB; inhibition efficiency (ηw%) of 2C12GeQS, 2C18GeQS%, and DTAB is 95.6%, 96.86%, and 52.8% for A3 carbon steel at 1 × 10−3 M.

Fluorescently visualizing the penetration of anionic surfactants across cytoplasmic membrane and the subsequent damage on human cells.

The extensive application of chemically synthesized anionic surfactants would cause serious pollution of water and increase health risk to humans. However, the adverse impact of anionic surfactant on human cells has never been systematically demonstrated. In this paper, a series of fluorescent anionic surfactants containing a varying length of alkyl chain from C8 to C18 and a fixed hydrophilic head of 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) were synthesized and utilized for visualizing the interaction between surfactants and cells. The obtained molecules exhibited blue fluorescence presenting a decreasing fluorescent intensity with the increasing length of alkyl chain from C8 to C18 while showed the same sequence of HPTS-C16>HPTS-C18>HPTS-C12>HPTS-C8 on either surface activity, cellular adsorption, or cytotoxicity. In opposite, HPTS which contained no hydrophobic chain and thus exhibited no surface activity showed no cellular adsorption and cytotoxicity. It seems that the ligand of the appropriate chain length (C16) onto the hydrophilic HPTS molecules could cause the largest surface activity, the most distinguished cellular adsorption as well as the most adverse cytotoxicity. As reflected by the dynamic fluorescent visualization, the surfactant molecules of HPTS-C16 initially bound with cell membrane and entered into the intracellular lumen before finally localized at the endoplasmic reticulum (ER) and damaged it into a swollen structure. It is most likely that the structure of hydrophobic chain could determine the surface activities of surfactants and hence affect their cellular uptake and cytotoxicity. This study could help us to understand the adverse impact of anionic surfactant on human cells and its correlation with the surface activities or, in another word, the hydrophobic chain length.

Synthesis and properties of stellate lactosamide quaternary ammonium surfactants

A number of stellate lactosamide quaternary ammonium salt surfactants (N-dodecyl-N, N-bis[(3-lactosamide) propyl]-N-alkylamine bromide, C n DBLB, where n represents hydrocarbon chain lengths of 12,14 and 16) was successfully synthesized from lactobionic acid, N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, and bromoalkane by a two-step method comprising a proamine ester reaction and post-quaternization. The surface activity, adsorption, and aggregation behavior of the surfactants in aqueous solutions were investigated by dynamic/static surface tension, contact angle, dynamic light scattering, proton nuclear magnetic resonance spectroscopy, and transmission electron microscopy measurements. The results demonstrated that the equilibrium surface tension ( γ cmc ) of the C n DBLB surfactant was in the range of 28–35 mN/m; thus, it had a strong ability to reduce the surface tension of water. Furthermore, with increase in the carbon chain length of the surfactant, the saturated adsorption amount (Г max ) increased while A min decreased. However, the adsorption duration of C n DBLB was long, and rapid equilibrium could not be achieved on the surface of the solution, indicating a mixed kinetic adsorption mechanism. All three surfactants formed spherical micelles in aqueous solutions. Because the hydrophobic carbon chain length increased, the molecular structure complexity, steric hindrance, and hydrophobic group–water interaction (repulsion) increased, accounting for the unique aggregation behavior of C n DBLB in aqueous solutions. With increase in the concentration of the C 12 DBLB surfactant, the size of the aggregates formed increased. The sizes of the C 14 DBLB and C 16 DBLB aggregates increased initially, decreased, and subsequently increased again. Moreover, the morphology of molecular self-assembly was discussed. C n DBLB surfactant at low concentration was low toxicity or non-toxic, with the increase of concentration, its toxicity will also increase.

Role of chain length and electrolyte on the micellization of anionic fluorinated surfactants in water

The micellization of ionic surfactants in aqueous media reflects a balance between the hydrophobic attraction of surfactant tails and the electrostatic repulsion of surfactant headgroups. We investigate here the effect on surfactant micellization of the hydrophobic chain length and electrolyte composition, by focusing on the fluorinated surfactants sodium perfluorohexanoate (NaPFHx) and sodium perfluorooctanoate (NaPFO) in aqueous solution without/with NaCl, and analyzing experimental data from surface tension, pyrene fluorescence, small-angle neutron scattering (SANS), and viscosity techniques. The CMC of NaPFHx in water was 200 mM, much higher than that of NaPFO, 30 mM, due to the additional two -CF2- groups of the latter. Upon addition of 0.25 M NaCl to the aqueous solution, the CMC of NaPFHx and NaPFO decreased by about 50% and 80%, respectively. The NaPFHx and NaPFO micelles are both ellipsoid in shape. NaPFHx forms smaller micelles compared to NaPFO: the association number for NaPFHx in D2O was 15 compared to 25 for NaPFO. Upon NaCl addition, the micelle shape became more elongated. This is the first report on the NaPFHx micelle structure. The information presented here supports the re-formulation and replacement of long-chain fluorinated surfactants with relatively safer long-chain surfactants.

The physicochemical and fire extinguishing performance of aqueous film‐forming foams based on a class of short‐chain fluorinated surfactants

AbstractAqueous film‐forming foams (AFFFs) are an important for fire extinguishing, and their key ingredient is fluorinated surfactant. In recent years, traditional long‐chain fluorinated surfactants have been banned by most countries because of their persistence, bio‐accumulation and toxicity. Therefore, increased attention has been paid to the research and development of short‐chain fluorinated surfactants. As is well known, the introduction of hydrophilic or hydrophobic groups in a surfactant affects its surface activity, and therefore, the fire extinguishing performance of AFFFs. In this work, a series of short‐chain fluorosurfactant‐based AFFFs with different hydrophobic chain lengths were prepared. The physicochemical performance of mixed systems (fluorinated surfactant plus sodium hexanesulfonate), including surface activity, spreading ability, foam expansion, drainage time, and the fire extinguishing and burn‐back performance of AFFFs were studied. The results show that the critical micelle concentration (CMC) and the surface tension (γCMC) at the CMC of mixed systems at 25°C are lower than 7.68 mmol/L and 16.51 mN/m, respectively. For mixed systems, the average spreading rate is more than 1.09 cm/s, the foam expansion is over 7.1, and the drainage time is greater than 3.28 min. The fire extinguishing time of AFFFs on fuels is less than 51 s while the burn‐back time is more than 15.18 min. The results imply a potential application prospect of the short‐chain fluorinated surfactants in AFFFs.

Removal of uranium from contaminated groundwater using monorhamnolipids and ion flotation

Mining of uranium for defense-related purposes has left a substantial legacy of pollution that threatens human and environmental health. Contaminated waters in the arid southwest are of particular concern, as water resource demand and water scarcity issues become more pronounced. The development of remediation strategies to treat uranium impacted waters will become increasingly vital to meet future water needs. Ion flotation is one technology with the potential to address legacy uranium contamination. The green biosurfactant rhamnolipid has been shown to bind uranium and act as an effective collector in ion flotation. In this study, uranium contaminated groundwater (∼440 μg L−1 U) from the Monument Valley processing site in northeast Arizona was used as a model solution to test the uranium removal efficacy of ion flotation with biosynthetic (bio-mRL) and three synthetic monorhamnolipids with varying hydrophobic chain lengths: Rha-C10-C10, Rha-C12-C12, and Rha-C14-C14. At the groundwater's native pH 8, and at an adjusted pH 7, no uranium was removed from solution by any collector. However, at pH 6.5 bio-mRL and Rha-C10-C10 removed 239.2 μg L−1 and 242.4 μg L−1 of uranium, respectively. By further decreasing the pH to 5.5, bio-mRL was able to reduce the uranium concentration to near or below the Environmental Protection Agency maximum contaminant level of 30 μg L−1. For the Rha-C12-C12 and Rha-C14-C14 collector ligands, decreasing the pH to 7 or below reduced the foam stability and quantity, such that these collectors were not suitable for treating this groundwater. To contextualize the results, a geochemical analysis of the groundwater was conducted, and a consideration of uranium speciation is described. Based on this study, the efficacy of monorhamnolipid-based ion flotation in real world groundwater has been demonstrated with suitable solution conditions and collectors identified.

Preparation and performance evaluation of sulfate-quaternary ammonium Gemini surfactant

Sulfate-quaternary ammonium amphoteric Gemini surfactants with hydrophobic chains (C12ZGS, C14ZGS and C16ZGS) were prepared using formic acid, formaldehyde, long-chain tertiary amine, epichlorohydrin, chlorosulfone and NaOH. Their structures were characterized by IR and 1H NMR, and the synthesized target products was confirmed. The critical micelle concentrations (CMCs) of C12ZGS, C14ZGS and C16ZGS were 5.4 × 10−4 mol/L, 3.1 × 10−4 mol/L and 2.8 × 10−4 mol/L, respectively. Their corresponding surface tensions were 28.62 mN/m, 30.98 mN/m and 32.45 mN/m. It was found that the surface tension increases with increasing hydrophobic chain length. The three Gemini surfactants have good emulsifying and foaming properties for kerosene, and they have good solubility at low temperature. The results of thermogravimetric analysis (TGA) showed that the decomposition temperatures of C12ZGS, C14ZGS and C16ZGS were 153 °C, 157 °C and 150 °C, respectively. The salinity resistance of C12ZGS reached 4 × 104 mg/L, C14ZGS reached 5 × 104 mg/L, and the salinity resistance of C16ZGS was worst. C12ZGS and C14ZGS can reduce the oil–water interfacial tension to 10−2 orders of magnitude, but C16ZGS can only reduce it by 10−1 orders of magnitude. The stability of the surfactant flooding system was evaluated by aging time. Under the simulated reservoir formation environment, three amphoteric Gemini surfactants with different chain length (C12ZGS, C14ZGS, C16ZGS) can enhance oil recovery by 11.63%, 10.91% and 9.87% respectively.

Probing the helical stability in a VEGF-mimetic peptide

The analysis of the forces governing helix formation and stability in peptides and proteins has attracted considerable interest in order to shed light on folding mechanism. We analyzed the role of hydrophobic interaction, steric hindrance and chain length on i, i + 3 position in QK peptide, a VEGF mimetic helical peptide. We focused on position 10 of QK, occupied by a leucine, as previous studies highlighted the key role of the Leu7-Leu10 interaction in modulating the helix formation and inducing an unusual thermodynamic stability. Leu10 has been replaced by hydrophobic amino acids with different side-chain length, hydrophobicity and steric hindrance. Ten peptides were, hence, synthesized and analyzed combining circular dichroism, calorimetry and NMR spectroscopy. We found that helical content and thermal stability of peptide QK changed when Leu10 was replaced. Interestingly, we observed that the changes in the helical content and thermal stability were not always correlated and they depend on the type of interaction (strength and geometry) that could be established between Leu7 and the residue in position 10.

Effect of surfactant lengths on gas-liquid oxygen mass transfer from a single rising bubble

This work is an experimental investigation of the effect of the nature of surfactants on oxygen mass transfer. The study focuses on three cationic surfactants with different hydrophobic chain lengths, and four nonionic surfactants with different hydrophilic chain lengths. Equilibrium adsorption isotherms are calculated for each surfactant from experimental values of surface tension in static conditions. Surfactant solutions at concentrations between 2.5 × 10-8 and 5 × 10-3 mol/L were prepared and oxygen transfer from millimetric air bubbles (between 0.82 and 1.08 mm) was measured by Planar Laser Induced Fluorescence with Inhibition (PLIF-I). When the bulk concentration of surfactant was increased, results showed a sharp decrease of bubble velocity, in the range of 283–75 mm/s, and of liquid-side mass transfer coefficient, in the range of 5.6 × 10-4–0.4 × 10-4 m/s. This effect was observed for all surfactants studied. However, the length of the hydrophilic chain did not appear to affect the hydrodynamics of the rising bubble or the oxygen transfer at the same bulk concentration. Furthermore, for the same bulk concentration, increasing the hydrophobic chain length had an impact on the velocity and the mass transfer coefficient of oxygen. Finally, the Sherwood number was calculated in each medium and compared with classical correlations for gas–liquid mass transfer prediction. Those correlations seemed to reach a limit for a very concentrated medium.

Alkyl Chain Length in Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers Regulates the Delivery of Hydrophobic Molecules: A Case of the Biodistribution and the Photodynamic Activity of the Photosensitizer Hypericin.

Self-assembled nanostructures of amphiphilic gradient copoly(2-oxazoline)s have recently attracted attention as promising delivery systems for the effective delivery of hydrophobic anticancer drugs. In this study, we have investigated the effects of increasing hydrophobic side chain length on the self-assembly of gradient copolymers composed of 2-ethyl-2-oxazoline as the hydrophilic comonomer and various 2-(4-alkyloxyphenyl)-2-oxazolines as hydrophobic comonomers. We show that the size of the formed polymeric nanoparticles depends on the structure of the copolymers. Moreover, the stability and properties of the polymeric assembly can be affected by the loading of hypericin, a promising compound for photodiagnostics and photodynamic therapy (PDT). We have found the limitation that allows rapid or late release of hypericin from polymeric nanoparticles. The nanoparticles entering the cells by endocytosis decreased the hypericin-induced PDT, and the contribution of the passive process (diffusion) increased the probability of a stronger photoeffect. A study of fluorescence pharmacokinetics and biodistribution revealed differences in the release of hypericin from nanoparticles toward the quail chorioallantoic membrane, a preclinical model for in vivo studies, depending on the composition of polymeric nanoparticles. Photodamage induced by PDT in vivo well correlated with the in vitro results. All formulations studied succeeded in targeting hypericin at cancer cells. In conclusion, we demonstrated the promising potential of poly(2-oxazoline)-based gradient copolymers for effective drug delivery and sequential drug release needed for successful photodiagnostics and PDT in cancer therapy.

Synthesis and surface properties of amide-based amphoteric surfactants with different hydrophobic carbon chain length

Synthesis and surface properties of amide-based amphoteric surfactants with different hydrophobic carbon chain length

Decisive Influence of Hydrophobic Side Chains of Polyesters on Thermoinduced Gelation of Triblock Copolymer Aqueous Solutions

A series of amphiphilic triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone-co-5-alkyl δ-lactone)s bearing distinct alkyl side groups were synthesized via ring-opening copolymerization of ε-caprolactone and a small amount of various 5-alkyl δ-lactones using PEG as the macroinitiator and metal-free diphenyl phosphate as the catalyst. The analysis of 1H NMR, GPC, DSC, and XRD confirmed that the synthetic copolymers had similar molecular weights and bulk properties; nevertheless, they exhibited quite different aqueous behaviors in response to temperature variations. While the polyesters without side chains simply presented a free-flowing sol over the entire examined temperature range, those bearing methyl or n-propyl side groups underwent a sol–gel transition upon heating and harvested a reversed thermosensitive hydrogel (T-Gel). Meanwhile, the sol–gel transition temperature of the polymer/water system could be easily tailored by adjusting the content of the n-propyl side group. In contrast, the polyesters containing longer n-amyl side groups formed a normal hydrogel (N-Gel) exhibiting a gel–sol (suspension) transition upon heating. Their different aqueous behaviors stemmed from the difference in the hydrophilic–hydrophobic equilibrium of the amphiphilic copolymers. The sol–gel transitions of the thermosensitive hydrogels were attributed to the aggregation of micelles and the dehydration of PEG. The copolymers bearing n-propyl side groups had good cytocompatibility and were fairly stable in a phosphate buffered saline for 80 days, whereas the formed thermosensitive hydrogel (20 wt %) was rapidly degraded via surface erosion within half a month after subcutaneous injection into mice. Consequently, this study indicates that subtle variation in the length of hydrophobic side chains plays a decisive role in the physical gelation of PEG/polyester copolymers. In addition, the thermosensitive hydrogels have the potential for drug and cell delivery based on their good biocompatibility and biodegradability.