Glycol Units Research Articles

Novel thermoresponsive homopolymers of poly[oligo(ethylene glycol) (acyloxy) methacrylate]s: LCST-type transition in water and UCST-type transition in alcohols

The study of thermoresponsive homopolymers has attracted great attention due to their broad application value. Herein, a series of novel thermoresponsive homopolymers of poly[oligo(ethylene glycol) (acyloxy) methacrylate]s containing oligo(ethylene glycol) (OEG) units and substituent groups of ester have been designed and prepared by RAFT polymerization. The solution properties of these polymers have been investigated in detail, which indicate that most of them exhibit lower critical solution temperature (LCST) in water and upper critical solution temperature (UCST) in alcohols, and their LCST-type or UCST-type cloud point temperature (TCPL or TCPU) is closely related to the OEG units and ester groups. Furthermore, the parameters affecting the thermoresponse of these polymers including polymerization degree (DP) and concentration have also been investigated. The present work not only discovers a series of novel thermoresponsive polymers, but also has certain guiding significance on the understanding of molecular structure and thermoresponsive property relationships, which is useful for the design of new thermosensitive polymers.

Engineered Ovalbumin Nanoparticles for Cancer Immunotherapy

AbstractOvalbumin (OVA) is a protein antigen that is widely used for eliciting cellular and humoral immune responses in cancer immunotherapy. As an alternative to solute OVA, engineering approach is developed herein towards protein nanoparticles (pNPs) based on reactive electrospraying. The resulting pNPs are comprised of polymerized OVA, where individual OVA molecules are chemically linked via poly(ethylene glycol) (PEG) units. Controlling the PEG/OVA ratio allows for fine‐tuning of critical physical properties, such as particle size, elasticity, and, at the molecular level, mesh size. As the PEG/OVA ratio decreased, OVA pNPs are more effectively processed by dendritic cells, resulting in higher OT‐I CD8+ cells proliferation in vitro. Moreover, pNPs with lower PEG/OVA ratios elicit enhanced lymphatic drainage in vivo and increased uptake by lymph node macrophages, dendritic cells, and B cells, while 500 nm OVA pNPs show poor draining lymph nodes delivery. In addition, pNPs with lower PEG/OVA ratios result in higher anti‐OVA antibody titers in vivo, suggesting improved humoral immune responses. Importantly, OVA pNPs result in significantly increased median survival relative to solute OVA antigen in a mouse model of B16F10‐OVA melanoma. This work demonstrates that precisely engineered OVA pNPs can improve the overall anti‐tumor response compared to solute antigen.

Thermoresponsive Nanogels from Dendronized Copolymers for Complexation, Protection and Release of Nucleic Acids

A series of thermoresponsive cationic dendronized copolymers and their corresponding nanogels containing dendritic oligoethylene glycol (OEG) units and guanidine groups were prepared, and their complexation, protection, and release of nucleic acids were investigated. The dendritic OEGs endow these copolymer materials with good biocompatibility and characteristic thermoresponsiveness, while cationic guanidine groups can efficiently bind with the nucleic acids. The dendritic topology also affords the copolymers specific shielding effect which plays an essential role in protecting the activity of nucleic acids. At room temperature, dendronized copolymers and the corresponding nanogels could efficiently capture and condense the nucleic acids, while above their cloud points (Tcps), more than 75% of siRNA could be released in 1 h triggered by ATP. More importantly, the copolymer showed protective capability to siRNA, while nanogels exhibit even better protection when compared to the copolymers due to the synergetic effect from the three-dimensional cross-linked network and high density of dendritic units in vicinity. This kind of smart dendronized copolymer nanogels form a novel class of scaffolds as promising materials for biomedical applications.

Development of Neutral pH-Responsive Microgels by Tuning Cross-Linking Conditions.

Polymer microgels that respond in a range of neutral pH can be useful for the development of molecular imaging tools and drug-delivery carriers. Here, we describe a simple approach in developing microgels that undergo volume phase transitions and substantial nuclear magnetic resonance (NMR) relaxometric changes within a narrow pH range of 6.4 to 7.4. The pH-responsive microgels were synthesized using methacrylic acid and a series of ethylene glycol dimethacrylate cross-linkers with repeating units of ethylene glycol that range from one to four. NMR relaxometry demonstrated that the transverse relaxation time (T2) of a suspension containing microgels that were cross-linked with diethylene glycol dimethacrylate sharply decreases at the pH where volume phase transition occurs. The polymer microgels cross-linked with 40 and 45 mol% of diethylene glycol dimethacrylate caused about 50% T2 reduction with decreasing pH from 6.8 to 6.4. These results demonstrated that responses of microgels to a range of neutral pH can be easily tuned by using appropriate cross-linkers with certain cross-linking degree. This approach can be useful in developing highly sensitive molecular sensors for magnetic resonance imaging (MRI) of tissue pH values.

Sol–Gel Transitions of Comb‐Like Polymethacrylate Copolymers by Mechano‐Thermal Stimuli in Water

AbstractSonogelation by supramolecular gelators is highlighted as a paradigm shift for their potential applications in material and biomedical sciences. Yet, these materials require organic solvents and low‐frequency ultrasound, limiting their utility. Here, a comb‐like polymethacrylate copolymer is synthesized with 2,6‐bis(1‐methylbenzimidazolyl)‐4‐oxypyridine tridentate ligand randomly distributed on poly(ethylene glycol) side chains. Upon addition of zinc perchlorate salt, this copolymer rapidly forms a hydrogel after exposure to either mechanical (i.e., ultrasound) or thermal stimuli. Spectroscopic analysis, to elucidate the mechanism, indicates metal ion coordination to ligand as well as the carbonyl and ethylene glycol units; interestingly, 1H‐NMR suggests that the coordination between tridentate ligand moiety and Zn2+ is unexpectedly weaker in water than in acetonitrile. Investigations by dynamic light scattering indicates that the copolymer forms nanodispersions in excess salt, which coalesces to form a hydrogel by either heating or high intensity focused ultrasound (HIFU). Rheological quantification of these gels suggests stronger crosslinking by HIFU compared to heating.

Estimation of Solubility of BTEX, Light Hydrocarbons and Sour Gases in Triethylene Glycol Using the SAFT Equation of State

An accurate prediction of the absorption and desorption of Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX) is important for the estimation of BTEX emissions from glycol units in natural gas processing plants. This work presents an approach to accurately model the solubilities of BTEX in triethylene glycol (TEG). The absorption of gases studied in this work into TEG is physical in nature, and therefore is treated as physisorption in modeling. The Huang-Radosz version of Statistical Associating Fluid Theory (SAFT-HR) Equation of State (EoS) was utilized to estimate the solubilities of BTEX in TEG. A new set of SAFT parameters for TEG, as well as a new set of binary interaction parameters between TEG and other components were obtained by fitting experimental vapor pressure and liquid density of TEG and available experimental binary VLE data, respectively. Using these parameters, solubility of multicomponent gases in TEG are accurately predicted. To have an estimate of the relative accuracy of SAFT-HR EoS, the results from Perturbed–Chain SAFT (PC–SAFT) and Peng–Robinson (PR) EoS are also reported. The overall average of root–mean–square deviation (RMSD) for binary and ternary systems studied in this work, using SAFT-HR, PC–SAFT, and PR EoS obtained equal to 0.12, 0.20, and 1.56, respectively.

Shell and CNOOC expand China venture

Shell and China National Offshore Oil Corp. (CNOOC) have agreed to expand their petrochemical joint venture in Huizhou, China. The project will include a 1.5 million-metric-ton-per-year ethylene cracker, as well as styrene, propylene oxide, polyols, ethylene glycol, polyethylene, and polypropylene units. The new complex will also include the first α-olefins plant in Asia to use Shell technology. The two companies started the joint venture in 2006 and expanded it in 2018. Its ethylene capacity is now 2.2 million metric tons.

Swelling properties and drug release of new biocompatible POEGOPGMA hydrogels with VPTT near to the human body temperature

Oligo (ethylene glycol) oligo (propylene glycol) methacrylates (OEGOPGMA) with different numbers of ethylene glycol (EG) and propylene glycol (PG) units in backbone were used for the preparation of new thermoresponsive POEGOPGMA hydrogels; EG6PG3MA and EG3PG6MA monomers were used; and three different POEGOPGMA hydrogels (PEG6PG3MA, PEG3PG6MA and P(EG6PG3/EG3PG6)MA copolymer with equal mol% of previous two) were fabricated from monomer–solvent (OEGOPGMA–water/ethanol) mixture by gamma radiation. Characterisation of the hydrogels was conducted by swelling, UV–Vis, scanning electron microscope, differential scanning calorimetry and in vitro biocompatibility (cytocompatibility and haemolytic activity) investigations. The modelling of drug release and diffusion characteristics was tested using cephalexin drug. For the first time, it was shown how to effectively tune the volume phase transition temperature (VPTT) values of the hydrogels by changing the ratio of more hydrophilic (EG) and more hydrophobic (PG) units in (EGPG) “block” pendant chains. The obtained hydrogels revealed the great potential for different biomedical applications not only due to the possibility to tune VPTT in the desired way but also due to the good biocompatibility and controlled drug delivery within the target temperature range.

Modification of silicon nitride with oligo(ethylene glycol)-terminated organophosphonate monolayers

Due to its unique properties, silicon nitride has found a wide variety of applications in nanodevice fabrication and biosensing. Self-assembled monolayers of phosphonic acids (SAMPs) can be applied to prepare well-defined organic interfaces suitable to anchor bioreceptor probes with a high surface density on different substrates. In this work, we report on the fabrication of SAMPs functional interfaces on silicon nitride. By using several surface analysis techniques, including contact angle (CA) measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS), we present a detailed characterization of the morphology, composition, and stability of the functional interface. In addition, we investigate the protective properties of organophosphonate functional interfaces containing only a few ethylene glycol (EG) units per SAMPs building block against non-specific surface binding of charged biomolecules by means of fluorescence spectroscopy.

Synthesis, characterization, and photophysical properties of paraben substituted cyclotriphosphazenes with hydrophilic side groups

In this study, five new paraben substituted cyclotriphosphazene compounds containing hydrophilic glycol groups were successfully synthesized. All synthesized cyclotriphosphazene compounds 1-10 were fully characterized via general spectroscopic techniques such as 1H, 31P NMR and MALDI-TOF mass spectrometry. In addition, the investigations of the UV-vis absorption and fluorescence emission properties of the 1-10 carried out via absorption and fluorescence spectroscopies in different solvents. The absorbance bands of the all synthesized compounds 1-10 were observed at about 230–300 nm in all solvents studied. Furthermore, the highest fluorescence emission intensity of the compounds 1-10 was observed in tetrahydrofuran at about 312 nm and the lowest emission intensity was observed in chloroform. The synthesized molecules can be used as custom designed molecules to investigate the DNA binding properties in automatic biosensor device in our laboratories, since they carry hydrophilic glycol units for water solubility and paraben derivatives for DNA effecting properties.

Synthesis and cancer cell growth inhibition effects of acetogenin analogs bearing ethylene glycol units for enhancing the water solubility

The syntheses of three thiophene-3-carboxamide analogs of annonaceous acetogenins were accomplished, where the obtained analogs bear ethylene glycol units that enhance their water solubilities. Evaluation of their growth inhibitory activities across 39 human cancer cell lines revealed that the analog bearing one ethylene glycol unit in the vicinity of its tetrahydrofuran ring moiety exhibited a comparable potent growth inhibitory activity to the lead compound, and the growth inhibitory patterns of these analogs are similar to those of mitochondrial complex I inhibitors. This result indicates the possibility of discovering new water-soluble antitumor agents derived from acetogenins through the introduction of ethylene glycol units.

Investigation of ring‐opening polymerization of 5‐[2‐{2‐(2‐methoxyethoxy)ethoxy}‐ethoxymethyl]‐5‐methyl‐1,3‐dioxa‐2‐one by organometallic catalysts

ABSTRACTTo develop new polymer‐based materials, the design of aliphatic carbonate has received attention and become a well‐known cyclic monomer. In view of carbonate ring polymer scope, poly(trimethylene carbonate) (PTMC) has been continuously developed for further applications due to its unique degradability. PTMC bearing oligo ethylene glycol units, PTMCM‐MOE3OM, were typically prepared via ring‐opening polymerization (ROP) using amidine‐based catalysts such as 1,8‐diazabicyclo[5.4.0] undec‐7‐ene (DBU) and benzyl alcohol (BnOH) as an initiator. To improve the polymer molecular weight or other properties, several know‐how synthetic catalysts based on organometallic complexes are under consideration as potential catalysts. With the existence of diverse classes of metallic complexes, the inorganic complexes were investigated for their catalytic activity based on tris(dimethylsilyl)amido chelating, bis(phenolate) chelating, and macrocyclic tetradentate (NNNN)‐type cyclen chelating with a metal‐core of tin (II), scandium (III), lutetium (III), and zinc (II). In this study, we found that involving a Zn(II) dimethylcyclen/alkoxide ligand and Mg complexes could accelerate the reaction and finish the polymerization under ambient conditions within 2 hr. Molecular weight reached 11,000 g/mol (40%) and 8,100 g/mol (> 96%). Subsequently, we concluded that Zn and Mg complexes were high reactivity for initiating the ROP of TMCM‐MOE3OM upon steadily degree of polymerization.

Nonionic Isatin Surfactants: Synthesis, Quantum Chemical Calculations, ADMET and Their Antimicrobial Activities

AbstractThe most challenge task in the building up of surface‐active molecules is maximizing their surface activity with good biological activity. A nonionic surfactant (N‐isatin‐EO m‐C n where m is 5, 7 and 9 ethylene glycol units and n is 8, 10 and 12) is achieved by first reacting isatin with chloroacetic acid and then with different types of ethoxylated (C8–C12) fatty alcohols that possess 5, 7 and 9 ethylene oxide units. The prepared surfactants were characterized by FTIR and 1H NMR to confirm the structure. The surface activity, biodegradability, antimicrobial, and antifungal activity of the surfactants were evaluated. In addition, quantum chemical calculations and computations of oral bioavailability were performed. The obtained data show that all the synthesized compounds had good surface activity, biodegradability and biological activity.

Polyethylene Glycol 35 (PEG35) Protects against Inflammation in Experimental Acute Necrotizing Pancreatitis and Associated Lung Injury.

Acute pancreatitis is an inflammatory disorder of the pancreas. Its presentation ranges from self-limiting disease to acute necrotizing pancreatitis (ANP) with multiorgan failure and a high mortality. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic, and water-soluble chemicals composed of repeating units of ethylene glycol. The present article explores the effect of PEG35 administration on reducing the severity of ANP and associated lung injury. ANP was induced by injection of 5% sodium taurocholate into the biliopancreatic duct. PEG35 was administered intravenously either prophylactically or therapeutically. Three hours after ANP induction, pancreas and lung tissue samples and blood were collected and ANP severity was assessed. To evaluate the inflammatory response, gene expression of pro-inflammatory cytokines and chemokine and the changes in the presence of myeloperoxidase and adhesion molecule levels were determined in both the pancreas and the lung. To evaluate cell death, lactate dehydrogenase (LDH) activity and apoptotic cleaved caspase-3 localization were determined in plasma and in both the pancreatic and lung tissue respectively. ANP-associated local and systemic inflammatory processes were reduced when PEG35 was administered prophylactically. PEG35 pre-treatment also protected against acute pancreatitis-associated cell death. Notably, the therapeutic administration of PEG35 significantly decreased associated lung injury, even when the pancreatic lesion was equivalent to that in the untreated ANP-induced group. Our results support a protective role of PEG35 against the ANP-associated inflammatory process and identify PEG35 as a promising tool for the treatment of the potentially lethal complications of the disease.

Separation performance of a new triptycene-based stationary phase with polyethylene glycol units and its application to analysis of the essential oil of Osmanthus fragrans Lour

This work presents a new triptycene-based stationary phase (TP-PEG) combining the three-dimensional (3D) triptycene (TP) framework with polyethylene glycol (PEG) moieties for gas chromatographic (GC) separations. Its statically coated capillary column showed high column efficiency of 5263 plates/m determined by naphthalene at 120 °C. Its Rohrschneider-McReynolds constants and Abraham solvation system constants were measured to characterize its polarity and molecular interactions with analytes of different types. As evidenced, the TP-PEG column showed high-resolution performance for the isomers of anilines, phenols, halobenzenes and alkanes with distinct advantages over the PEG columns, particularly those critical isomers such as 3,5-/2,3-xylidine (R = 2.94), m-/p-chlorotoluene (R = 1.92), p-/m-cresol (R = 1.89), 2,2-dimethylbutane/2-methylpentane (R = 1.51), 2,2,3-trimethylbutane /2,3-dimethyl pentane (R = 1.74) and 2,3-dimethylpentane/n-heptane (R = 1.92). In addition, it exhibited good column repeatability and reproducibility with the relative standard deviation (RSD) values of 0.02%–0.09% for run-to-run, 0.13%–0.22% for day-to-day and 2.7%–4.1% for column-to-column, respectively, and a wide operational temperature range (30 °C–280 °C) . Its application to GC–MS analysis of the essential oil of Osmanthus fragrans has proven its good potential for practical analysis of complex samples.

Synthesis of New Flexible Coumarin Dimers for Sodium and Potassium Differentiation.

Using fluorescence to detect biologically relevant metals has been studied extensively due to its rapid and low detection limit ability. Sodium and potassium differentiation is significant in diagnosis of many medical conditions. For this, we designed coumarin dimers as flexible fluorescent probes using ethylene glycol units for differentiation of sodium and potassium. To our best knowledge, use of these easy-to-synthesize coumarin dimers linked through ethylene glycol units are first in the literature. In fluorescence titration experiments, diethylene glycol linked coumarin-3-carboxylate dimer is responsive for sodium ions but not for potassium ions. The driving force for the complexation of metal cation and fluorescence probes is thought to be size-matching. To further explain the phenomenon, we synthesized coumarin dimer using 1,8- octanediol as the linker, and methyl ester of coumarin-3-carboxylic acid to investigate the effect of structural changes on the fluorescence intensity. These two compounds could not differentiate the sodium and potassium. Flexible coumarin dimers as fluorophores are shown to be useful for sensing sodium cation in the presence of potassium cation.

Amphiphilic ligand modified gold nanocarriers to amplify lanthanide loading for ultrasensitive DELFIA detection of Cronobacter.

Conventional dissociation-enhanced lanthanide (Ln3+) fluoroimmunoassays (DELFIAs) using Ln3+ chelate-labeled antibodies as molecular probes exhibit limited sensitivity because of their relatively low Ln3+ labeling ratio per biomolecule. Herein, we applied gold nanoflowers (AuNFs) as amplified nanocarriers to increase the Ln3+ labeling ratio in a single molecular binding event for improving the sensitivity of traditional DELFIA. Two thiolated amphiphilic ligands (thiolated ethylenediaminetetraacetic acid (EDTA) and thiolated acylhydrazine-terminated ligands), consisting of a hydrophobic alkane chain, oligo(ethylene glycol) unit, and functional terminal of the EDTA or acylhydrazine group, were designed for the surface modification of AuNFs. The resultant ligand-coated AuNFs exhibited dual functions of Ln3+ chelation via the EDTA group and oriented attachment of antibodies via the acylhydrazine group. By utilizing 80 nm AuNFs as amplified carriers, we demonstrated that the maximum Eu3+ loading amount reached 1.07 × 104 Eu3+ ions per AuNF, which is approximately two to three orders of magnitude higher than that of traditional molecular probes, thereby amplifying the luminescence signal and enhancing the sensitivity of DELFIA. By combining a magnetic-mediated sandwich-type DELFIA method, the designed amplified AuNF nanoprobes achieved an ultrasensitive luminescence detection of Cronobacter muytjensii with a limit of detection (LOD) of 1.2 × 102 cfu mL-1 in a powdered infant formula. This LOD value was ca. 230-fold lower than that of the traditional colorimetric immunoassay. The designed signal amplification strategy using bifunctional ligand-modified AuNFs as enhanced Ln3+ nanocarriers provided a huge potential for building various ultrasensitive luminescence immunoassays for in vitro biodetection.

Synthesis and Thermoresponsive Properties of Biocompatible and Biodegradable Triblock Copolymers Bearing Linear or Y‐Shaped OEG Pendants

AbstractBiocompatible and biodegradable thermoresponsive polymers are of great interest in “smart” biomedical applications. Herein, triblock copolymers (6a and 6b) comprised of hydrophobic poly(propylene glycol) (PPG) and OEGylated polypeptides bearing Y‐shaped or linear pendants are prepared by ring‐opening polymerization of reactive N‐carboxyanhydride monomers and subsequent side chain modification of polypeptides. OEGylated triblock copolymer bearing Y‐shaped (6a) or linear pendants (6b) with similar main chain length and the same amount of oligo(ethylene glycol) (OEG) units are successfully prepared as verified by 1H NMR, FTIR, and GPC. CD analysis reveals that 6a with Y‐shaped OEG pendants shows thermal‐ or salt‐induced destabilization of α‐helical conformation in water. Both 6a and 6b show reversible lower critical solution temperature (LCST)‐type phase transitions in DI H2O or PBS. Incorporation of a PPG segment leads to a significant decrease of the LCST‐type cloud point temperature (Tcp). Consequently, 6a and 6b show Tcp to human body temperature at low polymer concentrations (≤0.5 mg mL−1 in PBS). Moreover, 6a and 6b show low in vitro cytotoxicity and biodegradability in the presence of proteinase K. The results indicate that the thermoresponsive properties of LCST‐type polymers can be readily tuned by constructing Y‐shaped pendants as well as incorporation of hydrophobic polymer building blocks.

Development of novel aromatic ambidextrous gelators based on molecular design

Although large amounts of organogelators and hydrogelators have been available, the ambidextrous gelators that can gelate both organic solvents, especially, apolar solvents and water are very limited. Furthermore, most of them have been found out incidentally. In order to create powerful ambidextrous gelators it should be necessary to tackle a bottom-up approach based on organic synthesis. Thus, according to molecular design the amphiphilic aromatic compounds consisting of glutamate- or aspartate-based structure having two long alkyl chains and some ethylene glycol units have been prepared. The glutamate-based amphiphilic compounds having one ethylene glycol unit or two ethylene glycol units exhibited an excellent ambidextrous capability because they can only gelate benzene, toluene and water, however, introduction of three ethylene glycol units prevented gelating water. On the other hand the corresponding aspartate-based amphiphilic compound showed no such ambidextrous properties.

Monitoring the encapsulation of chlorin e6 derivatives into polymer carriers by NMR spectroscopy

The encapsulation of five derivatives of chlorin e6 with different hydrophobicity and aggregation properties into a series of five poloxamer-type triblock copolymer micelles (BCMs) with varying numbers of polyethylene and polypropylene glycol (PEG, PPG) units was monitored using 1H NMR spectroscopy. NMR chemical shift and line shape analysis, as well as dynamic methods including diffusion ordered spectroscopy (DOSY) and T1 and T2 relaxation time measurements of the chlorin and the polymer resonances, proved useful to assess the chlorin–BCM compatibility. The poloxamers had high capability to break up aggregates formed by chlorins up to intermediate hydrophobicity. Physically entrapped chlorins were always localized in the BCM core region. The loading capacity correlated with chlorin polarity for all poloxamers among which those with the lowest number of PPG units were most efficient. DOSY data revealed that relatively weakly aggregating chlorins partition between the aqueous bulk and micellar environment whereas more hydrophobic chlorins are well retained in the BCM core region, rendering these systems more stable. T1 and T2 relaxation time measurements indicated that motional freedom in the BCM core region contributes to encapsulation efficiency. The BCM corona dynamics were rather insensitive towards chlorin entrapment except for the poloxamers with short PEG chains. The presented data demonstrate that 1H NMR spectroscopy is a powerful complementary tool for probing the compatibility of porphyrinic compounds with polymeric carriers such as poloxamer BCMs, which is a prerequisite in the development of stable and highly efficient drug delivery systems suitable for medical applications like photodynamic therapy of tumors.