Ester End Groups Research Articles

Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen

In situ forming implants are appealing long-acting dosage forms for both preclinical and clinical applications due to their simple manufacturing process and easy delivery. This study aims to develop extended-release in situ forming solid implants for subcutaneous administration using two types of commercially available triblock poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) polymers, with either an acid or ester end group. Both types of polymers instantly form in situ implants when injected directly into an aqueous medium. The performance of these implants, containing a model compound ketoprofen, was evaluated by comparing the in vitro drug release profiles with the in vivo performance following subcutaneous administration in rats. Analytical characterizations of two representative in situ implants were conducted to understand their structural impact on polymer degradation and drug release. All tested in situ forming implants demonstrated prolonged drug release profiles both in vitro and in vivo. This study illustrates the successful preparation of sustained-release in situ forming implant formulations for ketoprofen using commercially available polymers, with the molecular weight and the end group of the polymers affecting their degradation and the drug release from the in situ formed implants.

Measuring Erosion of Biodegradable Polymers in Brimonidine Drug Delivery Implants by Quantitative Proton NMR Spectroscopy (q-HNMR)

Erosion of biodegradable polymeric excipients, such as polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), is generally characterized by microbalance for the remaining mass of PLA and/or PLGA and Gel Permeation Chromatography (GPC) for molecular weight (MW) decrease. For polymer erosion studies of intravitreal sustained release brimonidine implants, however, both microbalance and GPC present several challenges. Mass loss measurement by microbalance does not have specificity for excipient polymers and drug substances. Accuracy of the remaining mass by weighing could also be low due to sample mass loss through retrieval-drying steps, especially at later drug release (DR) time points. When measuring the decrease of polymer MW by GPC, trace amounts of polymeric degradants (oligomers and/or monomers) trapped inside the implants during DR tests may not be measurable due to sensitivity limitations of the GPC detector and column MW range. Previous efforts to measure remained PLGA weight of dexamethasone micro-implants using qNMR with external calibration have been performed, however, these measurements do not account for chemical structure changes (i.e. LA to GA ratio changes from time zero) of PLGA implants during drug release tests. Here, a qNMR method with an internal standard was developed to monitor the following changes in micro-implants during drug release tests: 1. The remaining overall PLA/PLGA mass. 2. The remaining lactic acid (LA), glycolic acid (GA) unit and PLGA's lauryl ester end group percentages. 3. The trace content of PLA/PLGA oligomers as degradants retained in the implants. Unlike microbalance analysis, qNMR has both specificity for drug substance, excipient polymer, and accuracy due to minimal implant loss during sample preparation. Compared to the overall PLA/PLGA remaining mass generally monitored in erosion studies, the percentage of remaining LA, GA, and the ester end group provide more information about the microstructure change (such as hydrophobicity) of PLA/PLGA. Additionally, the qNMR method can complement GPC methods by measuring the change of remaining PLA and PLGA oligomer concentrations in brimonidine implants, with tenfold less sample and no MW cutoff. The qNMR method can be used as a sensitive tool for both polymer excipient characterization and kinetics studies of brimonidine implant erosion.

Oxidative Carboxylation of Lignin: Exploring Reactivity of Different Lignin Types.

The increased interest in the utilization of lignin in biobased applications is evident from the rise in lignin valorization studies. The present study explores the responsiveness of lignin toward oxidative valorization using acetic acid and hydrogen peroxide. The pristine lignins and their oxidized equivalents were analyzed comprehensively using NMR and SEC. The study revealed ring opening of phenolic rings yielding muconic acid- and ester-end groups and side-chain oxidations of the benzylic hydroxyls. Syringyl units were more responsive to these reactions than guaiacyl units. The high selectivity of the reaction yielded oligomeric oxidation products with a narrower dispersity than pristine lignins. Mild alkaline hydrolysis of methyl esters enhanced the carboxylic acid content of oxidized lignin, presenting the potential to adjust the carboxylic acid content of lignin. While oxidation reactions in lignin valorization are well documented, this study showed the feasibility of employing optimized oxidation conditions to engineer tailored lignin-based material precursors.

Transformation of poly(l-lactide) crystals composed of linear chains into crystals composed of cycles

A poly(l-lactide) with a trifluoro ethyl ester end group and an average degree of polymerization (DP) of 50 was synthesized by ROP of l-lactide initiated with trifluoroethanol.

Design and synthesis of acyclic bis-triazole ligands: Complexation with metal ions, DFT calculations, and biological activity

Triazole-derived heterocyclic compounds have significant biological activities and pharmaceutical stability. A new series of acyclic bis-triazole ligands 16–20 with ester end groups were designed. The synthesized ligands were evaluated for their complexation ability with transition metals (Cu2+, Hg2+, Pb2+, and Zn2+). The molar conductivity of bis-1,2,3-triazole ligand-metal complexes was measured in acetonitrile at a temperature range 288.15–308.15 K. Furthermore, the thermodynamic quantities (∆H°, ∆S°, and ∆G°) were determined using the van't Hoff equation and the computational stability constants of the resulting 1:1 complexes were determined based on 1:1 stoichiometry. Meanwhile, the optimized geometry of ligands and ligand-metal complexes was computationally calculated using density fraction theory (DFT). Moreover, the antioxidant potential, in DPPH and ABTS assays, as well as the antibacterial activity of the bis-1,2,3-triazole ligands were evaluated. Ligands 16, 19, and 20 complexed with Hg2+ as well as ligand 17 with Cu2+, Hg2+, and Pb2+ showed a continuous decrease in molar conductivity on complexation, however, ligand 18 complexed with Cu2+, Hg2+, Pb2+, and Zn2+ begins to level off at a mole ratio of 1:1 (ligand:metal) indicating the formation of stable complexes. Noteworthy, ligand 17 formed a 1:2 and 2:1 ligand-to-metal ratio with Hg2+ and Pb+2 cations, respectively. The formation reactions of all ligand-metal complexes were exothermic and spontaneous indicating a strong triazole-metal interaction based on ∆H° and ∆G° values. Bis-triazole ligands 16–20 revealed antioxidant activity with IC50 values ranging from 89.0 to 156.1 µg/ml in DPPH and 91.3–167.2 µg/ml in ABTS assays. Ligands 16–19 exhibited antibacterial activity against the Gram-positive Bacillus cereus with MICs ranging from 150 to 250 µg/ml. The synthesized bis-triazole ligands have a potential application in the pharmaceutical and food industries. Moreover, the selectivity of ligands 16, 19, and 20 to Hg2+ could be useful for removing such a metal from industrial wastewater containing a variety of toxic heavy metals and ISE construct.

In vitro and in vivo evaluation of immune response of poly(lactic acid) nanoparticles with different end groups

Poly(lactic acid) (PLA) has excellent properties of biodegradability and biocompatibility, which is a US Food and Drug Administration (FDA) approved biopolymer for the preparation of safe and effective vaccines, drugs, and gene delivery systems. However, there still exists a great problem whether and how the end group affects the immune response of PLA vaccines. Therefore, the aim of this study was to evaluate the in vitro and in vivo of immune response of PLA nanoparticles (NPs) with carboxyl (COOH) and ester (COOR) end groups. In vitro experiments suggested COOH NPs could promote the higher phagocytosis and activation of bone marrow dendritic cells (BMDCs) with a lower cytotoxicity. In vivo experiments showed that COOR NPs and COOH NPs could strongly elicit IgG, IgG1, and IgG2a responses both in the short and long-terms. However, the highest T cell and B cell activation, and central memory T cells response was induced by COOH NPs. In addition, the COOH NPs could significantly enhance splenocytes proliferation and cytokines secretion. Thus, the PLA with the COOH end group shows greater potential as efficient carrier materials of NPs for enhancing cellular and humoral immune responses.

PLGA implants for controlled dexamethasone delivery: Impact of the polymer chemistry

The aim of this study was to better understand the impact of the chemistry of poly(lactic-co-glycolic acid) (PLGA) polymers on the resulting drug release kinetics from implants prepared by melting and molding. Dexamethasone was incorporated as the drug. The polymer molecular weight of the PLGA, lactic acid:glycolic acid ratio and type of end groups (ester versus free acid) were varied. The implants were characterized using optical macroscopy, SEM, X-ray powder diffraction, DSC, gravimetric monitoring of dynamic changes in the systems’ dry and wet mass upon exposure to the release medium as well as drug release and pH measurements. Interestingly, the shape of the drug release profiles was similar in all cases: No noteworthy burst effect was observed. Dexamethasone release set on after a lag time, the length of which strongly depended on the PLGA chemistry: The lag time decreased with decreasing polymer molecular weight, increasing glycolic acid content and was shorter for –COOH end groups compared to ester end groups. In all cases, drug release set on as soon as a critical hydrophilicity and polymer molecular weight were reached and substantial system swelling started: The penetration of large amounts of water into the implants allowed for complete dexamethasone dissolution and relatively rapid diffusion of the dissolved drug molecules through a highly swollen PLGA gel up to 100% drug release.

Dual Function of β-Hydroxy Dithiocinnamic Esters: RAFT Agent and Ligand for Metal Complexation.

The reversible addition-fragmentation chain-transfer (RAFT) process has become a versatile tool for the preparation of defined polymers tolerating a large variety of functional groups. Several dithioesters, trithiocarbonates, xanthates, or dithiocarbamates have been developed as effective chain transfer agents (CTAs), but only a few examples have been reported, where the resulting end groups are directly considered for a secondary use besides controlling the polymerization. Herein, it is demonstrated that β-hydroxy dithiocinnamic esters represent a hitherto overlooked class of materials, which are originally designed for the complexation of transition metals but may as well act as reversible CTAs. Modified with a suitable leaving group (R-group), these vinyl conjugated dithioesters indeed provide reasonable control over the polymerization of acrylates, acrylamides, or styrene via the RAFT process. Kinetic studies reveal linear evolutions of molar mass with conversion, while different substituents on the aromatic unit has only a minor influence. Block extensions prove the livingness of the polymer chains, although extended polymerization times may lead to side reactions. The resulting dithiocinnamic ester end groups are still able to form complexes with platinum, which verifies that the structural integrity of the end group is maintained. These findings open a versatile new route to tailor-made polymer-bound metal complexes.

Exploiting α-/ω-Reactivities during Polymerization for Controlled Heterotelechelic Poly(carbazole)s

The preparation of poly(N-alkyl-3,6-carbazole)s with defined α-/ω-end groups is investigated using a commercial Buchwald-type pre-catalyst. The applied excess of monofunctional aryl halide favored the Suzuki–Miyaura catalyst-transfer polymerization (SCTP) mechanism, leading to heterotelechelic polymers with defined molar masses, narrow dispersities, and high chemical yields (>85%). Notably, the absence of monofunctional aryl halide leads to quantitative formation of conjugated p-type poly(carbazole) macrocycles and the formation of longer chains via step-growth. The SCTP conditions lead to quantitative α-end group identity and up to 50% ω-end group identity due to the incomplete in situ post-polymerization capping step. The end groups were analyzed in depth by MALDI-ToF mass spectrometry on the basis of isotope simulations and relative end group distributions. The fractionation via preparative SEC yielded isolated polymer batches up to 6000 g/mol, very low dispersity values (<1.1), and confirmed end group identities (α: >99%, ω: up to 50%), including reactive azide and/or protected boronic ester end groups.

Tailoring Oligomeric Plasticizers for Polylactide through Structural Control.

Structural variations (oligolactide segments, functionalized end groups, and different plasticizer cores) were utilized to tailor the performances of biobased plasticizers for polylactide (PLA). Six plasticizers were developed starting from 1,4-butanediol and isosorbide as cores: two monomeric (1,4-butanediol levulinate and isosorbide levulinate) and four oligomeric plasticizers with hydroxyl or levulinate ester end groups (1,4-butanediol-based oligolactide, isosorbide-based oligolactide, 1,4-butanediol-based oligomeric levulinate, and isosorbide-based oligomeric levulinate). Structural variations in plasticizer design were reflected in the thermal stability, plasticizing efficiency, and migration resistance. The monomeric plasticizer 1,4-butanediol levulinate decreased the glass-transition temperature of PLA from 59 to 16 °C and increased the strain at break substantially from 6 to 227% with 20 wt % addition. 1,4-Butanediol-based oligomeric levulinate exhibited better thermal stability and migration resistance, though the plasticizing efficiency was slightly lower (glass-transition temperature = 28 °C; strain at break = 202%). Compared to PLA films plasticized by plasticizers with flexible butanediol cores, those plasticized by plasticizers with rigid isosorbide cores exhibited higher Young’s modulus and thermal stability and lower plasticizing efficiency. Furthermore, plasticizers with levulinate ester end groups had improved thermal stability, plasticizing efficiency, and migration resistance compared to the corresponding plasticizers with hydroxyl end groups. Hence, a set of controlled structural variations in plasticizer design were successfully demonstrated as a potent route to tailor the plasticizer performances.

SnOct2‐catalyzed ROPs of l‐lactide initiated by acidic OH‐ compounds: Switching from ROP to polycondensation and cyclization

AbstractRing‐opening polymerizations (ROPs) of l‐lactide are performed in bulk at 130°C with tin(II) 2‐ethylhexanoate as catalyst and various phenols of different acidity as initiators. Crystalline polylactides having phenyl ester end groups are isolated, which are almost free of cyclics. The dispersities and molecular weights are higher than those obtained from alcohol‐initiated ROPs under identical conditions. Polymerizations at 160°C yield higher molecular weights than expected from the monomer/initiator ratio and a considerable fraction of cycles. The fraction of cycles increases with higher reactivity of the ester end group indicating that the cycles are formed by end‐to‐end cyclization.

Designing of quaternized hyperbranched polyamidoamines dendrimers: Surface activity, pharmaceutical efficacy, and safety approach

The low solubility of the drug considers a major challenge for pharmaceutical formulation of both oral and parenteral products. In this work various generations of cationic hyperbranched polyamidoamine (PAMAM) quaternary ammonium salt dendrimers terminated with amine end groups were synthesized. The pharmaceutical application of these quaternized cationic surfactants ended with amine end groups and those ended with ester end groups which prepared in an earlier study were investigated. These dendrimers were compared as solubilizing agents for coenzyme Q10 (poorly soluble drug) and the dendrimers that showed high solubilizing potential (G2.5 C8, G2.5 C12) were selected to be evaluated as a dendrimer in dissolution study for coenzyme Q10 or Ledipasvir drug. In our investigation a comparison between four dissolution media with different surfactants namely, G2.5 C8, G2.5 C12, CTAB and Labrasol used for the dissolution test of Q10 was carried out. The results revealed that % Q10 released after 4 h was 86.7, 70.5, 43 and 10.5% for these dissolution media, respectively. These results indicated the priority of the synthesized cationic surfactants than the known commercial cationic surfactant (CTAB) or than Labrasol as recommended surfactant in previous lectures. Therefore, the profiles of the ledipasvir dissolution in the three-dissolution media (G2.5 C8, G2.5 C12 and FDA surfactant (1.5% tween 80 and 0.0075 mg/ml Butylated Hydroxytoluene (BHT)) are similar. The obtained results emphasized that the new surfactants can be used as alternative to FDA surfactant in the dissolution media of Ledipasvir.Eventually, the toxicity study was performed for two selected compounds from the prepared dendrimers, and these compounds were proved to be safe.

PAMAM dendron-grafted poly(vinyl alcohol) via click reaction

Poly(vinyl alcohol) (PVA) is a linear polymer of synthetic origin, biocompatible and inert, representing a good starting point to incorporate dendrons and potentiate their ability to act as drug-carrier releasers. This article reports the synthesis of G 1.5 PAMAM-type dendrons from propargylamine with methyl or tert-butyl ester end groups. Subsequently, these dendrons were grafted into PVA functionalized with azide groups (N3) through a click reaction. Dendron-grafted PVA showed different chemical and physical properties to those of PVA and azidated PVA, since PAMAM-type dendrons modified the molecular interactions between the different polymer chains and with the medium, resulting in changes in hydrodynamic radius (Rh) density, solubility, and glass transition temperature. Compared with PVA and azidated PVA, the grafting of methyl ester ended dendrons afforded a 94% water-soluble material at room temperature, with a decrease in its density and an increase in its Tg, while in the case of the tert-butyl ester ended dendrons only 69% of the material is water-soluble, and it presented the lowest density and the lowest Tg due to increasing in free volume. The Rh values of dendron-grafted PVA increased according to molecular weight. The obtained products were characterized by ATR-FTIR, UVvis, and/or NMR (1H, 13C).

Push or Pull Electrons: Acetoxy and Carbomethoxy-Substituted Isomerisms in Organic Solar Cell Acceptors.

Isomerism is a major factor affecting the properties of materials. Herein, two isomeric acceptors based on acetoxy and methyl ester end group substituents, BTIC-OCOMe and BTIC-COOMe are reported. When blended with PBDB-TF, devices based on BTIC-OCOMe achieve an inferior (8.32%) power conversion efficiency (PCE) while the BTIC-COOMe material has a superior PCE of 13.25%. We investigated the reasons why these two devices, which differ only in the isomeric substituents on the terminal site, have such a large difference in photovoltaic performance. Our investigation conducted theoretical calculations and examined UV-vis absorption, energy levels, exciton dissociation and bimolecular recombination, mobilities tests, photoluminescence, and packing modes. It is found that the energy levels of the materials are fine-tuned, the absorption spectra are adjusted, and the energy loss is regulated. Our studies explored the reasons for the properties of materials differing, and the acetoxy and carbomethoxy substitutions provided some useful information concerning high-performance acceptor materials.

Linear and cyclic oligomers in PET, glycol-modified PET and Tritan™ used for food contact materials

ABSTRACT Polyesters are commonly used as food contact materials. During manufacture of polyesters different low molecular mass oligomers (<1000 Da) are formed in the polymer melt. These so-called non-intentionally added substances (NIAS) are potential migrants into foods. In this work, different polyester samples made of polyethylene terephthalate (PET), glycol-modified PET (PETG) and Tritan™ were investigated on their qualitative and quantitative oligomer composition. The analysis of acetonitrile extracts by HPLC-DAD/ESI-MS revealed the presence of about 100 linear (different combinations of hydroxyl-, carboxyl-, methyl ester end groups) and cyclic oligomers depending on the main and co-monomers. The identified oligomers were quantified in different extracts and after reprecipitation by HPLC-DAD using bis-hydroxyethylene terephthalate (BHET) as external standard. The amount of oligomers isolated by reprecipitation ranged between 0.80 and 3.4% in the respective polyester. Cyclic oligomers generally made up 90% or more of the isolated oligomers. Compared to the exhaustive extracts the leaching of oligomers into 20% ethanol (1 h, 60 °C) resulted in a considerable change of the oligomer distribution with a predominant detection of linear oligomers. This suggests linear oligomers to be relevant for migration into aqueous foods despite the dominant amount of extractable cyclic oligomers in polyesters. Analysis of the extractable oligomers of a PET preform and a PETG container and their corresponding raw material pellets revealed that the injection moulding process did not significantly change the amount of cyclic oligomers but did increase the amount of low molecular mass linear oligomers about twofold.

New way of anionic ring-opening copolymerization of \u03b2-butyrolactone and \u03b5-caprolactone: determination of the reaction course

Poly(ε-caprolactone)-block-poly(β-butyrolactone) copolymers were prepared in two-step synthesis. Firstly, poly(ε-caprolactone) (PCL) was obtained by anionic ring-opening polymerization of CL initiated with anhydrous KOH activated 12-crown-4 cation complexing agent. Reaction was carried out in tetrahydrofuran solution and argon atmosphere at room temperature. Then, β-butyrolactone (BL) and 18-crown-6 were added to the system, resulting in PCL-block-PBL copolymer, which contains after methylation hydroxyl starting group and methyl ester end group. The main product was contaminated with PCL and PBL homopolymers formed in a side reactions. 13C NMR technique was used for determination of chemical structure of polymers obtained. The course of the studied processes was proposed. MALDI-TOF technique was used to reveal the macromolecules’ architecture where several series were found. The identified series shown that mainly copolymeric macromolecules were formed with scare contribution of homopolymeric polybutyrolactone with trans-crotonate starting groups and polycaprolactone, which is congruent with the proposed reaction mechanism. Moreover, critical approach concerning previously reported PCL-block-PBL copolymer synthesis by use of NaH as initiator was also presented.

Computational Investigation of the Binding Dynamics of Oligo p-Phenylene Ethynylene Fluorescence Sensors and Aβ Oligomers.

Amyloid protein aggregates are pathological hallmarks of neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases and are believed to be formed well before the onset of neurodegeneration and cognitive impairment. Monitoring the course of protein aggregation is thus vital to understanding and combating these diseases. We have recently demonstrated that a novel class of fluorescence sensors, oligomeric p-phenylene ethynylene (PE)-based electrolytes (OPEs) selectively bind to and detect prefibrillar and fibrillar aggregates of AD-related amyloid-β (Aβ) peptides over monomeric Aβ. In this study, we investigated the binding between two OPEs, anionic OPE12- and cationic OPE24+, and to two different β-sheet rich Aβ oligomers using classical all-atom molecular dynamics simulations. Our simulations have revealed a number of OPE binding sites on Aβ oligomer surfaces, and these sites feature hydrophobic amino acids as well as oppositely charged amino acids. Binding energy calculations show energetically favorable interactions between both anionic and cationic OPEs with Aβ oligomers. Moreover, OPEs bind as complexes as well as single molecules. Compared to free OPEs, Aβ protofibril bound OPEs show backbone planarization with restricted rotations and reduced hydration of the ethyl ester end groups. These characteristics, along with OPE complexation, align with known mechanisms of binding induced OPE fluorescence turn-on and spectral shifts from a quenched, unbound state in aqueous solutions. This study thus sheds light on the molecular-level details of OPE-Aβ protofibril interactions and provides a structural basis for fluorescence turn-on sensing modes of OPEs.

How Intramolecular Vibrational Energy Transport Changes with Rigidity and Polarity of the Environment?

Vibrational energy transport through oligomeric polyethylene glycol (PEG) chains can occur ballistically via optical vibrational chain bands, showing fast and constant transport speed and high efficiency of the transport, thus offering means to transfer significant quanta of energy, exceeding 1000 cm–1, to large distances exceeding 60 A. We report how the intramolecular energy transport time, through-chain transport speed, and end-group cooling rate depend on the rigidity and polarity of the environment. The experiments were performed with end-group labeled PEG oligomers using two-dimensional infrared (2DIR) spectroscopy. The ballistic energy transport was initiated at one end of the chain by exciting an azido moiety at ca. 2100 cm–1 and recorded at another end of the chain by probing the carbonyl stretching mode of succinimide ester. We found that the rigidity of the environment, polystyrene (PS) matrix vs. a solution of similar polarity, did not change the energy transport times much, nor the through-chain transport speed. These results suggest that in mildly polar media, dynamic fluctuations, occurring in solution but largely frozen in a solid matrix, are not the dominant cause of the dephasing of the chain states, despite the presence of fast relaxation components in the solution. The similarity of the transport times in different media suggests that the secondary chain structure does not affect much the transport in PEG chains. The solvent polarity affected the intramolecular transport significantly: the transport efficiency in polar DMSO is ca. 1.6 fold smaller than that in nonpolar CCl4 or PS. The cooling time of the succinimide ester end group is reduced in more polar solvents affecting the waiting time dependence shape and thus the energy arrival time to the reporter. The analysis of different ways of extracting the energy arrival time from the data is presented. The observed dependences of the through-chain transport time on the solvent polarity suggests the presence of multiple wavepackets propagating in the PEG chain with different group velocities.

An inherently flame-retardant polyamide 6 containing a phosphorus group prepared by transesterification polymerization

During the hydrolysis polymerization of caprolactam, melt polycondensation requires that the stoichiometry of the carboxyl-terminal and amine-terminal groups be kept in balance, which greatly limits the copolymerization modification of polyamide 6 (PA6). In this paper, we designed a PA6 prepolymer and modified 9,10-dihydro-10-[2,3-di(hydroxycarbonyl)propyl]-10-phosphaphenanthrene-10-oxide (DDP) monomers so that they have the same ethylene glycol ester end groups. Based on the principle of transesterification to achieve chain growth, an intrinsic flame-retardant polyamide 6 (FR-PA6) is prepared. Our research results show that the FR-PA6 prepared by the synthetic route outlined in this article not only maintains the excellent performance of polyamide 6 but also allows the molecular weight growth of the polyamide 6 polymer to behave independently of the stoichiometric balance of the terminal groups. This method breaks the limitation of the copolymerization reaction caused by hetero end groups after the hydrolysis of caprolactam and ensures a stable degree of polymerization when a high proportion of modifier is added. When the EDE content is increased to 8%, the phosphorus content in the polymer reaches 4640 ppm, the limiting oxygen index reaches 29.5%, and the vertical combustion reaches V-0. The flame-retardant mechanism is analysed by cone calorimetry and pyrolysis gas chromatography-mass spectrometry. This method can prepare flame-retardant PA6 on traditional polyester equipment and can be widely used in the fields of plastics and fibres.

Synthesis of diosgenin prodrugs: anti-inflammatory and antiproliferative activity evaluation

In this work, we evaluated the antiproliferative and anti-inflammatory activities of two diosgenin prodrugs. The prodrugs were obtained by esterification of diosgenin at position 3 with 4-oxo-4-(prop-2-yn-1-yloxy)butanoic acid followed by click reaction on terminal alkyne with 3-azidopropan-1-ol N-alkylated dendrons, resulting in a prodrug with methyl ester end-groups and a derivative with tert-butyl ester end-groups, hydrolysis of tert-butyl ester derivative afforded a prodrug with carboxylic acid terminals. All compounds were fully characterized by 1H and 13C NMR, ATR-FTIR and HR-ESI TOF. Studies of the anti-inflammatory effects on mouse ear edema of prodrugs methyl ester and carboxylic acid, ended, using diosgenin and dexamethasone as positive controls, showed the superiority of methyl ester ended prodrug with an ED50 four times lower than that of dexamethasone. Further, carboxylic acid ended prodrug was found to be more active than diosgenin as an antiproliferative agent, according to crystal violet assay. Diosgenin was transformed to ester and acid prodrugs through succinic ester and a 1,2,3-triazole linkers. The prodrug with methyl ester terminals was four times more active than dexamethasone as anti-inflammatory compound, while prodrug with carboxylic acid terminals improved antiproliferative activity over MCF-7 cells.