Phosphonate-Functionalized Polycarbonates Synthesis through Ring-Opening Polymerization and Alternative Approaches.

Well-defined phosphonate-functionalized polycarbonate with low dispersity (Ð = 1.22) was synthesized using organocatalyzed ring-opening polymerization (ROP) of novel phosphonate-based cyclic monomers. Copolymerization was also performed to access different structures of phosphonate-containing polycarbonates (PC). Furthermore, phosphonate-functionalized PC was successfully synthesized using a combination of ROP and post-modification reaction.

Optically traceable PLGA-silica nanoparticles for cell-triggered doxorubicin delivery.

Fluorescent silica nanoparticles with a polymer shell of poly (D, L-lactide-co-glycolide) (PLGA) can provide traceable cell-triggered delivery of the anticancer drug doxorubicin (DOX), protecting the cargo while in transit and releasing it only intracellularly. PLGA with 50:50 lactide:glycolide ratio was grown by surface-initiated ring-opening polymerization (ROP) from silica nanoparticles of ca. 50 nm diameter, doped with a perylenediimide (PDI) fluorescent dye anchored to the silica structure. After loading DOX, release from the core-shell particles was evaluated in solution at physiological pH (7.4), and in human breast cancer cells (MCF-7) after internalization. The hybrid silica-PLGA nanoparticles can accommodate a large cargo of DOX, and the release in solution (PBS) due to PLGA hydrolysis is negligible for at least 72 h. However, once internalized in MCF-7 cells, the nanoparticles release the DOX cargo by degradation of the PLGA. Accumulation of DOX in the nucleus causes cell apoptosis, with the drug-loaded nanoparticles found to be as potent as free DOX. Our fluorescently traceable hybrid silica-PLGA nanoparticles with cell-triggered cargo release offer excellent prospects for the controlled delivery of anticancer drugs, protecting the cargo while in transit and efficiently releasing the drug once inside the cell.

Polythioesters Prepared by Ring-Opening Polymerization of Cyclic Thioesters and Related Monomers.

Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polyesters with a wide range of applications; in particular, they currently stand as promising alternatives to conventional polyolefin-based "plastics". The introduction of sulfur atoms within the PHAs backbone can endow the resulting polythioesters (PTEs) with differentiated, sometimes enhanced thermal, optical and mechanical properties, thereby widening their versatility and use. Hence, PTEs have been gaining increasing attention over the past half-decade. This review highlights recent advances towards the synthesis of well-defined PTEs by ring-opening polymerization (ROP) of cyclic thioesters - namely thiolactones - as well as of S-carboxyanhydrides and thionolactones; it also covers the ring-opening copolymerization (ROCOP) of cyclic thioanhydrides or thiolactones with epoxides or episulfides. Most of the ROP reactions described are of anionic type, mediated by inorganic, organic or organometallic initiators/catalysts, along with a few enzymatic reactions as well. Emphasis is placed on the reactivity of the thio monomers, in relation to their ring-size ranging from 4- to 5-, 6- and 7-membered cycles, the nature of the catalyst/initiating systems implemented and their efficiency in terms of activity and control over the PTE molar mass, dispersity, topology, and microstructure.

Novel Poly(Methylenelactide-g-L-Lactide) Graft Copolymers Synthesized by a Combination of Vinyl Addition and Ring-Opening Polymerizations.

In this work, a novel poly (methylenelactide-g-L-lactide), P(MLA-g-LLA) graft copolymer was synthesized from poly(methylenelactide) (PMLA) and L-lactide (LLA) using 0.03 mol% liquid tin(II) n-butoxide (Sn(OnBu)2) as an initiator by a combination of vinyl addition and ring-opening polymerization (ROP) at 120 °C for 72 h. Proton and carbon-13 nuclear magnetic resonance spectroscopy (1H- and 13C-NMR) and Fourier-transform infrared spectroscopy (FT-IR) confirmed the grafted structure of P(MLA-g-LLA). The P(MLA-g-LLA) melting temperatures (Tm) range of 144-164 °C, which was lower than that of PLA (170-180 °C), while the thermal decomposition temperature (Td) of around 314-335 °C was higher than that of PLA (approx. 300 °C). These results indicated that the grafting reaction could widen the melt processing range of PLA and in doing so increase PLA's thermal stability during melt processing. The graft copolymers were obtained with weight-average molecular weights (M¯w) = 4200-11,000 g mol-1 and a narrow dispersity (D = 1.1-1.4).

Alkali and Alkaline Earth Metal Complexes as Versatile Catalysts for Ring-Opening Polymerization of Cyclic Esters.

Biodegradable polyesters such as poly(ϵ-caprolactone) (PCL) and poly(lactic acid) (PLA) have been considered for use in several areas, such as drug delivery devices, sutures, tissue engineering, and GBR membranes, due to its bio-renewability, biodegradability, and biocompatibility. Several synthetic techniques for the preparation of polyesters have been reported in the literature, amongst which the ring-opening polymerization (ROP) of cyclic esters is the most efficient. A convenient approach to access iso-selective PLAs is polymerization of racemic lactide (rac-LA), which shows excellent stereoregularity without the need for costly chiral auxiliaries or ligands. In this personal account, we review a series of methods that have been practiced to the synthesis of biodegradable polyesters from various cyclic monomers using alkali and alkaline earth metal complexes as efficient catalysts.

Structurally nanoengineered antimicrobial peptide polymers: design, synthesis and biomedical applications.

Antimicrobial resistance not only increases the contagiousness of infectious diseases but also a threat for the future as it is one of the health care concern around the globe. Conventional antibiotics are unsuccessful in combating chronic infections caused by multidrug-resistant (MDR) bacteria, therefore it is important to design and develop novel strategies to tackle this problems. Among various novel strategies, Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPPs) have been introduced in recent years to overcome this global health care issue and they are found to be more efficient in their performance. Many facile methods are adapted to synthesize complex SNAPPs with required dimensions and unique functionalities. Their unique characteristics and remarkable properties have been exploited for their immense applications in various fields including biomedicine, targeting therapies, gene delivery, bioimaging, and many more. This review article deals with its background, design, synthesis, mechanism of action, and wider applications in various fields of SNAPPs.

Thermoresponsive Polypeptoids.

Stimuli-responsive polymers have been widely studied in many applications such as biomedicine, nanotechnology, and catalysis. Temperature is one of the most commonly used external triggers, which can be highly controlled with excellent reversibility. Thermoresponsive polymers exhibiting a reversible phase transition in a controlled manner to temperature are a promising class of smart polymers that have been widely studied. The phase transition behavior can be tuned by polymer architectures, chain-end, and various functional groups. Particularly, thermoresponsive polypeptoid is a type of promising material that has drawn growing interest because of its excellent biocompatibility, biodegradability, and bioactivity. This paper summarizes the recent advances of thermoresponsive polypeptoids, including the synthetic methods and functional groups as well as their applications.

PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA.

As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

Mannosylated brush copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) as multivalent lectin-binding nanomaterials.

A class of linear and four-arm mannosylated brush copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) is presented here. The synthesis through ring-opening and atom transfer radical polymerizations provided high control over molecular weight and functionality. A post-polymerization azide-alkyne cycloaddition allowed for the formation of glycopolymers with different mannose valencies (1, 2, 4, and 8). In aqueous media, these macromolecules formed nanoparticles that were able to bind lectins, as investigated by concanavalin A binding assay. The results indicate that carbohydrate-lectin interactions can be tuned by the macromolecular architecture and functionality, hence the importance of these macromolecular properties in the design of targeted anti-pathogenic nanomaterials.

Macromolecular Brushes Based on Poly(L-Lactide) and Poly(ε-Caprolactone) Single and Double Macromonomers via ROMP. Synthesis, Characterization and Thermal Properties.

Single and double poly(L-lactide) (PLLA) and poly(ε-caprolactone) (PCL) macromonomers having a norbornenyl polymerizable group were prepared by conventional Ring Opening Polymerization (ROP). These macromonomers were further subjected to ring opening metathesis polymerization (ROMP) reactions in order to produce double polymer brushes consisting of PLLA or PCL side chains on a polynorbornene (PNBE) backbone. Statistical or block ring opening metathesis copolymerization of the PLLA and PCL macromonomers afforded the corresponding random and block double brushes. Sequential ROMP of the single PLLA, PCL and PLLA macromonomers resulted in the synthesis of the corresponding triblock copolymer brush. The molecular characteristics of the macromolecular brushes were obtained by 1H-NMR spectroscopy and Size Exclusion Chromatography. The thermal properties of the samples were studied by thermogravimetric analysis, TGA, Differential Thermogravimetry, DTG and Differential Scanning Calorimetry, DSC.

Fluorescent CDs@PCL hybrids via tartaric acid, CDs-cocatalyzed polymerization.

In this paper, the environment-friendly, water-soluble carbon dots (CDs) with stable photoluminescence (PL) have been prepared via the one-step pyrolysis of lotus leaf. Then the as-prepared CDs containing abundant hydroxylic and carboxylic groups were employed as cocatalyst with tartaric acid (TA) in ring-opening polymerization (ROP) of ε-caprolactone (ε-CL). The low-toxic organic acid TA, as main catalyst, was used to catalyze the ROP of ε-CL efficiently. The fluorescent CDs@PCL hybrids were obviously hydrophobic and they exhibited an excellent biocompatibility, and biodegradability due to the existence of PCL. Therefore the hydrophobic, biodegradable and multi-color fluorescent CDs@PCL hybrids may have potential applications in biomedicine, photocatalyst, bioimaging, and environmental analysis. Furthermore the application of CDs in catalyzing and initiating polymerization reaction will exemplify the versatility of CDs in the most unexpected fields.

Synthesis of Hybrid-Polypeptides m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) and Study of Their Structure and Aggregation. Influence of Hydrophobic Copolypeptides on the Properties of Poly(L-histidine).

The highly diverse and sophisticated action of proteins results from their equally diverse primary structure, which along with the nature of interactions between the amino acids, defines the higher self-assembly of proteins. The interactions between amino acids can be very complicated, and their understanding is necessary in order to elucidate the protein structure-properties relationship. A series of well-defined hybrid-polypeptidic diblock copolymers of the type m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) was synthesized through the ring opening polymerization of the N-carboxyanhydrides of the corresponding amino acids, with a molar ratio of the hydrophobic peptide to histidine at 10%, 20% and 40%. The excellent purity of the monomers combined with the high vacuum techniques resulted in controlled polymerization with high molecular and compositional homogeneity. FT-IR, as well as circular dichroism, were employed to investigate the secondary structure of the polymers, while DLS, SLS and ζ-potential were utilized to study the aggregates formed in aqueous solutions, as well as their pH responsiveness. The results revealed that the randomly distributed monomeric units of glycine or alanine significantly influence L-histidine's structure. Depending on the pH, aggregates with a different structure, different molecular characteristics and a different surface charge are formed, potentially leading to very interesting bioapplications.

Synthesis of well-defined bisbenzoin end-functionalized poly(ε-caprolactone) macrophotoinitiator by combination of ROP and click chemistry and its use in the synthesis of star copolymers by photoinduced free radical promoted cationic polymerization.

A new well-defined bisbenzoin group end-functionalized poly(ε-caprolactone) macrophotoinitiator (PCL-(PI)2) was synthesized by combination of ring opening polymerization (ROP) and click chemistry. The ROP of ε-CL monomer in bulk at 110 °C, by means of a hydroxyl functional initiator namely, 3-cyclohexene-1-methanol in conjunction with stannous-2-ethylhexanoate, (Sn(Oct)2), yielded a well-defined PCL with a cyclohexene end-chain group (PCL-CH). The bromination and subsequent azidation of the cyclohexene end-chain group gave bisazido functionalized poly(ε-caprolactone) (PCL-(N3)2). Separately, an acetylene functionalized benzoin photoinitiator (PI-alkyne) was synthesized by using benzoin and propargyl bromide. Then the click reaction between PCL-(N3)2 and PI-alkyne was performed by Cu(I) catalysis. The spectroscopic studies revealed that poly(ε-caprolactone) with bisbenzoin photoactive functional group at the chain end (PCL-(PI)2) with controlled chain length and low-polydispersity was obtained. This PCL-(PI)2 macrophotoinitiator was used as a precursor in photoinduced free radical promoted cationic polymerization to synthesize an AB2-type miktoarm star copolymer consisting of poly(ε-caprolactone) (PCL, as A block) and poly(cyclohexene oxide) (PCHO, as B block), namely PCL(PCHO)2.

Combination of lignin and L-lactide towards grafted copolymers from lignocellulosic butanol residue.

A series of BBL-graft-poly (L-lactide) copolymers were synthesized via ring-opening polymerization (ROP) of L-lactide (L-LA) with a biobutanol lignin (BBL) initiator and a triazabicyclodecene (TBD) catalyst under free-solvent at 135 °C. By manipulating the mass ratio of BBL/LLA, BBL-g-PLLA copolymers with tunable number-average molecular weight (Mn) (2544-7033 g mol(-1)) were obtained. The chemical structure of PLLA chains was identifiable by FT-IR, (1)H NMR and (13)C NMR spectroscopies, in combination with UV-vis spectra to provide support for the existence of the BBL in the copolymer. This provided solid evidence for the successful synthesis of BBL-g-PLLA copolymer. The thermal properties and surface characterization of BBL-g-PLLA copolymers were different from those of linear PLLA. Furthermore, the BBL-g-PLLA copolymer film showed good absorption capacity in the UV region and high transparency in the visible light region, which was expected to find significant applications in UV-protective coating film.

Modelling and Validation of Synthesis of Poly Lactic Acid Using an Alternative Energy Source through a Continuous Reactive Extrusion Process.

PLA is one of the most promising bio-compostable and bio-degradable thermoplastic polymers made from renewable sources. PLA is generally produced by ring opening polymerization (ROP) of lactide using the metallic/bimetallic catalyst (Sn, Zn, and Al) or other organic catalysts in a suitable solvent. In this work, reactive extrusion experiments using stannous octoate Sn(Oct)2 and tri-phenyl phosphine (PPh)3 were considered to perform ROP of lactide. Ultrasound energy source was used for activating and/or boosting the polymerization as an alternative energy (AE) source. Ludovic® software, designed for simulation of the extrusion process, had to be modified in order to simulate the reactive extrusion of lactide and for the application of an AE source in an extruder. A mathematical model for the ROP of lactide reaction was developed to estimate the kinetics of the polymerization process. The isothermal curves generated through this model were then used by Ludovic software to simulate the "reactive" extrusion process of ROP of lactide. Results from the experiments and simulations were compared to validate the simulation methodology. It was observed that the application of an AE source boosts the polymerization of lactide monomers. However, it was also observed that the predicted residence time was shorter than the experimental one. There is potentially a case for reducing the residence time distribution (RTD) in Ludovic® due to the 'liquid' monomer flow in the extruder. Although this change in parameters resulted in validation of the simulation, it was concluded that further research is needed to validate this assumption.

Novel microwave-assisted synthesis of poly(D,L-lactide): the influence of monomer/initiator molar ratio on the product properties.

Poly(D,L-lactide) synthesis using tin(II) 2-ethylhexanoate initiated ring-opening polymerization (ROP) takes over 30 hours in bulk at 120 °C. The use of microwave makes the same bulk polymerization process with the same initiator much faster and energy saving, with a reaction time of about 30 minutes at 100 °C. Here, the poly(lactide) synthesis was done in a microwave reactor, using frequency of 2.45 GHz and maximal power of 150 W. The reaction temperature was controlled via infra-red system for in-bulk-measuring, and was maintained at 100 °C. Different molar ratios of monomer and initiator, [M]/[I], of 1,000, 5,000 and 10,000 were used. The achieved average molar masses for the obtained polymers (determined by gel permeation chromatography) were in the interval from 26,700 to 112,500 g/mol. The polydispersion index was from 2.436 to 3.425. For applicative purposes, the obtained material was purified during the procedure of microsphere preparation. Microspheres were obtained by spraying a fine fog of polymer (D,L-lactide) solution in tetrahydrofuran into the water solution of poly(vinyl alcohol) with intensive stirring.