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The exponential increase in the use of plastic demands that biosourced and biodegradable polymers such as poly( l -lactide)s (PLLA)s be considered to replace some petroleum based polymers in a range of applications. In order to produce PLLA in the greenest manner, i.e. by ring-opening polymerization (ROP) of l -lactide using an organocatalyst in solvent free conditions at high temperature (in bulk) has proven to be a significant challenge. Indeed, the high required temperature (180 °C) has led to poorly controlled polymerizations as a result of transesterification reactions of the PLLA backbone, racemization of the lactide monomers as well as the degradation and thus deactivation of the organocatalyst. We report herein the efforts made over the past 20 years in order to conduct the ROP of l -lactide in bulk by using organic molecules and the problems encountered by the scientific community in addressing this challenge to date. [ABSTRACT FROM AUTHOR]

Abstract: Environmental concerns along with the need to develop aliphatic polycarbonate materials free of any toxic compounds have driven scientists to implement macromolecular engineering processes by replacing potentially toxic and carcinogenic metal-based catalysts traditionally used for the ring-opening polymerization of cyclic carbonates by organic compounds. This issue is of particular importance as aliphatic polycarbonates are gaining increasing credibility for biomedical applications owing to their biocompatibility and bioresorbability. This review provides a complete account of the various metal-free catalysts that has been developed so far as well as comprehensive investigations on the related polymerization mechanisms. [Copyright &y& Elsevier]

Abstract: Several methods for polymerizing 4-methyl-2-oxetanone (β-butyrolactone, BL) were developed allowing the controlled synthesis of polymers with molar masses up to 100kDa. Although new catalytic systems have been described for the living anionic polymerization of BL, no detailed studies have been published on the influence of the monomer purity on the polymerization reaction. In the present study, nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are used for assessing monomer purity. These techniques indicate that an additional reaction of BL with an oxidizing agent such as potassium permanganate produces a monomer of higher purity as demonstrated by the higher rate of BL polymerization and improved control over the polymerization process that is initiated with either tetrabutylammonium acetate or carboxylic acid/phosphazene base (P1-t-Bu, P2-t-Bu and P4-t-Bu) systems. [Copyright &y& Elsevier]

Abstract: Tandem mass spectrometry is increasingly applied to polymer ions in the context of in-depth structural characterization. In particular, the well-known collision-induced dissociation (CID) methodology is nowadays advantageously used to characterize end-groups and to distinguish isomeric polymer ions. When applied to sodium-cationized polyesters, CID was demonstrated to mainly involve charge remote fragmentation processes and consecutive as well as competitive dissociation pathways. In the present report, an experimental and theoretical study of collision induced dissociation of isomeric sodium cationized polylactide was investigated. The investigated polymers were designed to obtain oligomers only differentiated on the basis of regioisomeric end-groups, using ortho-, meta-, and para-methylbenzyl alcohols as initiators. The CID spectra revealed the presence of competitive charge driven and charge remote fragmentations. In particular, the charge induced fragmentations allowed the minute distinction between the three isomeric end-groups. The intermediacy of an ion/neutral complex was proposed to account for the observed decomposition and some theoretical calculations were performed to support the proposal. [Copyright &y& Elsevier]

Abstract: 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) organic catalyst has generated a tremendous impact in the metal-free ring-opening polymerization of (di)lactones. Interestingly, its extraction after use has never been studied so far and a simple deactivation by addition of benzoic acid to generate the corresponding salt has always been supposed to kill its activity. This study reveals and highlights the importance of the work-up to remove or at least drastically limit the presence of the benzoic acid/DBU salt from poly(l-lactide). Three different extraction methods allowed us to conclude that a two-step work-up gathering liquid/liquid extractions and a drop by drop precipitation is highly required to keep the enantiomerically pure lactic acid polymer safe. If not perfectly extracted the benzoic acid/DBU salt has been proved to degrade the materials during a melt process even during a differential scanning calorimetry experiment. [Copyright &y& Elsevier]

Abstract: New brush-like copolymers have been synthesized using functional polymethacrylate backbones bearing pendant sugars. Ring-opening polymerization (ROP) of l-lactide and ε-caprolactone have been performed using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) carbohydrate residues on the polymethacrylate chains. The latter have been first synthesized by copolymerization of three methacrylate monomers including methyl methacrylate (MMA), α-methoxy, ω-methacrylate poly(ethylene oxide) (MAPEO), and 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-d-galactopyranose (MAIGP) by atom transfer radical polymerization (ATRP) in toluene at 80°C using CuBr ligated with 1,1,4,7,10,10 hexamethyltriethylenetetramine (HMTETA) as catalytic complex. The protected sugars have been selectively deprotected using an aqueous solution of formic acid. The molecular characterization of those copolymers was performed by 1H-NMR spectroscopy, FT-IR spectroscopy and gel permeation chromatography (GPC) analysis. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we describe the design and characterization of regioregular poly(3-hexylthiophene)-poly(ε-caprolactone) di- and tri-block copolymers (RRP3HT-b-PCL and PCL-b-RRP3HT-b-PCL). The well-controlled synthesis of (di)hydroxyl-terminated RRP3HT makes possible to design block copolymer structures with a narrow molecular weight distribution. The microscopic morphology is investigated by atomic force microscopy, which reveals self-assembled fibrillar structures with the RRP3HT nanoribbons separated by narrow domains of insulating PCL. The charge transport properties are characterized in thin films field-effect transistors, and comparison between the devices performances is carried out in view of the nanoscale morphology within the transistor channel. [Copyright &y& Elsevier]

Abstract: Biodegradable polymers represent a class of extremely useful materials for many biomedical and pharmaceutical applications, as exemplified by drug delivery systems, which in recent years have taken advantage of (bio)degradable polymeric matrices. However, before being selected for any biomedical application, a biodegradable polymer requires careful investigation of its interactions and compatibility within the human body. To date, polyesters, both natural and synthetic, constitute the most fully developed class of degradable biomaterials. Poly(ε-caprolactone) (PCL) and polylactides (PLAs), recognized as biocompatible and biodegradable polyesters, are very promising for controlled drug delivery devices. Bacterial polyesters and malic acid-based polymers (poly(malic acid), PMLA and derivatives) are poly(β-hydroxyacid)-type polyesters that represent excellent alternatives for temporary therapeutic applications. Although these polyesters can be produced by polycondensation, high molecular weight structures have, until now, been produced almost exclusively by ring-opening polymerization (ROP) of the corresponding cyclic monomers. The ability of aluminum alkoxides (AlR x (OR′)3− x ) and tin(II) bis(2-ethylhexanoate) (Sn(Oct)2) to control the ROP of (di)lactones in terms of molecular parameters has opened the way to a wide range of molecular structures and topologies. Beyond the mechanistic and thermodynamic aspects of ROP of (di)lactones using organometallic compounds, this review is focused on new non-organometallic N-heterocyclic carbenes recently reported as catalysts for the controlled ROP of cyclic esters. Interestingly, the use of these simple organic molecules as catalysts or promoters in asymmetric polymer synthesis has provided organocatalytic alternatives to traditional organometallic reagents. [Copyright &y& Elsevier]

[Display omitted] • RGD-NanoStar micellar nanoassemblies loaded with Doxorubicin against osteosarcoma. • Impact of RGD on nanoparticles surface for osteosarcoma chemotherapy. • Dox released from RGD-NanoStar reach the nucleus unlike untargeted NanoStar. • Preserving Doxorubicin from degradation occurring under physiological conditions. • Sustained and prolonged Dox release from RGD-NanoStar@Dox. We developed cyclic RGD-tagged polymeric micellar nanoassemblies for sustained delivery of Doxorubicin (Dox) endowed with significant cytotoxic effect against MG63, SAOS-2, and U2-OS osteosarcoma cells without compromising the viability of healthy osteoblasts (hFOBs). Targeted polymeric micellar nanoassemblies (RGD-NanoStar@Dox) enabled Dox to reach the nucleus of MG63, SAOS-2, and U2-OS cells causing the same cytotoxic effect as free Dox, unlike untargeted micellar nanoassemblies (NanoStar@Dox) which failed to reach the nucleus and resulted ineffective, demonstrating the crucial role of cyclic RGD peptide in driving cellular uptake and accumulation mechanisms in osteosarcoma cells. Micellar nanoassemblies were obtained by nanoformulation of three-armed star PLA-PEG copolymers properly synthetized with and without decoration with the cyclic-RGDyK peptide (Arg-Gly-Asp-D-Tyr-Lys). The optimal RGD-NanoStar@Dox nanoformulation obtained by nanoprecipitation method (8 % drug loading; 35 % encapsulation efficiency) provided a prolonged and sustained drug release with a rate significantly lower than the free drug under the same experimental conditions. Moreover, the nanosystem preserved Dox from the natural degradation occurring under physiological conditions (i.e., dimerization and consequent precipitation) serving as a slow-release "drug reservoir" ensuring an extended biological activity over the time. [ABSTRACT FROM AUTHOR]

Abstract: Novel synthetic transfection vectors with linear triblock and star-shaped diblock copolymer architectures have been synthesized by atom transfer radical polymerization (ATRP). Based on 2-(dimethylamino)ethyl methacrylate (DMAEMA) and copolymerization with poly(ethyleneglycol) α-methoxy, ω-methacrylate (MAPEG), the synthesis was realized using CuBr ligated with 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA) as catalytic complex and either ethyl 2-bromoisobutyrate (EBiB) or bis(α-bromoisobutyryl) N-methyl diethanolamine (DEA) or tris(α-bromoisobutyryl) triethanolamine (TEA) as (multifunctional)initiator. The polymers were characterized by GPC and NMR. The solution properties of these homopolymers and palm-tree-like copolymers were investigated by viscometry either in pure water or in buffered aqueous solutions. Interestingly, all the synthesized polymers show polyelectrolyte effect in Millipore water (25°C) and in Hepes (20mM) buffer solution (pH 7.4, NaCl 155mM, 25°C). Fitting of these viscometric data according to either Fuoss or Fedors equation allows for calculating the intrinsic viscosity of the polymers. These results are compared with dynamic light scattering (DLS) experiments to determine absolute masses. Finally, DEA based palm-tree-like copolymer is investigated to AFM measurement and micelles were observed at pH 8. [Copyright &y& Elsevier]

Polylactide is one of the most versatile biopolymers, but its slow crystallization limits its temperature usage range. Hence finding ways to enhance it is crucial to widen its applications. Linear and cyclic poly (L -lactide) (l -PLLA and c -PLLA) of similarly low molecular weights (MW) were synthesized by ring-opening polymerization of L -lactide, and ring-expansion methodology, respectively. Two types of blends were prepared by solution mixing: (a) l -PLLA/ c -PLLA, at extreme compositions (rich in linear or in cyclic chains), and (b) blends of each of these low MW materials with a commercial high MW linear PLA. The crystallization of the different blends was evaluated by polarized light optical microscopy and differential scanning calorimetry. It was found, for the first time, that in the l -PLLA rich blends, small amounts of c -PLLA (i. e., 5 and 10 wt%) increase the nucleation density, nucleation rate (1/τ 0), spherulitic growth rate (G), and overall crystallization rate (1/τ 50%), when compared to neat l -PLLA, due to a synergistic effect (i. e., nucleation plus plasticization). In contrast, the opposite effect was found in the c -PLLA rich blends. The addition of small amounts of l -PLLA to a matrix of c -PLLA chains causes a decrease in the nucleation density, 1/τ 0 , G , and 1/τ 50% values, due to threading effects between cyclic and linear chains. Small amounts of l -PLLA and c -PLLA enhance the crystallization ability of a commercial high MW linear PLA without affecting its melting temperature. The l -PLLA only acts as a plasticizer for the PLA matrix, whereas c -PLLA has a synergistic effect in accelerating the crystallization of PLA that goes beyond simple plasticization. The addition of small amounts of c -PLLA affects not only PLA crystal growth but also its nucleation due to the unique cyclic chains topology. [Display omitted] [ABSTRACT FROM AUTHOR]

The preparation of stereoregular isotactic P( l -BnMA) and PLLA by ring-opening polymerization (ROP) of 5-( S )-[(benzyloxycarbonyl)methyl]-1,3-dioxolane-2,4-dione ( l -malOCA) and ( S )-5-methyl-1,3-dioxolane-2,4-dione ( l -lacOCA) is reported. The polymerization process was shown to be well controlled using two easily accessible single organocatalyst/initiator systems, pyridine/ l -benzyl(Bn)malate and pyridine/lactic acid (Py·LA) ion pair adducts respectively. The obtained biodegradable polymers displayed narrow dispersity ( Đ M ) and excellent molar mass control. All ROP reactions were conducted at ambient temperature. The stereoregularity and thermal properties of the materials were thoroughly studied, demonstrating the retention of high levels of isotactic enrichment. [ABSTRACT FROM AUTHOR]

Polyesteramides (PEAs) are considered intriguing materials due to the combination of the favorable degradable capacity of aliphatic polyesters given by the hydrolizable ester groups and the desirable thermal and mechanical behavior of polyamides given by the amide groups. Between polyamides and polyester families, poly(ε-caprolactam) and poly( l -lactide) stand out due to their commercial value and outstanding properties. Nevertheless, to date these two monomers have not been co-polymerized due to their different reactivities. In this work, we report for the first time, up to our knowledge, the synthesis of poly(ε-caprolactam- co - l -lactide) copolymers with different compositions. Two different catalysts: (a) Brønsted acid ionic liquid 1-(4-sulfobutyl)-3-methylimidazolium hydrogen sulfate (BAIL) and (b) Brønsted base P 4 - t -Bu have been explored. In the presence of Brønsted acid the l -lactide reactivity is higher than the ε-caprolactam while in the presence of Brønsted base the opposite behavior is observed. Using Kelen-Tudos method the monomer reactivity ratios are calculated and obtained as r CLa = 0.39 and r LA = 1.6 and r CLa = 2.2 and r LA = 0.1 using BAIL and P 4 - t -Bu, respectively. These differences in the monomer reactivity ratios give us the possibility to create copolymers with different chain microstructure depending on the employed catalyst between 2 and 9 kDa. Thus, using P 4 - t -Bu random copolymers can be obtained at high l -lactide concentration and blocky character copolymers at high ε-caprolactam concentration. Meanwhile, using BAIL catalyst random like copolymers are obtained at high ε-caprolactam contents and blocky character at high l -lactide contents. [ABSTRACT FROM AUTHOR]

Highlights: [•] Assessment of end-group functionality in ATRP of NiPAm. [•] Synthesis of well-defined “smart” amphiphilic block copolymers. [•] Relevance of side reactions and diffusional limitations in ATRP of NiPAm. [ABSTRACT FROM AUTHOR]

Abstract: We report a method for inkjet-printing an organic semiconductor layer on top of the electrolyte insulator layer in polyelectrolyte-gated OFETs by using a surface modification treatment to overcome the underlying wettability problem at this interface. The method includes depositing an amphiphilic diblock copolymer (P3HT-b-PDMAEMA). This material is designed to have one set of blocks that mimics the hydrophobic properties of the semiconductor (poly(3-hexylthiophene) or P3HT), while the other set of blocks include polar components that improve adhesion to the polyelectrolyte insulator. Contact angle measurements, atomic force microscopy, and X-ray photoelectron spectroscopy confirm formation of the desired surface modification film. Successful inkjet printing of a smooth semiconductor layer allows us to manufacture complete transistor structures that exhibit low-voltage operation in the range of 1V. [Copyright &y& Elsevier]

Abstract: Regioregular head-to-tail α-bromo-ω-carboxystyryl poly(3-hexylthiophene) (P3HT-COOH) has been prepared by a Wittig reaction of α-bromo-ω-formyl poly(3-hexylthiophene) (P3HT-CHO) with [(4-carboxyphenyl)methyl]triphenylphosphonium bromide. This carboxylic end-group functionalized polymer was used to functionalize TiO2 nanoparticles in view of improving the miscibility between poly(3-hexylthiophene) and the nanoparticles, for future photovoltaic applications. The anchoring of the polymer on the surface of the TiO2 nanoparticles was demonstrated by sedimentation tests in THF, and by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), 1H MAS solid-state NMR, UV–vis and X-ray photoelectron spectroscopies. Films were produced by solvent casting and the dispersion of the TiO2 nanoparticles was evaluated by atomic force microscopy (AFM). Fluorescence quenching studies in CHCl3 were performed on these hybrids materials. [Copyright &y& Elsevier]

Abstract: The synthesis of amphiphilic and adaptative block copolymers has been envisioned following a commutative two-step strategy involving atom transfer radical polymerization (ATRP) and the Huisgen-1,3-dipolar cycloaddition techniques. The reliability of this strategy is based on the use of an azido-containing ATRP initiator, the 2-(2-azidoethoxy)ethylbromoisobutyrate (N3E i BBr), able to be “clicked” to an alkyne-terminated derivative and to promote the ATRP polymerization from the active site. In the context of this work, an alkyne-terminated poly(ε-caprolactone) produced by ring-opening polymerization (ROP) of CL was employed as hydrophobic “clickable” segment. The N3E i BBr initiator was obtained by nucleophilic substitution of the chloride atom from 2-(2-chloroethoxy)ethanol by an azide function and followed by the esterification of the hydroxy function by bromoisobutyryl bromide. This initiator was employed in polymerization of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA) monomer by ATRP in THF at 60°C using CuBr complexed by 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA) as catalytic complex. Low initiation efficiencies were obtained and they were ascribed to intramolecular cyclization during the polymerization as evidenced by ESI-MS and 2D NMR spectroscopy. The “Click” coupling reaction was performed in THF at r.t. and was found to be efficient when using CuBr complexed by 2,2′-bipyridine ligand. To circumvent the low initiation efficiency, the N3E i BBr could be “clicked” in a first step to PCL precursors before initiating the polymerization of DMAEMA monomer by ATRP. In this context, various catalytic complexes in different composition ratio were employed to optimize the “click” coupling step. Moreover, this strategy was found to be suitable to produce well-defined PCL-b-PDMAEMA block copolymers, characterized by narrow polydispersity indices. Since ATRP and the Huisgen-1,3-dipolar cycloaddition both require the use of a copper(I)-based catalyst, the two first strategies were merged in a “one-pot” process in order to obtain in one step a well-defined block copolymer characterized by a narrow polydispersity index and predictable composition and block lengths. [Copyright &y& Elsevier]

We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c -PLA, c -PLA-FA, c -PLA-Rhod) obtained by an optimized combination of ROP and click chemistry reactions. Cyclo -PLA having a number average molecular weight of 6000 g mol−1 and a polydispersity index of 1.52 was synthetized by click ring-closure of well-defined α,ω-heterodifunctional linear precursors, followed by quaternarization of N 3 -triazole nodes, and subsequent CuAAC with azido-folate and azido-rhodamine yielding jellyfish-shaped c -PLA-FA and c-PLA-Rhod. Salinomycin (Sal) was loaded into jellyfish-shaped c -PLA-FA and c -PLA-Rhod nanoparticles (NPs) by nanoprecipitation, with a good encapsulation efficiency (79% and 84%, respectively) and loading content (7.1% and 7.6%, respectively). The biological studies focused on their antiproliferative effects on osteosarcoma bulk MG63 and cancer stem cells (CSCs). The cycloPLA-based NPs, with a size ranging between 125 and 385 nm, killed CSCs and MG63, with a higher efficacy on CSCs; they (unloaded or Sal-loaded) evoked on CSCs a cellular response similar to the payload, with a higher effect than the free Sal. Internalization studies indicated a fast cellular uptake (within 2 h) and sarcospheres remained fluorescent till 72 h. To the best of our knowledge, this is the first study reporting anti-CSCs properties of cycloPLA with jellyfish architecture and we believe could contribute to the development of effective strategies for osteosarcoma targeting. Unlabelled Image • New cyclopolylactides were obtained combining ROP and click chemistry reactions. • Salinomycin was loaded into cyclo -PLA nanoparticles decorated with folate or rhodamine. • Cyclo -PLA nanoparticles affected osteosarcoma bulk MG63 and cancer stem cells fate. • Internalization studies indicated a fast cellular uptake (within 2 h). • Positive charged jellyfish-shaped cyclo -PLA as anti-cancer stem cells agent. [ABSTRACT FROM AUTHOR]