Poly(Sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA)

Poly­(sarcosine) (PSar) is a non-ionic hydrophilic polypeptoid with numerous biologically relevant properties, making it an appealing candidate for the development of amphiphilic block copolymer nanostructures. In this work, the fabrication of poly­(sarcosine)-based diblock copolymer nano-objects with various morphologies via aqueous reversible addition–fragmentation chain-transfer (RAFT)-mediated photoinitiated polymerization-induced self-assembly (photo-PISA) is reported. Poly­(sarcosine) was first synthesized via ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride, using high-vacuum techniques. A small molecule chain transfer agent (CTA) was then coupled to the active ω-amino chain end of the telechelic polymer for the synthesis of a poly­(sarcosine)-based macro-CTA. Controlled chain-extensions of a commercially available water-miscible methacrylate monomer (2-hydroxypropyl methacrylate) were achieved via photo-PISA under mild reaction conditions, using PSar macro-CTA. Upon varying the degree of polymerization and concentration of the core-forming monomer, morphologies evolving from spherical micelles to worm-like micelles and vesicles were accessed, as determined by dynamic light scattering and transmission electron microscopy, resulting in the construction of a detailed phase diagram. The resistance of both colloidally stable empty vesicles and enzyme-loaded nanoreactors against degradation by a series of proteases was finally assessed. Overall, our findings underline the potential of poly­(sarcosine) as an alternative corona-forming polymer to poly­(ethylene glycol)-based analogues of PISA assemblies for use in various pharmaceutical and biomedical applications

Block Copolymers of Macrolactones/Small Lactones by a "Catalyst-Switch" Organocatalytic Strategy. Thermal Properties and Phase Behavior

Poly(macrolactones) (PMLs) can be considered as biodegradable alternatives of polyethylene; however, controlling the ring-opening polymerization (ROP) of macrolactone (ML) monomers remains a challenge due to their low ring strain. To overcome this problem, phosphazene (t-BuP_4), a strong superbase, has to be used as catalyst. Unfortunately, the one-pot sequential block copolymerization of MLs with small lactones (SLs) is impossible since the high basicity of t-BuP_4 promotes both intra- and intermolecular transesterification reactions, thus leading to random copolymers. By using ROP and the “catalyst-switch” strategy [benzyl alcohol, t-BuP_4/neutralization with diphenyl phosphate/(t-BuP_2)], we were able to synthesize different well-defined PML-b-PSL block copolymers (MLs: dodecalactone, ω-pentadecalactone, and ω-hexadecalactone; SLs: δ-valerolactone and ε-caprolactone). The thermal properties and the phase behavior of these block copolymers were studied by differential scanning calorimetry and X-ray diffraction spectroscopy. This study shows that the thermal properties and phase behavior of PMLs-b-PSLs are largely influenced by the PMLs block if PMLs components constitute the majority of the block copolymers

Block Copolymers of Macrolactones/Small Lactones by a "Catalyst-Switch" Organocatalytic Strategy. Thermal Properties and Phase Behavior

Poly(macrolactones) (PMLs) can be considered as biodegradable alternatives of polyethylene; however, controlling the ring-opening polymerization (ROP) of macrolactone (ML) monomers remains a challenge due to their low ring strain. To overcome this problem, phosphazene (t-BuP_4), a strong superbase, has to be used as catalyst. Unfortunately, the one-pot sequential block copolymerization of MLs with small lactones (SLs) is impossible since the high basicity of t-BuP_4 promotes both intra- and intermolecular transesterification reactions, thus leading to random copolymers. By using ROP and the “catalyst-switch” strategy [benzyl alcohol, t-BuP_4/neutralization with diphenyl phosphate/(t-BuP_2)], we were able to synthesize different well-defined PML-b-PSL block copolymers (MLs: dodecalactone, ω-pentadecalactone, and ω-hexadecalactone; SLs: δ-valerolactone and ε-caprolactone). The thermal properties and the phase behavior of these block copolymers were studied by differential scanning calorimetry and X-ray diffraction spectroscopy. This study shows that the thermal properties and phase behavior of PMLs-b-PSLs are largely influenced by the PMLs block if PMLs components constitute the majority of the block copolymers

Self-assembly of telechelic tyrosine end-capped PEO and poly(alanine) polymers in aqueous solution

The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(l-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers—in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide–polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped “associative polymers”. Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-group

Synthesis and characterization of linear triblock polymers

Block copolymers self-assemble into periodic nanoscale domains have attracted great interest as nanolithographic templates. Due to the ability to control both the morphologies and periodicity of the pattern on the scale of tens of nanometer over large area, thin films of block copolymers have been used extensively to pattern nanowire arrays, semiconductors and storage devices. The main purpose of this study is the synthesis of tribock terpolymers poly(butadiene-b-styrene-b-methyl methacrylate) (PB1,4-b-PS-b-PMMA), poly(styrene-b-butadiene-b-methyl methacrylate) (PS-b-PB1,4-b-PMMA) and poly(isoprene-b-styrene-b-2-vinyl pyridine) (PΙ-b-PS-b-P2VP) by anionic polymerization and the use of these triblocks for pattern transfer into silica. An array of silica rings has been demonstrated from (PB-b-PS-b-PMMA) triblock terpolymer lithography by adjusting the solvent-annealing vapor and film thickness. After selectively etching away PB and PMMA domains, the ring pattern was transferred by a reactive ion etch method. Furthermore, by using the PS-b-PB-b-PMMA triblock, we create original patterns which can be used as magnetic domain wall. Last but not least, by using the PI-b-PS-b-P2VP triblock we showed a simple way for a defect free array of metal deposit.Η αυτοοργάνωση των συμπολυμερών και η καλή διευθέτησή τους σε κλίμακα νανομέτρων βρίσκει τεράστια εφαρμογή στην επιστήμη της λιθογραφίας. Η ικανότητα των συμπολυμερών να δημιουργούν επιφάνειες δεκάδων νανομέτρων με συγκεκριμένη μορφολογία έχει χρησιμοποιηθεί εκτενώς για την δημιουργία νανοκαλωδίων, ημιαγωγών και συσκευών αποθήκευσης πληροφοριών. Σκοπός της παρούσας εργασίας είναι η σύνθεση των τρισυσταδικών τριπολυμερών πολυβουταδιένιο 1,4-b-πολυστυρένιο-b-πολυμεθακρυλικός μεθυλεστέρας (PB1,4-b-PS-b-PMMA), πολυστυρένιο-b-πολυβουταδιένιο 1,4-b-πολυμεθακρυλικός μεθυλεστέρας (PS-b-PB1,4-b-PMMA) και πολυισοπρένιο-b-πολυστυρένιο-b-πολυ-2-βινυλοπυριδίνη (PΙ-b-PS-b-P2VP) με ανιοντικό πολυμερισμό και η χρησιμοποίησή τους για τη μεταφορά σχεδίου σε επιφάνεια πυριτίου. Μια περιοχή από δαχτυλίδια δημιουργήθηκε χρησιμοποιώντας το τριπολυμερές PB1,4-b-PS-b-PMMA και ρυθμίζοντας κατάλληλα παραμέτρους όπως το πάχος του πολυμερικού υμενίου και την ανόπτηση με διαλύτη. Μετά την εκλεκτική απομάκρυνση των συστάδων PB και PMMA εφαρμόζοντας εγχάραξη με αντιδρώντα ιόντα, το σχέδιο των δαχτυλιδιών μεταφέρθηκε με επιτυχία. Επιπλέον, χρησιμοποιώντας το τριπολυμερές PS-b-PB1,4-b-PMMA δημιουργήθηκαν πρωτότυπα σχέδια τα οποία θα μπορούσαν να χρησιμοποιηθούν για τη δημιουργία διακριτών μαγνητικών περιοχών. Τέλος μελετήθηκε η εναπόθεση μετάλλου στο τριπολυμερές PΙ-b-PS-b-P2VP και οδήγησε σε μεταλλικές περιοχές με πολύ καλή διευθέτηση

pH-Sensitive nanogates based on poly(l-histidine) for controlled drug release from mesoporous silica nanoparticles

The design and synthesis of novel poly(l-histidine)-grafted mesoporous silica nanoparticles (MSNs) by a surface-initiated ring-opening polymerization process (ROP) is reported. Using (3-aminopropyl)triethoxysilane (APTES) to introduce primary amino groups onto the MSN outer surface that work as ROP initiators, the nanoparticles were decorated with a uniform pH-sensitive poly(l-histidine) (PHis) shell. The method applied for the MSN functionalization, guaranteed that PHis chains were not grafted inside the MSNs' nanochannels. Successful grafting of the PHis chains was confirmed by FT-IR spectroscopy, TEM and TGA, while the controlled character of the polymerization was monitored by SEC analysis. Dynamic light scattering (DLS) and zeta potential analysis were used to reveal the pH-responsive nature of the polypeptide-gated MSNs. The role of the grafted PHis chains as pH-sensitive nanogates for the MSN pores was verified by drug loading and release studies, using the model anticancer drug doxorubicin (DOX). DOX was efficiently loaded within the nanochannels of the hybrid MSN@PHis nanostructures (approximately 90%), and was released in a relatively controlled pH-triggered manner. Overall, the described materials are promising candidates as nanocarriers for potential drug delivery applications. © The Royal Society of Chemistry 2016

Well-Defined Cyclic Triblock Terpolymers: A Missing Piece of the Morphology Puzzle

Two well-defined cyclic triblock terpolymers, missing pieces of the terpolymer morphology puzzle, consisting of poly­(isoprene), polystyrene, and poly­(2-vinylpyridine), were synthesized by combining the Glaser coupling reaction with anionic polymerization. An α,ω-dihydroxy linear triblock terpolymer (OH-PI_1,4-<i>b</i>-PS-<i>b</i>-P2VP-OH) was first synthesized followed by transformation of the OH to alkyne groups by esterification with pentynoic acid and cyclization by Glaser coupling. The size exclusion chromatography (SEC) trace of the linear terpolymer precursor was shifted to lower elution time after cyclization, indicating the successful synthesis of the cyclic terpolymer. Additionally, the SEC trace of the cyclic terpolymer produced, after cleavage of the ester groups, shifted again practically to the position corresponding to the linear precursor. The first exploratory results on morphology showed the tremendous influence of the cyclic structure on the morphology of terpolymers

Anionic Polymerization of Styrene and 1,3-Butadiene in the Presence of Phosphazene Superbases

The anionic polymerization of styrene and 1,3-butadiene in the presence of phosphazene bases (t-BuP4, t-BuP2 and t-BuP1), in benzene at room temperature, was studied. When t-BuP1 was used, the polymerization proceeded in a controlled manner, whereas the obtained homopolymers exhibited the desired molecular weights and narrow polydispersity (Ð &lt; 1.05). In the case of t-BuP2, homopolymers with higher than the theoretical molecular weights and relatively low polydispersity were obtained. On the other hand, in the presence of t-BuP4, the polymerization of styrene was uncontrolled due to the high reactivity of the formed carbanion. The kinetic studies from the polymerization of both monomers showed that the reaction rate follows the order of [t-BuP4]/[sec-BuLi] &gt;&gt;&gt; [t-BuP2]/[sec-BuLi] &gt;&gt; [t-BuP1]/[sec-BuLi] &gt; sec-BuLi. Furthermore, the addition of t-BuP2 and t-BuP1 prior the polymerization of 1,3-butadiene allowed the synthesis of polybutadiene with a high 1,2-microstructure (~45 wt %), due to the delocalization of the negative charge. Finally, the one pot synthesis of well-defined polyester-based copolymers [PS-b-PCL and PS-b-PLLA, PS: Polystyrene, PCL: Poly(ε-caprolactone) and PLLA: Poly(L-lactide)], with predictable molecular weights and a narrow molecular weight distribution (Ð &lt; 1.2), was achieved by sequential copolymerization in the presence of t-BuP2 and t-BuP1

Controlled polymerization of histidine and synthesis of well-defined stimuli responsive polymers. Elucidation of the structure–aggregation relationship of this highly multifunctional material

We present the synthesis of the novel monomer Nim-trityl-protected N-carboxy anhydride of l-histidine (Trt-HIS-NCA) for the synthesis of poly(l-histidine) (PHIS). Kinetic studies of the ring opening polymerization of Trt-HIS-NCA followed first order kinetics, indicating that the polymerization is &quot;living&quot;. The high purity of the synthesized monomer along with the use of high vacuum techniques resulted in the controlled polymerization of histidine in a variety of macromolecular architectures exhibiting high degrees of molecular and compositional homogeneity. The conformation of poly(l-histidine) (PHIS) was studied at different pH values and temperatures by circular dichroism, revealing that it adopts a random coil conformation at low pH and temperatures, a β-sheet conformation at higher pH, and probably a broken β-sheet conformation at higher temperatures. We found that the pKa of the PHIS homopolymer depends on the molecular weight. Addition of hydrophobic amino acids randomly distributed along the PHIS chain hinders the organization of PHIS, resulting in the formation of the random coil conformation even at higher pH. The influence of either leucine (LEU) or γ-benzyl-l-glutamate (BLG) randomly distributed along the PHIS chain on the pKa and degree of protonation in the terpolymers revealed that although the pKa is lower, the protonation of PHIS increases at lower pH values, while it is lower at a higher pH as compared to that obtained for PHIS. The aggregates of PEO-b-P(HIS-co-PLEU(BLG)) in water were found to swell more by decreasing the pH and increasing the hydrophobic amino acids, and eventually become disrupted. Surprisingly, at pH = 7.4, the increase in temperature leads to lower aggregation of the PEO-b-PHIS due to the transition of the secondary structure. The results indicate that it is possible to fine-tune the protonation of PHIS as a function of pH and temperature, and thus to control the conditions where the aggregates will be disrupted, a prerequisite for drug and gene delivery applications. © 2014 the Partner Organisations