Types and properties of metal-free catalysts for living polymerizations of biomaterials

Syntéza biokompatibilních a biodegradabilních polyesterů, použitelných převážně v medicíně, využívá pro polymeraci za otevření kruhu katalyzátory na bázi kovu (např. Sn, Al atd.), které se mohou po implantaci deponovat v těle. Podstatou bakalářské práce je popis netoxických "metal-free" karbenových sloučenin a jejich vlastností použitelných jako katalyzátory pro polymeraci cyklických esterů. Příprava těchto stabilních karbenových katalyzátorů a jejich charakterizace je cílem experimentání práce.Synthesis of biocompatible and biodegradable polyesters applicable mainly in biomedicine uses metal catalysts (based on Sn, Al etc.) for ring opening polymerization, which could be deposited in a body after implantation. Objective of the bachelor thesis is description of non-toxic metal-free carbene compounds and their properties utilizable as catalysts for polymerization of cyclic esters. Preparation of these stable free carbene catalysts and their characterization is the main goal of the experimental work.

Novel "green" catalysts for controlled ring-opening polymerization of lactide

Syntéza polylaktidu (PLA) polymerací za otevření kruhu cyklického monomeru (ROP) může být uskutečněna různými způsoby. Literatura uvádí více než 100 katalytických systémů, jejichž pomocí lze polylaktid a jiné biodegradabilní alifatické polyestery získat. Například organokovové katalyzátory na bázi Sn, Zn, Al atd. se po splnění své polymerační funkce stávají kontaminanty a pro humánní implantáty je použití takového materiálu diskutabilní. V současné době jsou v centru výzkumné pozornosti nové N-heterocyklické karbenové katalyzátory. Tyto „metal-free“ katalytické struktury jsou schopné reprodukovatelně řídit syntézu polymerů předem definované molekulové hmotnosti s definovanými koncovými skupinami a nízkou polydisperzitou, která je charakteristická pro živý průběh polymerace. Nabízí se možnost syntézy blokových kopolymerů a různorodých makromolekulárních architektur. Předložená diplomová práce se zabývá studiem polymerace cyklického monomeru D,L-laktidu katalyzované N-heterocyklickým karbenem. Polymerace byly vedeny v přítomnosti benzylalkoholu jako iniciátoru v roztoku THF. Byl sledován vliv složení reakčního systému monomer – iniciátor – katalyzátor. Dále byly připraveny polymery opticky čistého L-laktidu s makroiniciátory PEG s Mn = 1000 a 2000 g/mol. Střední číselná molekulová hmotnost (Mn) a polydisperzita (PDI) byly stanoveny pomocí GPC. Definovatelnost koncových skupin vybraných polymerů byla prokázána pomocí 1H NMR.The synthesis of polylactide (PLA) by ring-opening polymerization (ROP) of cyclic monomer can be realized by different routes. More than 100 catalysts for the synthesis of polylactide and other biodegradable aliphatic polyesters are published in the literature. For example organometallic catalysts based on Sn, Zn, Al etc. after finishing polymerization function became contaminants and using obtained polymer material in human body is controversial. At present, the research is focused on novel N-hererocyclic carbene catalysts. These metal-free catalysts are able to produce polymers with controlled molecular weight, narrow polydispersity, end-group fidelity with high reproducibility as well as to synthesize the block copolymers and complex macromolecular architectures, which is characteristic for living polymerization system. This diploma thesis is focused on study of polymerization of cyclic monomer D,L-lactide catalyzed by N-hererocyclic carbene. Polymerizations were carried out at the presence of benzylalcohol as initiator at THF. We were focused on the influence of composition of reaction system monomer – initiator – catalyst. Polymers of optically pure L-lactide with macroinitiators PEG with Mn of 1000 a 2000 g/mol were prepared as well. Number average molecular weight (Mn) and polydispersity index (PDI) was determined by GPC. 1H NMR was used to prove end-group fidelity.

a structure-activity correlation

The polymerization of octamethylcyclotetrasiloxane (D4) is investigated using several five-, six- and seven-membered N-heterocyclic carbenes (NHCs). The catalysts are delivered in situ from thermally susceptible CO2 adducts. It is demonstrated that the polymerization can be triggered from a latent state by mild heating, using the highly nucleophilic 1,3,4,5-tetramethylimidazol-2-ylidene as organocatalyst. This way, high molecular weight PDMS is prepared (up to >400 000 g/mol, 1.6 < ÐM < 2.5) in yields >95%, using low catalyst loadings (0.2–0.1 mol %). Furthermore, the results suggest that a nucleophilic, zwitterionic mechanism is in operation, in preference to purely anionic polymerization

Melt block copolymerization of ε-caprolactone and L-lactide

AB block copolymers of ε-caprolactone and (L)-lactide could be prepared by ring-opening polymerization in the melt at 110°C using stannous octoate as a catalyst and ethanol as an initiator provided ε-caprolactone was polymerized first. Ethanol initiated the polymerization of ε-caprolactone producing a polymer with ε-caprolactone derived hydroxyl end groups which after addition of L-lactide in the second step of the polymerization initiated the ring-opening copolymerization of L-lactide. The number-average molecular weights of the poly(ε-caprolactone) blocks varied from 1.5 to 5.2 × 103, while those of the poly(L-lactide) blocks ranged from 17.4 to 49.7 × 103. The polydispersities of the block copolymers varied from 1.16 to 1.27. The number-average molecular weights of the polymers were controlled by the monomer/hydroxyl group ratio, and were independent on the monomer/stannous octoate ratio within the range of experimental conditions studied. When L-lactide was polymerized first, followed by copolymerization of ε-caprolactone, random copolymers were obtained. The formation of random copolymers was attributed to the occurrence of transesterification reactions. These side reactions were caused by the ε-caprolactone derived hydroxyl end groups generated during the copolymerization of ε-caprolactone with pre-polymers of L-lactide. The polymerization proceeds through an ester alcoholysis reaction mechanism, in which the stannous octoate activated ester groups of the monomers react with hydroxyl groups

Compare and contrast the reaction coordinate diagrams for chemical reactions and cytoskeletal force generators.

Reaction coordinate diagrams are used to relate the free energy changes that occur during the progress of chemical processes to the rate and equilibrium constants of the process. Here I briefly review the application of these diagrams to the thermodynamics and kinetics of the generation of force and motion by cytoskeletal motors and polymer ratchets as they mediate intracellular transport, organelle dynamics, cell locomotion, and cell division. To provide a familiar biochemical context for discussing these subcellular force generators, I first review the application of reaction coordinate diagrams to the mechanisms of simple chemical and enzyme-catalyzed reactions. My description of reaction coordinate diagrams of motors and polymer ratchets is simplified relative to the rigorous biophysical treatment found in many of the references that I use and cite, but I hope that the essay provides a valuable qualitative representation of the physical chemical parameters that underlie the generation of force and motility at molecular scales. In any case, I have found that this approach represents a useful interdisciplinary framework for understanding, researching, and teaching the basic molecular mechanisms by which motors contribute to fundamental cell biological processes

Straightforward synthesis of functionalized cyclic polymers in high yield via RAFT and thiolactone-disulfide chemistry

An efficient synthetic pathway toward cyclic polymers based on the combination of thiolactone and disulfide chemistry has been developed. First, heterotelechelic linear polystyrene (PS) containing an alpha-thiolactone (TLa) and an omega-dithiobenzoate group was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, employing a newly designed TLa-bearing chain transfer agent (CTA). The subsequent reaction of this heterotelechelic polymer with an amine, which acts as a nucleophile for both the TLa and dithiobenzoate units, generated the alpha,omega-thiol-telechelic PS under ambient conditions without the need for any catalyst or other additives. The arrangement of thiols under a high dilution afforded single cyclic PS (c-PS) through an oxidative disulfide linkage. The cyclic PS (c-PS) disulfide ring formation was evidenced by SEC, MALDI-TOF MS and H-1-NMR characterization. Moreover, we demonstrated a controlled ring opening via either disulfide reduction or thiol-disulfide exchange to enable easy and clean topology transformation. Furthermore, to illustrate the broad utility of this synthetic methodology, different amines including functional ones were employed, allowing for the one-step preparation of functionalized cyclic polymers with high yields

Vinylic Addition Polynorbornene in Catalysis

Vinylic addition polynorbornenes (VA-PNB) result from the insertion polymerization of norbornene or specific norbornene derivatives catalyzed by transition metal com- plexes. The VA-PNB skeleton is completely aliphatic and keeps the bicyclic structure of norbornene. This saturated polymer is thermally and chemically very stable and it is a very robust scaffold to support catalysts or reagents for catalytic applications. Several VA-PNBs are now available with suitable functional groups (halogen, alkenyl, carbonates) that can be used as starting materials to introduce the functionalization of choice by post-polymerization reactions. This has been applied to anchor organocatalysts on VA-PNB as well as ligands that can be used to synthesize supported metal catalysts. The reported examples of the use of VA-PNB-linked catalysts and their recyclability will be presented. VA-PNBs have also proved useful in the context of organotin chemistry to solve the problem of tin contamination by an efficient separation and the reuse of tin byproducts. Its uses in the Stille cross-coupling reaction and tin-hydride radical proc- esses will be discussed.MINECO (SGPI, grant CTQ2016-80913-P)Junta de Castilla y León (grants VA062G18 and VA051P17 and a fellowship to RGL

End-group functionalization of poly(2-oxazoline)s using methyl bromoacetate as initiator followed by direct amidation

Poly(2-alkyl/aryl-2-oxazoline)s (PAOx) are an alluring class of polymers for many applications due to the broad chemical diversity that is accessible for these polymers by simply changing the initiator, terminating agent and the monomer(s) used in their synthesis. Additional functionalities (that are not compatible with the cationic ring-opening polymerization) can be introduced to the polymers via orthogonal post-polymerization modifications. In this work, we expand this chemical diversity and demonstrate an easy and straightforward way to introduce a wide variety of functional end-groups to the PAOx, by making use of methyl bromoacetate (MeBrAc) as a functional initiator. A kinetic study for the polymerization of 2-ethyl-2-oxazoline (EtOx) in acetonitrile (CH3CN) at 140 degrees C revealed relatively slow initiation and slower polymerization than the commonly used initiator, methyl tosylate (MeOTs). Nonetheless, well-defined polymers could be obtained with MeBrAc as initiator, yielding polymers with near-quantitative methyl ester end-group functionality. Next, the post-polymerization modification of the methyl ester end-group with different amines was explored by introducing a range of functionalities, i.e. hydroxyl, amino, allyl and propargyl end-groups. The lower critical solution temperature (LCST) behavior of the resulting poly(2-ethyl-2-oxazoline)s was found to vary substantially in function of the end-group introduced, whereby the hydroxyl group resulted in a large reduction of the cloud point transition temperature of poly(2-ethyl-2-oxazoline), ascribed to hydrogen bonding with the polymer amide groups. In conclusion, this paper describes an easy and fast modular approach for the preparation of end-group functionalized PAOx

Ultra-high molecular weight silphenylene-siloxane polymers

Silphenylene-siloxane copolymers with molecular weights above one million were prepared using a two stage polymerization technique. The technique was successfully scaled up to produce 50 grams of this high polymer in a single run. The reactive monomer approach was also investigated using the following aminosilanes: bis(dimethylamino)dimethylsilane, N,N-bis(pyrrolidinyl)dimethylsilane and N,N-bis(gamma-butyrolactam)dimethylsilane). Thermal analyses were performed in both air and nitrogen. The experimental polymers decomposed at 540 to 562 C, as opposed to 408 to 426 C for commercial silicones. Differential scanning calorimetry showed a glass transition (Tg) at -50 to -55 C for the silphenylene-siloxane copolymer while the commercial silicones had Tg's at -96 to -112 C