Gotowa bibliografia na temat „Periodically Grafted Amphiphilic Copolymers (PGACs)”

The mutual immiscibility between the three segments, namely backbone HC, and pendant PEG and FC segments, causes zigzag folding of the polymer such that FC segments lie on one side and PEG on the other, thereby generating Janus-type folded chains.

Block copolymers can self-assemble into a variety of periodic nanostructures and therefore, are promising candidates for a diverse range of applications. While self-assembly of block copolymers has been widely studied and exploited, graft copolymers have remained far less explored in this context. One of the primary reasons for this is that the most commonly used methods to prepare graft copolymers leads to polymers that do not have precisely defined structures; specifically, controlling the precise location of the grafted segments is a synthetically difficult challenge. In typical chain polymerization processes, statistically random incorporation of monomers takes place and consequently, the periodicity of the grafted segment along the backbone is very difficult to control precisely; therefore, such methods cannot be utilized to prepare periodically grafted copolymers. Some recent efforts towards the preparation of sequence regulated copolymers using controlled radical polymerization in conjunction with periodic dosing of a commoner could provide an alternative to better regulate the periodicity, although this will also not be perfectly periodic. The only approach to control the periodicity perfectly is to utilize condensation polymerization approaches, wherein one of the monomers serve as a spacer whereas the other provides the opportunity to install the graft segment, as depicted in Scheme 1. One of the earliest examples of the utilization of a condensation approach to locate desired units at periodic intervals was reported by Wagener and co-workers using Acrylic Diene Metathesis (ADMET) process.1 ]n periodicity ]n graft segment Scheme 1. Synthetic scheme for the preparation of periodically grafted copolymers using condensation polymerization. From our lab, Roy et al. developed periodically grafted amphiphilic copolymers (PGAC), based on a readily available starting material, diethyl malonate;2 melt trans-esterification between diethyl malonate, containing a pendant hexaethylene glycol monomethyl ether (HEG) segment and 1,22-docosane diol resulted in PGAC wherein the hydrophilic oligo ethylene glycol units were placed on every 27th atom along the backbone (Scheme 2). Such PGAC underwent self-segregation and adopted a folded zigzag conformation, which was driven by the intrinsic immiscibility of the alkylene and HEG segments and was reinforced by the strong tendency for long chain alkylene segments to crystallize in a paraffinic lattice. However, one of the drawbacks of the above approach was that the hydrophilic pendant unit was installed at the monomer stage and consequently, the synthetic approach does not allow easy variation of the hydrophilic grafted segment; this limits the flexibility and any structural variation of the pendant segment would be synthetically tedious. 150 oC DBTDL 5 20 DBTDL = Dibutyltin dilaurate Scheme 2. Synthesis of PGAC, based on diethyl malonate, and immiscibility-driven folding of such PGACs. Mandal et al. developed a more general strategy for the synthesis of such periodically grafted systems; they prepared periodically clickable polyesters carrying propargyl groups at regular intervals, by the solution polycondensation of 2-propargyl-1,3-propanediol or 2,2-dipropargyl-1,3-propanediol and the acid chloride of 1,20-eicosanedioic acid. Such periodically clickable polyesters were shown to react quantitatively with a fluoroalkyl azide3 and PEG 350 azide4, thus allowing them to place different kinds of functionalities precisely along the backbone, as shown in Scheme 3. The immiscibility of the alkylene and fluoroalkyl/PEG segments caused the polymer chains to fold in a zigzag fashion, thereby facilitating the segregation of these segments, as observed earlier in the study by Roy et al.2 The objective of this study was to place various desired functionalities along the polymer backbone and examine their effect on the self-assembly behaviour and morphology of such periodically clicked systems. Scheme 3. Synthetic scheme for the generation of periodically clickable polyesters and their subsequent functionalization via Cu-catalysed click chemistry. In Chapter 2, we describe an alternative general strategy for the scalable synthesis of periodically graftable polyesters and their subsequent functionalization to generate a wide variety of periodically grafted systems. The importance of our approach lies in our choice of the monomer, which is based on itaconic acid, an inexpensive and bio-sourced molecule. We demonstrated that dibutyl itaconate can be melt-condensed with aliphatic diols to generate unsaturated polyesters (Scheme 4); importantly, we showed that the double bonds in the itaconate moiety remain unaffected during the melt polymerization. A particularly useful attribute of these polyesters is that the exo-chain double bonds are conjugated to the ester carbonyl and therefore, can serve as excellent Michael acceptors. A variety of organic thiols, such as alkane thiols, MPEG thiol, thioglycerol, derivative cysteine etc., were shown to quantitatively Michael-add to the exo-chain double bonds and generate interesting functionalized polyesters; similarly, organic amines, such as N-methylbenzylamine, diallyl amine and proline also underwent Michael addition across the double bond (Scheme 4). Thus, such poly(alkylene itaconate)s could be utilized to place diverse functionalities at regular intervals along the polymer backbone. Scheme 4. Preparation of periodically graftable polyesters, based on itaconic acid, and their subsequent modification by Michael addition. In Chapter 3, we examined a series of periodically grafted polyesters carrying long crystallizable alkylene (C-20) segments along the backbone and pendant polyethylene glycol monomethyl ether (MPEG) segments grafted at periodic intervals. Such periodically grafted amphiphilic copolymers (PGAC) having MPEG graft segments of varying lengths were prepared by utilizing the activated exo-chain double bonds in poly(icosyl itaconate) (PII) that carries a 20-carbon alkylene segment; MPEG thiols of varying lengths (TREG, 350, 550 and 750) were quantitatively grafted under standard Michael addition conditions to yield the required graft copolymers, as shown in Scheme 5. Scheme 5. Synthesis of a series of periodically grafted amphiphilic copolymers (PGAC) utilizing post-polymerization modification via Michael addition with MPEG thiols of varying lengths. The immiscibility of the backbone alkylene and pendant MPEG segments, and the strong propensity of the alkylene segments to crystallize in a paraffinic lattice, drive these systems to fold in a zigzag fashion and subsequently organize into a lamellar morphology, as shown in Scheme 6. Interestingly, all the graft copolymers exhibited a clear and invariant melting transition at ~44°C that suggested the crystallization of the backbone C-20 segment; the MPEG segments were, however, amorphous except in the case of polymers carrying MPEG 550/MPEG-750 segments, wherein a second melting transition corresponding to the independent crystallization of the PEG segment was also seen. SAXS studies indicated that all of the samples exhibited lamellar morphologies wherein more importantly, the inter-lamellar spacing was seen to increase linearly with the MPEG length (Scheme 6). This study provides a new design for controlling the dimensions of the microphase-separated nanostructures at significantly smaller length scales (sub-10 nm) than is typically possible using block copolymers. Scheme 6. Schematic representation of formation of lamellar morphology in PGACs and control of interlamellar spacing in such systems. In order to understand the influence of having a mixture of MPEG lengths on the self-assembled morphology, in Chapter 4 we prepared a series of PGACs by co-grafting the parent poly(icosyl itaconate) with a mixture of two different MPEG thiols, namely MPEG-350 and MPEG-750; the mole-ratios of these two PEGs were varied to generate co-grafted PGACs, carrying different amounts of the two MPEG segments randomly distributed along the chain (Scheme 7). Parallely, we also examined the behaviour of physical mixtures of two different PGACs, one bearing MPEG-350 and the other MPEG-750 grafts; keeping the total MPEG content constant, we sought to examine the differences in the behaviour of randomly co-grafted polymers and physical mixtures. Scheme 7. Preparation of co-grafted PGACs and physical mixtures of two different PGACs. The co-grafted PGACs also exhibited a lamellar morphology; interestingly, the inter- lamellar spacing increased linearly with the total volume of PEG domain. This suggested that despite the presence of MPEG segments of two different lengths in the co-grafted samples, there occurred a reorganization of the PEG chains within the amorphous domain ensuring that the condition of incompressibility is not violated, thereby giving rise to a weighted average interlamellar spacing, as shown in Scheme 8. In contrast, the SAXS patterns of the physical mixtures revealed the presence of two distinct lamellar domains in the sample; this indicated that the two homo-grafted samples do not mix and form separate lamellar domains. The self- segregation induced folding and subsequent crystallization of the central alkylene segments clearly appeared to dominate the final morphology. Scheme 8. Schematic depiction of the possible scenarios that could arise when MPEG segments of two different lengths, namely MPEG350 and MPEG750, are present in the PGACs; top panel depicts the co-grafted PGACs, whereas the bottom panel shows the case of mixtures of PGACs with two different MPEG lengths. In Chapter 5, we have dealt with the design and synthesis of chain-end functionalizable polyalkylene itaconates. Changing the monomer from dibutyl itaconate to dipropargyl itaconate and using it in controlled excess allowed us to generate chain-end functionalizable polymers containing propargyl groups at the chain ends, in addition to the exo-chain double bonds along the backbone, thereby providing the opportunity for orthogonal functionalization. In order to obtain three different telechelic polymers with target DPs (degree of polymerization) of 5, 10 and 20 respectively, 3 different mole ratios of the two monomers (dipropargyl itaconate and 1,20-eicosanediol) were used (Scheme 9). Scheme 9. Synthetic scheme for the generation of chain-end functionalizable polyalkylene itaconates. Orthogonal functionalization of the resultant polymers was carried out using thiol-Michael addition and Cu(I)-catalysed alkyne-azide cycloaddition (AAC), without interference between the functional handles present along the polymer backbone and the chain-end, respectively. Michael addition with triethylene glycol thiol and subsequent Cu-catalysed click reaction with MPEG 750 azide led to the generation of ABA type triblock copolymers where the middle block is a periodically grafted amphiphilic block and the two linear end blocks are hydrophilic in nature. Furthermore, such propargyl-terminated polyalkylene itaconates were used as macromonomers to prepare multiblock copolymers. The telechelic polymers were first treated with PEG 600 diazide, resulting in the formation of alternating multiblock copolymers; these multiblock copolymers were further reacted with thioglycerol to generate amphiphilic multiblock copolymers where one of the blocks is a periodically functionalized amphiphilc block, as depicted in Scheme 10. In both these amphiphilic block copolymer systems, a key feature is that the periodically functionalized amphiphilic block folds into a zigzag form, as evident from the presence of a nearly invariant melting peak corresponding to the crystallization of the alkylene segment. Scheme 10. Preparation of multiblock copolymers utilizing propargyl-terminated polyalkylene itaconates as a macromonomer. In summary, the thesis has demonstrated the design and synthesis of a series of novel amphiphilic copolymers using a bio-sourced monomer, wherein the driving theme is the immiscibility driven self-segregation that leads to the folding of the chain; these have been thoroughly examined using DSC, SAXS, WAXS, variable temperature FT-IR and AFM measurements. References (1) Berda, E. B.; Lande, R. E.; Wagener, K. B. Macromolecules 2007, 40, 8547. (2) Roy, R. K.; Gowd, E. B.; Ramakrishnan, S. Macromolecules 2012, 45, 3063. (3) Mandal, J.; Krishna Prasad, S.; Rao, D. S. S.; Ramakrishnan, S. Journal of the American Chemical Society 2014, 136, 2538. (4) Mandal, J.; Ramakrishnan, S. Langmuir 2015, 31, 6035.

In 1980’s a new class of material named as dendrimer became popular both in the field of polymer science and engineering. Dendrimer is an example of symmetric, highly branched three dimensional globular nano-object. It possess several interesting physical and chemical properties like low solution and melt-viscosity, lower intermolecular chain entanglement, large number of end groups placed at the molecular periphery, relatively high solubility with respect to their linear counterpart. In order to get this perfectly branched structure, one has to go through the tedious multistep synthetic approach, repetitive chromatographic purification and protection-deprotection strategies in every step; all of which limits the large scale production and thus commercialization. On the other hand, hyperbranched polymer, a highly branched analogue of dendritic polymer with few defects in their branching architecture, which can be prepared in a single step, show similar physical and chemical properties as that of dendrimer. Polymerization of AB2 monomer is one of the well established method to generate hyperbranched polymer which upon polymerization, generates plenty of ‘B ’groups at the periphery along with a single ‘A’ group as a focal point in the resulting hyperbranched polymer as shown in Figure 1. From the structural point of view, hyperbranched polymers consist of three distinctly different compartments such as periphery, interior and a (single) focal point. During the past decade our lab have developed a novel melt trans-etherification process to generate polyethers and have utilized to access to a wide variety of hyperbranched structures. One of the challenges we addressed is to selectively functionalize the periphery of the hyperbranched polymer during the polymerization process. Polycondensation of ‘AB2’ monomer is not sufficient enough to generate a wide variety of hyperbranched polymer as the periphery of hyperbranched polymer is limited to the ‘B’ functional group unless it could be modified via ‘post-polymerization modifications’. Copolymerization of ‘AB2’ monomer with stoichiometric amount of ‘A-R’ monomer should result in hyperbranched polymer decorated with ‘R’ groups in the periphery that can be prepared in a single step. One of the prerequisite in the ‘AB2+A-R’ approach is that the comonomer ‘A-R’ should have silent ‘R’ group which does not interfere during the polymerization. During the copolymerization process with stoichiometric amount of ‘A-R’ monomer, ‘AB2’ monomer having one equivalent excess of ‘B’ can react with the ‘A’ group from ‘A-R’ monomer eventually generating the hyperbranched structure with peripheral ‘R’ groups. By appropriately choosing the ‘R’ group, one can access a wide class of hyperbranched polymer with the required functionality. Further by having a reactive ‘R’ group that is not participating in polymerization can act as a handle for post-polymerization modifications. For instance, copolymerization of 1-(6-Hydroxyhexyloxy)-3,5-bis(methoxymethyl)-2,4,6-trimethylbenzene (Hydroxy as ‘A’ and methoxy as ‘B’) and 6-bromo-1-hexanol where ‘OH’ and ‘-(CH2)6Br’ is ‘A’ and ‘R’ functional groups respectively, generates hyperbranched polymer with peripheral alkyl bromide functional groups as shown in Figure 2. The peripheral alkylbromides has been quantitatively transformed to quaternary ammonium or pyridinium salts using trimethyl amine or pyridine respectively. Thus by the post polymerization modification, we have transformed a hydrophobic hyperbranched polymer to a water soluble cationic hyperbranched polymer by simple and efficient post-polymerization modification. In a slightly different objective we Another problem that I have addressed is the difficulty associated with the aforementioned copolymerization approach. In spite of the fact that stoichiometric amounts of ‘A-R’ type monomer was taken in ‘AB2 + A-R’ approach, the extent of peripheral functionalization i.e. the incorporation of ‘R’ group is relatively lower. Further the molecular weight of the hyperbranched polymer obtained is also not high. One of the reasons we adopted ‘AB2 + A-R’ approach is to provide a functional handle for the subsequent post-polymerization modification. We modified the ‘AB2’ type monomer with a functionalizable handle to circumvent the lower amount of incorporation of the ‘A-R’ type monomer in ‘AB2 + A-R’ approach. Of all the readily functionalizable handles, click chemistry found to be a very useful tool for the post-polymerization modifications as the reactions conditions are mild, no side product, high selectivity, easy purification, etc. Another advantage of this reaction is that, we can incorporate any type of functional group starting from a single clickable parent hyperbranched polymer. In this particular project, I have Earlier design of the ‘AB2’ type monomer in our group, to prepare hyperbranched polymer via melt transetherification process, involved benzylic methoxy groups as ‘B’ in ‘AB2’ monomer leading to a hyperbranched polymer with peripheral methoxy groups. Transetherification under melt-conditions is an equilibrium reaction which was driven towards the hyperbranched polymer by continuous removal of methanol from the system as a volatile alcohol. In the new design of ‘AB2’ monomer; we have used benzylic allyloxy groups as ‘B’ in ‘AB2’ monomer, where in polymerization is driven by the continuous removal of allyl alcohol (instead of methanol as in the previous case), generates hyperbranched polymer with peripheral allyloxy group containing hyperbranched polymer. The allyloxy groups can be subsequently functionalized with a variety of thiol, we prepared a hydrocarbon-soluble octadecyl-derivative, amphiphilic systems using 2-mercaptoethanol and chiral amino acid (N-benzoyl cystine) hyperbranched structures by using thiol-ene click reactions (Figure 3). Polymers prepared from the parent hyperbranched polymer have significantly different physical properties like glass transition temperature (Tg), melting point (Tm) etc; thus considering the versatility of functionalization, parent polymer could be envisioned as a clickable hyperscaffold. More interestingly by functionalizing cystine derivative, we have demonstrated the possibility of biconjugation of the hyperbranched polymer. In summary, the limitations of ‘AB2+A-R’ copolymerization approach (low molecular weight Molecular weight and molecular weight distribution are very important parameters that influence the physical property and thus the application of the polymeric materials. As predicted by Flory, hyperbranched polymers are inherently polydisperse in nature and it tends to infinity when the percent of conversion is very high. Experimentally observed value of polydispersity is also significantly higher compared to their linear analogues. Control of the molecular weight and polydispersity of hyperbranched polymer by using a suitable amount of reactive multifunctional core has been demonstrated in this project. We have substantiated by using very little amount of ‘B3’ core along with ‘AB2’ monomer; wherein ‘B’ in ‘B3’ are more reactive than ‘B’ in ‘AB2’ monomer, regulate the molecular weight and polydispersity of the resulting hyperbranched polymer. As the ratio of core to monomer increases the molecular weight and polydispersity reduces in nearly linear fashion. In a slightly different objective, the core and periphery are functionalized with two different fluorophore by using orthogonal click reactions and demonstrated the possibility of energy transfer from periphery to the core of the hyperbranched polymer. In this section of my thesis, the self-assembly behavior of a periodically grafted amphiphilic copolymer has been studied. Polymer was synthesized via melt transesterification approach where hexaethylene glycol monomethyl ether (HEG) containing diester monomers are reacted with alkylyne diol monomers with varying carbon spacer (C12 and Another interesting problem, I approached is to functionalize the interior part of the hyperbranched polymer. In the case of dendrimer, as it is a step-wise synthesis, internal functionalization could be accomplished with the order of monomer addition i.e. by putting the internal functional group containing monomer first followed by other monomer not having those functional groups, whereas it is a bit challenging task for hyperbranched polymers especially when dealing with polycondensation of AB2 monomers, as it is a single step polymerization process. For a hyperbranched polymer in the polycondensation of ‘AB2’ monomer, the internal functional group should reside in between of the ‘A’ and ‘B’ functional group wherein the internal functional groups are silent during the process of polymerization. In order to do so, we have designed and synthesized a new AB2 monomer (a in Figure: 4). Here decanol is the volatile condensate that was removed during the transetherification reactions leading to a hyperbranched polymer having allyl group as the internal functional group and decyloxy as the peripheral functional group (b in Figure: 4). As a post-polymerization modification, the interior allyl groups were modified by thiol-ene click reaction with variety of thiol derivatives. In one example, the inherent hydrophobic nature of the parent hyperbranched polymer which is enhanced by the decyl chain at the molecular periphery, is converted to a alkaline water soluble hyperbranched polymer by the click reaction with mercapto succinic acid (d in Figure: 4) or mercapto propionic acid (c in Figure: 4) to the internal allyl groups, generating a novel amphiphilic hypersystem. This kind of amphiphilic systems are very interesting to study for their self-assembly behavior, in this particular case, the modified hyperbranched polymer adopts as a large spherical aggregates in alkaline water evidenced by FESEM (Figure: 4) and AFM images. Further investigation is being carried out to understand the exact nature of these aggregates. As the hyperbranched polymer contained ‘-S-‘ group in the interior, we utilized this as the scaffold for scavenging heavy metal ions like Hg2+ from aqueous solutions to the chloroform solution containing polymer. This hyperbranched polymer could trap Hg2+ ions even when present in ppm level of contamination.