Controlling Conformation of Macromolecules by Immiscibility Driven Self-Segregation

Controlling conformation of macromolecules, both in solution and solid state, has remained an exciting challenge till date as it confronts the entropy driven random coil conformation. Folded forms of biomacromolecules, like proteins and nucleic acids, have served as role-models to the scientists in terms of designing synthetic foldamers. The folded functional forms of proteins and nucleic acids have been shown to rely heavily on various factors, like directional hydrogen bonding, intrinsic conformational preferences of the backbone, solvation (e.g. hydrophobic effects), coulombic interactions, charge-transfer interactions, metal-ion complexation, etc. Chapter-1 discusses various designs of synthetic polymers explored by research groups world-over to emulate the exquisite conformational control exercised by biomacromolecular systems. Our laboratory has been extensively involved since 2004 in designing charge-transfer complexation induced folding of flexible donor-acceptor (DA) polymeric systems, such as those shown in Scheme 1. It was observed that such polymers adopt a folded conformation in polar solvents, like methanol, in the presence of an excess of an appropriate alkali metal ion. To explore folding in the solid state, Jonas and co-workers recently showed that a polyethylene-like polyester with long alkylene segments containing periodically located pendant propyl group forms a semicrystalline morphology with alternating crystalline and amorphous regions primarily because of the periodic folding of the backbone due to the steric exclusion of the propyl branches from the crystalline domains. In order to explore immiscibility-driven folding of polyethylene-like polyesters, Roy et al. designed a periodically grafted amphiphilic copolymer (PGAC) containing long alkylene segments (mimicking polyethylene) and pendant oligoethyleneglycol chains at periodic intervals (Scheme 2). Scheme 2: Proposed folding of a periodically grafted amphiphilic copolymer It was demonstrated that immiscibility between the hydrocarbon backbone and pendant PEG segments drives the polymer to adopt a folded zigzag conformation as shown in Scheme 2. The above synthetic strategy, however, does not permit easy structural variation of the side chain segments because the side-chain segment is covalently linked to the malonate monomer. In Chapter-2, a more general strategy to prepare periodically grafted copolymers has been described. In an effort to do so, we designed a series of clickable polyesters carrying propargyl/allyl functionality at regular intervals along the polymer backbone, as shown in Scheme 3. Scheme 3: Periodically clickable polyesters for the preparation of periodically grafted copolymers The polyesters were prepared by reacting either 2-propargyl-1,3-propanediol, 2,2-dipropargyl-1,3-propanediol or 2-allyl-2-propargyl-1,3-propanediol with an alkylene diacid chloride, namely 1,20-eicosanedioic acid chloride, under solution polycondensation conditions. Since these polyesters carry either, one propargyl, two propargyls or one propargyl and one allyl group on every repeat unit, it provides us an opportunity to synthesise exact graft copolymers with one side chain, two side chains or even two dissimilar side chains per repeat unit. In Chapter-3, the periodically clickable polyesters were reacted with MPEG-350 (PEG 350 monomethyl ether) azides using Cu(I) catalyzed azide-yne click reaction to generate periodically grafted amphiphilic copolymers (PGAC) carrying crystallizable hydrophobic backbone and pendant hydrophilic MPEG-350 side-chains (Scheme 4). Since the PGACs carry either one or two pendant MPEG-350 chains on every repeat unit, it allowed us to examine the effect of steric crowding on the crystallization propensity of the central alkylene segment. Scheme 4: Functionalization of periodically clickable polyesters with MPEG 350 azide by azide-yne click reaction From DSC studies, it was observed that increase in steric crowding at junctions resulting from increased side-chain volume hinders effective packing of the hydrocarbon backbone. As a result, both transition temperatures and the enthalpies associated with these transitions decreases. SAXS and AFM studies revealed the formation of lamellar morphology with alternate domains of PEG and hydrocarbon. Based on these observations, we proposed that self-segregation between hydrophobic backbone and hydrophilic side-chains induce the backbone to adopt a folded zigzag conformation (Scheme 5). Scheme 5: Schematic depiction of self-segregation induced folding of PGAC and their assembly on mica surface (AFM image) In order to study the effect of solvent polarity on conformational evolution of the periodically grafted amphiphilic copolymers, we randomly incorporated pyrene in the backbone of the polymer by reacting a small fraction (~ 5 mole %) of the propargyl groups with pyrene azide. Fluorescence study of the pyrene labelled polymer showed that increase in solvent polarity increases the intensity of the excimer band dramatically; this suggests the possible collapse of the polymer chain to the folded zigzag form. In an extension of this work, the PGAC was further used as template to synthesise layered silicates that appears to replicate the lamellar periodicity seen in the polymer. In order to study the effect of reversing the amphiphilicity on self-segregation, in Chapter-4, we synthesised a series of clickable polyesters carrying PEG segments of varying lengths, namely PEG 300, PEG 600 and PEG 1000, along the polymer backbone. The polymers were prepared by trans-esterification of 2-propargyl dihexylmalonate with different PEG-diols. These polyesters were then clicked with docosyl (C22) azide using Cu(I) catalyzed azide-yne click reaction to generate the desired periodically grafted amphiphilic polymers carrying crystallizable hydrophobic pendant chains at periodic intervals; the periodicity in this case was governed by the length of the PEG diols (Scheme 6). Scheme 6: PGACs carrying hydrophilic PEG backbone and crystallizable hydrophobic pendant docosyl chains Varying the average periodicity of grafting provided an opportunity to examine its consequences on the self-segregation behavior. Given the strong tendency of the pendant docosyl segments to crystallize, DSC studies proved useful to analyse the self-segregation; DOCOPEG 300 clearly exhibited the most effective self-segregation, whereas both DOCOPEG 600 and DOCOPEG 1000 showed weaker segregation. Based on the observations from DSC studies, we proposed that the PEG backbone adopts a hairpin like conformation (Scheme 7). Scheme 7: Proposed self-segregation through hairpin like conformation of backbone PEG segments In order to confirm the bulk morphology, we carried out small angle X-ray scattering (SAXS) and atomic force microscopic (AFM) studies. The SAXS profiles confirmed the observations from DSC studies, and only DOCOPEG 300 exhibited well-defined lamellar ordering. Thus, it is clear that the length of the backbone PEG segment (volume-fraction) strongly influences the morphology of the PGACs. Based on the inter-lamellar spacing from SAXS and the height measurements from AFM studies (Scheme 8), we proposed that these polymers form lamellar morphology through inter-digitation of the pendant docosyl side-chains. The observations from Chapters 3 and 4 suggested that the crystallization of the backbone has a dramatic effect on the conformation of the polymer backbone. In order to explore the possibility of independent crystallization of both backbone and pendant side-chains, the periodically clickable polyesters, described in Chapter-2, were quantitatively reacted with a fluoroalkyl azide, namely CF3(CF2)7CH2CH2N3 using Cu(I) catalyzed azide-yne click reaction; Chapter-5 describes these polyesters carrying long chain alkylene segments along the backbone and either one or two perfluoroalkyl segments located at periodic intervals along the polymer chain (Scheme 9). DSC thermograms of two of the samples showed two distinct endotherms associated with the melting of the individual domains, while the WAXS patterns confirm the existence of two separate peaks corresponding to the inter-chain distances within the crystalline lattices of the hydrocarbon (HC) and fluorocarbon (FC) domains; this confirmed the occurrence of independent crystallization of both the backbone and side chains. Scheme 10: Left-variation of SAXS profile of all three polymers as a function of temperature, Right- molecular modelling of representative FC-HC-FC triblock structures. Interestingly, a smectic-type liquid crystalline phase was observed at temperatures between the two melting transitions. SAXS data, on the other hand, revealed the formation of an extended lamellar morphology with alternating domains of HC and FC (Scheme 10). The inter-lamellar spacing calculated from SAXS matches reasonably well with those estimated from TEM images. Based on these observations, we proposed that the FC modified polymers adopt a folded zigzag conformation whereby the backbone alkylene (HC) segment becomes colocated at the center and is flanked by the perfluoroalkyl (FC) groups on either side, as depicted in Scheme 11. Melting of alternate HC domains first leads to the formation of a smectic-type liquid crystalline mesophase, wherein the crystalline FC domains retain the smectic ordering; this was confirmed by polarizing light microscopic observations. Scheme 11: Schematic presentation of self-segregation induced folding of polymer chains; and hence crystallization assisted assembly of these singly folded chains to form lamellar structure One interesting challenge would be to create unsymmetrical folded structures, wherein the top and bottom segments of the zigzag folded form would be occupied by two different segments, such as PEG and FC, whereas the backbone alkylene segment would form the central domain; this would lead to the possible formation of consecutive domains of PEG, HC and FC through immiscibility driven self-segregation process. In Chapter-6, several approaches to access such systems have been described; one such design that could have resulted in the successful synthesis of a periodically clickable polymer carrying orthogonally clickable propargyl and allyl groups along the backbone in an alternating fashion is depicted in (Scheme 12). The parent polyester was successfully synthesized and the propargyl group was first clicked with the FC-azide to yield the FC-clicked polyester; however, several attempts to click MPEG-SH onto the allyl groups using thiol-ene click reaction failed. Scheme 12: Scheme for the synthesis of alternating orthogonally clickable polymer In order to accomplish our final objective, we chose to first prepare the FC-clicked diacid chloride and polymerize it with an azide-alkyne clickable macro-diol, as depicted in Scheme 13; this approach was successful and yielded the desired clickable polyester bearing the FC segments at every alternate location. This polymer was then clicked with PEG-750 azide to yield the final targeted polymer that carries mutually immiscible FC and PEG-750 segments at alternating positions along the polymer backbone. The occurrence of self-segregation of FC, PEG-750 and the alkylene backbone (HC) was first examined by DSC studies, which appeared to suggest the presence of three peaks, although these were not very well-resolved. Scheme 13: Schematic for the synthesis of the polymer carrying FC and PEG 750 alternatingly along the backbone A schematic depiction of the anticipated organization of such unsymmetric folded macromolecules is shown in Scheme 15; it is evident that because of mutual immiscibility, the layers will be organized such that the FC domains of adjacent layers will be together and similarly the PEG domains of adjacent layers will also be together. Such an organization would lead to an estimated spacing that would correspond to a bilayer of the folded structures. Interestingly, SAXS study (Scheme 14) reveals the formation of lamellar morphology with a d-spacing of 14.6 nm. Scheme 14: Figure 6.10: SAXS profile of the polymer PE-FC-PEG 750 In order to gain an estimate of the expected inter-lamellar spacing, the end-to-end distance of a model repeat-unit was computed to be ~ 9.4 nm. It is, therefore, evident that the inter-lamellar spacing of 14.6 nm seen in the SAXS is significantly larger and must represent a bilayer type organization (Scheme 15). In this regard it is important to say that the organization of these alternatingly functionalized folded chains should give a variety of d-spacings. Because of highest electron density contrast of FC among PEG, HC and FC, we proposed that the d-spacing calculated from the SAXS profile corresponds to ‘d4’ in Scheme 15. This first demonstration of the formation of zigzag folded unsymmetric entities bearing dissimilar segments on either side of the folded chain holds exciting potential for a variety of different applications and beckons further investigations. Scheme 15: Schematic for the proposed self-assembly of the singly folded polymer chain

Tuning and in situ monitoring of surface-initiated, atom-transfer radical polymerization of acrylamide derivatives in water-based solvents

In order to gain better control over the growth and dispersity of surface-tethered poly(acrylamides), the SI-ATRP kinetics of N-isopropylacrylamide (NIPAM), N,N-dimethylacrylamide (DMAM) and N-hydroxyethyl acrylamide (HEAM) have been systematically investigated in situ in an 80 : 20 ethanol/water mixture by means of the quartz crystal microbalance with dissipation (QCM-D). The addition of tetraethylammonium chloride (tEtAmCl) or tetraethylammonium bromide (tEtAmBr) in association with additional CuIIX2 (X = Cl or Br) resulted in improved control over the polymerization kinetics. Evidence for such improved SI-ATRP kinetics was provided by a slower and more linear decrease in the resonance frequency of the QCM-D sensors, indicating a linear increase in solvated brush mass as a function of polymerization time. This was further validated by carrying out multiple re-initiations and measuring the growth of the polymer brushes upon each initiation, by means of both QCM-D and ellipsometry. An indirect estimation of the effect of improving the living nature of polymer brush growth on their dispersity was performed by carrying out nanoindentation experiments by means of colloidal-probe atomic force microscopy on polymer brushes grown under different reaction conditions. For an identical indentation load, polymer brushes grown in the absence of CuIIX2 and tEtAmX exhibited a much larger indentation depth, indicating a substantially softer structure, presumably as a consequence of the higher degree of chain-length dispersity

Impact of Dispersity and Hydrogen Bonding on the Lubricity of Poly(acrylamide) Brushes

The effects of chain‐length dispersity and monomer type on the lubricity of acrylamide‐based polymer brushes have been examined in aqueous media. The polymer brushes used have been synthesized by surface‐initiated, atom‐transfer radical polymerization of N,N‐dimethylacrylamide (DMAM), N‐hydroxyethyl acrylamide (HEAM), and N‐isopropylacrylamide. Polymerization reactions have been performed in the presence and also in the absence of CuX2 and tEtAmX (X = Cl or Br), in order to achieve polymer brushes with substantial differences in their chain‐length dispersities. While an influence of the dispersity on the lubricity of the polymer brushes can be observed, it is convoluted with the competing phenomena of hydrogen bonding and increased water content. The most hydrophilic, p(HEAM) brush exhibits the highest friction coefficient (μ) of ≈0.04 compared to ≈0.004 in the case of the p(DMAM) brush. Such a large difference is presumed to originate from the hydrogen bonding between the tribological countersurface (plasma‐oxidized poly(dimethylsiloxane)) and the p(HEAM) chains, as evidenced by the substantial reduction in μ when the friction measurements are performed in 5 m urea solution instead of pure milli‐Q water.ISSN:2196-735

Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and Reversal of Amphiphilicity

Two series of periodically clickable polyesters were prepared; one of them carries alkylene segments along its backbone, whereas the other carries poly­(ethylene glycol) (PEG) segments. These polyesters were clicked with either MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic copolymers (PGACs) carrying either flexible hydrophilic or crystallizable hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG segments causes both of these systems to fold in either a zigzag or hairpin-like conformation; the hairpin-like conformation appears to be preferred when flexible PEG segments are present in the backbone. The folded chains further reorganize in the solid state to develop a lamellar morphology that permits the collocation of the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies revealed the formation of an extended lamellar structure, whereas AFM images showed uniform layered morphology with layer heights that matched reasonably well with the interlamellar spacing obtained from the SAXS study. Labeling one representative PGAC, carrying crystallizable long alkylene segments in the backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene fluorophore permitted the examination of the conformational transition that occurs upon going from a good to a poor solvent; this single-chain folded conformation, we postulate, is the intermediate that organizes into the lamellar morphology

Synthesis of acrylamide-based block-copolymer brushes under flow: monitoring real-time growth and surface restructuring upon drying

A series of block-copolymer brushes has been synthesized under continuous flow by surface-initiated, atom-transfer radical polymerization of the acrylamide derivatives: N-isopropylacrylamide (NIPAM), N,N-dimethylacrylamide (DMAM) and N-hydroxyethyl acrylamide (HEAM). The formation of individual blocks was monitored in real time by means of a quartz-crystal microbalance with dissipation monitoring (QCM-D). The chemical composition, as well as the surface properties of the block-copolymer brushes, were examined in their dry state with X-ray photoelectron spectroscopy (XPS) and by measuring the water contact angle following each stage of the polymerization. In most cases, the block-copolymer brushes exhibited surface compositions and properties that closely resembled those of a homopolymer brush of similar composition to the final block. This was not the case when the final block consisted of p(HEAM), where the surface composition and properties were found to resemble those of the penultimate block. XPS depth-profile analysis and dynamic-contact-angle (DCA) measurements indicated that p(HEAM)-terminated block-copolymer brushes undergo interlayer mixing upon drying, driven by surface-energy effects

Oxygen inhibition of free-radical polymerization is the dominant mechanism behind the “mold effect” on hydrogels

Hydrogel surfaces are of great importance in numerous applications ranging from cell-growth studies and hydrogel-patch adhesion to catheter coatings and contact lenses. A common method to control the structure and mechanical/tribological properties of hydrogel surfaces is by synthesizing them in various mold materials, whose influence has been widely ascribed to their hydrophobicity. In this work, we examine possible mechanisms for this “mold effect” on the surface of hydrogels during polymerization. Our results for polyacrylamide gels clearly rule out the effect of mold hydrophobicity as well as any thermal-gradient effects during synthesis. We show unequivocally that oxygen diffuses out of certain molding materials and into the reaction mixture, thereby inhibiting free-radical polymerization in the vicinity of the molding interface. Removal of oxygen from the system results in homogeneously cross-linked hydrogel surfaces, irrespective of the substrate material used. Moreover, by varying the amount of oxygen at the surface of the polymerizing solutions using a permeable membrane we are able to tailor the surface structures and mechanical properties of PAAm, PEGDA and HEMA hydrogels in a controlled manner.ISSN:1744-683XISSN:1744-684

Bayesian network aided grasp and grip efficiency estimation using a smart data glove for post-stroke diagnosis

Stroke is one of the major causes behind the increased mortality rate throughout the world and disability among the survivors. Such disabilities include several grasp and grip related impairment in daily activities like holding a glass of water, counting currency notes, producing correct signature in bank, etc., that seek serious attention. Present therapeutic facilities, being expensive and time-consuming, fail to cater the poverty stricken rural class of the society. In this paper, on the basis of an investigation, we developed a smart data glove based diagnostic device for better treatment of such patients by providing timely estimation of their grasp quality. Data collected from a VMG30 motion capture glove for six patients who survived stroke and two other healthy subjects was fused with suitable hypothesis obtained from a domain expert to reflect the required outcome on a Bayesian network. The end result could be made available to a doctor at a remote location through a smart phone for further advice or treatment. Results obtained clearly distinguished a patient from a healthy subject along with supporting estimates to study and compare different grasping gestures. The improvement in mobility could be assessed after physiotherapeutic treatments using the proposed method

Towards a Polymer-Brush-Based Friction Modifier for Oil

To meet the need for oil-compatible friction modifier additives that can significantly reduce energy consumption in the boundary-lubrication regime, a macromolecular design approach has been taken. The aim was to produce a lubricious polymer film on the sliding surfaces. A series of readily functionalizable block copolymers carrying an oleophilic poly(dodecyl methacrylate) block and a functionalizable poly(pentafluorophenyl methacrylate) block of various lengths was synthesized by means of reversible addition-fragmentation chain-transfer (RAFT) polymerization. The poly(pentafluorophenyl methacrylate) block was used to attach surface-active nitrocatechol anchoring groups to the polymer. The friction-reduction properties of these polymers were assessed with 0.5 wt% solutions in hexadecane by means of rolling-sliding macroscopic tribological tests. Block copolymers with roughly equal block lengths and moderate molecular weights were significantly more effective at friction reduction than all other architectures investigated. They also displayed lower friction coefficients than glycerol monooleate-a commercially used additive. The film-formation ability of these polymers was examined using a quartz-crystal microbalance with dissipation (QCM-D), by monitoring their adsorption onto an iron oxide-coated QCM crystal. The polymer with highest lubrication efficiency formed a thin film of similar to 17 nm thickness on the crystal, indicating the formation of a polymer brush. Interferometric rolling-sliding experiments with the same polymer showed a separating film thickness of similar to 20 nm, which is consistent with the QCM-D value, bearing in mind the compression of the adsorbed layers on the two sliding surfaces during tribological testing.ISSN:1023-8883ISSN:1573-271