Stereospecific Radical Polymerization of a Side-Chain Transformable Bulky Acrylamide Monomer and Subsequent Post-Polymerization Modification for Syntheses of Isotactic Polyacrylate and Polyacrylamide.

We report syntheses of isotactic polyacrylate and polyacrylamide via a stereospecific radical polymerization of a pendant-transformable monomer, acrylamide carrying isopropyl-substituted ureidosulfonamide (1), followed by post-polymerization modification (PPM). The study in the alcoholysis and aminolysis reactions of the model compound (2) for evaluation of the transformation ability of the electron-withdrawing pendant group on the repeating unit 1 revealed the following points: the pendant of the polymer became more reactive than that of monomer; the pendant was active enough for aminolysis reaction affording the amide compound quantitatively without additive/catalyst; the addition of a lithium triflate [Li(OTf)] and triethylamine (Et3 N) was effective as for promotion of the alcoholysis reaction. Poly(methyl acrylate) (PMA) was quantitatively obtained via the radical polymerization of 1 in the presence of Li(OTf) at 60 °C and the subsequent addition of methanol along with Et3 N. Thus-obtained PMA showed higher isotacticity [m=74 %] than that directly obtained via radical polymerization of methyl acrylate (MA) (m=51 %). The isotacticity was further increased as the temperature and monomer concentration were lower, and eventually m was increased up to 93 %. The aminolysis PPM after the iso-specific radical polymerization of 1 gave various isotactic polyacrylamides carrying different alkyl pendant groups, including poly(N-isopropylacrylamide) (PNIPAM).

Stereomodulation of Poly(4-methyl-1-pentene): Adoption of a Neglected and Misunderstood Commercial Polyolefin.

A toolbox of living coordination polymerization methods based on CPAM group 4 metal initiators has been applied for the stereomodulation of poly(4-methyl-1-pentene) (PMP) tacticity to provide new fundamental forms in which thermal phase transitions, Tg and Tm , can be adjusted over a wide range. Also reported for the first time are the synthesis and properties of authenticated 1,2-regioregular atactic PMP, which serves to correct past errors regarding this fundamental polyolefin.

Determination of Polylactide Microstructure by Homonuclear Decoupled 1 H NMR Spectroscopy.

The ring-opening polymerization (ROP) of lactide (the dilactone of lactic acid) produces poly(lactide) commonly referred to as poly(lactic acid) (PLA). The monomer lactide, has two stereogenic centers and thus, three stereoisomers are possible, namely: D-(R,R), L-(S,S) and meso-lactide. The rac-lactide is an equimolar mixture of D- and L-enantiomers. Depending upon the relative configuration of the stereogenic centers in the polymeric chain, different tacticities (isotactic, syndiotactic, heterotactic and atactic) arise in the PLA chains. The study of the tacticity of a polymer is fundamental since it plays a crucial role in determining the physical properties of the polymer. NMR spectroscopy is a powerful analytical technique for the determination of the tacticity of PLA. This article describes in details the tacticity assignment for PLA derived from ROP of rac-lactide and meso-lactide, using homonuclear proton-decoupled 1 H NMR. The detailed tetrad level assignment pertinent to the methine hydrogen signal is the key for the determination of tacticity.

ATRP of N-Hydroxyethyl Acrylamide in the Presence of Lewis Acids: Control of Tacticity, Molecular Weight, and Architecture.

Good control of tacticity, molecular weight, and architecture is attained via atom transfer radical polymerization (ATRP) of N-hydroxyethyl acrylamide (HEAA), in a one-pot process in the presence of Y(OTf)3 . The effect of temperature, ratio of [Y(OTf)3 ]/[HEAA], and ATRP procedure on the tacticity and degree of control over the polymerization is investigated in detail. Under optimal conditions, using photo ATRP and 15% Y(OTf)3, the content of meso dyads (m) can be increased from 42% to 80% in a homopolymer with a dispersity D = 1.22. Well-defined stereoblock copolymers, atactic- b -isotactic poly(HEAA), with D = 1.27, are obtained by adding Y(OTf)3 at a specific conversion, initially started without Y(OTf)3 .

Functional Precision Polymers via Stereo- and Regioselective Polymerization Using Group 6 Metal Alkylidene and Group 6 and 8 Metal Alkylidene N-Heterocyclic Carbene Complexes.

The concepts of functional precision polymers and the latest accomplishments in their synthesis are summarized. Synthetic concepts based on chain growth polymerization are compared to iterative synthetic approaches. Here, the term "functional precision polymers" refers to polymers that are not solely hydrocarbon-based but contain functional groups and are characterized by a highly ordered primary structure. If insertion polymerization is used for their synthesis, olefin metathesis-based polymerization techniques, that is, ring-opening metathesis polymerization (ROMP), acyclic diene metathesis (ADMET) polymerization, and the regio- and stereoselective cyclopolymerization of α,ω-diynes are almost exclusively applied. Particularly with regio- and stereospecific ROMP and with cyclopolymerization, the synthesis of tactic polymers and copolymers with high regio-, stereo-, and sequence control can be accomplished; however, it requires carefully tailored transition metal catalysts. The fundamental synthetic concepts and strategies are outlined.

Exploring the Self-Assembled Tacticity in Aurophilic Polymeric Arrangements of Diphosphanegold(I) Fluorothiolates.

Despite the recurrence of aurophilic interactions in the solid-state structures of gold(I) compounds, its rational control, modulation, and application in the generation of functional supramolecular structures is an area that requires further development. The ligand effects over the aurophilic-based supramolecular structures need to be better understood. This paper presents the supramolecular structural diversity of a series of new 1,3-bis(diphenylphosphane)propane (dppp) gold(I) fluorinated thiolates with the general formula [Au2(SRF)2(µ-dppp)] (SRF = SC6F5 (1); SC6HF4-4 (2); SC6H3(CF3)2-3,5 (3); SC6H4CF3-2 (4); SC6H4CF3-4 (5); SC6H3F2-3,4 (6); SC6H3F2-3,5 (7); SC6H4F-2 (8); SC6H4F-3 (9); SC6H4F-4 (10)). These compounds were synthesized and characterized, and six of their solid-state crystalline structures were determined using single-crystal X-ray diffraction. In the crystalline arrangement, they form aurophilic-bridged polymers. In these systems, the changes in the fluorination patterns of the thiolate ligands tune the aurophilic-induced self-assembly of the compounds causing tacticity and chiral differentiation of the monomers. This is an example of the use of ligand effects on the tune of the supramolecular association of gold complexes.

Effect of tacticity-derived topological constraints in bactericidal peptides.

Topology is a key element in structure-activity relationship estimation while designing physiologically-active molecular constructs. Peptides may be a preferred choice for therapeutics, principally due to their biocompatibility, low toxicity and predictable metabolism. Peptide design only guarantees functional group constitution by opting specific amino acid sequence, and not their spatial orientation to bind and incite physiological response on chosen targets. This is principally because peptide conformation is subject to external flux, due to the isotactic stereochemistry of the peptide chain. Stereochemical engineering of the peptide main chain offers the possibility of multiplying the structural space of a typical sequence to many orders of magnitude, and limiting the otherwise fluxional non-specific functional group dispensation in space by offering greater conformational rigidity. We put to test, this conceptual possibility already established in theoretical models, by designing amphipathic peptide systems and experimenting with them on Gram-positive, Gram-negative and antibiotic-resistant bacteria. The unusual conformational rigidity and stability of syndiotactic peptides enable them to retain the designed electrostatic environment, while they encounter the membrane surface. All the six designed systems exhibited bactericidal activity, pointing to the utility and specificity of stereo-engineered peptide systems for therapeutic applications. Overall, we hope that this work provides important insights and useful directives in designing novel peptide systems with antimicrobial activity, by expanding the design space, incorporating D-amino acid as an additional design variable.

Block Copolymer Stereoregularity and Its Impact on Polymeric Micellar Nanodrug Delivery.

Stereoregularity of polymers is known to influence their physicochemical and functional properties in the bulk form. Recent studies have also provided evidence for the effect of polymer stereoregularity on the physicochemical and functional properties of their self-assembled nanostructures. Research in this area has witnessed a relatively rapid pace in the past few years; however, to the best of our knowledge, a proper review of the literature has not been made to date. The goal of this review article was to fill this gap and provide a detailed overview on the current knowledge and understanding on the effect of block copolymer stereoregularity on the properties of their self-assembled nanocarriers such as size, morphology, thermodynamic and kinetic stability, and drug loading and release. Emphasis is placed on poly(ester) containing block copolymers because of their safe history of human use and extensive application in drug delivery research.

Investigation of Tacticity and Living Characteristics of Photoredox-Mediated Metal-Free Ring-Opening Metathesis Polymerization.

This study investigated the microstructures of polymers produced via photoredox-mediated metal-free ring-opening metathesis polymerization. Polynorbornene, poly(exo-dihydrodicyclopentadiene), and poly(endo-dicyclopentadiene) were found to have cis olefin contents of 23%, 24%, and 28%, respectively. Additionally, the cis/trans ratio remained consistent during the course of norbornene polymerization. Polymer tacticity was evaluated by quantitative 13 C NMR spectroscopy, which revealed each polymer to be largely atactic. Specifically, the three polymers were estimated to be 33%, 58%, and 55% syndiotactic, respectively. In parallel, this study also explored the ability to produce diblock copolymers from norbornene and exo-dihydrodicyclopentadiene. Successful diblock copolymerization was achieved using either monomer order. In each case, however, the results suggested to us that chain-chain coupling (increased molecular weight) and irreversible termination (dead chains observed during attempted chain extension) occurred when reaction times were extended.

Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research.

In 1968, Heskins and Guillet published the first systematic study of the phase diagram of poly(N-isopropylacrylamide) (PNIPAM), at the time a "young polymer" first synthesized in 1956. Since then, PNIPAM became the leading member of the growing families of thermoresponsive polymers and of stimuli-responsive, "smart" polymers in general. Its thermal response is unanimously attributed to its phase behavior. Yet, in spite of 50 years of research, a coherent quantitative picture remains elusive. In this Review we survey the reported phase diagrams, discuss the differences and comment on theoretical ideas regarding their possible origins. We aim to alert the PNIPAM community to open questions in this reputably mature domain.

Leveraging Insulator's Tacticity in Semiconducting Polymer Blends.

Blending conjugated polymers with insulating matrices is often utilized for engineering extrinsic properties in organic electronics. Semiconductor/insulator blends are typically processed to form a uniformly distributed network of conductive domains within the insulating matrix, marrying electronic and physical properties from individual components. Understanding of polymer-polymer interactions in such systems is thus crucial for property co-optimization. One of the commonly overlooked parameters is the structural configuration of the insulator on the resulting properties, especially the electronic properties. This study investigated how the tacticity of the matrix polymer, among other relevant parameters in play, impacts solid state crystallization in semiconductor/matrix blends and hence the resulting charge transport properties. We found an intricate dependence of the film morphology, aggregation behavior, electronic charge transport, and mixed ionic-electronic coupling properties on the insulator's tacticity. Our experimentally iterative approach shows that for a given application, when selecting semiconductor/insulator combinations, the tacticity of the matrix can be leveraged to optimize performance and vary solid-state structure.

Bandgap formation mechanism in tacticity inspired elastic mechanical metastructures.

Tacticity is long known as a significant contributor in changing the chemical and mechanical properties of the polymers drastically. This study explores mechanism of bandgap formation in elastic mechanical metastructures designed with a focus on tacticity. We introduce metabeams, comprising a primary slender beam embedded with short secondary beams featuring end masses at their tips. The investigation delves into the numerically simulated vibration characteristics of metabeams using finite element analysis, with a subsequent comparison to experimental results for fabricated metabeams. Employing a unit-cell design approach that manipulates spatial and physical parameters, we explore a wide range of uniform and non-uniform metabeam configurations based on the distance between secondary beams and distribution of local resonators as per tacticity. Hence, drawing inspiration from tacticity, we extend our investigation to isotactic and syndiotactic metabeams, altering physical parameters (mass) within the unit cell for both configurations. The strategic distribution of end masses on attached secondary beams introduces unique characteristics to isotactic and syndiotactic metabeams, allowing for the modulation of bandgaps without altering the natural frequencies of the resonators in symmetric and anti-symmetric metabeam designs. Our research demonstrates, incorporating tacticity in metabeam design offers a novel and unconventional approach to modulate the bandgap formation mechanism.

NMR Analyses and Statistical Modeling of Biobased Polymer Microstructures-A Selected Review.

NMR analysis combined with statistical modeling offers a useful approach to investigate the microstructures of polymers. This article provides a selective review of the developments in both the NMR analysis of biobased polymers and the statistical models that can be used to characterize these materials. The information obtained from NMR and statistical models can provide insights into the microstructure and stereochemistry of appropriate biobased polymers and establish a systematic approach to their analysis. In suitable cases, the analysis can help optimize the synthetic procedures and facilitate the development of new or modified polymeric materials for various applications. Examples are given of the studies of poly(hydroxyalkanoates), poly(lactic acid), and selected polysaccharides, e.g., alginate, pectin, and chitosan. This article may serve as both a reference and a guide for future workers interested in the NMR sequence analysis of biobased materials.

Mechanistic Insights into the Stereoselective Cationic Polymerization of N-Vinylcarbazole.

The synthesis of stereoregular polymers through ionic mechanisms using asymmetric ion-pairing (AIP) catalysis is emerging as an effective strategy to achieve differentiated material properties from readily available building blocks. Stereoselective cationic polymerization in particular is primed for advancement using AIP by leveraging the breadth of Brønsted and Lewis acid small-molecule catalysis literature; however, mechanistic studies that address polymer-specific phenomena are scarce and, as a result, the lack of mechanistic understanding has limited catalyst design. In a recent study, we demonstrated the only example of a stereoselective and helix-sense-selective cationic vinyl polymerization of N-vinylcarbazole using chiral scandium-bis(oxazoline) Lewis acids. To better understand the mechanism of this highly stereoselective polymerization and elicit design principles for future advances, we present a combined experimental and computational study into the relevant factors that determine tacticity and helicity control. Key mechanistic experiments suggest two competing elementary steps-chain-end conformation equilibration and propagation-whose relative rates can be influenced by monomer concentration, isotope effects, and catalyst design to tune tacticity. In contrast, helicity is influenced by complex relationships between the stereoselectivity of the first monomer propagation and a time-dependent initiator-catalyst mixing time. The more complete understanding of stereoselective cationic polymerization through AIP developed herein provides insights into polymer-specific mechanisms for stereocontrol, which we believe will motivate continued catalyst discovery and development for stereoselective vinyl polymerization.

Effect of poly(tert-butyl methacrylate) stereoregularity on polymer film interactions with peptides, proteins, and bacteria.

The impact of polymer stereoregularity on its interactions with peptides, proteins and bacteria strains was studied for three stereoregular forms of poly(tert-butyl methacrylate) (PtBMA): isotactic (iso), atactic (at) and syndiotactic (syn) PtBMA. Principal component analysis of the time-of-flight secondary ion mass spectrometry data recorded for thin polymer films indicated a different orientation of ester groups, which in the case of iso-PtBMA are exposed away from the surface whereas for at-PtBMA and syn-PtBMA these are located deeper within the film. This arrangement of chemical groups modified the interactions of iso-PtBMA with biomolecules when compared to at-PtBMA and syn-PtBMA. For peptides, the affected interactions were explained by the preferential hydrogen bonding and electrostatic interaction between the exposed polar ester groups of iso-PtBMA and positively charged peptides. In turn, for protein adsorption no impact on the amount of adsorbed proteins was observed. However, the polymer stereoregularity influenced the orientation of immunoglobulin G and induced conformational changes in bovine serum albumin structure. Moreover, the impact of polymer stereoregularity occurred equally for their interactions with Gram-positive bacteria (S. aureus), which absorbed preferentially onto iso-PtBMA films as compared to two other stereoregularities.

The Effect of Various Poly (N-vinylpyrrolidone) (PVP) Polymers on the Crystallization of Flutamide.

In this study, several experimental techniques were applied to probe thermal properties, molecular dynamics, crystallization kinetics and intermolecular interactions in binary mixtures (BMs) composed of flutamide (FL) and various poly(N-vinylpyrrolidone) (PVP) polymers, including a commercial product and, importantly, samples obtained from high-pressure syntheses, which differ in microstructure (defined by the tacticity of the macromolecule) from the commercial PVP. Differential Scanning Calorimetry (DSC) studies revealed a particularly large difference between the glass transition temperature (Tg) of FL+PVPsynth. mixtures with 10 and 30 wt% of the excipient. In the case of the FL+PVPcomm. system, this effect was significantly lower. Such unexpected findings for the former mixtures were strictly connected to the variation of the microstructure of the polymer. Moreover, combined DSC and dielectric measurements showed that the onset of FL crystallization is significantly suppressed in the BM composed of the synthesized polymers. Further non-isothermal DSC investigations carried out on various FL+10 wt% PVP mixtures revealed a slowing down of FL crystallization in all FL-based systems (the best inhibitor of this process was PVP Mn = 190 kg/mol). Our research indicated a significant contribution of the microstructure of the polymer on the physical stability of the pharmaceutical-an issue completely overlooked in the literature.

Determining paracrystallinity in mixed-tacticity polyhydroxybutyrates.

Recently, the authors reported on the development of crystallinity in mixed-tacticity polyhydroxybutyrates. Comparable values reported in the literature vary depending on the manner of determination, the discrepancies being partially attributable to scattering from paracrystalline portions of the material. These portions can be qualified by peak profile fitting or quantified by allocation of scattered X-ray intensities. However, the latter requires a good quality of the former, which in turn must additionally account for peak broadening inherent in the measurement setup, and due to limited crystallite sizes and the possible presence of microstrain. Since broadening due to microstrain and paracrystalline order both scale with scattering vector, they are easily confounded. In this work, a method to directionally discern these two influences on the peak shape in a Rietveld refinement is presented. Allocating intensities to amorphous, bulk and paracrystalline portions with changing tactic disturbance provided internal validations of the obtained directional numbers. In addition, the correlation between obtained thermal factors and Young's moduli, determined in earlier work, is discussed.

Gradient of Segmental Dynamics in Stereoregular Poly(Methyl Methacrylate) Melts Confined between Pristine or Oxidized Graphene Sheets.

Segmental dynamics in unentangled isotactic, syndiotactic, and atactic poly(methyl methacrylate) (i-, a-, and s-PMMA) melts confined between pristine graphene, reduced graphene oxide, RGO, or graphene oxide, GO, sheets is studied at various temperatures, well above glass transition temperature, via atomistic molecular dynamics simulations. The model RGO and GO sheets have different degrees of oxidization. The segmental dynamics is studied through the analysis of backbone torsional motions. In the vicinity of the model nanosheets (distances less than ≈2 nm), the dynamics slows down; the effect becomes significantly stronger with increasing the concentration of the surface functional groups, and hence increasing polymer/surface specific interactions. Upon decreasing temperature, the ratios of the interfacial segmental relaxation times to the respective bulk relaxation times increase, revealing the stronger temperature dependence of the interfacial segmental dynamics relative to the bulk dynamics. This heterogeneity in temperature dependence leads to the shortcoming of the time-temperature superposition principle for describing the segmental dynamics of the model confined melts. The alteration of the segmental dynamics at different distances, d, from the surfaces is described by a temperature shift, ΔTseg(d) (roughly speaking, shift of a characteristic temperature). Next, to a given nanosheet, i-PMMA has a larger value of ΔTseg than a-PMMA and s-PMMA. This trend correlates with the better interfacial packing and longer trains of i-PMMA chains. The backbone torsional autocorrelation functions are shown in the frequency domain and are qualitatively compared to the experimental dielectric loss spectra for the segmental α-relaxation in polymer nanocomposites. The εT″(f) (analogous of dielectric loss, ε″(f), for torsional motion) curves of the model confined melts are broader (toward lower frequencies) and have lower amplitudes relative to the corresponding bulk curves; however, the peak frequencies of the εT″(f) curves are only slightly affected.

Retention of polypropylene stereoisomers in solvent gradient interaction chromatography on porous graphitic carbon as influenced by temperature and mobile phase composition.

The behavior of isotactic, syndiotactic and atactic polypropylene stereoisomers on porous graphitic carbon (PGC) at different column temperatures is investigated with 1-decanol, decalin and decane as the adsorption promoting solvents using gradient interaction chromatography (SGIC). Column temperatures between 120 - 180 °C are investigated for the three adsorption promoting solvents with 1,2,4-trichlorobenzene (TCB) as the desorption promoting solvent. Owing to the different stereochemistry of the isomers, their interaction with the atomic level flat surface (ALFS) of porous graphitic carbon is observed to be different when injected from the three different adsorption promoting solvents. Atactic and isotactic polypropylene are not separable when 1-decanol is used as the adsorption solvent but can be separated from syndiotactic PP at column temperatures of between 120 - 180 °C. The three stereoisomers have almost similar elution volumes when decalin is used as the adsorption promoting solvent between 120 - 170 °C. Decane allows for both adsorption and desorption of the stereoisomers at distinct peak elution volumes at the studied column temperatures of 120 - 160 °C. Furthermore, it is shown that increasing the column temperature while maintaining other chromatographic conditions can either decrease or increase retention depending on the adsorption promoting solvent. More importantly, retention is influenced by adsorption conditions (temperature and adsorption promoting solvent) which may affect macromolecular conformations upon injection onto the PGC stationary phase. This is the first study on PP stereoisomers highlighting this behaviour.

Topological effects on the designability and bactericidal potency of antimicrobial peptides.

New ideas and methods are being developed to generate highly designable small functional protein folds beyond the confines of natural structures, from secondary to quaternary level. Highly designable folds can have multiple sequence solutions, which are thermodynamically and kinetically stable. We have previously described how short syndiotactic helices can be exceptionally stable energetically, and how they can be used as a template for designing antibacterial agents. In this work, we have designed four syndiotactic, single turn, amphipathic; cationic 7-mer peptides which are the sequence and structural subset of earlier published 12-mer sequences. We examined the stability of the designed structures and its effects on the biological activity of such short peptide sequences. This was achieved by making objective comparisons between 12-mer and 7-mer sequences in terms of their antibacterial activity. Further, we investigated the mechanistic origins of clearly different bactericidal potency of single (7-mer) and double (12-mer) turn syndiotactic helices using molecular dynamics simulations. Our results suggest that conformationally constrained stable short double turn peptide scaffolds are highly designable, whereas single turn structures are more likely to be disordered. The stability of the designed peptide structure provides a platform for inclusion of multiple sequence variables and defined electrostatic fingerprints. Therefore, a stable peptide scaffold along with pre-defined electrostatic signatures can together be utilized for the design of novel antimicrobial peptides.