Controlled Chain Length Research Articles

Precision Design of Sequence‐Defined Polyurethanes: Exploring Controlled Folding Through Computational Design

AbstractThis study presents the exploration of sequence‐defined polyurethanes (PUs) as a new class of heteropolymers capable of precise conformational control. Utilizing molecular dynamics simulations, the folding behavior of polyurethane chains is investigated of varying lengths (11, 20, and 50 monomers) in both vacuum and aqueous environments. The simulations reveal that the heterogeneous chains systematically refold to approach the designed target structures better than non‐designed chains or chains with artificially disrupted hydrogen‐bond networks. The subsequent synthesis of an optimized 11‐mer sequence (P1) is achieved through solid‐phase chemistry, with thorough characterization via NMR, MS, and SEC confirming the accuracy of the predicted sequence and its controlled chain length. Solubility tests showed favorable results across multiple solvents, highlighting the versatility of the designed polymer. This research underscores the potential of sequence‐defined polyurethanes to emulate the structural and functional attributes of biological macromolecules, opening new pathways for their application in catalysis, drug delivery, and advanced material design. The findings illustrate a promising direction for the development of synthetic polymers with tailored properties, emphasizing the transformative impact of sequence control in polymer chemistry.

Characterization of well‐defined PHEMA‐based bottlebrushes with controlled chain length and grafting density

AbstractBottlebrushes with controlled horizontal‐ and vertical‐axis scales, which have a high density of graft chains on their main chains, are useful as a nanomaterial. The properties of bottlebrushes depend on the polymer‐type, ‐chain length, and grafting density. We fabricate well‐defined bottlebrushes based on poly(2‐hydroxyethyl methacrylate) (PHEMA) using the grafting from method. Macroinitiators with different compositions of an atom transfer radical polymerization (ATRP) initiator group are prepared, and two bottlebrushes are consequently synthesized by ATRP of HEMA with the macroinitiator: a concentrated bottlebrush with graft chains on the repeating units and a semi‐dilute bottlebrush with graft chains on approximately 10%. The hydrodynamic and gyration radii of the concentrated‐ and semi‐dilute bottlebrushes are Rh = 9.2 nm (Rg = 24.9 nm) and Rh = 69.1 nm (Rg = 130 nm), respectively. The shape factors (Rg/Rh) of these bottlebrushes indicate both solid‐rods. The virial coefficient of semi‐dilute bottlebrush, calculated from static light scattering measurements, is higher than that of concentrated bottlebrush, owing to the flexibility and solvation structure. The grafting density play a more prominent role than the graft‐chain length in the excluded volume effect of the bottlebrush. These results provide useful insights for the construction of polymethacrylate‐based bottlebrushes with specific hydrodynamic properties.

Controllable synthesis of polyaspartic acid: Studying into the chain length effect for calcium scale inhibition

Polyaspartic acid (PASP) has been disclosed as a green and degradable antiscalant for inhibiting the calcium scale for >30 years. Although the chain length of PASP has been known as one of the key factors to influence the inhibition performance of both CaCO3 and CaSO4 scale, the very limited methods for the controllable synthesis of PASP make it hard to examine the core cause. Herein, a simple two-step method has been established for the synthesis of PASPs (PASP-1–PASP-6) with narrow dispersity (Ð) and controllable chain length (from 12 to 36). The static antiscaling experiments show that while PASP-4 with chain length of 24 has the best inhibition performance against CaCO3 scale, PASP-1 with the chain length of 12 gives the best result against CaSO4 scale. Furthermore, detailed scale-inhibition study shows that with the variation of chain length of PASP, the core cause for determining the antiscaling effect of CaCO3 or CaSO4 scale is different. While the antiscaling effect for CaCO3 scale inhibition involves chelation, dispersion, lattice distortion, and threshold effect, the effect for CaSO4 scale inhibition only includes chelation, dispersion and threshold effect. No lattice distortion effect was observed for the latter. This study not only proves the best chain length of PASP for CaCO3 and CaSO4 scale inhibition for the first time, but also is meaningful for guiding the design of other new green polymer-based antiscalants.

Enhanced production and control of liquid alkanes in the hydrogenolysis of polypropylene over shaped Ru/CeO2 catalysts

The hydrogenolysis of polypropylene waste to liquid hydrocarbons offers a promising pathway for the chemical recycling of waste polymers. This work describes the importance of reaction conditions and support morphology to produce high liquid yields with enhanced control of chain length over highly active shaped and non-shaped Ru/CeO2 catalysts. The shaped 2 wt% Ru/CeO2 exhibit high liquid alkane yields (58–81%) when compared to the non-shaped 2 wt% Ru/CeO2 (liquid yield: 34–58%) under optimized reaction conditions (220 °C, 16 h, 30 bar H2). In particular, the 2 wt% Ru/CeO2 nanocube catalyst exhibits the highest activity yielding lighter hydrocarbons. This was rationalized to be a combination of small Ru cluster formation and enhanced metal-support interactions. The influence of larger Ru particles (≥1.5 nm) was confirmed mechanistically using a computational density functional theory study on the hydrogenolysis of pentane (C5) to determine the favorable formation of methane in the non-shaped Ru/CeO2 catalyst.

Relative Activities of the β-Ketoacyl-CoA and Acyl-CoA Reductases Influence the Product Profile and Flux in a Reversed β-Oxidation Pathway

The β-oxidation pathway, normally involved in the catabolism of fatty acids, can be functionally made to act as a fermentative, iterative, elongation pathway when driven by the activity of a trans-enoyl-CoA reductase (TER). The terminal acyl-CoA reduction to alcohol can occur on substrates with varied chain lengths, leading to a broad distribution of fermentation products in vivo. Tight control of the average chain length and product profile is desirable, as the chain length greatly influences the molecular properties and the commercial value. Lacking a termination enzyme with a narrow chain length preference, we sought alternative factors that could influence the product profile and pathway flux in the iterative pathway. In this study, we reconstituted the reversed β-oxidation (R-βox) pathway in vitro with a purified tri-functional complex (FadBA) responsible for the thiolase, enoyl-CoA hydratase, and hydroxyacyl-CoA dehydrogenase activities, a TER, and an acyl-CoA reductase. Using this system, we determined the rate-limiting step of the elongation cycle and demonstrated that by controlling the ratio of these three enzymes and the ratio of NADH and NADPH, we can influence the average chain length of the alcohol product profile.

Chain-Length-Dependent Hydrogen-Bonded Self-Assembly of Terminally Functionalized Discrete Polyketones

Here, we report the synthesis and the chain-length-dependent self-assembling behaviors of discrete di-, tetra-, and hexaketones terminally functionalized with hydrogen-bonding carboxyl (C1, C2, and C3) and 3-acylaminopyridine groups (P1, P2, and P3). These polyketones were prepared by the coupling reactions of silylated analogues of 3,3-dimethylpentane-2,4-dione and t-butyl 2,2-dimethyl-3-oxobutanoate and the subsequent hydrolysis or amidation with 3-aminopyridine. Single-crystal X-ray diffraction analysis revealed that C1 and C2 form helical assemblies in which the components are connected by the dimerization of terminal carboxyl groups, whereas the longer C3 showed infinite hydrogen-bonded chains mediated by 1,4-dioxane used as a crystallization solvent. Pyridine-terminated P1 exhibited a three-dimensional hydrogen-bonded network owing to multiple NH···N(pyridine) hydrogen bonds in the solid state. P2 generated a double-helix-like fiber structure in the crystalline state. Among the pyridine-terminated polyketones P1–P3, only P2 showed gelation behavior in chloroform (100 mM concentration) at 25 °C. The scanning electron microscopy measurement of xerogel P2 revealed the formation of rod-like structures with a thickness of approximately 0.5–3.5 μm. These results demonstrate that the precise control of the polyketone chain length can significantly alter hydrogen-bonded self-assembly in the solid state and in solution even with the same terminal structures.

The Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases.

The nonreducing iterative type I polyketide synthases (NR-PKSs) CoPKS1 and CoPKS4 of the webcap mushroom Cortinarius odorifer share 88 % identical amino acids. CoPKS1 almost exclusively produces a tricyclic octaketide product, atrochrysone carboxylic acid, whereas CoPKS4 shows simultaneous hepta- and octaketide synthase activity and also produces the bicyclic heptaketide 6-hydroxymusizin. To identify the region(s) controlling chain length, four chimeric enzyme variants were constructed and assayed for activity in Aspergillus niger as heterologous expression platform. We provide evidence that the β-ketoacyl synthase (KS) domain determines chain length in these mushroom NR-PKSs, even though their KS domains differ in only ten amino acids. A unique proline-rich linker connecting the acyl carrier protein with the thioesterase domain varies most between these two enzymes but is not involved in chain length control.

Synthesis and Higher-order Structural Characterization of Polyimides Containing Chain-length-controlled Polysiloxanes

The synthesis of polyimides (PIs) containing polydimethylsiloxane (PDMS) with controlled chain length and the formation of higher-order structures were studied. Polycondensation was carried out using diphenyl-3,3',4,4'-tetracarboxylic dianhydride (BPDA) and diamine oligomers having amino groups on both ends of PDMS. The obtained poly(amic acid) (PAA) and PI showed good solubility in several common polar solvents while less soluble in non-protic amide polar solvents. The obtained bulk films of PI suggested forming a microphase-separated structure with domains based on PDMS and other aromatic moieties.

Protein-Resistant Amphiphilic Copolymers Containing Fluorosiloxane Side Chains with Controllable Length

Molecular-scale compositional heterogeneities can slash the nonspecific interaction between proteins and surfaces, resisting surface contamination. In this work, an amphiphilic copolymer containing a soft fluorosilicone macromonomer with controllable chain length as low-surface-energy hydrophobic component and a zwitterionic monomer as hydrophilic component was prepared to establish molecular-scale compositional heterogeneities. The length of the fluorosiloxane side chains can significantly impact the surface compositional heterogeneities, thus influencing the antifouling performance of the copolymer coatings. Even under water, the coating still retains a large number of low-surface-energy fluorosilicone segments on the surface. The balance between hydrophilic and hydrophobic segments on the surface provides a better synergistic effect, which endows the copolymer coatings with excellent resistance to various proteins.

Engineering Yarrowia lipolytica to Produce Tailored Chain-Length Fatty Acids and Their Derivatives.

Microbial production of value-added chemicals derived from fatty acids is a sustainable alternative to petroleum-derived chemicals and unsustainable lipids from animals and plants. Fatty acids with different carbon chain lengths including short- (<C6), medium- (C6-C12), long- (C14-C20), and very-long- (>C20), with either even or odd number of carbons, have significantly different characteristics and wide applications in energy, material, medicine, and nutrition. Tailoring chain-length specificity of these compounds using metabolic engineering would be of high interest. Yarrowia lipolytica, as an oleaginous yeast, is a superior industrial chassis for the production of tailored chain-length fatty acids and their derivatives due to its hyper-oil-producing capability. In this Review, we cover metabolic engineering approaches that can lead to fatty acid chain length control in this microorganism. These approaches involve the manipulation of the fatty acid synthase, the thioesterase, the β-oxidation pathway, the elongation and desaturation pathway, the polyketide synthase-like polyunsaturated fatty acid synthase pathway, and the odd-chain fatty acids synthesis pathway. Finally, we also discuss alternative strategies that can be used in the future to tailored chain-length control.

Controllable Polymerization of N -Substituted β-Alanine N -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

Controllable Polymerization of <i>N</i> -Substituted β-Alanine <i>N</i> -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

Tandem ROMP/Hydrogenation Approach to Hydroxy-Telechelic Linear Polyethylene.

Hydroxy-telechelic polyalkenamers have long been synthesized using ring-opening metathesis polymerization (ROMP) in the presence of an acyclic olefin chain-transfer agent (CTA); however, this route typically requires protected diols in the CTA due to the challenge of alcohol-mediated degradation of ruthenium metathesis catalysts that can not only deactivate the catalysts, but also compromise the CTA. We demonstrate the synthesis and implementation of a new hydroxyl-containing CTA in which extended methylene spacers isolate the olefin and alcohol moieties to mitigate decomposition pathways. This CTA enabled the direct ROMP synthesis of hydroxy-telechelic polycyclooctene with controlled chain lengths dictated by the initial ratio of monomer to CTA. The elimination of protection/deprotection steps resulted in improved atom economy. Subsequent hydrogenation of the backbone olefins was performed by a one-pot, catalytic approach employing the ruthenium complex used for the initial ROMP. The resultant approach is a streamlined, atom-economic, and low-waste route to hydroxy-telechelic linear polyethylene that uses a green solvent, succeeds with miniscule quantities of catalyst (0.005 mol %), and requires no additional purification steps.

Linear Assembly of Two-Patch Silica Nanoparticles and Control of Chain Length by Coassembly with Colloidal Chain Stoppers.

The self-assembly of patchy nanosized building blocks is an efficient strategy for producing highly organized materials. Herein we report the chaining of divalent silica nanoparticles with polystyrene patches dispersed in tetrahydrofuran triggered by lowering the solvent quality. We study the influence of the patch-to-particle size ratio and show that the nature of the added nonsolvent, for example, ethanol, water, or salty water, and its volume fraction should be carefully adjusted. We demonstrate that colloidal assembly initially obeys the kinetic model of step-growth polymerization and that beyond a certain length, the chains have the possibility to cyclize. We also show that the length of the chains can be controlled by the addition of one-patch silica nanoparticles, which act as colloidal analogues of chain stoppers.

ABC-Type Triblock Copolyacrylamides via Copper-Mediated Reversible Deactivation Radical Polymerization.

The aqueous Cu(0)-mediated reversible deactivation radical polymerization (RDRP) of triblock copolymers with two block sequences at 0.0 °C is reported herein. Well-defined triblock copolymers initiated from PHEAA or PDMA, containing (A) 2-hydroxyethyl acrylamide (HEAA), (B) N-isopropylacrylamide (NIPAM) and (C) N, N-dimethylacrylamide (DMA), were synthesized. The ultrafast one-pot synthesis of sequence-controlled triblock copolymers via iterative sequential monomer addition after full conversion, without any purification steps throughout the monomer additions, was performed. The narrow dispersities of the triblock copolymers proved the high degree of end-group fidelity of the starting macroinitiator and the absence of any significant undesirable side reactions. Controlled chain length and extremely narrow molecular weight distributions (dispersity ~1.10) were achieved, and quantitative conversion was attained in as little as 52 min. The full disproportionation of CuBr in the presence of Me6TREN in water prior to both monomer and initiator addition was crucially exploited to produce a well-defined ABC-type triblock copolymer. In addition, the undesirable side reaction that could influence the living nature of the system was investigated. The ability to incorporate several functional monomers without affecting the living nature of the polymerization proves the versatility of this approach.

Grafting polymers from cellulose nanocrystals via surface‐initiated atom transfer radical polymerization

AbstractCellulose nanocrystals (CNC) are rod‐like nanoparticles extracted from cellulose. Due to their fascinating properties—renewable, biocompatible, non‐toxic, biodegradable, excellent mechanical performances, high specific surface area, water dispersible, can be assemble in chiral nematic phases—CNC have shown promise in various fields, including oil recovery, polymer composites reinforcing, hydrogels, aerogels, supercapacitors, energy saving buildings, cosmetics, papermaking, coatings, liquid crystals, and waste water treatment. However, the hydrophilic surface of CNC hinders their broader applications. In this context, surface modification of CNC via polymer grafting can be used to finely tune their surficial properties and endow CNC with a variety of functionalities, such as conductivity, pH or temperature responsiveness, reactivity…In particular, surface‐initiated atom transfer radical polymerization (SI‐ATRP) is a powerful tool to graft various polymers with a high grafting density and controlled chain length. In this review, the precise control of grafted polymers from CNC via SI‐ATRP is first discussed, including issues related to the polymer grafting density, chain length and possibility to perform an asymmetric grafting. Then, the properties and applications of CNC grafted with a variety of polymers are presented. Finally, some challenges and outlook related to the SI‐ATRP method applied to the field of CNC is discussed.

Precise Amphiphilic Giant Polymeric Chain Based on Nanosized Monomers with Exact Regio-Configuration.

Polymeric chains made of "giant" monomers at a larger length scale provide intriguing insights into the fundamental principles of polymer science. In this study, we modularly prepared a library of discrete amphiphilic polymeric chains using molecular nanoparticles as repeat units, with exact control of composition, chain length, surface property, and regio-configuration. These giant polymeric chains self-assembled into a rich collection of highly ordered phases. The precise chemical structure and uniform chain length eliminate all the inherent molecular "defects", while the nanosized monomer amplifies minute structural differences, providing an ideal platform for a systematic scrutiny of the self-assembly behaviors at a larger length scale. The compositional and regio-configurational contribution was carefully studied. The regio-regularity is found to have a direct and profound impact on the chain conformation, leading to a distinct molecular packing scheme and therefore shifting the phase boundaries. With increasing the length of the linker, the regio-constraint gradually diminishes, and the neighboring particles would eventually be decoupled.

Production of Coenzyme Q10 in Recombinant Schizosaccharomyces Pombe through Metabolic Engineering Approaches

Coenzyme Q10 is an important cofactor in the electron transport chain, which powers oxidative phosphorylation. Similar to other cofactors such as vitamin B12, deficiency in coenzyme Q10 (CoQ) manifests as clinical symptoms. Hence, coenzyme Q10 can be used as a health supplement. But, difficulty in extracting it from natural sources and the high cost involved explains continuing interest in improving its production titer in various cellular hosts. A metabolic cofactor, and thus naturally of low cellular abundance, various genetic engineering approaches are explored for improving its concentration in heterologous hosts ranging from Escherichia coli to Schizosaccharomyces pombe. While the native pathway for CoQ biosynthesis feeds into that of cholesterol, and is conserved across the three domains of life, slight variation in pathway architecture exists. Specifically, some segments of the pathway are truncated for improving overall metabolic efficiency in hosts. Hence, choice of organisms as production host for CoQ10 is crucial and these typically exhibit high growth rates with ease for genetic manipulation such as heterologous expression of missing pathway genes. Whole cell metabolomics profiled by high performance liquid chromatography tandem mass spectrometry (HPLC- MS/MS) coupled with metabolic flux analysis (MFA) and metabolic flux control (MCA), points to specific metabolic choke points where enhanced expression of enzyme increase the cellular concentration of important precursors and the final coenzyme product. One such choke point is the rate limiting enzyme, HMG-CoA reductase, whose over-expression improves CoQ titer. Systematic exploration of how fermentation parameters affect production yield is another important approach given myriad problems and challenges affecting the industrial use of recombinant CoQ production hosts. But CoQ production by recombinant routes usually results in CoQ of different side chain lengths; thus, efforts are directed towards tunable control of CoQ side chain moiety from the metabolic engineering perspective, which improves product quality and pharmaceutical properties. Another interesting basic science angle involves the conjugation of different cell localization signals for probing subcellular localization of CoQ. Finally, RNA interference (RNAi) mediated modulation of CoQ expression is a useful tool for indirectly assessing cellular energy state and redox balance, which opens up its use in studies examining how energy status affect physiological response to various nutrition and environment stressors. Collectively, much effort has focused on improving CoQ yield through metabolic engineering, and effecting tunable control of side chain length. However, important questions remain on understanding the subcellular localization of CoQ and examining the utility of tuning CoQ expression level for affecting cellular energy level, and its use as a physiology probe.

Modification of polystyrene cell-culture-dish surfaces by consecutive grafting of poly(acrylamide)/poly(N-isopropylacrylamide) via reversible addition-fragmentation chain transfer-mediated polymerization

Reversible addition-fragmentation chain transfer (RAFT)-mediated and radiation-induced grafting of poly(acrylamide) (PAAm) from polystyrene (PS) cell-culture Petri dishes and subsequent chain extension of the grafts by poly(N-isopropylacrylamide) (PNIPAAm) have been achieved by pre-irradiation of PS by electron beam. Utilizing RAFT polymerization during the construction of both blocks enables the control of chain length of PAAm and PNIPAAm segments hence the thickness of both hydrophilic and hydrophobic layers within 100 nm which is crucial for the cell sheet attachment-detachment process. Characterization of the synthesized copolymers by XPS and ATR-FTIR spectroscopies, elemental and thermogravimetric analyses and ellipsometry measurements revealed grafting of double polymeric layer from PS dish surfaces. The grafted Petri dish specimens were found to be noncytotoxic. Water contact angle measurements demonstrated that dishes modified by PAAm-block-PNIPAAm brushes showed significant temperature-dependent interfacial properties in aqueous media.

Modulation of flexo-rigid balance in photoresponsive thymine grafted copolymers towards designing smart healable coating.

Efficacy and durability of the photovoltaic device mandates its protection against hot, humid weather condition, high energy of UV light and unwanted scratches. Such challenges can be mitigated by smart polymeric coating with inherent properties e.g. hydrophobicity to prevent moisture, optimal viscocity for better processibility and crack-healing. The hydrophobic polymers TP1–TP4 containing pendant photo-crosslinkable thymine moieties are designed that undergo [2 + 2] photocycloaddition upon UVB irradiation and can be dynamically reverted back upon irradiation with UVC light. A judicious control of solvent environment, chain length, functionality% and concentration of the polymers regulate the aspects of photodimerization thereby, rendering intra or inter-chain collapse to form diverse nanostructures. Photodimerization of the thymine moieties renders coil to globule transformation in dilute condition whereas irradiation performed at high macromolecular concentration regime exhibits higher order nanostructures. The photoresponsive chain collapse leads to the formation of rigid crosslinked domains within flexible polymer chains akin to the hard–soft phases of thermoplastic elastomers. Such rigidification of the crosslinked segments endows a tool to photomodulate the glass transition temperature (Tg) that can dynamically revert back upon decrosslinking. Further, the structural modulation of the polymers is explored towards autonomic and nonautonomic self-healing behaviour at ambient conditions. Moreover, the self-healing efficacy can be tuned with the film thickness and it remains unaltered upon using solar simulator or direct sunlight. Overall, such hydrophobic low Tg polymers display photo-regulated self-healing mechanism consisting of both autonomic and non-autonomic self-healing and may find applications in designing smart protective coatings for photovoltaic devices.

Structure and Mechanism of the Ketosynthase-Chain Length Factor Didomain from a Prototypical Polyunsaturated Fatty Acid Synthase.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential ingredients of the human diet. They are synthesized by LC-PUFA synthases (PFASs) expressed in marine bacteria and other organisms. PFASs are large enzyme complexes that are homologous to mammalian fatty acid synthases and microbial polyketide synthases. One subunit of each PFAS harbors consecutive ketosynthase (KSc) and chain length factor (CLF) domains that collectively catalyze the elongation of a nascent fatty acyl chain via iterative carbon-carbon bond formation. We report the X-ray crystal structure of the KS-CLF didomain from a well-studied PFAS in Moritella marina. Our structure, in combination with biochemical analysis, provides a foundation for understanding the mechanism of substrate recognition and chain length control by the KS-CLF didomain as well as its interaction with a cognate acyl carrier protein partner.