Poly(epsilon-caprolactone)-b-polysarcosine (PCL-b-PSar) is an amphiphilic block copolymer (BCP) with excellent biocompatibility, yet its crystallization-driven self-assembly (CDSA) in alcohols typically produces multilayer lamellae containing screw dislocations. To suppress these defects and obtain uniform monolayer lamellae, the effects of a series of hydrogen-bond donor additives on the CDSA of PCL-b-PSar in alcohols are systematically investigated. The results demonstrate that acidic additives, such as acetic acid, effectively suppress screw dislocations, yielding elongated truncated lozenge-shaped monolayer lamellae. It is proposed that the hydrogen-bonding interactions between acids and both blocks of PCL-b-PSar play a key role in modulating the CDSA. Acid-PSar interactions enhance the solubility and local chain deformability of PSar, thereby releasing interglobular repulsion, while acid-PCL interactions decelerate the crystallization of PCL, facilitating regular rearrangement of the unimers at the growth front. These two effects synergically promote ordered crystallization of PCL-b-PSar and suppress screw dislocation formation during crystal growth. This study provides new insights into the acid-mediated CDSA of PCL-b-PSar and establishes a viable strategy for controlling screw dislocations in polymer lamellae.

The chemical synthesis of random poly(proline-co-glycine) (PPrG), a collagen-inspired polypeptide with promising biomedical applications, was challenging and underexplored due to the poor solubility of long glycine (Gly) and proline (Pro) segments forming β-sheets and all-cis right-handed type I (PPI) helices, respectively. Owing to the new developments in the ring-opening polymerization (ROP) of amino acid N-thiocarboxyanhydrides (NTAs), we herein reported a well-controlled statistical copolymerization of Pro-NTA with Gly-NTA in benzonitrile (PhCN) catalyzed by carboxylic acids. In the optimized polymerization conditions, premature precipitations were effectively suppressed, and statistical copolymers of PPrG were synthesized with predictable molecular weights (2.4 ~ 25.6 kg/mol), narrow dispersity, designable Gly compositions (0 ~ 47 mol%) and composition drifting structure with reactivity ratios (rGly = 1.42, rPro = 0.108). PPrGs exhibited random coil structure in aqueous solution and formed gels at elevated concentrations ( 14.6 wt%). In addition, a third α-amino acid monomer including leucine-NTA (Leu-NTA), alanine-NTA (Ala-NTA) and phenylalanine-NTA (Phe-NTA) was able to be incorporated into backbones randomly without modification of the polymerization conditions. This contribution provided a versatile platform to synthesize collagen-inspired polypeptides with tunable structures, expanding the scope of advanced biomaterials

Poly(hemiacetal ester)s featuring labile backbones are emerging as promising candidates for marine-degradable materials but remain unexplored due to the limited molecular weight and ill-defined structures. In the contribution, we describe the synthesis of poly(1,3-dioxolan-4-one) (PDXO) with exclusively cyclic architecture via zwitterionic ring-expansion polymerization even with high monomer concentration, catalyzed by commercially available rare-earth, transition, and main-group metal salts, which completely avoids formaldehyde elimination. The resulting cyclic PDXO is a semicrystalline polymer with a melting temperature of 53 degrees C and a number-average molecular weight up to 70.8 kg/mol, demonstrating a tensile strength of 16.4 MPa. PDXO is capable of both depolymerizing back to its monomer and degrading in seawater at 0 degrees C, achieving a 70% decline in molecular weight within five months. The efficient zwitterionic polymerization strategy provides the first instance of a mechanically robust poly(hemiacetal ester) with substantial marine degradability.

Poly(ε-caprolactone) (PCL) possesses considerable biocompatibility, biodegradability, and favorable mechanical properties, yet the lack of functional groups on the PCL backbone or side chain limits its applications. α-Ethylidene-δ-vinyl-δ-valerolactone (EVL), an intermediate derived from carbon dioxide (CO2) and 1,3-butadiene, possesses abundant carbon-carbon double bonds that provide sites for modification. In this contribution, the living and controlled copolymerization of CL with EVL is achieved at 0 °C with TBD as catalyst, resulting in linear P(EVL-co-CL) with number average molecular weights (Mn) up to 22.7 kg/mol. Using methoxy poly(ethylene glycol) (mPEG) as macroinitiator, PEG-b-P(EVL-r-CL) with modifiable double bonds are synthesized and functionalized via thiol-ene “click” reactions. The resulting block copolymers are capable of forming micelles in aqueous solution and the introduction of thioether and carboxyl groups enables the formation of stimuli-responsive micelles, whereas the introduction of amino groups leads to micelles that are degradable under alkaline conditions. This method offers a straightforward approach to synthesize amphiphilic block terpolymers from CO2, 1,3-butadiene, CL and PEG.

It is promising but challenging to prepare poly(amino acid)s that directly bond to alcohols, especially saccharides. Herein, we report a novel method for the controlled ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride (Sar-NCA) quantitatively initiated by hydroxyl groups using lutetium triflate (Lu(OTf)3) as catalyst. Lu(OTf)3 is devised to slow down the propagation by reducing the nucleophilicity of the amino group on the propagating chain end, thus realizing quantitative initiation efficiency (IE) of alcohol. Polysarcosine (PSar) samples with controlled molecular weights (Mn = 2.2-12.7 kg/mol) and low dispersities (Đ = 1.11-1.15) are obtained and full IE of the hydroxyl group is realized. Kinetic studies reveal that the propagation rate of Sar-NCA is significantly decreased in the presence of Lu(OTf)3. The addition of Lu(OTf)3 converts the characteristic of alcohol-initiated ROP of Sar-NCA from "slow initiation and fast propagation" to "fast initiation and slow propagation" which is essential of the polymerization control. Density functional theory (DFT) calculations provide mechanistic insights that Lu(OTf)3 is prone to coordinate with the propagating chain end species of secondary amino and carbamate groups in the form of five- or eight-membered rings and retards the propagation. PSar products bearing glucose or mannose ester end groups, analogs of glycoproteins, are successfully synthesized by applying this protocol. The obtained mannose-functionalized PSar shows significantly accelerated ingestion by cancer cells.

Exploiting carbon dioxide (CO2) to produce sustainable and high-performance polymeric materials from commodity feedstocks such as olefins has long been an attractive yet challenging goal. Here, we present a new strategy to create cyclopolyester thermoplastics derived from CO2 and 1,3-butadiene via ring-opening polymerization of α-alkyl-α,δ-divinyl-δ-valerolactone (DVLR) monomers, followed by polymer backbone editing via ring-closing metathesis. Ultra-high-molecular-weight (MW) (absolute MW up to 768.4 kg/mol) polyester PDVLRs are synthesized using N-heterocyclic carbene and urea binary catalysts. Ring-closing metathesis of PDVLRs is employed to construct cyclopolyester PCHELRs (CO2 content up to 32 wt %) with a hindered cyclohexene structure incorporated into the backbone. These PCHELRs are degradable and amorphous with tunable glass transition temperatures of 30.1°C–56.2°C, which behave as tough thermoplastics with ultimate tensile strength up to 31.1 MPa and elongation at break up to 333.5%. This work paves the way for polyester thermoplastics from CO2 and highlights the potential of sustainable feedstocks in polymeric materials.

Poly(amino acid)s have garnered significant attention in biomedical materials due to their excellent biocompatibility and degradability. The ring-opening polymerization of N-thiocarboxyanhydrides (NTAs) represents a promising synthetic approach owing to their air and moisture stability. However, challenges of controllability arise when NTAs cannot be fully dissolved. To address this, a thermal regulation strategy was employed to control the polymerization loci, realizing Interfacial Polymerization at Solid (iPaS) to interlocked polymerization inside cocrystals (iPiC) via decreasing temperature. Using dl-leucine NTA as a model monomer, polymerization at 15 and 25 degrees C produced polypeptides with broad molecular weight distributions (D = 1.3-1.5) and mixed kinetic manners, which were further deconvoluted into zeroth-order and first-order terms. On the contrary, polymerization at low temperature (0 degrees C) followed the iPiC mechanism and enabled precise control (D < 1.1). Adsorption energy calculations and polymerization pathway mapping were introduced to demonstrate the difference between iPiC and iPaS. This work established both theoretical and practical foundations for developing robust and efficient temperature-driven heterogeneous NTA polymerization systems.

Thermoplastic elastomers (TPEs) are extensively used in daily life, yet their synthesis relying on fossil-derived feedstocks raises environmental concerns. alpha-Amino acids, as fundamental building blocks of proteins in nature, provide a promising route to develop sustainable biobased TPEs. In this contribution, a novel category of thermoplastic poly(alpha-amino acid) elastomers has been successfully synthesized in one pot via Janus polymerization. Catalyzed by trimethylsilyl triflate, cationic ring-opening polymerization of tetrahydrofuran (THF) and anionic polymerization of sarcosine N-carboxyanhydrides (Sar-NCA) are carried out simultaneously at the two ends of a single polymer chain, respectively. Subsequent intermolecular coupling reactions of the cationic and anionic living ends yield multiblock copolymers [PSar-b-PTHF] n . The products exhibit mechanical properties superior to those of commercial elastomers, with a tensile strength of 39.3 +/- 2.0 MPa, an elongation at break of 1245 +/- 82%, and a tensile toughness of 234 +/- 29 MJ/m3. It presents the first example of metal-free catalyzed Janus polymerization to produce a promising environmentally friendly alternative to conventional TPEs.

N-Phenyloxycarbonyl-amino acids (NPCs) are promising monomers to synthesize both polypeptides and polypeptoids exhibiting great tolerance for nucleophiles. However, the polymerization mechanism of NPCs remains unclear since it is hard to distinguish intermediates including N-carboxyanhydrides (NCA) from byproducts of direct polycondensation. In this contribution, the polycondensation pathway is disproved by the impossible polymerization of alanine dimer NPC. Isocyanate acid (ICA) has been captured as an intermediate of NPC polymerization. In an attempt to monitor the polymerization of 15N-labeled leucine-NPC by 15N NMR for the first time, reactive species including ICA are identified and traced. A kinetic model is established based on the 15N NMR data and validated by Monte Carlo simulation. Two possible polymerization pathways are evidenced by a density functional theory (DFT) calculation. The ICA-meditated NCA ring-closing pathway is preferred over the direct NCA ring-closing pathway for lower Gibbs energy barriers. A direct ring-closing path is feasible only for Sar-NPC, which explains its low polymerization reactivity.

The current study explores the organocatalytic ring-opening polymerization (ROP) of gamma-n-butoxyl-e-caprolactone (BCL) and its one-pot block copolymerization with a strained bridged ester N-Boc-substituted proline lactone (NBocPL), using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the catalyst. The TBD-catalyzed ROP of BCL in toluene demonstrates the first-order polymerization kinetics and exhibits living polymer characteristics within moderate monomer conversion. It effectively suppresses inter-and intramolecular transesterification side reactions to the minimum, which are commonly observed in base-promoted ROP of lactone monomers. It provides acceptable control over the molecular weight of poly(gamma-n-butoxyl-e-caprolactone) (PBCL) by simply tuning the initial monomer-to-initiator molar ratio and controlling the monomer conversion. For instance, the polymerization using bifunctional 1,4-butanediol as the initiator can produce narrowly distributed PBCL with Mn,SEC up to 34.5 kg mol-1 and Mw/Mnof less than 1.20. The TBD-catalyzed copolymerization of BCL with NBocPL is successful to synthesize block copolymers. Notably, the one-pot copolymerization of the two monomers demonstrates a strictly sequential monomer consumption with NBocPL polymerizing first followed by BCL. This unique copolymerization behavior enables the synthesis of block copolymers via a one-pot procedure, and tri-, penta-, and heptablock copolymers are accordingly synthesized by introducing monomers simultaneously or in multiple steps. The polymer structures are characterized using NMR, FT-IR spectroscopy, MALDI-TOF MS, and SEC. The thermal characteristics and self-assembly behavior of the polymers in aqueous solutions are further evaluated using TGA, DSC, and DLS. Additionally, the cytotoxicity of the Boc-deprotected triblock copolymers towards mouse fibroblasts (3T3 cells) and their hemolytic effects on rat red blood cells are further investigated, with the detailed results presented in subsequent sections.

A novel synthetic method towards recyclable polyesters rich in double bonds is highly desirable yet remains a considerable challenge. α-Ethylidene-δ-vinyl-δ-valerolactone (EVL), a lactone derived from CO2 and butadiene, is an attractive intermediate for the production of sustainable and functional copolymers. However, its anionic ring-opening polymerization (ROP) is significantly impeded by undesired conjugate addition of the tiglate groups. This study presents the chemoselective and controlled ring-opening copolymerization (ROCP) of EVL with α-(1-(alkylthio)ethyl)-δ-vinyl-δ-valerolactones (ATEVL), which are derivatives of EVL and thiols, utilizing 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the catalyst. Conducted at temperatures ranging from −20 °C to 20 °C, the copolymerizations achieved 100

Poly(L-lactide) (PLLA) microspheres have excellent biocompatibility and biodegradability and already been applied as biomedical materials in tissue engineering. However, hydrophobic PLLA exhibits low degradation rate, bringing an obstacle to the generation of new tissues. Incorporating hydrophilic blocks endows diblock copolymer poly(L-lactide)-b-poly(ethylene glycol) (PELA) with improved biodegradability. In the present contribution, degradation behaviors of PLLA and PELA microspheres including mass loss, molecular weight changes, viscosity variation and microscopic morphology difference are monitored and analyzed. The accelerating of PEG blocks is validated. The addition of enzymes including proteinase K and lipase shows negligible effect on the degradation, thus hydrolysis in bulk polymer is proved to be the dominant degradation mechanism. Degradation characteristics including accelerates degradation rate, low surface degradation efficiency and hydrolysis nature make PELA microspheres promising candidate for dermal filler materials.

A trade-off relationship between enhancing controllability and increasing reaction rate is always a challenge, as achieving better controlled polymerization typically requires reducing the reaction rate. Synchronous raises of polymerization rate and controllability require specially designed catalysts. In the contribution, living and controlled polymerizations of N-phenoxycarbonyl 3,4-dihydroxy-l-phenylalanine (DOPA-NPC) with increased rate are carried out using an organic "acid-and-base" catalytic system, producing poly(3,4-dihydroxy-l-phenylalanine) (PDOPA) with controlled molecular weights (6.3-16.1 kg/mol) and narrow distributions (& Dstrok; < 1.15). Kinetic studies demonstrate that benzoic acid effectively inhibits the side reaction to form 3,6-bis(3,4-dihydroxybenzyl)piperazine-2,5-dione (DDP) while N,N-diisopropylethylamine dramatically accelerates monomer consumption. PDOPA exhibits reversible chelation of ferric ions in proper pH ranges.

Polymerization of N-phenoxycarbonyl N-substituted glycines (NNPCs) is a promising approach toward functional polypeptoids due to the excellent tolerance to nucleophilic impurities. However, side reactions in NNPC polymerization are hard to avoid, and the mechanism has not been understood. In the present work, well controlled polymerizations of N-ethyl glycine NPC (NEG-NPC) and N-butyl glycine NPC (NBG-NPC) catalyzed by acetic acid are successfully carried out with designable molecular weights and low dispersities (D < 1.11). The severe side reaction in sarcosine NPC (Sar-NPC, a.k.a. N-methyl glycine NPC) polymerization is inhibited by maintaining low initiator concentration. A kinetic investigation reveals the differences among Sar-NPC, NEG-NPC, and NBG-NPC as well as the mechanism of the side reaction, i.e., oligomers backbite to form 1,4-dialkylpiperazine-2,5-dione (DAP), which is further validated by a density functional theory study. Block and statistical copolymerizations of Sar-NPC with NEG-NPC and NBG-NPC are conducted, producing the corresponding copolypeptoids with designed compositions. In the copolymerization of Sar-NPC with NEG-NPC, the reactivity ratios are 1.133 (Sar-NPC) and 0.969 (NEG-NPC), and in the case of Sar-NPC with NBG-NPC, they are 1.067 (Sar-NPC) and 1.038 (NBG-NPC). The approximately equal values confirm the essentially statistical copolymerization and the ideal random distributions of the two repeating units in polypeptoids. Poly(sarcosine-r-N-butyl glycine)s possess lower critical solution temperatures, and their cloud point temperatures (T(cp)s) are tunable between 37 and 82 degrees C with the sarcosine molar fractions from 58% to 70%.

The challenging ring-opening homopolymerization of α-ethylidene-δ-vinyl-δ-valerolactone (EVL), derived from CO2 and 1,3-butadiene, has aroused extensive attention in consideration of economic efficiency and functionalization potential. In the contribution, we achieve the first cationic ring-opening polymerization (CROP) of EVL through a carbenium-based mechanism, yielding well-defined cyclic polyester PEVL with a number-average molecular weight (Mn) up to 12.8 kg/mol and a low dispersity of 1.2. The carbenium-based CROP results in PEVL containing two kinds of structural units derived from EVL, evidenced by NMR, MALDI-ToF MS, and density functional theory (DFT) calculation. The fast intramolecular transfer reaction and slow initiation are responsible for the cyclic topology fidelity of PEVL. The Mn of PEVL is tunable from 6.5 to 12.8 kg/mol by decreasing the polymerization temperature from 10 to -30 °C. PEVL possessing a low glass transition temperature (Tg) of -33.6 °C is ready for postpolymerization functionalization, as showcased by modification with 1-octadecanethiol, which endows the polymer with a melting point (Tm) of 42.2 °C.

Elevated expression of the mechanosensitive ion channel PIEZO1 in response to abnormal mechanical stimuli is implicated in many diseases, including myocardial infarction (MI). However, no effective strategy is currently available to normalize PIEZO1 expression for disease management. This study investigates the therapeutic potential of mechanically adapted cardiac patches in reversing PIEZO1 elevation and treating MI. Increased mechanical stress and PIEZO1 upregulation are observed in ischemic cardiomyopathy myocardium. Using finite element analysis, elastomeric patches are designed and applied on MI rats to reduce left ventricular (LV) wall stress and mitigate LV remodeling. Molecular analysis reveals that patch treatment suppresses stress-induced chromatin opening of the Piezo1 promoter, reversing PIEZO1 elevation and restoring heart contraction gene expression. The patch's therapeutic benefits correlate with the reversal of PIEZO1 elevation is further validated in a porcine model. Notably, constant high expression of endogenous PIEZO1 partially blocks the patch's therapeutic effects, confirming that the mechanism of patch treatment involves reversing PIEZO1 expression, in addition to providing physical support. In conclusion, cardiac patches reduce LV wall stress, preserving cardiac function and geometry by both physically supporting and biologically reversing PIEZO1 expression, highlighting the potential of medical devices in normalizing PIEZO1 expression and treating related diseases.

Chemical synthesis of polymers from carbon dioxide (CO2) has been attracting a continuous amount of attention. This contribution explores the copolymerization of ethylidene-6-vinyltetrahydro-2H-pyran-2-one (EVL) synthesized from CO2 and 1,3-butadiene with various cyclic carbonates (CC) derived from CO2 and biomass diols. Following the "scrambling polymerizations" mechanism, EVL units are incorporated into polycarbonate backbones, resulting in random poly(ester-co-carbonate) P(EVL-co-CC) with functionalizable C=C double bonds. Kinetic studies and characterizations are conducted by NMR, MALDI-ToF MS, and SEC techniques. The obtained degradable P(EVL-co-CC)s having varying topologies, CO2 and C=C double bond contents, and glass transition temperatures are suitable for diverse applications. Modification in situ or via a postpolymerization "thiol-ene" reaction produces a copolymer with tunable tensile strength and amphiphilic and hydrophilic properties. This work presents an advancement in the utilization of CO2 to synthesize functional poly(ester-co-carbonate)s, contributing to the development of sustainable and green polymer chemistry.

The stereochemistry of t -BuLi initiated styrene polymerization in cyclohexane yields isotactic-rich polystyrene in the presence of sodium 4-methylbenzenesulfonate (SMBS).

Effective and accurate molecular imaging methods are particularly desirable for specifically non-invasive biological diagnosis. However, highly sensitive and smart probes on a single platform for contrast imaging remain challenging. Simultaneous detecting multiple physiological parameters immensely decreases misdiagnosis. In this contribution, we report the first difluoroboron beta-diketone-based dual-modal nanosensor for luminescence bioimaging with synergistic response of hypoxia and pH combined with magnetic resonance imaging (MRI). Acidic pH associated with hypoxia-stimulated luminescence enhancement makes the nanosensor more suitable for early diagnosis of tumors. Furthermore, the highly stable Gd3+ coordinated nanoparticles efficiently enhance relaxivity and have excellent biocompatibility. The smart dual-modal system is promising for further applications in bioimaging and theragnostic integrative biomedical techniques.

alpha-Ethylidene-delta-vinyl-delta-valerolactone (EVL), a substituted delta-lactone synthesized through the telomerization of CO2 with 1,3-butadiene, is highly functionalized, containing a six-membered ring and two C=C double bonds. In this contribution, we report the copolymerization of 3-(1-(2-hydroxy ethylthio) ethyl)-6-vinyl valerolactone (HEVL), an inimer derived from EVL, with epsilon-caprolactone (epsilon-CL) to yield a novel multifunctional hyperbranched copolyester, P(HEVL-co-CL). The structure of P(HEVL-co-CL)s was characterized by 1H, 13C, 13C-1H HSQC, 1H-1H COSY NMR, MALDI-ToF MS, and SEC-MALS. The simultaneously initiating and ring-cleavage of HEVL facilitates the formation of a hyperbranched topology of the copolymers. The influences of monomer feed ratio, monomer concentration, reaction time, and temperature on the copolymerization, along with the composition and architecture of the copolymer, were investigated. The P(HEVL-co-CL) exhibits distinctive molecular characteristics, featuring an abundance of tailored functionalities, enabling the synthesis of polyester microspheres and polyurethane elastomers via thiol-ene and hydroxyl-isocyanate cross-linking post-polymerization modifications. This protocol significantly expands the potential for developing advanced sustainable materials from CO2 and olefin-based feedstocks.