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Accounts of Chemical Research Jul 2022This Account discusses the evolution of our strategy to conduct environmentally responsible research in the field of polymer chemistry. To contextualize our work, we... (Review)
Review
This Account discusses the evolution of our strategy to conduct environmentally responsible research in the field of polymer chemistry. To contextualize our work, we begin with a broad historical overview of the modern environmental movement, the rise of sustainability as a concept, and how chemistry has responded to these forces, which were often sharply critical of our field. We then trace our own responses, from graduate school onward, chronicling a series of experiences and research projects that molded, challenged, and reshaped how we think about sustainability in polymer science.Since beginning our independent careers in 2004, we have recognized and worked to resolve the tension between designing synthetic polymers for specific desired thermomechanical properties and minimizing environmental impact. In our early years, we were most strongly guided by the 12 Principles of Green Chemistry (12PGC), which had only recently been proposed. The authors' early research agendas had a rather narrow focus on two areas, specifically catalysis and biobased monomers, which we saw as strongly linked to sustainability. Over time, we found these areas to be too narrow in their focus, ignoring important considerations such as the capacity of monomer supply to support scale-up and the impact polymers have at the end of their usage lifetimes. With respect to monomers and catalysts, we consider descriptive metrics that quantify waste production and the toxicity of compounds used during synthesis. In terms of polymer end-of-life, we discuss hydrophobicity as a tool to help understand susceptibility to degradation in the environment as well as some of the concerns with design for degradation, a critical component of 12PGC.Now, after nearly two decades of investigation, we believe that achieving sustainability in polymer science will require us to move beyond the qualitative use of the 12PGC to a portfolio of metrics. We note a heartening increase in the availability and use of such metrics and tools across the field. These include items that provide limited insight but are relatively trivial to integrate into existing workflows such as E factor or the Toxicity Estimation Software Tool. We also appreciate the increased use of Life Cycle Assessment (LCA), which is both dramatically more thorough and difficult to deploy. Finally, we propose the creation of a national LCA center, similar to instrumental core facilities. Such a resource would enable the use of this tool across multiple phases of research and we hope would more effectively guide us to a sustainable future.
Topics: Catalysis; Environment; Polymers
PubMed: 35758829
DOI: 10.1021/acs.accounts.2c00194 -
Journal of the American Chemical Society Apr 2022Simple and efficient methods are a key consideration for small molecule and polymer syntheses. Direct arylation polymerization (DArP) is of increasing interest for...
Simple and efficient methods are a key consideration for small molecule and polymer syntheses. Direct arylation polymerization (DArP) is of increasing interest for preparing conjugated polymers as an effective approach compared to conventional cross-coupling polymerizations. As DArP sees broader utilization, advancements are needed to access materials with improved properties and different monomer structures and to improve the scalability of conjugated polymer synthesis. Presented herein are considerations for developing new methods of conjugated polymer synthesis from small molecule transformations, exploring how DArP has successfully used this approach, and presenting how emerging polymerization methodologies are developing similarly. While it is common to adapt small molecule methods to polymerizations, we demonstrate the ways in which information gained from studying polymerizations can inform and inspire greater advancements in small molecule transformations. This circular approach to organic synthetic method development underlines the value of collaboration between small molecule and polymer-based synthetic research groups.
Topics: Polymerization; Polymers
PubMed: 35380440
DOI: 10.1021/jacs.1c12455 -
ACS Biomaterials Science & Engineering Oct 2022At high concentration or in the aggregated state, most of the traditional luminophores suffer from the general aggregation-caused quenching (ACQ) effect, which... (Review)
Review
At high concentration or in the aggregated state, most of the traditional luminophores suffer from the general aggregation-caused quenching (ACQ) effect, which significantly limits their biomedical applications. On the contrary, a few fluorophores exhibit an aggregation-induced emission (AIE) feature which is just the opposite of ACQ. The luminophores with aggregation-induced emission (AIEgens) have exhibited noteworthy advantages to get tunable emission, excellent photostability, and biocompatibility. Incorporating AIEgens into polymer design has yielded diversified polymer systems with fascinating photophysical characteristics. Again, stimuli-responsive polymers are capable of undergoing chemical and/or physical property changes on receiving signals from single or multiple stimuli. The combination of the AIE property and stimuli responses in a single polymer platform provides a feasible and effective strategy for the development of smart polymers with promising biomedical applications. Herein, the advancements in stimuli-responsive polymers with AIE characteristics for biomedical applications are summarized. AIE-active polymers are first categorized into conventional π-π conjugated and nonconventional fluorophore systems and then subdivided based on various stimuli, such as pH, redox, enzyme, reactive oxygen species (ROS), and temperature. In each section, the design strategies of the smart polymers and their biomedical applications, including bioimaging, cancer theranostics, gene delivery, and antimicrobial examples, are introduced. The current challenges and future perspectives of this field are also stated at the end of this review article.
Topics: Fluorescent Dyes; Humans; Neoplasms; Polymers; Reactive Oxygen Species; Stimuli Responsive Polymers
PubMed: 36054823
DOI: 10.1021/acsbiomaterials.2c00656 -
Journal of Biomaterials Science.... Feb 2024Various nanomaterials have been studied for their biomedical application in recent years. Among them, nanocomposites have a prominent medical application in the... (Review)
Review
Various nanomaterials have been studied for their biomedical application in recent years. Among them, nanocomposites have a prominent medical application in the prevention, diagnosis, and treatment of various diseases. Nanocomposites are made up of polymeric matrix layers composed of synthetic or natural polymers like chitosan, polyethylene glycol, etc. Polymer nanocomposites are inorganic nanoparticles dispersed in a polymer matrix. There are two types of polymeric nanocomposites which include natural and synthetic polymer nanocomposites. These nanocomposites have various biomedical applications, such as medical implants, wound healing, wound dressing, bone repair and replacement, and dental filling. Polymeric nanocomposites have a wide range of biomedical applications due to their high stability, non-immunogenic nature, sustained drug delivery, non-toxic, and can escape reticuloendothelial system uptake along with drug bioavailability improvement. In this review, we have discussed various types of natural and synthetic polymer nanocomposites and their biomedical applications.
Topics: Polymers; Chitosan; Nanoparticles; Prostheses and Implants; Nanocomposites
PubMed: 37962432
DOI: 10.1080/09205063.2023.2283910 -
Angewandte Chemie (International Ed. in... May 2021Protein-polymer conjugates are increasingly being applied in biomedicine because of the unique combination of the biological activity of the proteins and the... (Review)
Review
Protein-polymer conjugates are increasingly being applied in biomedicine because of the unique combination of the biological activity of the proteins and the multifunctionality and flexibility of the polymers. However, traditional protein-polymer conjugation techniques suffer from some unavoidable drawbacks, including nonspecificity and low efficiency. In this Minireview, we discuss a new approach based on "precision conjugation" for the construction of the next-generation protein-polymer conjugates in a more controlled, more efficient, and tailorable fashion for a broad range of advanced applications. In illustrating the concept, we highlight two general methods: site-specific in situ growth and intrinsically disordered polypeptide fusion, with a focus on the in situ, efficient, and controllable formation of protein-polymer conjugates. At the end, the challenges associated with this emerging concept are further discussed.
Topics: Polymerization; Polymers; Proteins
PubMed: 32437042
DOI: 10.1002/anie.202003708 -
Accounts of Chemical Research Jun 2022Poor waste management and unchecked consumption underpin our current paradigm of plastics use, which is demonstrably unsustainable in the long term. Nonetheless, the...
Poor waste management and unchecked consumption underpin our current paradigm of plastics use, which is demonstrably unsustainable in the long term. Nonetheless, the utility and versatility of plastics suggest that the notion of a plastic-free society is also unsustainable. Responses to this conundrum are increasing, and among these are research efforts focused on the development of more sustainable plastics. This Account, written by trained chemists, reflects an academic research journey culminating in an appreciation of the importance of improving and enabling the overarching systems that plastics exist within. Our primary initial focus was on catalyst development because catalysts are key drivers of sustainability by improving the efficiency and ease of polymerization. Metal catalysts ranging in ligand structure and the incorporated metal(s) were developed for the preparation of traditional polyesters such as poly(lactic acid) and polycaprolactone. The central themes in these works were stereocontrol (tacticity), efficiency (polymerization rate), and versatility (monomer scope). Alongside insights gained by systematically varying catalyst structure came impressive results gained through collaboration, including the remarkably high activity of novel heterometallic zinc catalysts toward various cyclic esters.This catalysis work was complemented by and slowly transitioned to a focus on polymer functionality and monomer design. Several fundamental studies focus on polymer topology, specifically star-shaped polyesters, tuned arm number, length, and tacticity. These reports feature emphases on the end of life (solvolysis) and physical properties of polymers, which were increasingly important themes as work shifted toward new methods of incorporating functionality in polymers produced by ring-opening polymerization. Three key highlights demonstrate this shift: the first two rely upon the exploitation of olefin metathesis (cross- and ring-closing) to functionalize polyesters or polyethers, and the third involves the manipulation of ring-opening polymerization equilibrium to enable selective monomer recovery from a polyester. Our foundational work on 1,3-dioxolan-4-one (DOX) monomers is then discussed because this emerging class of molecules offers a distinct synthetic pathway toward functional polyesters, both conventional and novel. With this DOX framework, polyesters that are usually challenging to synthesize (e.g., poly(mandelic acid)) are accessible because polymerization is driven by the concomitant, controlled extrusion of small molecules (acetone or formaldehyde).After these polyester-focused highlights, the foundation of our ongoing work is presented, namely, that polymer sustainability must be viewed from a systems-level perspective, including economic and social components alongside the environmental considerations. Material design must be driven by practice, and we have to involve key players in academia, industry, and government in a concerted effort to enable positive and robust change. The key goal is to develop sustainable systems that retain plastics in their highest value state for as long as possible by designing materials and products for a particular (and assured) end-of-life fate, whether that be reuse, recycling, (bio)degradation, or energy recovery.
Topics: Metals; Plastics; Polyesters; Polymerization; Polymers
PubMed: 35579567
DOI: 10.1021/acs.accounts.2c00134 -
Journal of Pharmaceutical Sciences Jun 2022Polymer conjugation to biologics is of key interest to the pharmaceutical industry for the development of potent and long acting biotherapeutics, with poly(ethylene...
Polymer conjugation to biologics is of key interest to the pharmaceutical industry for the development of potent and long acting biotherapeutics, with poly(ethylene glycol) (PEG) being the gold standard. Within the last years, unwanted PEG-related side effects (immunological reactions, antibody formation) arose, therefore creating several attempts to establish alternative polymers with similar potential to PEG. In this article, we synthesized N-terminal bioconjugates of the potential therapeutic human interleukin-4 (hIL-4 WT) with linear polyglycerol (LPG) of 10 and 40 kDa and compared it with its PEG analogs of same nominal weights. Polyglycerol is a highly hydrophilic polymer with good biocompatibility and therefore represents an alternative polymer to PEG. Both polymer types resulted in similar conjugation yields, comparable hydrodynamic sizes and an unaltered secondary structure of the protein after modification. LPG- and PEG-bioconjugates remained stable in human plasma, whereas binding to human serum albumin (HSA) decreased after polymer modification. Furthermore, only minor differences in bioactivity were observed between LPG- and PEG-bioconjugates of same nominal weights. The presented findings are promising for future pharmacokinetic evaluation of hIL-4-polymer bioconjugates.
Topics: Glycerol; Humans; Interleukin-4; Polyethylene Glycols; Polymers
PubMed: 34728175
DOI: 10.1016/j.xphs.2021.10.032 -
ACS Nano Jul 2023As a clinical unmet need, uncontrolled inflammation is characterized by the crosstalk between oxidative stress and an inflammatory response. Ferroptotic cell death plays...
As a clinical unmet need, uncontrolled inflammation is characterized by the crosstalk between oxidative stress and an inflammatory response. Ferroptotic cell death plays an essential role in uncontrolled inflammation. Hence ferroptosis inhibition is capable of managing hyper-inflammation, but the small molecular inhibitors show poor residence in cell membranes. The plasma membrane is the major site of lipid peroxidation that is the key event of ferroptosis. To address such a challenge, chiral radical trapping polymers were engineered by mimicking the structure of the cell membrane with imbedded helical proteins. The polymers were tailored to show an α-helix conformation that enabled increased hydrophobicity, prolonged membrane retention, and enhanced lipid radical trapping. The chiral polymers are amphiphilic, and the self-assembled micelles exhibited an extended blood circulation. At the lipopolysaccharide-induced macrophage and mice models, chiral polymer micelles effectively suppressed ferroptosis and repressed inflammatory cytokines. The current work provides an innovative means for attenuating uncontrolled inflammation by anti-ferroptotic polymer micelles.
Topics: Mice; Animals; Polymers; Micelles; Cell Death; Lipid Peroxidation; Inflammation
PubMed: 37352508
DOI: 10.1021/acsnano.2c12356 -
Acta Biomaterialia Oct 2022For the first time, the present review critically evaluates biodegradable polymer matrix composites containing graphene-related materials (GRMs) for antibacterial... (Review)
Review
For the first time, the present review critically evaluates biodegradable polymer matrix composites containing graphene-related materials (GRMs) for antibacterial applications while discussing their development, processing routes, mechanical properties, and antibacterial activity. Due to its suitable biological properties and processability, chitosan has been the most widely used biodegradable polymer for the fabrication of GRM-containing composites with antibacterial properties. The majority of biodegradable polymers (including cellulose-, gelatine-, PVA-, PCL-, and PHA-based polymers) exhibit little to no antibacterial effect alone; however, they show significant antibacterial activity (>70%) when combined with GRMs. In vitro and in vivo studies indicate that GRMs functionalization with biodegradable polymers also reduces potential GRM cytotoxicity. Overall, GRMs in biodegradable polymer matrices provide attractive antibacterial activity against a broad spectrum of bacteria (>30 different bacteria) along with improved mechanical properties over pristine polymers, where the type and the degree of improvement provided by GRMs depend on the specific matrix. For example, the addition of GRMs into chitosan, PVA, and PCL matrices increases their tensile strength by 80%, 180%, and 40%, respectively. Challenges remain in understanding the effects of processing routes and post-processing methods on the antibacterial activity and biocompatibility of biodegradable polymer/GRM composites. Given their promising properties and functionality, research on these composites is expected to further increase along with the implementation of new composite systems. These would include a wide range of applications, e.g., wound dressings, tissue engineering, drug delivery, biosensing, and photo-thermal therapy, as well as non-medical use, e.g., antibacterial food packaging, water treatment, and antibacterial fabrics. STATEMENT OF SIGNIFICANCE: Graphene-related materials (GRMs) in polymer matrices can provide excellent antibacterial activity against a broad spectrum of bacteria together with improved mechanical properties (e.g., tensile strength and elastic modulus) over pristine polymers; thus, research efforts and applications of biodegradable polymer matrix composites containing GRMs have increased notably in the last ten years. For the first time, the present review critically evaluates biodegradable polymer matrix composites containing GRMs for antibacterial applications while discussing their development, processing routes, mechanical properties, and antibacterial activity. Future research directions for each composite system are proposed to shed light on overcoming the existing challenges in composite performance (e.g., mechanical properties, toxicity) reported in the literature.
Topics: Anti-Bacterial Agents; Cellulose; Chitosan; Graphite; Polymers; Tensile Strength
PubMed: 35921991
DOI: 10.1016/j.actbio.2022.07.048 -
Proceedings of the National Academy of... Apr 2023Biomolecular phase separation has emerged as an essential mechanism for cellular organization. How cells respond to environmental stimuli in a robust and sensitive...
Biomolecular phase separation has emerged as an essential mechanism for cellular organization. How cells respond to environmental stimuli in a robust and sensitive manner to build functional condensates at the proper time and location is only starting to be understood. Recently, lipid membranes have been recognized as an important regulatory center for biomolecular condensation. However, how the interplay between the phase behaviors of cellular membranes and surface biopolymers may contribute to the regulation of surface condensation remains to be elucidated. Using simulations and a mean-field theoretical model, we show that two key factors are the membrane's tendency to phase-separate and the surface polymer's ability to reorganize local membrane composition. Surface condensate forms with high sensitivity and selectivity in response to features of biopolymer when positive co-operativity is established between coupled growth of the condensate and local lipid domains. This effect relating the degree of membrane-surface polymer co-operativity and condensate property regulation is shown to be robust by different ways of tuning the co-operativity, such as varying membrane protein obstacle concentration, lipid composition, and the affinity between lipid and polymer. The general physical principle emerged from the current analysis may have implications in other biological processes and beyond.
Topics: Polymers; Cell Membrane; Membranes; Membrane Proteins; Lipids
PubMed: 37018196
DOI: 10.1073/pnas.2212516120