Effect of oxygen-containing functional group contents on sorption of lead ions by acrylate-functionalized hydrochar.

The surface functional groups of hydrochar are crucial to its surface properties, and their contents are strongly positively correlated with the adsorption performance. In this study, acrylate-functionalized hydrochar (AHC) with varying contents of O-containing functional groups (OFGs) was synthesized via hydrothermal carbonization (HTC) of bamboo, acrylic acid and an initiator, and then deprotonated with NaOH. The AHCs were analyzed by various characterization techniques. During HTC, the higher amount of acrylic acid added led to higher carbon, oxygen and carboxyl contents, and to the larger specific surface area and pore volume of AHC. The adsorption kinetics, isotherms, thermodynamic, ionic strength and pH effects of Pb(II) on AHC were studied. Adsorption isotherms and kinetics obeyed Langmuir and pseudo-second-order models, respectively, indicating adsorption is monolayer chemical process. The adsorptive ability was well linearly related to the OFG contents of AHC. When acrylic acid was added to 25 mL during HTC, the adsorbing ability of AHC over Pb(II) reached 193.90 mg g-1. Hence, direct HTC of acrylic acid, biomass and an initiator can prepare hydrochar with controllable OFG contents, which is a prospective adsorbent for treating metal cations.

Water-compatible cross-linked pyrrolidone acrylate pressure-sensitive adhesives with persistent adhesion for transdermal delivery: Synergistic effect of hydrogen bonding and electrostatic force.

Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.

Block Copolymers of Polyolefins with Polyacrylates: Analyzing and Improving the Blocking Efficiencies Using MILRad/ATRP Approach.

Despite their industrial ubiquity, polyolefin-polyacrylate block copolymers are challenging to synthesize due to the distinct polymerization pathways necessary for respective blocks. This study utilizes MILRad, metal-organic insertion light-initiated radical polymerization, to synthesize polyolefin-b-poly(methyl acrylate) copolymer by combining palladium-catalyzed insertion-coordination polymerization and atom transfer radical polymerization (ATRP). Brookhart-type Pd complexes used for the living polymerization of olefins are homolytically cleaved by blue-light irradiation, generating polyolefin-based macroradicals, which are trapped with functional nitroxide derivatives forming ATRP macroinitiators. ATRP in the presence of Cu(0), that is, supplemental activators and reducing agents , is used to polymerize methyl acrylate. An increase in the functionalization efficiency of up to 71% is demonstrated in this study by modifying the light source and optimizing the radical trapping condition. Regardless of the radical trapping efficiency, essentially quantitative chain extension of polyolefin-Br macroinitiator with acrylates is consistently demonstrated, indicating successful second block formation.

Facile fabrication of cellulose-based hydrophobic paper via Michael addition reaction.

The inherent highly hydrophilic feature of cellulose-based paper hinders its application in many fields. Herein, a cellulose-based hydrophobic paper was fabricated based on surface chemical modification. Firstly, the hydrophobic acrylate components were bonded to the cellulose acetoacetate (CAA) fibers to obtain CAA graft acrylate (CAA-X) fibers through Michael addition reaction. Subsequently, CAA-X fibers were processed into paper via wet papermaking technology. The resulting paper exhibited good hydrophobic performance (water contact angle was up to 135°) with an air permeability of 24.8 µm/Pa·s. The hydrophobicity of paper was very stable and remained even after treating with different solvents. Moreover, the hydrophobic properties of this paper could be adjusted by changing the type of acrylate component. It should be noted that the surface modification strategy has no obvious effects on the whiteness (79.8%), writing, and printing properties of the cellulose fibers. Thus, it is a simple, benign, and efficient strategy for the construction of cellulose-based hydrophobic paper, which has great potential to be used in paper tableware, oil-water separation, watercolor protection, and food packaging fields.

Photo Fenton RAFT Polymerization of (Meth)Acrylates in DMSO Sensitized by Methylene Blue.

A novel open-to-air photo RAFT polymerization of a series of acrylate and methacrylate monomers mediated by matching chain transfer agent irradiated by far-red light in DMSO is reported. Hydroxyl radical (•OH) generated from methylene blue (MB) sensitized decomposition of H2 O2 via photo-Fenton like-reaction is used for polymerization initiation. The "living/control" characteristic is evidenced by kinetic study, in which a pseudo first order curve and linearly increases of molecular weight with the increase of monomer conversion are observed. The living end-group fidelity is characterized by MALDI-TOF-MS and 1 H NMR results, and confirmed by successful chain extension. The temporary controllability is proved by light on/off switch experiment.

Thiol-Michael Addition Microparticles: Their Synthesis, Characterization, and Uptake by Macrophages.

Polymeric microparticles are promising biomaterial platforms for targeting macrophages in the treatment of disease. This study investigates microparticles formed by a thiol-Michael addition step-growth polymerization reaction with tunable physiochemical properties and their uptake by macrophages. The hexafunctional thiol monomer dipentaerythritol hexa-3-mercaptopropionate (DPHMP) and tetrafunctional acrylate monomer di(trimethylolpropane) tetraacrylate (DTPTA) were reacted in a stepwise dispersion polymerization, achieving tunable monodisperse particles over a size range (1-10 µm) relevant for targeting macrophages. An off-stoichiometry thiol-acrylate reaction afforded facile secondary chemical functionalization to create particles with different chemical moieties. Uptake of the microparticles by RAW 264.7 macrophages was highly dependent on treatment time, particle size, and particle chemistry with amide, carboxyl, and thiol terminal chemistries. The amide-terminated particles were non-inflammatory, while the carboxyl- and thiol-terminated particles induced pro-inflammatory cytokine production in conjunction with particle phagocytosis. Finally, a lung-specific application was explored through time-dependent uptake of amide-terminated particles by human alveolar macrophages in vitro and mouse lungs in vivo without inducing inflammation. The findings demonstrate a promising microparticulate delivery vehicle that is cyto-compatible, is non-inflammatory, and exhibits high rates of uptake by macrophages.

Influence of Molecular Structures of Organic Foulants on the Antifouling Properties of Poly(2-methoxyethyl acrylate) and Its Analogs: A Molecular Dynamics Study.

Elucidating the fouling phenomena of polymer surfaces will facilitate the molecular design of high-performance biomedical devices. Here, we investigated the remarkable antifouling properties of two acrylate materials, poly(2-methoxyethyl acrylate) (PMEA) and poly(3-methoxypropionic acid vinyl ester) (PMePVE), which have a terminal methoxy group on the side chain, via molecular dynamics simulations of binary mixtures of acrylate/methacrylate trimers with n-pentane or 2,2-dimethylpropane (neopentane), that serve as the nonpolar organic probe (organic foulants). The second virial coefficient (B2) was determined to assess the aggregation/dispersion properties in the binary mixtures. The order of the B2 values for the trimer/pentane mixtures indicated that the terminal methoxy group of the side chain plays an important role in enhancing the fouling resistance to nonpolar organic foulants. Here, we hypothesized that the antifouling properties of PMEA/PMePVE surfaces originate from the resistance. To evaluate the molecular-level accessibility of organic foulants to acrylate/methacrylate materials, we examined the radial distribution functions (RDFs) of the terminal methyl groups of neopentane around the main chains of the acrylate/methacrylate trimers. As a result, the third distinct RDF peaks are observed only for the methacrylate trimers. The peaks are attributed to the hydrophobic interactions between the methyl group of neopentane and that of the main chain of the trimer. Accordingly, the methyl group of the main chain of methacrylate materials, such as poly(2-hydroxyethyl methacrylate) and poly(2-methoxyethyl methacrylate), unfavorably induces fouling with organic foulants. In this study, we clarify that preventing hydrophobic interactions between an organic foulant and polymeric material is essential for enhancing the antifouling property. Our approach has great potential for evaluating the molecular-level affinities of organic foulant with polymer surfaces for the molecular design of excellent antifouling polymeric materials.

Visible Light Induced Degradation of Poly(methyl methacrylate-co-methyl α-chloro acrylate) Copolymer at Ambient Temperature.

Poly(methyl methacrylate) (PMMA) is a well-known and widely used commodity plastic. High production amount of PMMA causes excessive waste creation that highlights the necessity of recycling. Conventional recycling methods require elevated temperatures to induce degradation or depolymerization. In this work, visible light induced photodegradation system by using dimanganese decacarbonyl (Mn2 (CO)10 ) with high halogen affinity is reported. Halide functional photodegradable polymers are prepared by copolymerization of methyl methacrylate and methyl α-chloroacrylate by conventional reversible addition-fragmentation chain-transfer polymerization. Synthesized copolymers are efficiently degraded to low molecular weight oligomers under visible light irradiation in the presence of Mn2 (CO)10 . Characteristics of precursors, degraded polymers, and kinetics of depolymerization are investigated by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourrier transform infrared (FTIR), and proton nuclear magnetic resonance (1 H-NMR) spectroscopies. The reported approach is expected to trigger further development of more environmentally friendly recycling techniques in the near future as we  are moving toward a greener and more sustainable world.

Poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith with bonded Tris ligands for use in hydrophilic interaction capillary electrochromatography.

The facile preparation of a monolithic capillary column with surface bound polar ligands for use in hydrophilic interaction capillary electrochromatography is described. It involved the conversion of poly(carboxyethyl acrylate[CEA]-co-ethylene glycol dimethacrylate[EDMA]) precursor monolith (the so-called carboxy monolith) into a Tris bonded monolith by a post-polymerization functionalization process in the presence of a water soluble carbodiimide, namely N-(3-dimethylaminopropyl)-N´-ethylcarbodiimidehydrochloride. The carbodiimide assisted conversion, allowed the covalent attachment of the carboxyl group of the precursor monolith to the amino group of the Tris ligand via a stable amide linkage. This resulted in the formation of Tris poly(CEA-co-EDMA) monolith, which exhibited the typical retention behavior of hydrophilic interaction stationary phase when analyzing polar and slightly polar neutral or charged compounds. In fact, neutral polar species such as dimethylformamide, formamide and thiourea were retained in the order of increased polarity with acetonitrile rich mobile phase. Also, neutral p-nitrophenyl maltooligosaccharides (PNP-maltooligosaccharides) served as a polar homologous series for gauging the hydrophilicity of the Tris poly(CEA-co-EDMA) monolith, thus forming a versatile testing homologous series for other hydrophilic columns. Other polar anionic species (e.g., hydroxy benzoic acids and nucleotides) and weakly polar anionic compounds (e.g., dansyl amino acids and phenoxy acid herbicides) as well as polar weak bases namely nucleobases and nucleosides were used to probe the hydrophilic characters of the Tris poly(CEA-co-EDMA) monolith. The various polar and weakly polar compounds just mentioned revealed the wide potentiality of the hydrophilic interaction column under investigation.

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith with bonded (S)-(-)-1-(2-naphthyl) ethylamine ligands for use in chiral and achiral separations by capillary electrochromatography.

In this research report, the previously developed poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith (referred to as carboxy monolith) is further exploited in the preparation of a chiral stationary phase for enantiomeric separations. The carboxy monolith precursor was subjected to post polymerization functionalization (PPF) with the chiral selector (S)-(-)-1-(2-naphthyl) ethylamine (NAS) at room temperature in the presence of N, N´-dicyclohexylcarbodiimide (DCC) in chloroform. The DCC, which is an organic soluble carbodiimide, permits the linkage for the amine functionality of the chiral ligand NAS to the carboxy group of the monolithic surface forming a stable amide linkage. The NAS column thus obtained allowed not only enantiomeric separations in the RP mode via its chiral site but also the separation of nonpolar species via its achiral functionality offering both hydrophobic and π-π interactions for aromatic compounds such toluene derivatives and polyaromatic hydrocarbons. The dual interaction sites (e.g., chiral, and achiral) of the NAS present a convenient column for the separations of slightly polar and nonpolar chiral and achiral solutes in the RP mode.

Structure-Property Relationships of Shape Memory, Semicrystalline Polymers Fabricated by In Situ Polymerization and Crosslinking of Octadecyl Acrylate/Polybutadiene Blends.

The current work presents the study of a semicrystalline, shape memory polymer synthesized by simultaneous free radical polymerization and crosslinking in a blend of polybutadiene (PB) and octadecyl acrylate. Blending elastomers and phase change materials provide a modular method for new smart materials, such as shape memory polymers. In this system, grafted, side-chain crystalline poly(octadecyl acrylate) (PODA) fixes a programmed shape in the shape memory cycle, while crosslinked polybutadiene drives shape recovery. This work focuses on improving material parameters important for shape memory (crystallinity, gel fraction, melting temperature) by tuning the processing and formulation parameters (amount of crosslinker and PB weight fraction). The result is a shape memory PB-PODA copolymer that can be fabricated by melt processing and programmed without cooling below ambient temperature. It is found that good shape memory (i.e., high shape fixity and recovery) is obtained at a low PB weight fraction where a percolating PODA crystal network is formed at room temperature. The optimized sample shows excellent shape memory properties (fixity > 99%, recovery = 96%). It is shown that it is possible to mold this material into complex 3D shapes or topography with potential use in anticounterfeiting and antitampering applications.

Mussel-inspired poly(hydroxyethyl acrylate-co-itaconic acid)-catechol/hyaluronic acid drug-in-adhesive patches for transdermal delivery of ketoprofen.

This research aimed to create new hydrophilic drug-in-adhesive patches for transdermal drug delivery. Poly(hydroxyethyl acrylate-co-itaconic acid)-catechol (PHI-cat) and hyaluronic acid (HA) were used as main components in the pressure-sensitive adhesive. Citric acid and aluminium hydroxide were exploited as crosslinking agents and ketoprofen was employed as a model delivering compound. The adhesive performance, physicochemical properties, drug-polymer interaction, drug crystallization, drug content, drug permeation through the skin, and coordination polymer network of the patches were investigated. In addition, skin irritation and adhesion potential in human subjects were assessed. Due to the ability of catechol groups to form interaction with the skin tissue, the patches containing PHI-cat and HA offered a considerably greater adhesion ability to human skin compared with the patches without catechol and commercial patches. Furthermore, the patches had good physical and chemical stability. Therefore, these catechol-functionalized patches may be potential transdermal drug delivery systems with excellent adhesive properties for the delivery of a drug through the skin.

Domino Aza-Michael-SNAr-Heteroaromatization Route to C5-Substituted 1-Alkyl-1H-Indole-3-Carboxylic Esters.

A new synthesis of C5-substituted 1-alkyl-1H-indole-3-carboxylic esters is reported. A series of methyl 2-arylacrylate aza-Michael acceptors were prepared with aromatic substitution to activate them towards SNAr reaction. Subsequent reaction with a series of primary amines generated the title compounds. Initially, the sequence was expected to produce indoline products, but oxidative heteroaromatization intervened to generate the indoles. The reaction proceeded under anhydrous conditions in DMF at 23-90 °C using equimolar quantities of the acrylate and the amine with 2 equiv. of K2CO3 to give 61-92% of the indole products. The reaction involves an aza-Michael addition, followed by SNAr ring closure and heteroaromatization. Since the reactions were run under nitrogen, the final oxidation to the indole likely results from reaction with dissolved oxygen in the DMF. Substrates incorporating a 2-arylacrylonitrile proved too reactive to prepare using our protocol. The synthesis of the reaction substrates, their relative reactivities, and mechanistic details of the conversion are discussed.

Rapid Oxygen-Tolerant Synthesis of Protein-Polymer Bioconjugates via Aqueous Copper-Mediated Polymerization.

The synthesis of protein-polymer conjugates usually requires extensive and costly deoxygenation procedures, thus limiting their availability and potential applications. In this work, we report the ultrafast synthesis of polymer-protein bioconjugates in the absence of any external deoxygenation via an aqueous copper-mediated methodology. Within 10 min and in the absence of any external stimulus such as light (which may limit the monomer scope and/or disrupt the secondary structure of the protein), a range of hydrophobic and hydrophilic monomers could be successfully grafted from a BSA macroinitiator, yielding well-defined polymer-protein bioconjugates at quantitative yields. Our approach is compatible with a wide range of monomer classes such as (meth) acrylates, styrene, and acrylamides as well as multiple macroinitiators including BSA, BSA nanoparticles, and beta-galactosidase from Aspergillus oryzae. Notably, the synthesis of challenging protein-polymer-polymer triblock copolymers was also demonstrated, thus significantly expanding the scope of our strategy. Importantly, both lower and higher scale polymerizations (from 0.2 to 35 mL) were possible without compromising the overall efficiency and the final yields. This simple methodology paves the way for a plethora of applications in aqueous solutions without the need of external stimuli or tedious deoxygenation.

Poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith with bonded anthracenyl ligands for use in reversed-phase capillary electrochromatography based on hydrophobic and π-π interactions.

In this research report, the post polymerization functionalization (PPF) of a carboxyethyl acrylate (CEA)-co-ethylene glycol dimethacrylate (EDMA) [poly-CEA-co-EDMA)] precursor monolith with 2-aminoanthracene was carried out in the presence of an organic solvent soluble carbodiimide, namely N,N´-dicyclohexylcarbodiimide (DCC), yielding the so-called anthracenyl-poly-CEA-co-EDMA monolith. This novel monolith proved to be an excellent monolithic stationary for reversed-phase capillary electrochromatography (RP-CEC) with hydrophobic and π-π interactions of a wide range of nonpolar solutes including those bearing aryl functional groups in their structures such as polycyclic aromatic hydrocarbons (PAHs), toluene derivatives and aniline derivatives as well as solutes carrying in their structures electron withdrawing substituents such as dinitrophenyl-amino acids (DNP-AAs) and di-DNP-AAs. The retention behaviors of the just mentioned solutes obtained on the anthracenyl-poly-CEA-co-EDMA monolithic column were compared to those obtained on octadecyl-poly-CEA-co-EDMA monolithic column prepared from the same carboxy-precursor monolith. The results demonstrated the superiority of anthracenyl column over the octadecyl column for the separation and enhanced selectivity for aromatic solutes since it provides not only hydrophobic interactions but also π-π interactions with aromatic nonpolar solutes.

Polyethylenes with Combined In-Chain and Side-Chain Functional Groups from Catalytic Terpolymerization of Carbon Monoxide and Acrylate.

Linear polyethylenes with a combination of incorporated in-chain keto as well as side-chain ester groups are formed by Ni(II)-catalyzed terpolymerization of ethylene, carbon monoxide, and methyl acrylate. These possess a random structure, with largely isolated nonalternating in-chain keto groups as well as ester-substituted units adjacent to the polyethylene chain, whereas the solid-state structure of polyethylene is retained. Molecular weights of the terpolymers (Mn ∼ 20.000 g mol-1) are predominantly determined by chain transfer after acrylate incorporation.

RAFT Step-Growth Polymerization of Diacrylates.

RAFT step-growth polymerization was previously demonstrated with monomers that bear low rate of homopropagation to favor the chain transfer process; by contrast, acrylates are known to be fast homopropagating monomers, thereby posing serious challenges for RAFT step-growth. Here, we identified a chain transfer agent (CTA) that rapidly yields single unit monomer inserted (SUMI) CTA adducts with a model acrylate monomer. Using a bifunctional reagent of this CTA, we successfully demonstrated RAFT step-growth polymerization with diacrylates, yielding linear polymer backbones. Furthermore, we achieved inclusion of functionality (i.e., disulfide) into RAFT step-growth polymer via a disulfide incorporated bifunctional CTA. Grafting from this backbone resulted in molecular brush polymers with cleavable functionality in each repeat unit of the backbone, allowing selective degradation to afford well-defined unimolecular species of two polymeric side chains. Given the wide selection of commercially available diacrylates, RAFT step-growth polymerization of diacrylates will further enable facile synthesis of complex architectures with modular backbones.

Hydrocarbon-Based Statistical Copolymers Outperform Block Copolymers for Stabilization of Ethanol-Water Foams.

Well-defined block copolymers have been widely used as emulsifiers, stabilizers, and dispersants in the chemical industry for at least 50 years. In contrast, nature employs amphiphilic proteins as polymeric surfactants whereby the spatial distribution of hydrophilic and hydrophobic amino acids within the polypeptide chains is optimized for surface activity. Herein, we report that polydisperse statistical copolymers prepared by conventional free-radical copolymerization can provide superior foaming performance compared to the analogous diblock copolymers. A series of predominantly (meth)acrylic comonomers are screened to identify optimal surface activity for foam stabilization of aqueous ethanol solutions. In particular, all-acrylic statistical copolymers comprising trimethylhexyl acrylate and poly(ethylene glycol) acrylate, P(TMHA-stat-PEGA), confer strong foamability and also lower the surface tension of a range of ethanol-water mixtures to a greater extent than the analogous block copolymers. For ethanol-rich hand sanitizer formulations, foam stabilization is normally achieved using environmentally persistent silicone-based copolymers or fluorinated surfactants. Herein, the best-performing fully hydrocarbon-based copolymer surfactants effectively stabilize ethanol-rich foams by a mechanism that resembles that of naturally-occurring proteins. This ability to reduce the surface tension of low-surface-energy liquids suggests a wide range of potential commercial applications.

Feasibility and application of machine learning enabled fast screening of poly-beta-amino-esters for cartilage therapies.

Despite the large prevalence of diseases affecting cartilage (e.g. knee osteoarthritis affecting 16% of population globally), no curative treatments are available because of the limited capacity of drugs to localise in such tissue caused by low vascularisation and electrostatic repulsion. While an effective delivery system is sought, the only option is using high drug doses that can lead to systemic side effects. We introduced poly-beta-amino-esters (PBAEs) to effectively deliver drugs into cartilage tissues. PBAEs are copolymer of amines and di-acrylates further end-capped with other amine; therefore encompassing a very large research space for the identification of optimal candidates. In order to accelerate the screening of all possible PBAEs, the results of a small pool of polymers (n = 90) were used to train a variety of machine learning (ML) methods using only polymers properties available in public libraries or estimated from the chemical structure. Bagged multivariate adaptive regression splines (MARS) returned the best predictive performance and was used on the remaining (n = 3915) possible PBAEs resulting in the recognition of pivotal features; a further round of screening was carried out on PBAEs (n = 150) with small variations of structure of the main candidates from the first round. The refinements of such characteristics enabled the identification of a leading candidate predicted to improve drug uptake > 20 folds over conventional clinical treatment; this uptake improvement was also experimentally confirmed. This work highlights the potential of ML to accelerate biomaterials development by efficiently extracting information from a limited experimental dataset thus allowing patients to benefit earlier from a new technology and at a lower price. Such roadmap could also be applied for other drug/materials development where optimisation would normally be approached through combinatorial chemistry.