Candidate Monomers Research Articles

Gradient boosting decision tree algorithms for accelerating nanofiltration membrane design and discovery

Interfacial polymerization is the most widely used strategy for nanofiltration membrane fabrication. Despite extensive research on this technology, further improvement in permeance and salt rejection is still essential due to its multidimensional characteristics, including the types of membrane material and the conditions of membrane optimizing fabrication. Herein, we applied four gradient boosting decision tree algorithms to precisely identify the candidate monomers (represented by the molecular descriptors) and their fabrication conditions. The result of the model evaluation indicated the Extreme Gradient Boosting (XGBoost) algorithm had the best predictive performance in accuracy and generalization in predicting membrane permeance and salt rejection, with the corresponding determination coefficients on the test set being 0.76 and 0.88. Shapley additive explanation analysis showed that the aqueous monomer concentration was the most influential fabrication condition in membrane performance. Besides, the partition coefficient (Log P) and topological polar surface area were the most important molecular descriptors in water permeance and salt rejection, respectively. Overall, this study proposed innovative machine learning algorithms to disentangle the multidimensional interactions of various influencing factors on membrane performance, thus initiating a paradigm shift in the development of high-performance nanofiltration membranes.

Optimization of Cr(VI) ion-imprinted polymer with imidazole derivatives as functional monomers and its binding mechanism

Cr(VI) is a representative heavy metal which has significant toxicity to biological organisms. Ion-imprinted polymers (IIPs) have been recognized as effective adsorbents to remove Cr(VI) from environment. Among them, imidazole derivatives are expected to serve as potential monomers for Cr(VI)-IIPs, but the binding mechanisms of monomers with Cr(VI) remain unclear, which makes Cr(VI)-IIPs design having rare sound theory to be guideline. In this work, the suitable functional monomer of Cr2O72--IIPs was screened among five imidazole derivatives (adenine, cytosine, uric acid, l-histidine, 1-methacryloyl imidazole) with a target-monomer binding affinity guide strategy, and the optimal self-assembling conditions were investigated using theoretical calculations and experimental methods. Adenine exhibited the highest potential among the five candidate monomers, followed by cytosine. The optimal ratio of target and monomer was determined to be 2:3. Furthermore, a 5:5 mixture of ethanol and cyclohexane was identified as the most suitable solvent for the pre-polymerization environment, while epichlorohydrin acted as the most appropriate crosslinker. Additionally, the binding nature of non-covalent interaction between target and monomer was identified to be electrostatic-dominated hydrogen bonding. These mechanistic insights provide valuable theoretical support for the rational design of Cr2O72--IIPs, which are significant for IIPs development as adsorbents for contaminants detection and removal from environment.

Biomarkers and coptis chinensis activity for rituximab-resistant diffuse large B-cell lymphoma: Combination of bioinformatics analysis, network pharmacology and molecular docking.

Rituximab resistance is one of the great challenges in the treatment of diffuse large B-cell lymphoma (DLBCL), but relevant biomarkers and signalling pathways remain to be identified. Coptis chinensis and its active ingredients have antitumour effects; thus, the potential bioactive compounds and mechanisms through which Coptis chinensis acts against rituximab-resistant DLBCL are worth exploring. To elucidate the core genes involved in rituximab-resistant DLBCL and the potential therapeutic targets of candidate monomers of Coptis chinensis. Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Similarity Ensemble Approach and Swiss Target Prediction, the main ingredients and pharmacological targets of Coptis chinensis were identified through database searches. Through the overlap between the pharmacological targets of Coptis chinensis and the core targets of rituximab-resistant DLBCL, we identified the targets of Coptis chinensis against rituximab-resistant DLBCL and constructed an active compound-target interaction network. The targets and their corresponding active ingredients of Coptis chinensis against rituximab-resistant DLBCL were molecularly docked. Berberine, quercetin, epiberberine and palmatine, the active components of Coptis chinensis, have great potential for improving rituximab-resistant DLBCL via PIK3CG. This study revealed biomarkers and Coptis chinensis-associated molecular functions for rituximab-resistant DLBCL.

SMiPoly: Generation of a Synthesizable Polymer Virtual Library Using Rule-Based Polymerization Reactions.

Recent advances in machine learning have led to the rapid adoption of various computational methods for de novo molecular design in polymer research, including high-throughput virtual screening and inverse molecular design. In such workflows, molecular generators play an essential role in creation or sequential modification of candidate polymer structures. Machine learning-assisted molecular design has made great technical progress over the past few years. However, the difficulty of identifying synthetic routes to such designed polymers remains unresolved. To address this technical limitation, we present Small Molecules into Polymers (SMiPoly), a Python library for virtual polymer generation that implements 22 chemical rules for commonly applied polymerization reactions. For given small organic molecules to form a candidate monomer set, the SMiPoly generator conducts possible polymerization reactions to generate an exhaustive list of potentially synthesizable polymers. In this study, using 1083 readily available monomers, we generated 169,347 unique polymers forming seven different molecular types: polyolefin, polyester, polyether, polyamide, polyimide, polyurethane, and polyoxazolidone. By comparing the distribution of the virtually created polymers with approximately 16,000 real polymers synthesized so far, it was found that the coverage and novelty of the SMiPoly-generated polymers can reach 48 and 53%, respectively. Incorporating the SMiPoly library into a molecular design workflow will accelerate the process of de novo polymer synthesis by shortening the step to select synthesizable candidate polymers.

A network pharmacology approach to decipher the total flavonoid extract of Dracocephalum Moldavica L. in the treatment of cerebral ischemia- reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a major injury that seriously endangers human health and is characterized by high mortality and high disability. The total flavonoid extract of Dracocephalum moldavica L.(TFDM) in the treatment of CIRI has been proved by clinical practice. But the mechanism for the treatment of CIRI by TFDM has not been systematically revealed. The active compounds contained in TFDM were screened by literature mining and pharmacokinetic parameters, and the targets related to CIRI were collected by searching Drugbank, Genecards and OMIM databases. Cytoscape software was used to construct the protein interaction network of TFDM for the prevention and treatment of CIRI. Geneontology and signal pathway enrichment were analyzed. The key target pathway network of TFDM compounds was constructed and verified by pharmacological experiment in vitro. 21 active components were screened, 158 potential drug targets for the prevention and treatment of CIRI were obtained, 53 main targets were further screened in the protein-protein interaction network, and 106 signal pathways, 76 biological processes, 26 cell components and 50 molecular functions were enriched (P<0.05). Through the compound-target-pathway network, the key compounds that play a role in the prevention and treatment of CIRI, such as acacetin, apigenin and other flavonoids, as well as the corresponding key targets and key signal pathways, such as AKT1, SRC and EGFR were obtained. TFDM significantly decreased LDH, MDA levels and increased the NO activity levels in CIRI. Further studies have shown that TFDM increases the number of SRC proteins, and TFDM also increases p-AKT/ AKT. Molecular docking results showed that acacetin-7-O (- 6''-acetyl) -glucopyranoside, acacetin7-O-β-D-glucopyranoside, apigenin-7-O-β-D-galactoside respectively had good affinity for SRC protein. Acacetin-7-O (- 6''-acetyl) -glucopyranoside,acacetin-7-O-β-D-glucuronide, acacetin7-O-β-D-glucopyranoside had good affinity for AKT1 protein, respectively. Our research showed that TFDM had the characteristics of multi-component, multi-target and multi-channel in the treatment of CIRI. The potential mechanism may be associated with the following signaling pathways:1) the signaling pathways of VEGF/SRC, which promote angiogenesis, 2) the signaling pathways of PI3K/AKT, which inhibit apoptosis, and 3) acacetin-7-O (- 6''-acetyl) -glucopyranoside is expected to be used as a candidate monomer component for natural drugs for further development.

3-Alkoxyphthalides as Nonhomopolymerizable, Highly Reactive Comonomers for ABC Pseudo-Periodic Terpolymers and Degradable Polymers via Cationic Co- and Terpolymerizations with Oxiranes and/or Vinyl Ethers

3-Alkoxyphthalides (ROPTs) are promising candidate monomers that react with a cationic species at the carbonyl group and subsequently undergo ring-opening to generate a carbocation adjacent to both aryl and alkoxy groups (oxocarbenium ion). In this study, cationic polymerizations of ROPTs bearing methoxy, isopropoxy, tert-butoxy, or phenoxy groups were investigated with a particular focus on the copolymerizations with oxiranes. Cationic homopolymerization of ROPTs did not occur under any of the examined conditions. In contrast, cationic copolymerizations of ROPT with oxiranes, such as 4-vinyl-1-cyclohexene-1,2-epoxide (VCHO), proceeded smoothly via very frequent crossover reactions. The copolymers could be degraded under acidic conditions due to the cleavage of the acetal moieties generated by the crossover reactions from ROPT to VCHO. Cationic copolymerizations of ROPT with most of the examined vinyl ethers (VEs) and styrene derivatives did not proceed, likely due to inefficient crossover reactions from the vinyl monomers to ROPT. However, cationic terpolymerizations of VE, oxirane, and ROPT successfully proceeded via highly selective crossover reactions, resulting in ABC-type pseudo-periodic terpolymers under optimized conditions.

Synthesis of a Novel Rigid Semi-Alicyclic Dianhydride and Its Copolymerized Transparent Polyimide Films' Properties.

A new series of colorless polyimides (CPIs) with outstanding thermal properties and mechanical properties were fabricated by the copolymerization of a novel dianhydride and 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) with 2,2′-bistrifluoromethyl benzidine (TFDB). The novel dianhydride, 10-oxo-9-phenyl-9-(trifluoromethyl)-9,10-dihydroanthracene-2,3,6,7-tetraacid dianhydride (3FPODA), possessed a rigid semi-alicyclic structure, –CF3 and phenyl side groups, and an active carbonyl group. Benefitting from the special structure of 3FPODA, the glass transition temperatures (Tg) of the new CPIs improved from 330 °C to 377 °C, the coefficient of thermal expansion (CTE) decreased from 46 ppm/K to 24 ppm/K, and the tensile strength (TS), tensile modulus (TM), and elongation at break (EB) increased from 84 MPa to 136 MPa, 3.2 GPa to 4.4 GPa, and 2.94% to 4.13% with the increasing amount of 3FPODA, respectively. Moreover, the active carbonyl group of the 3FPODA could enhance the CPI’s adhesive properties. These results render the new dianhydride 3FPODA an ideal candidate monomer for the fabrication of high-performance CPIs.

Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

Research Progress on the Antiosteoarthritic Mechanism of Action of Natural Products

Background Osteoarthritis (OA) is a clinical joint degenerative disease, the pathogenic factors of which include age, obesity, and mechanical injury. Its main pathological features include cartilage loss, narrowing of joint space, and osteophyte formation. At present, there are a variety of treatment methods for OA. Natural products, which are gradually being applied in the treatment of OA, are advantageous as they present with low toxicity and low costs and act on multiple targets. Methods The terms “natural products,” “osteoarthritis,” and “chondrocytes” were searched in PubMed to screen the related literature in the recent 10 years. Results We comprehensively introduced 62 published papers on 48 natural products involving 6, 3, 5, 12, 4, and 5 kinds of terpenoids, polysaccharides, polyphenols, flavonoids, alkaloids, and saponins, respectively (and others). Conclusion The mechanisms of their anti-OA action mainly involve reducing the production of inflammatory factors, reducing oxidative stress, regulating the metabolism of chondrocytes, promoting the proliferation of chondrocytes, or inhibiting chondrocyte apoptosis. This article summarizes the anti-OA activity of natural products in the last 10 years and provides candidate monomers for further study for use in OA treatment.

Identification of Known and Novel Monomers for Poly(hydroxyurethanes) from Biobased Materials

Sourcing polymers from biobased materials is desirable for a transition to a more sustainable world. However, finding new monomers sourced from biobased molecules requires extensive experimental effort, due to the fact that most biomolecules lack the functional groups or properties needed to serve as a monomer in a particular polymeric system without chemical modification. Here, we demonstrate a computational screening method to obtain monomers of a nonisocyanate polyurethane (NIPU), polyhydroxyurethane (PHU), from biomolecules. Our method generates candidate monomers from a list of 15 selected biobased starting molecules by performing chemical transformations that are standard to chemical catalysis and organic synthesis on these starting molecules and then screening the results for molecules with moieties that can be used as monomers for a PHU. Product molecules from two generations of reaction, a total number of 22,571, were analyzed automatically to identify molecules that have two or more epoxy or cyclic carbonate functional groups as candidates for further derivatization. These 21 candidate molecules were then subjected to another two generations of reaction, producing a set of 17,913 additional molecules. Further scrutiny of this set for desired functional groups characterizing PHUs and querying against the PubChem database were carried out, and 15 known molecules that are commercially available were identified, with the desirable features that they are predicted to be derived from biobased starting molecules in four or fewer steps. Moreover, molecule space generated from this process was primarily comprised of molecules that were not known to PubChem, indicating the framework also has the ability to generate novel candidate monomers that originate from biobased starting points.

Discovery of (meth)acrylate polymers that resist colonization by fungi associated with pathogenesis and biodeterioration.

Fungi have major, negative socioeconomic impacts, but control with bioactive agents is increasingly restricted, while resistance is growing. Here, we describe an alternative fungal control strategy via materials operating passively (i.e., no killing effect). We screened hundreds of (meth)acrylate polymers in high throughput, identifying several that reduce attachment of the human pathogen Candida albicans, the crop pathogen Botrytis cinerea, and other fungi. Specific polymer functional groups were associated with weak attachment. Low fungal colonization materials were not toxic, supporting their passive, anti-attachment utility. We developed a candidate monomer formulation for inkjet-based 3D printing. Printed voice prosthesis components showed up to 100% reduction in C. albicans biofilm versus commercial materials. Furthermore, spray-coated leaf surfaces resisted fungal infection, with no plant toxicity. This is the first high-throughput study of polymer chemistries resisting fungal attachment. These materials are ready for incorporation in products to counteract fungal deterioration of goods, food security, and health.

Sustainable isosorbide-based transparent pressure-sensitive adhesives for optically clear adhesive and their adhesion performance

A biomass-based isosorbide acrylate (ISA) was synthesized in a one-pot reaction at low temperature with a quite slow dropwise technique using a syringe pump. Using the ISA monomer, UV-cured transparent acrylic pressure-sensitive adhesives (PSAs) composed of semi-interpenetrating networks were prepared. The effect of ISA on the adhesion performance of the resulting acrylic PSAs was investigated by changing the ISA content, while fixing the mole ratio between 2-ethylhexyl acrylate and 2-hydroxyethyl acrylate in the PSAs. The prepared acrylic PSAs, with ISA content ranging from 3.2 to 14.3 mol%, were evaluated in terms of 180° peel strength, probe tack, static shear testing and optical properties. Increasing the ISA content in the acrylic PSAs improved the adhesion properties, such as 180° peel strength (0.25–0.32 N/25 mm), shear holding power (0.086–0.023 mm) and probe tack (1.21–2.26 N). Dynamic mechanical analysis indicated that ISA is a good candidate monomer, playing the role of adhesion promoter and hard monomer in the acrylic PSAs. © 2017 Society of Chemical Industry

Functional monomer screening and preparation of dibenzothiophene-imprinted polymers on the surface of carbon microsphere

Three candidate monomers (methacrylic acid, 2-vinyl pyridine, and 2-acrylamide-2-methyl sulfuric acid) were screened through computational simulation method to prepare effective surface molecularly imprinted polymers (SMIPs) based on carbon microspheres (CMSs) for dibenzothiophene removal from fuels. The optimized structures of complexes were described using density functional theory calculation at B3LYP/6-311++G(d,p) level and frequency calculations for each molecule and complex were conducted to provide insights into electrostatic interaction between monomers and template DBT. Besides, the reliability of computational simulation method for screening was tested by comparing the theoretical data with experimental results from gas chromatography. The computational data suggest that methacrylic acid (MAA) was the preferred monomer with the largest absolute binding energy (14.79 kJ mol−1), which is in accordance with the experimental results. The saturated adsorption of PMAA-SMIPs/CMSs was the best (41.73 mg g−1). Besides, PMAA-SMIPs/CMSs show highest special selectivity for dibenzothiophene against benzothiophene, and the relative selectivity coefficient k′ was 2.02. The computational simulation method can be effectively used in monomer screening. This work may help understand the mechanisms of polymerization and recognition process between SMIPs and template and design SMIPs with improved adsorption performance.

ChemInform Abstract: Sulfamic Acid as a Cost‐Effective Catalyst for Synthesis of α‐Acyloxyacrylate Esters as Candidate Monomers for Biobased Polymers by Acylation of Pyruvate Esters.

Abstract Sulfamic acid was used as an efficient catalyst and green alternative for metal-containing acidic material to promote the acylation of pyruvate esters to produce α-acyloxyacrylate esters, which were candidate monomers for biobased polymers. Polymers from these monomers were useful materials for bio-based plastics, which showed high heat resistance and transparency. A series of α-acyloxyacrylate esters were converted from pyruvate esters by using sulfamic acid as a catalyst and good yields were obtained. The reaction in the presence of the sulfamic acid catalyst was carried out in the liquid phase and showed greater productivity than synthesis with a conventional liquid inorganic acid.

Density functional theory study on the structural, reactivity, and electronic properties of all mono-, di-, tri-, tetra-, and penta-fluoroanilines as monomers for conducting polymers

Electrical and structural properties of mono-, di-, tri-, tetra-, and penta-fluoroanilines as candidate monomers for new conducting polymers have been investigated using hybrid density functional theory (B3LYP/6–311+G**) based methods. The effects of the number and position of the fluorine atoms on the electrical and structural properties of fluoroanilines and their radical cations have also been investigated. The values of the vibrational frequencies, charge and spin-density distributions, ionization potentials, dipole moments, electric polarizabilities, HOMO-LUMO gaps, and the NICS values of these compounds have been calculated and analyzed as well. The results showed that the double bonds in 2-fluoroaniline and 2,5-difluoroaniline are more delocalized compared with other fluoroanilines; therefore, these molecules have the most aptitude for the electropolymerization reactions. The frequency analysis showed that the electrochemical stability of 2-fluoroaniline is greater than the other fluoroanilines. Also, this molecule possesses the largest NICS value compared to the other fluoroanilines. Consequently, 2-fluoroaniline has the largest ring current and the highest conductivity among all other monomers. Based on the results obtained, 2-fluoroaniline and 2,5-difluoroaniline are the best candidate monomers among all fluoroanilines for the synthesis of corresponding conducting polymers.

Sulfamic Acid as A Cost-Effective Catalyst for Synthesis of α-Acyloxyacrylate Esters as Candidate Monomers for Biobased Polymers by Acylation of Pyruvate Esters

Sulfamic acid was used as an efficient catalyst and green alternative for metal-containing acidic material to promote the acylation of pyruvate esters to produce α-acyloxyacrylate esters, which were candidate monomers for biobased polymers. Polymers from these monomers were useful materials for bio-based plastics, which showed high heat resistance and transparency. A series of α-acyloxyacrylate esters were converted from pyruvate esters by using sulfamic acid as a catalyst and good yields were obtained. The reaction in the presence of the sulfamic acid catalyst was carried out in the liquid phase and showed greater productivity than synthesis with a conventional liquid inorganic acid.

Chemoenzymatic synthesis of each enantiomer of orthogonally protected 4,4-difluoroglutamic acid: a candidate monomer for chiral Brønsted acid peptide-based catalysts.

We have accomplished an asymmetric synthesis of each enantiomer of 4,4-difluoroglutamic acid. This α-amino acid has been of interest in medicinal chemistry circles. Key features of the synthesis include highly scalable procedures, a Reformatsky-based coupling reaction, and straightforward functional group manipulations to make the parent amino acid. Enantioenrichment derives from an enzymatic resolution of the synthetic material. Conversion of the optically enriched compounds to orthogonally protected forms allows for the selective formation of peptide bonds. 4,4-Difluoroglutamic acid, in a suitably protected form, is also shown to exhibit enhanced catalytic activity in both an oxidation reaction and a reduction reaction, in comparison to the analogous glutamic acid derivative.

Theoretical study on the electronic, structural, properties and reactivity of a series of mono-, di-, tri- and tetrachlorothiophenes as well as corresponding radical cation forms as monomers for conducting polymers.

In this paper, electrical and structural properties of mono-, di-, tri- and tetrachlorothiophenes and their radical cations have been studied using the density functional theory and B3LYP method with 6-311++G** basis set. The effects of the number and position of the substituent of chlorine atoms on the properties of the thiophene ring for all chlorothiophenes and their radical cations have been studied. Vibrational frequencies, nuclear chemical shielding constants, spin-density distribution, size and direction of dipole moment vector, ionization potential, electric polarizabilities and NICS values of these compounds have been calculated as well. The analysis of these data showed that double bonds in 3-chlorothiophene are more delocalized and it is the best possible candidate monomer among all chlorothiophenes for the synthesis of corresponding conducting polymers with modified characteristics.

Theoretical study on the electronic, structural, properties and reactivity of a series of mono-, di-, tri- and tetrafluorothiophenes as monomers for new conducting polymers

Electrical and structural properties of mono-, di-, tri- and tetrafluorothiophenes and their radical cations have been studied using density functional theory and B3LYP method with 6-311++G** basis set. The effects of the number and position of the substituent of fluorine atoms on the properties of the thiophene ring have been studied using optimized structures obtained for these molecules and their radical cations. Vibrational frequencies, spin-density distribution, size and direction of dipole moment vector, ionization potential, electric polarizability, HOMO–LUMO gaps and NICS values of these compounds have been calculated as well. The analysis of these data showed that double bonds in 3-fluorothiophene are more delocalized and it is the best possible candidate monomer among all fluorothiophenes for the synthesis of corresponding conducting polymers with modified characteristics.

Genome-wide characterization of centromeric satellites from multiple mammalian genomes

Despite its importance in cell biology and evolution, the centromere has remained the final frontier in genome assembly and annotation due to its complex repeat structure. However, isolation and characterization of the centromeric repeats from newly sequenced species are necessary for a complete understanding of genome evolution and function. In recent years, various genomes have been sequenced, but the characterization of the corresponding centromeric DNA has lagged behind. Here, we present a computational method (RepeatNet) to systematically identify higher-order repeat structures from unassembled whole-genome shotgun sequence and test whether these sequence elements correspond to functional centromeric sequences. We analyzed genome datasets from six species of mammals representing the diversity of the mammalian lineage, namely, horse, dog, elephant, armadillo, opossum, and platypus. We define candidate monomer satellite repeats and demonstrate centromeric localization for five of the six genomes. Our analysis revealed the greatest diversity of centromeric sequences in horse and dog in contrast to elephant and armadillo, which showed high-centromeric sequence homogeneity. We could not isolate centromeric sequences within the platypus genome, suggesting that centromeres in platypus are not enriched in satellite DNA. Our method can be applied to the characterization of thousands of other vertebrate genomes anticipated for sequencing in the near future, providing an important tool for annotation of centromeres.