Cancer Chemopreventive Effect of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone on Diethylnitrosamine-Induced Early Stages of Hepatocarcinogenesis in Rats.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.

Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations.

The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CLpro). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CLpro, along with cytotoxicity on Vero cells. The protein-ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the in vitro investigation demonstrated that four flavonoids, namely, tectochrysin (7), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (9), panduratin A (19), and genistein (20), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein (20), an isoflavone discovered in Millettia brandisiana, has potential for further development as a SARS-CoV-2 3CLpro inhibitor.

Correction: Turn-on fluorogenic sensors based on an anthraquinone signaling unit for the detection of Zn(II) and Cd(II) ions.

Correction for 'Turn-on fluorogenic sensors based on an anthraquinone signaling unit for the detection of Zn(II) and Cd(II) ions' by Chawanakorn Kongsak et al., Org. Biomol. Chem., 2023, 21, 7367-7381, https://doi.org/10.1039/D3OB01223A.

Turn-on fluorogenic sensors based on an anthraquinone signaling unit for the detection of Zn(II) and Cd(II) ions.

Turn-on fluorescent chemosensors based on an anthraquinone moiety, N,N'-(9,10-dioxo-9,10-dihydroanthracene-1,8-diyl)bis(2-(bis(pyridin-2-ylmethyl)amino)acetamide) (1) and N,N'-(9,10-dioxo-9,10-dihydroanthracene-2,6-diyl)bis(2-(bis(pyridin-2-ylmethyl)amino)acetamide) (2), have been successfully synthesized with the overall yields of 61% and 90%, respectively. The structures of both chemosensors 1 and 2 were elucidated using several spectroscopic techniques such as 1H NMR, 13C NMR, 2D-NMR, FTIR and HRMS. The target chemosensor 1 is a promising tool for the detection of trace levels of d10 metal ions, such as Zn(II) and Cd(II) ions, by exhibiting a significant fluorescence enhancement via a turn-on photoinduced electron transfer (PET) mechanism with a rapid and highly reproducible signal, and low detection limit values of 0.408 µM and 0.246 µM, for Zn(II) and Cd(II), respectively.

Microwave-assisted commercial copper-catalyzed aerobic oxidative synthesis of AChE quinazolinone inhibitors under solvent free conditions.

A facile and green one-pot synthesis of AChE quinazolinone inhibitors was developed using microwave irradiation under solvent free conditions. Quinazolinones were synthesized from 2-aminobenzamide derivatives and various alcohols such as benzyl alcohol derivatives and butanol using economical commercially available copper as a catalyst in the presence of base, Cs2CO3. The desired products were achieved in moderate to high yields with up to 92% isolated yield. These quinazolinone products were then evaluated for acetylcholinesterase inhibition so that they can be developed as promising anti-acetylcholinesterase agents.

Structure-Activity Relationship and Molecular Docking of Quinazolinones Inhibiting Expression of COX-2, IL-1ß, iNOS, and TNF-α through NF-κB Pathways.

The quinazolinone scaffold is found in natural products and biologically active compounds, including inflammatory inhibitors. Major proteins or enzymes involved in the inflammation process are regulated by the amount of gene expression. Quinazolinone derivatives were investigated and developed against the inflammatory genes cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cell line. The mRNA expressions were measured using a real-time quantitative polymerase chain reaction (RT-qPCR). Quinazolinone compounds at 62.5 µM demonstrated anti-COX-2 and anti-IL-1ß mRNA expressions down to 0.50% and 3.10% gene expression, respectively, via inhibition of nuclear factor κB (NF-κB). Molecular docking was performed to explain the interaction between the binding site and the developed compounds as well as the structure-activity relationship of the quinazolinone moiety.

Pentagalloyl Glucose-Targeted Inhibition of P-Glycoprotein and Re-Sensitization of Multidrug-Resistant Leukemic Cells (K562/ADR) to Doxorubicin: In Silico and Functional Studies.

Combining phytochemicals with chemotherapeutic drugs has demonstrated the potential to surmount drug resistance. In this paper, we explore the efficacy of pentagalloyl glucose (PGG) in modulating P-gp and reversing multidrug resistance (MDR) in drug-resistant leukemic cells (K562/ADR). The cytotoxicity of PGG was evaluated using a CCK-8 assay, and cell apoptosis was assessed using flow cytometry. Western blotting was used to analyze protein expression levels. P-glycoprotein (P-gp) activity was evaluated by monitoring the kinetics of P-gp-mediated efflux of pirarubicin (THP). Finally, molecular docking, molecular dynamics simulation, and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) calculation were conducted to investigate drug-protein interactions. We found that PGG selectively induced cytotoxicity in K562/ADR cells and enhanced sensitivity to doxorubicin (DOX), indicating its potential as a reversal agent. PGG reduced the expression of P-gp and its gene transcript levels. Additionally, PGG inhibited P-gp-mediated efflux and increased intracellular drug accumulation in drug-resistant cells. Molecular dynamics simulations and MM-GBSA calculation provided insights into the binding affinity of PGG to P-gp, suggesting that PGG binds tightly to both the substrate and the ATP binding sites of P-gp. These findings support the potential of PGG to target P-gp, reverse drug resistance, and enhance the efficacy of anticancer therapies.

2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone from Cleistocalyx nervosum var. paniala seeds attenuated the early stage of diethylnitrosamine and 1,2-dimethylhydrazine-induced colorectal carcinogenesis.

BACKGROUND: Dichloromethane extract of Cleistocalyx nervosum var. paniala seeds exhibited an anticarcinogenicity against chemically-induced the early stages of carcinogenesis in rats. This study aimed to identify anticarcinogenic compounds from C. nervosum seed extract (CSE). METHODS: Salmonella mutation assay was performed to determine mutagenicity and antimutagenicity of partially purified and purified compounds of CSE. The anticarcinogenic enzyme-inducing activity was measured in Hepa1c1c7. Moreover, the anticancer potency was examined on various human cancer cell lines. The anticarcinogenicity of DMC was investigated using dual-organ carcinogenicity model. The number of preneoplastic lesions was evaluated in the liver and colon. The inhibitory mechanisms of DMC on liver- and colorectal carcinogenesis were investigated. RESULTS: Six partially purified fractions (MK1 - MK6) and purified compounds, including 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) and hariganetin, were obtained from CSE. Among these fractions, MK4 and DMC presented the greatest antimutagenicity against indirect mutagens in bacterial model. Moreover, MK5 possessed an effective anticarcinogenic enzyme inducer in Hepa1c1c7. The MK4, DMC and CSE showed greater anticancer activity on all cell lines and exhibited the most effective toxicity on colon cancer cells. Furthermore, DMC inhibited the formation of colonic preneoplastic lesions in carcinogens-treated rats. It reduced PCNA-positive cells and frequency of BCAC in rat colon. DMC also enhanced the detoxifying enzyme, GST, in rat livers. CONCLUSIONS: DMC obtained from CSE may be a promising cancer chemopreventive compound of colorectal cancer process in rats. It could increase detoxifying enzymes and suppress the cell proliferation process resulting in prevention of post-initiation stage of colorectal carcinogenesis.

Study on the absolute configuration and biological activity of rotenoids from the leaves and twigs of Millettia pyrrhocarpa Mattapha, Forest & Hawkins, sp. Nov.

BACKGROUND: M. pyrrhocarpa is a new plant in the Fabaceae: Faboideae family that is found in Thailand. A literature search revealed that the Milletia genus is rich in bioactive compounds possessing a wide range of biological activities. In this study, we aimed to isolate novel bioactive compounds and to study their bioactivities. METHODS: The hexane, ethyl acetate, and methanol extracts from the leaves and twigs of M. pyrrhocarpa were isolated and purified using chromatography techniques. These extracts and pure compounds were tested in vitro for their inhibitory activities against nine strains of bacteria, as well as their anti-HIV-1 virus activity and cytotoxicity against eight cancer cell lines. RESULTS: Three rotenoids, named 6aS, 12aS, 12S-elliptinol (1), 6aS, 12aS, 12S-munduserol (2), dehydromunduserone (3), and crude extracts were evaluated for antibacterial, anti-HIV, and cytotoxic activities. It was found that compounds 1-3 inhibited the growth of nine strains of bacteria, and the best MIC/MBC values were obtained at 3/ > 3 mg/mL. The hexane extract showed anti-HIV-1 RT with the highest %inhibition at 81.27 at 200 mg/mL, while 6aS, 12aS, 12S-elliptinol (1) reduced syncytium formation in 1A2 cells with a maximum EC50 value of 4.48 µM. Furthermore, 6aS, 12aS, 12S-elliptinol (1) showed cytotoxicity against A549 and Hep G2 cells with maximum ED50 values of 2.27 and 3.94 µg/mL. CONCLUSION: This study led to the isolation of constituents with potential for medicinal application, providing compounds (1-3) as lead compounds against nine strains of bacteria. The hexane extract showed the highest %inhibition of HIV-1 virus, Compound 1 showed the best EC50 in reducing syncytium formation in 1A2 cells, and it also showed the best ED50 against human lung adenocarcinoma (A549) and human hepatocellular carcinoma (Hep G2). The isolated compounds from M. pyrrhocarpa offered significant potential for future medicinal application studies.

2',4'-Dihydroxy-6'­methoxy-3',5'-dimethylchalcone and its amino acid-conjugated derivatives induce G0/G1 cell cycle arrest and apoptosis via BAX/BCL2 ratio upregulation and in silico insight in SiHa cell lines.

We modified the chemical structure of 2',4'-dihydroxy-6'­methoxy-3',5'-dimethylchalcone (DMC, 1), a phytochemical found in the seed of Syzygium nervosum A.Cunn. ex DC., by conjugation with the amino acid L-alanine (compound 3a) or L-valine (compound 3b) to enhance anticancer activity and water solubility. Compounds 3a and 3b had antiproliferative activity in human cervical cancer cell lines (C-33A, SiHa and HeLa), with half-maximal inhibitory concentrations (IC50) of 7.56 ± 0.27 and 8.24 ± 0.14 µM, respectively in SiHa cells; these values were approximately two-fold greater than DMC. We investigated the biological activities of compounds 3a and 3b based on a wound healing assay, a cell cycle assay and messenger RNA (mRNA) expression analysis to determine the possible mechanism of anticancer activity. Compounds 3a and 3b inhibited SiHa cell migration in the wound healing assay. After treatment with compounds 3a and 3b, there was an increase in SiHa cells in the G1 phase, indicative of cell cycle arrest. Moreover, compound 3a showed potential anticancer activity by upregulating TP53 and CDKN1A that resulted in upregulation of BAX and downregulation of CDK2 and BCL2, leading to apoptosis and cell cycle arrest. The BAX/BCL2 expression ratio was increased after treatment with compound 3avia the intrinsic apoptotic pathway. In silico molecular dynamics simulation and binding free energy calculation shed light on how these DMC derivatives interact with the HPV16 E6 protein, a viral oncoprotein associated with cervical cancer. Our findings suggest that compound 3a is a potential candidate for anti-cervical cancer drug development.

Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CLPro Inhibitors: In Silico Molecular Docking, Molecular Dynamics, and In Vitro Enzymatic Activity.

The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CLPro is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual screening against SARS-CoV-2 3CLPro. Following the virtual screening, the top 15 compounds based on binding energy and their interactions with key amino acid Cys145 were obtained. Subsequently, they were further evaluated for protein-ligand complex stability via molecular dynamics simulation and binding free energy calculation using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches. Following drug-likeness and ADME/Tox assessments, seven bisbenzylisoquinolines were obtained, including neferine (3), liensinine (4), isoliensinine (5), dinklacorine (8), tiliacorinine (13), 2'-nortiliacorinine (14), and yanangcorinine (15). These compounds computationally showed a higher binding affinity than native N3 and GC-373 inhibitors and attained stable interactions on the active site of 3CLpro during 100 ns in molecular dynamics (MD) simulation. Moreover, the in vitro enzymatic assay showed that most bisbenzylisoquinolines could experimentally inhibit SARS-CoV-2 3CLPro. To our delight, isoliensinine (5) isolated from Nelumbo nucifera demonstrated the highest inhibition of protease activity with the IC50 value of 29.93 µM with low toxicity on Vero cells. Our findings suggested that bisbenzylisoquinoline scaffolds could be potentially used as an in vivo model for the development of effective anti-SARS-CoV-2 drugs.

Scalable and Room-Temperature Ring-Opening Polymerization of ε-Caprolactone Catalyzed by Active Lithium Tetramethylene-Tethered Bis[N-(N'-butylimidazol-2-ylidene)] N-Heterocyclic Carbene as a Lewis Acid Organocatalyst.

The Lewis acid organocatalytic system of lithium tetramethylene-tethered bis[N-(N'-butylimidazol-2-ylidene)] N-heterocyclic carbene (1,4-bisNHC) including lithium benzyloxide and benzyl alcohol has been successfully utilized in the ring-opening polymerization (ROP) of ε-caprolactone (CL) for the first time. The catalytic performance of this organic catalyst in the synthesis of high-molecular-weight polymers was investigated via bulk polymerization using different combinations of tetramethylene-tethered bis[N-(N'-butylimidazolium)] hexafluorophosphate (1,4-bis[Bim][PF6]), benzyl alcohol (BnOH), and n-butyl lithium (nBuLi) ([1,4-bis[Bim][PF6]]/[BnOH]/[nBuLi]) with the molar ratios of 0:2:2, 1:1:3, 1:2:3, and 1:2:4. The results showed that the molar ratio of 1:2:3 efficiently and rapidly initiated the bulk ROP of CL at room temperature with a high molar ratio of CL to 1,4-bis[Bim][PF6] of 3000/1 and produced the highest number of average-molecular-weight (Mn) poly(ε-caprolactone) (103,057 g mol-1) with the dispersity (D̵) and %conversion of 1.73 and 98% in a short period of time (152 s). From comparative studies, the relative polymerization rates of the bulk ROP of CL with different [1,4-bis[Bim][PF6]]/[BnOH]/[nBuLi] molar ratios was determined in the following order: 1:2:4 > 1:1:3 > 1:2:3 > 0:2:2. For mechanistic investigation, the bulk ROP mechanism of CL with our organic catalyst was proposed through the intramolecular bis-lithium-carbene interaction pathway for 1,4-bisNHC1,1,3, 1,4-bisNHC1,2,3, and 1,4-bisNHC1,2,4 systems.

Pentagalloyl Glucose and Cisplatin Combination Treatment Exhibits a Synergistic Anticancer Effect in 2D and 3D Models of Head and Neck Carcinoma.

Although cisplatin is a first-line chemotherapy drug for head and neck squamous cell carcinoma (HNSCC), its therapeutic efficacy is limited owing to serious side effects and acquired drug resistance. This study determined whether combining pentagalloyl glucose (PGG) and cisplatin enhanced their anti-tumor activities on HNSCC cell lines. We investigated the anticancer effect of PGG combined with cisplatin in 2D and 3D multicellular spheroid cell culture. The results revealed that PGG combined with cisplatin inhibited cell viability and produced synergistic effects. PGG potentiates the anticancer effect of cisplatin by promoting apoptosis and inhibiting cell migration. The western blot and molecular docking analysis revealed that the synergistic effect of the combination treatment may be related to the PGG-mediated reduced expression of phosphorylated STAT3 and phosphorylated Akt. Furthermore, we found that the combined treatment of PGG and cisplatin's effect on 3D multicellular spheroid size was more potent than the monotherapies. Our findings indicated that the combination therapy of PGG and cisplatin synergistically inhibited HNSCC cancer cell viability and induced apoptosis in 2D and 3D models. The present results suggested that PGG may be a promising adjunct drug used with cisplatin for a practical therapeutic approach to head and neck cancer.

Hydrosoluble Perylene Monoimide-Based Telomerase Inhibitors with Diminished Cytotoxicity.

Telomerase is essential for the immortality characteristics of most cancers. Telomerase-specific inhibitors should render cancer cells to replicative senescence without acute cytotoxicity. Perylene-based G-quadruplex (G4) ligands are widely studied as telomerase inhibitors. Most reported perylene-based G4 ligands are perylene diimides (PDIs), which often suffer from self-aggregation in aqueous solutions. Previously, we found that PM2, a perylene monoimide (PMI), exhibited better solubility, G4 binding affinity, and telomerase inhibition than PIPER, the prototypic PDI. However, the acute cytotoxicity of PM2 was about 20-30 times more than PIPER in cancer cells. In this report, we replaced the piperazine side chain of PM2 with ethylenediamine to yield PM3 and replaced the N,N-diethylethylenediamine side chain of PM2 with the 1-(2-aminoethyl) piperidine to yield PM5. We found that asymmetric PMIs with two basic side chains (PM2, PM3, and PM5) performed better than PIPER (the prototypic PDI), in terms of hydrosolubility, G4 binding, in vitro telomerase inhibition, and suppression of human telomerase reverse transcriptase (hTERT) expression and telomerase activity in A549 cells. However, PM5 was 7-10 times less toxic than PM2 and PM3 in three cancer cell lines. We conclude that replacing the N,N-diethylethylenediamine side chain with the 2-aminoethylpiperidine on PMIs reduces the cytotoxicity in cancer cells without impacting G4 binding and telomerase inhibition. This study paves the way for synthesizing new PMIs with drug-like properties for selective telomerase inhibition.

Microwave-Assisted Extraction of Anticancer Flavonoid, 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethyl Chalcone (DMC), Rich Extract from Syzygium nervosum Fruits.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethyl chalcone (DMC) is a biological flavonoid that is present in the fruits of Syzygium nervosum (Ma-Kiang in Thai). Microwave-assisted extraction (MAE), which utilizes microwave radiation to heat the extraction solvent quickly and effectively, was used to recover DMC-rich extract from Syzygium nervosum fruit. To determine the DMC content, a highly accurate and precise HPLC technique was developed. The influences of MAE conditions, including the solid-liquid ratio, microwave power, and microwave duration on the content of DMC, were sequentially employed by a single factor investigation and response surface methodology (RSM) exploratory design. The predicted quadratic models were fitted due to their highly significant (p < 0.0001) and excellent determination coefficient (R2 = 0.9944). The optimal conditions for producing DMC-rich extract were a ratio of sample to solvent of 1:35 g/mL, a microwave power of 350 W, and a microwave time of 38 min. Under the optimal MAE setting, the DMC content reached 1409 ± 24 µg/g dry sample, which was greater than that of the conventional heat reflux extraction (HRE) (1337 ± 37 µg/g dry sample) and maceration (1225 ± 81 µg/g dry sample). The DMC-rich extract obtained from MAE showed stronger anticancer activities against A549 (human lung cancer cells) and HepG2 (human liver cancer cells) than the individual DMC substance, which makes MAE an effective method for extracting essential phytochemicals from plants in the nature.

Effects of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone from Syzygium nervosum Seeds on Antiproliferative, DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Cervical Cancer Cell Lines.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a natural product derived from Syzygium nervosum A. Cunn. ex DC., was investigated for its inhibitory activities against various cancer cell lines. In this work, we investigated the effects of DMC and available anticervical cancer drugs (5-fluorouracil, cisplatin, and doxorubicin) on three human cervical cancer cell lines (C-33A, HeLa, and SiHa). DMC displayed antiproliferative cervical cancer activity in C-33A, HeLa, and SiHa cells, with IC50 values of 15.76 ± 1.49, 10.05 ± 0.22, and 18.31 ± 3.10 µM, respectively. DMC presented higher antiproliferative cancer activity in HeLa cells; therefore, we further investigated DMC-induced apoptosis in this cell line, including DNA damage, cell cycle arrest, and apoptosis assays. As a potential anticancer agent, DMC treatment increased DNA damage in cancer cells, observed through fluorescence inverted microscopy and a comet assay. The cell cycle assay showed an increased number of cells in the G0/G1 phase following DMC treatment. Furthermore, DMC treatment-induced apoptosis cell death was approximately three- to four-fold higher compared to the untreated group. Here, DMC represented a compound-induced apoptosis for cell death in the HeLa cervical cancer cell line. Our findings suggest that DMC, a phytochemical agent, is a potential candidate for antiproliferative cervical cancer drug development.

Krabasinolide A with anti-HIVs activity from the leaves and twigs of Croton krabas.

One new clerodane-type diterpenoid, together with one known, was isolated from the leaves and twigs of C. krabas. The structures of these compounds were elucidated as krabasinolide A (1) and taraxerol (2) by spectroscopic methods (UV, IR, HRESIMS, 1 D, and 2 D NMR), and the relative stereochemistry was confirmed by X-ray diffraction analysis with graphite monochromated Mo-Kα (λ = 0.71073 Å) radiation at 296(2) K. Extracts and compounds 1-2 were evaluated for in vitro antiviral activity.

Organocatalytic Ring-Opening Polymerization of ε-Caprolactone Using bis(N-(N'-butylimidazolium)alkane Dicationic Ionic Liquids as the Metal-Free Catalysts: Polymer Synthesis, Kinetics and DFT Mechanistic Study.

In this work, we successfully synthesized high thermal stable 1,n-bis(N-(N'-butylimidazolium)alkane bishexafluorophosphates (1,n-bis[Bim][PF6], n = 4, 6, 8, and 10) catalysts in 55-70% yields from imidazole which were applied as non-toxic DILs catalysts with 1-butanol as initiator for the bulk ROP of ε-caprolactone (CL) in the varied ratio of CL/nBuOH/1,4-bis[Bim][PF6] from 200/1.0/0.25-4.0 to 700/1.0/0.25-4.0 by mol%. The result found that the optimal ratio of CL/nBuOH/1,4-bis[Bim][PF6] 400/1.0/0.5 mol% at 120 °C for 72 h led to the polymerization conversions higher than 95%, with the molecular weight (Mw) of PCL 20,130 g mol-1 (D~1.80). The polymerization rate of CL increased with the decreasing linker chain length of ionic liquids. Moreover, the mechanistic study was investigated by DFT using B3LYP (6-31G(d,p)) as basis set. The most plausible mechanism included the stepwise and coordination insertion in which the alkoxide insertion step is the rate-determining step.

Development of an Antimicrobial-Coated Absorbable Monofilament Suture from a Medical-Grade Poly(l-lactide-co-ε-caprolactone) Copolymer.

In this study, a medical-grade poly(l-lactide-co-ε-caprolactone) (PLC) copolymer with a monomer ratio of l-lactide (L) to ε-caprolactone (C) of 70:30 mol % for use as an absorbable surgical suture was synthesized via ring-opening polymerization (ROP) using a novel soluble liquid tin(II) n-butoxide (Sn(OnC4H9)2) as an initiator. In fiber fabrication, the process included copolymer melt extrusion with a minimal draw followed by sequential controlled hot-drawing and fixed-annealing steps to obtain oriented semicrystalline fibers with improved mechanical strength. For healing enhancement, the fiber was dip-coated with "levofloxacin" by adding the drug into a solution mixture of acetone, poly(ε-caprolactone) (PCL), and calcium stearate (CaSt) in the ratio of acetone/PCL/CaSt = 100:1% w/v:0.1% w/v. The tensile strength of the coated fiber was found to be increased to ∼400 MPa, which is comparable with that of commercial polydioxanone (PDS II) of a similar size. Finally, the efficiency of the drug-coated fiber regarding its controlled drug release and antimicrobial activity was investigated, and the results showed that the coated fiber was able to release the drug continuously for as long as 30 days. For fiber antimicrobial activity, it was found that a concentration of 1 mg/mL was sufficient to inhibit the growth of Staphylococcus aureus (MRSA), Escherichia coli O157:H7, and Pseudomonas aeruginosa, giving a clear inhibition zone range of 20-24 mm for 90 days. Cytotoxicity testing of the drug-coated fibers showed a %viability of more than 70%, indicating that they were nontoxic.

Novel Poly(Methylenelactide-g-L-Lactide) Graft Copolymers Synthesized by a Combination of Vinyl Addition and Ring-Opening Polymerizations.

In this work, a novel poly (methylenelactide-g-L-lactide), P(MLA-g-LLA) graft copolymer was synthesized from poly(methylenelactide) (PMLA) and L-lactide (LLA) using 0.03 mol% liquid tin(II) n-butoxide (Sn(OnBu)2) as an initiator by a combination of vinyl addition and ring-opening polymerization (ROP) at 120 °C for 72 h. Proton and carbon-13 nuclear magnetic resonance spectroscopy (1H- and 13C-NMR) and Fourier-transform infrared spectroscopy (FT-IR) confirmed the grafted structure of P(MLA-g-LLA). The P(MLA-g-LLA) melting temperatures (Tm) range of 144-164 °C, which was lower than that of PLA (170-180 °C), while the thermal decomposition temperature (Td) of around 314-335 °C was higher than that of PLA (approx. 300 °C). These results indicated that the grafting reaction could widen the melt processing range of PLA and in doing so increase PLA's thermal stability during melt processing. The graft copolymers were obtained with weight-average molecular weights (M¯w) = 4200-11,000 g mol-1 and a narrow dispersity (D = 1.1-1.4).