Properties and Degradability of Poly(Butylene Adipate-Co-Terephthalate)/Calcium Carbonate Films Modified by Polyethylene Glycol

Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable polymer synthesized from petrochemical resources. PBAT has an exceptionally high elongation at break values which makes it one of the most promising substitutes for LDPE packaging films. However, the applicability of PBAT films is still limited by low strength and high production costs. In this work, we used polyethylene glycol 600 (PEG-600) as a coating agent to modify the surface of calcium carbonate and improve compatibility with the polymer matrix. A series of PBAT/CaCO3 composite films having different CaCO3 particle size and content of coating agent was prepared using extrusion blow molding. The effect of particle size of CaCO3 filler and the content of a coating agent on the mechanical and rheological properties of composite films have been studied. The biodegradation properties have been tested by burying the samples in soil or keeping them in artificial seawater for 90 days. It was shown that the addition of PEG-600 improves compatibility between the matrix and CaCO3 filler as polar –OH groups of PEG have a high affinity toward the polar surface of CaCO3. Moreover, the hydrophilicity of PEG-600 increased the diffusivity of water molecules and facilitated PBAT degradation. This work provides experimental data and theoretical guidance that support the development of high-performance PBAT/calcium carbonate films for the single use packaging industry

Effect of Diisocyanates as Compatibilizer on the Properties of BF/PBAT Composites by In Situ Reactive Compatibilization, Crosslinking and Chain Extension

Due to the hydrophobic nature of poly (butylene terephthalate) (PBAT), and the hydrophilic nature of bamboo flour (BF), a BF/PBAT (50/50) blend shows low mechanical properties, and especially shows poor impact strength. In order to increase the interfacial adhesion between BF and PBAT, diisocyanate was used as a reactive compatibilizer to modify bamboo powder. A series of BF/PBAT composites were prepared by the method of mixing and melting in an internal mixer. After adding reactive compatibilizer 4,4′-methylenebis(phenyl isocyanate) (MDI), BF/PBAT (50/50) composites with high mechanical properties were successfully prepared. The tensile strength, elongation at break, and impact strength of the BF/MDI-2/PBAT composite with 2 wt % MDI content were increased by 1.9, 6.8, and 4.3 times respectively over the BF/PBAT blend without the added MDI. The higher toughening effect of MDI in BF/PBAT composites can be mainly ascribed to the improved interface bonding between BF and PBAT. The isocyanate group of MDI can react with the hydroxyl group on the BF surface and in situ formation of the carbamate group on the BF surface. The residual isocyanate can then react with the hydroxyl group of PBAT and form carbamate groups. The rheological behaviors demonstrate that addition of appropriate amounts of MDI, 1 wt % and 2 wt %, can promote the flowability of the molten BF/PBAT composites due to the decrease in interparticle interaction between bamboo powder and the increase in the thermal motion of the molecules

Mechanistic aspects for the direct oxidative esterification of aldehydes with alcohols over Pd catalyst: A computational study

The detailed transformation mechanism of methacrolein with methanol to methyl methacrylate over Pd was investigated by density functional theory (OFT) calculation as an attempt to gain more insight into the oxidative esterification reaction. The entire catalytic cycle and reaction energies are computed for various possible paths over Pd20 cluster. It is found that the hydrogen elimination of MAL following acyl group reaction with methoxyl appears to be an energetically favorable pathway in catalyst cycle. The formation of unsaturated alcohol by H addition, and that of saturated aldehyde through the C=C addition by methoxyl and H are also competitive. The formation of hemiacetal intermediate is not necessary for the production of MMA. (C) 2012 Elsevier B.V. All rights reserved

Macrocyclization of linear molecules by deep learning to facilitate macrocyclic drug candidates discovery

Abstract Interest in macrocycles as potential therapeutic agents has increased rapidly. Macrocyclization of bioactive acyclic molecules provides a potential avenue to yield novel chemical scaffolds, which can contribute to the improvement of the biological activity and physicochemical properties of these molecules. In this study, we propose a computational macrocyclization method based on Transformer architecture (which we name Macformer). Leveraging deep learning, Macformer explores the vast chemical space of macrocyclic analogues of a given acyclic molecule by adding diverse linkers compatible with the acyclic molecule. Macformer can efficiently learn the implicit relationships between acyclic and macrocyclic structures represented as SMILES strings and generate plenty of macrocycles with chemical diversity and structural novelty. In data augmentation scenarios using both internal ChEMBL and external ZINC test datasets, Macformer display excellent performance and generalisability. We showcase the utility of Macformer when combined with molecular docking simulations and wet lab based experimental validation, by applying it to the prospective design of macrocyclic JAK2 inhibitors

Data_Sheet_1_The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistant Acinetobacter baumannii.XLSX

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.</p

Data_Sheet_2_The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistant Acinetobacter baumannii.docx

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.</p