Efficiency of liquid tin(ii) n-alkoxide initiators in the ring-opening polymerization of l-lactide: kinetic studies by non-isothermal differential scanning calorimetry

Novel soluble liquid tin(ii) n-butoxide (Sn(OnC₄H₉)₂), tin(ii) n-hexoxide (Sn(OnC₆H₁₃)₂), and tin(ii) n-octoxide (Sn(OnC₈H₁₇)₂) initiators were synthesized for use as coordination–insertion initiators in the bulk ring-opening polymerization (ROP) of l-lactide (LLA). In order to compare their efficiencies with the more commonly used tin(ii) 2-ethylhexanoate (stannous octoate, Sn(Oct)₂) and conventional tin(ii) octoate/n-alcohol (SnOct₂/nROH) initiating systems, kinetic parameters derived from monomer conversion data were obtained from non-isothermal differential scanning calorimetry (DSC). In this work, the three non-isothermal DSC kinetic approaches including dynamic (Kissinger, Flynn–Wall, and Ozawa); isoconversional (Friedman, Kissinger–Akahira–Sunose (KAS) and Ozawa–Flynn–Wall (OFW)); and Borchardt and Daniels (B/D) methods of data analysis were compared. The kinetic results showed that, under the same conditions, the rate of polymerization for the 7 initiators/initiating systems was in the order of liquid Sn(OnC₄H₉)₂ > Sn(Oct)₂/nC₄H₉OH > Sn(Oct)₂ ≅ liquid Sn(OnC₆H₁₃)₂ > Sn(Oct)₂/nC₆H₁₃OH ≅ liquid Sn(OnC₈H₁₇)₂ > Sn(Oct)₂/nC₈H₁₇OH. The lowest activation energies (E_a = 52, 59, and 56 kJ mol⁻¹ for the Kissinger, Flynn–Wall, and Ozawa dynamic methods; E_a = 53–60, 55–58, and 60–62 kJ mol⁻¹ for the Friedman, KAS, and OFW isoconversional methods; and E_a = 76–84 kJ mol⁻¹ for the B/D) were found in the polymerizations using the novel liquid Sn(OnC₄H₉)₂ as the initiator, thereby showing it to be the most efficient initiator in the ROP of l-lactide.

The efficiency of homogeneous liquid tin(ii) n-alkoxide initiators in the ROP of l-lactide was reported in this work by non-isothermal DSC kinetic approaches.     

Effect of topology of poly(L-lactide-co-ε-caprolactone) scaffolds on the response of cultured human umbilical cord Wharton’s jelly-derived mesenchymal stem cells and neuroblastoma cell lines

In this study, for the first time, a biodegradable poly(L-lactide-co-ε-caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds in reconstructive nerve surgery. The effect of the surface topology and pore architecture were studied on the biocompatibility for supporting the growth of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were prepared by electrospinning and phase immersion precipitation with particulate leaching and nonporous PLC membranes were prepared by solvent casting. From the results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better than the nonporous PLC membrane, and the interconnected pore scaffold prepared by electrospinning exhibited a more significant supporting attachment of the cells than the open pore and nonporous membranes. We can consider that these electrospun PLC membranes with 3-D interconnecting fiber networks and a high porosity warrant a potential use as nerve guides in reconstructive nerve surgery.     

Labdane‐type diterpenes from Hedychium gardnerianum with potent cytotoxicity against human small cell lung cancer cells

Seven labdane‐type diterpenes, coronarin E, coronarin A, yunnancoronarin A, yunnancoronarin B, hedyforrestin B, villosin, and hedyforrestin C were isolated from the rhizome of Hedychium gardnerianum and evaluated for cytotoxic activity against human small cell lung cancer (NCI‐H187) and non‐cancerous Vero cells. The results showed that villosin exhibited potent cytotoxic activity with IC₅₀ of 0.40 μM, which was higher than that of the drug ellipticine (IC₅₀ 1.79 μM). Moreover, ellipticine was very toxic to Vero cells (IC₅₀ 7.47 μM) whereas the toxicity of villosin was undetectable at concentration lower than 166.42 μM. The results have indicated that the lactone ring is essential for high cytotoxic activity and that the presence of a hydroxyl group at the 6 or 7 position causes decrease in activity. The very high cytotoxicity against the NCI‐H187 cells and the exceptionally high selectivity index (>416) of villosin suggested that this compound may be used as a potential lead molecule for antitumor therapeutic development. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC, 1) was isolated from seeds of Syzygium nervosum A.Cunn. ex DC. exhibiting intriguing biological activities. Herein, thirty three DMC derivatives including 4′-O-monosubstituted-DMC (2), 7-O-acylated-4-hydroxycoumarin derivatives (3), stilbene–coumarin derivatives (4), 2′,4′-disubstituted-DMC (5), and flavanone derivatives (6), were synthesised through acylation, alkylations, and sulfonylation. These semi-synthetic DMC derivatives were evaluated for in vitro cytotoxicity against six carcinoma cell lines. It was found that most derivatives exhibited higher cytotoxicity than DMC. In particular, 4′-O-caproylated-DMC (2b) and 4′-O-methylated-DMC (2g) displayed the strongest cytotoxicity against SH-SY5Y with IC₅₀ values of 5.20 and 7.52 μM, respectively. Additionally, 4′-O-benzylated-DMC (2h) demonstrated the strongest cytotoxicity against A-549 and FaDu with IC₅₀ values of 9.99 and 13.98 μM, respectively. Our structure–activity relationship (SAR) highlights the importance of 2′-OH and the derivatisation pattern of 4′-OH. Furthermore, molecular docking simulation studies shed further light on how these bioactive compounds interact with cyclin-dependent kinase 2 (CDK2).

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.      

In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand

Aim of study

This study screened for anthelmintic and/or antitumour bioactive compounds from Thai indigenous plants and evaluated effectiveness against three different worm species and two cancer cell lines.

Materials and methods

Methylene chloride and methanol extracts of 32 plant species were screened for in vitro anthelmintic activity against three species of worms, the nematode Caenorhabditis elegans, the digeneans Paramphistomum epiclitum and Schistosoma mansoni (cercariae). Cytotoxicity of the extracts was evaluated against two cancer cell lines: human amelanotic melanoma (C32) and human cervical carcinoma (HeLa) by the SRB assay. Anthelmintic and anticancer activities were evaluated by the inhibiting concentration at 50% death (IC₅₀) and the selectivity index (SI) relative to human fibroblasts.

Results and conclusions

None of the extracts were active against Paramphistomum epiclitum. Plumbagin, a pure compound from Plumbago indica, had the strongest activity against Caenorhabditis elegans. The methylene chloride extract of Piper chaba fruits had the strongest activity against schistosome cercariae. Strong cytotoxicity was shown by the methylene chloride extract of Michelia champaca bark and the methanol extract of Curcuma longa rhizome against C32 and HeLa, respectively. These extracts had higher SI (>100) than positive controls in relation to either the worms or the cell lines. The methanol extract of Bouea burmanica had a slightly lower activity towards C32 cells than did Michelia champaca but had a much higher SI (>27,000).

Ethnopharmacological relevance

The plant species screened in this research was recorded by several indigenous medicinal practitioners as antiparasitic, anticancer and/or related activities to the human major organ system.     

Room-Temperature Lewis Acid Organocatalysts for Bulk Ring-Opening Polymerization of Bis-Lithium N-Heterocyclic Carbenes Complexes Activated on ε-Caprolactone: Synthetic,Experimental, and Density Functional Theory of Mechanistic Studies

This work investigates the high catalytic activity of bi-functional lithium N-heterocyclic carbene (bisLiNHCs) complexes in bulk ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) monomer at room temperature. The study employs a bulk ROP technique using tetramethylene-tethered bis[N-(N′-alkyl/arylimidazolium)] bishexafluorophosphate (bis[Bim][PF₆]), benzyl alcohol (BnOH), and n-butyl lithium (nBuLi) in molar ratios of 1:2:4. The results show that 1,4-bisLiNHC ( 3a ) has the highest catalytic capability, producing the highest molecular weight of PCL with acceptable dispersity in only 93 s (59 361 g mol⁻¹, Đ = 1.8). However, longer and aromatic linker chains ( 3b - 3g ) are found to be less effective due to the increased steric effect for complex formation with the monomer, leading to longer reaction times and lower molecular weight PCL with wider dispersity. Additionally, the study conducts a mechanistic analysis using the DFT method with B3LYP (6-31G(d,p)) as the basis set. The most plausible mechanism proposed involves continuous and coordinated insertion with low energy barriers.