Search

Sweet clovers are belonging to the fabaceae and are important for animal nutrition and health in terms of the secondary metabolites it contains. Besides, sweet clovers increase the quality of short-term pastures to be established in arid and poor soils, and their feed quality is high and the swelling problem is less than compared to the alfalfa and trefoil species. In this study, it was aimed to determine the total phenolic (TP), total flavonoid (TF), radical scavenging activity (DPPH) and condensed tannin contents (CT) of 17 white sweet clover (Melilotus alba Desr.) collected from the natural flora of Bilecik. As a result, the average TP, TF, DPPH, and CT contents of white sweet clover genotypes were determined as 3.901 mg GA g-1 17.962 mg QE g-1, 26.523%, and 0.611%, respectively, and there were differences between the white sweet clover genotypes in terms of these compounds. Besides, these compounds determined in the study are very important in terms of feed quality and animal health, and the results will shed light on future studies., Baklagiller familyasında yer alan taş yoncaları içermiş olduğu ikincil metabolitler ile hayvan besleme ve sağlığı açısından önem teşkil etmektedir. Diğer taraftan, kıraç ve fakir topraklarda kurulacak kısa süreli meraların kalitesinin artırılmasında kullanılan taş yoncalarının yem kalitesi yüksek olmakla birlikte, yonca ve üçgül türlerine göre şişme problemi daha azdır. Bu araştırma, Bilecik ili doğal florasından toplanan 17 adet aktaş yoncası genotipinin (Melilotus alba Desr.) toplam fenolik, toplam flavonoid, radikal kovucu aktivite (DPPH) ve kondanse tanen içeriklerinin belirlenmesi amacı ile yapılmıştır. Araştırma sonucuna göre, genotiplerin ortalama fenolik, flavonoid, DPPH ve kondanse tanen içerikleri sırasıyla 3.901 mg GA g-1, 17.962 mg QE g-1, %26.523 ve %0.611 olarak belirlenmiş olup, söz konusu bileşikler bakımından aktaş yoncası genotipleri arasında farklılıklar olmuştur. Ayrıca, çalışmada belirlenen bu bileşikler yem kalitesi ve hayvan sağlığı açısından çok önemli olup, sonuçlar ileride yapılacak çalışmalara ışık tutacak niteliktedir.

This review article highlights the research focused on the synthesis of polylactide (PLA) based copolymers by combination of reversible-deactivation radical polymerization (RDRP) techniques with ring-opening polymerization (ROP) processes. In particular atom-transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization, and nitroxide-mediated polymerization (NMP) will be addressed as RDRP techniques mechanistically different from ROP in the design of various sophisticated macromolecular structures. The combination of ROP with RDRP techniques has been extensively applied to prepare PLA copolymers. We discuss the synthetic methods applicable to prepare linear and star-shaped block copolymers by use of heterofunctional initiators as well as other end functionalization methods. This is complemented with the adaption of the synthetic pathways generally used for the preparation of comb and graft copolymers, i.e. , macromonomer, grafting-from and grafting-onto approaches, to the requirements of PLA-based building blocks.

The synthesis of retinol initiated polylactide (PLA) by ring opening polymerization (ROP) of L-lactide via in situ calcium alkoxide formation with all-trans-retinol and Ca[N(SiMe3)2]2(THF)2 is described. PLAs with degree of polymerization (DP) values ranging from 13 to 60 were obtained and characterized in detail by means of 1H nuclear magnetic resonance (NMR) spectroscopy, size exclusion chromatography (SEC), UV/vis spectroscopy and (tandem) mass spectrometry techniques. Stable nanoparticles (NPs) were prepared via a nanoprecipitation method and characterized by DLS and SEM. The stability of retinol upon conjugation to PLA as well as the nanoparticle formulation was investigated in detail and found to be significantly affected by the storage conditions such as exposure to light, oxygen and temperature.

A series of dual pH- and ultrasound responsive statistical copolymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The RAFT-controlled nature of the (co)polymerizations was verified by detailed kinetic studies. The chemical structure and the co-monomer composition of the copolymers were confirmed by 1H NMR spectroscopy. The number-average molar mass values (Mn) and dispersities (ĐM = Mw/Mn) of the copolymers were estimated by size exclusion chromatography (SEC). The thermal properties of the (co)polymers were analyzed by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the DMAEMA moieties of the copolymers were quaternized with an excess of methyl iodide. The synthesized polymers self-assemble into nanoparticles in aqueous media via the nanoprecipitation method and were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Zeta potential measurements revealed that all DMAEMA containing nanoparticles undergo a surface charge conversion from positive to negative at slightly acidic pH values. However, quaternized DMAEMA nanoparticles possess pH independent positive surface charges. At acidic pH values, the nanoparticles disassemble and dissolve in water due to the protonation of the DMAEMA moieties and/or due to the acidic hydrolysis of the THP-HEMA groups. It was found that the surface charge and the stability of the nanoparticles were greatly affected by the DMAEMA content of the polymers, meaning that the isoelectric point (IEP), at which the charge is reversed and the pH value at which the disassembly occurs, increased with the higher DMAEMA content in the copolymer. Moreover, it was proven that the ionization of the carboxyl RAFT end-group of the polymers enhanced the anionic character and the stability of the nanoparticles at neutral pH values. DLS and scanning electron microscopy (SEM) measurements revealed that these nanoparticles can be further disrupted by ultrasound exposure. Nile Red was encapsulated into nanoparticles as a model hydrophobic drug. The release profile of the Nile Red was significantly accelerated in acidic media or under ultrasound exposure. The cytotoxicity assay results showed that negatively charged nanoparticles are non-toxic and biocompatible, whereas positively charged nanoparticles are extremely toxic to L929 cells.

A block copolymer library of polylactide (PLA) and poly(2-hydroxyethyl acrylate) (PHEA) was prepared via sequential ring opening polymerization (ROP) and reversible addition fragmentation chain transfer (RAFT) polymerization in a one-pot approach. The whole process was conducted at room temperature in THF without employing any protection chemistry or intermediate purification steps. The ROP of L-lactide was performed via in situ calcium alkoxide formation by using 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol (CDP) and [(THF)2Ca{N(SiMe3)2}2]. The PLA based macro chain transfer agent (CTA) (Mn = 2550 g mol−1, Đ = 1.18) was characterized in-depth by (tandem) mass spectrometry and proved to be suitable to obtain PHEA blocks with Mn values up to 10 000 g mol−1 (Đ ≤ 1.28). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurements indicated an increased miscibility between both blocks in bulk as the length of the PHEA unit increases. The amphiphilic block copolymers self-assembled into micellar structures in aqueous media, which were studied by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM).

A series of amphiphilic heterografted comb polymers comprising various ratios of oligomeric polylactide (PLA) and poly(2-ethyl-2-oxazoline) (PEtOx) side chains was synthesized via the grafting-through method employing the reversible addition–fragmentation chain transfer copolymerization. Two well-defined PLA macromonomers were prepared via ring opening polymerization (ROP) of L-lactide using a calcium-based pre-catalyst, pyrenebutanol as an initiator and methacryloyl chloride as an end-capping agent. The PEtOx macromonomer was obtained from the cationic ROP of EtOx and end-capping with methacrylic acid. The amphiphilic comb polymers self-assembled in aqueous solution to form spherical and worm-like micelles, vesicles and more complex morphologies as a function of the composition, as is evident from dynamic light scattering and cryo-transmission electron microscopy studies. All polymers were found to be non-toxic to L929 cells up to a concentration of 200 μg mL−1. Cellular uptake studies with HEK-293 cells by live cell confocal fluorescence microscopy revealed localization in the cytosol after 4 h and suggest an energy-driven cellular uptake mechanism.

In order to obtain a novel, pH responsive polymersome system, a series of pH responsive block copolymers were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected 2-hydroxyethyl methacrylate (HEMA) (2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA)) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) using p(THP-HEMA) as a macro chain transfer agent (mCTA). The degree of polymerization (DP) of the p(THP-HEMA) block was fixed to 35, whereas the DP of the p(DMAEMA) block was systematically varied from 21 to 50. In aqueous solution, the block copolymer with the shortest p(DMAEMA) block (DP = 21) self-assembled into vesicles, while the polymer with 30 units of p(DMAEMA) formed a mixture of micelles and vesicles. The polymer with the longest p(DMAEMA) block (DP = 50) formed exclusively micelles. The corresponding polymersomes exhibited a morphology transition from vesicles at neutral pH values to micelles upon lowering the pH value down to endosomal pH value as investigated by DLS and cryo-TEM. The capability of polymersomes to encapsulate both hydrophobic (e.g., Nile Red) and hydrophilic (e.g., doxorubicin hydrochloride (DOX·HCl)) cargos was verified by in vitro studies. Drug release studies demonstrated that the DOX·HCl release is significantly accelerated under acidic pH values compared to physiological conditions. Cytotoxicity studies revealed that DOX·HCl loaded polymersomes exhibited an efficient cell death comparable to free DOX·HCl. CLSM and flow cytometry studies showed that DOX·HCl loaded vesicles were easily taken up by L929 cells and were mainly located in the cytoplasm and cell nuclei.

Novel difunctional monomers are synthesized which are able to dimerize as well as oligomerize via the hetero-Diels–Alder (HDA) mechanism. These monomers are based on 3-aryl-2-cyanothioacrylamides, which are used as functional units for the HDA reaction to form 3,4-dihydro-2H-thiopyrans. Different substituents of the aromatic ring are utilized to shift the equilibrium to the dimeric or oligomeric species. The HDA reaction is reversible and can be influenced by the temperature as well as the concentration. In contrast, the N,N-dimethylthioacrylamide analogues do not dimerize or the dimerization is not reversible. The most promising compound is furthermore investigated in detail by 1H NMR spectroscopy to elucidate the dimerization kinetics. In addition, a difunctional molecule is able to oligomerize reversibly, as confirmed by means of 1H NMR, size exclusion chromatography (SEC), and ESI MS measurements. A respective alcohol is employed as initiator for the ring-opening polymerization of l-lactide resulting in an end-functional polymer that undergoes reversible dimerization as confirmed by SEC measurements.