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V článku věnujeme pozornost novému trendu v přípravě UHMWPE se zvýšenou odolností vůči otěru, obecně uváděnému jako síťování (crosslinking). Takto modifikovaný UHMWPE lze charakterizovat vyšším stupněm příčných vazeb a žádným, resp. minimálním počtem volných radikálů. Síťovaný UHMWPE se získává ve dvou krocích. Nejprve se UHMWPE za určitých, přesně daných podmínek ozáří ionizujícím zářením a následně prochází tepelnou úpravou, kterou se likvidují vzniklé zbytkové radikály. Správným způsobem modifikovaný polymer vykazuje výrazně vyšší odolnost vůči otěru.
In the article, we focus on a new trend in the preparation of UHMWPE, generally called cross-linking, that provides for a greater resistance to abrasion. UHMWPE thus modified features a higher degree of perpendicular fiber structure and none or rather minimal quantity of loose radicals. Cross-linked UHMWPE is produced in two steps. Firstly, UHMWPE is exposed to ionized radiation, under certain strictly controlled conditions and, subsequently, it undergoes thermal processing that liquidates any remaining loose radicals. Polymer properly modified in this manner possesses distinctly higher resistance to wear.
The study compared the physico-chemical and biological properties of a water-soluble star-like polymer nanomedicine with three micellar nanomedicines formed by self-assembly of amphiphilic copolymers differing in their hydrophobic part (statistical, block and thermosensitive block copolymers). All nanomedicines showed a pH-responsive release of the drug, independent on polymer structure. Significant penetration of all polymer nanomedicines into tumor cells in vitro was demonstrated, where the most pronounced effect was observed for statistical- or diblock copolymer-based micellar systems. Tumor accumulation in vivo was dependent on the stability of the nanomedicines in solution, being the highest for the star-like system, followed by the most stable micellar nanomedicines. The star-like polymer nanomedicine showed a superior therapeutic effect. Since the micellar systems exhibited slightly lower systemic toxicity, they may exhibit the same efficacy as the star-like soluble system when administered at equitoxic doses. In conclusion, treatment efficacy of studied nanomedicines was directly controlled by the drug pharmacokinetics, namely by their ability to circulate in the bloodstream for the time needed for effective accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. Easy and scalable synthesis together with the direct reconstitution possibility for nanomedicine application made these nanomedicines excellent candidates for further clinical evaluation.
Tento příspěvek shrnuje současný stav znalostí o vinylpyrrolidonu, jeho homopolymerech i kopolymerech a zesíťovaných strukturách na jeho bázi, a přináší bohatý přehled různých aplikací se zvláštním zaměřením na biomedicinu. Uvedena je rovněž stručná historie tohoto materiálu. Jsou popsány metody přípravy a technické parametry jak monomerního N-vinylpyrrolidonu, tak jeho různých polymerů. Důležité údaje jsou uvedeny v tabulkách.
This contribution summarizes the present-state of knowledge on vinylpyrrolidone, its (co)polymers, crosslinked structures based on it, and offers a rich survey of various applications, with a special focus on (bio)medicine. A brief history of this material is also given. Methods of preparation and technical parameters of both vinylpyrrolidone monomer and its various polymers are described. Important data are presented in tables.
- MeSH
- hydrogely aplikace a dávkování chemie terapeutické užití MeSH
- jodovaný povidon aplikace a dávkování terapeutické užití MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- polymerizace MeSH
- polymery chemická syntéza MeSH
- povidon * aplikace a dávkování chemie MeSH
- vinylové sloučeniny chemie MeSH
- Check Tag
- lidé MeSH
Solid-phase synthesis of purine derivatives bearing an α-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-α-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.
The synthesis of different diketomorpholines via N-acyl-3,4-dihydro-2 H-1,4-oxazine-3-carboxylic acids is reported in this article. The key intermediates were prepared using a convenient solid-phase synthesis starting from polymer-supported Ser( tBu)-OH. After subsequent sulfonylation with 4-nitrobenzenesulfonyl chloride (4-Nos-Cl), alkylation with an α-bromoketone, cleavage of the 4-Nos group and acylation with an α-halocarboxylic acids, acid-mediated cleavage from the resin yielded dihydrooxazine-3-carboxylic acids in high crude purities. Depending on the reaction conditions, exposure to base resulted in cyclization to either oxazino[3,4- c][1,4]oxazine-diones or 3-methylidenemorpholine-2,5-diones. Further reaction with triethylsilane-trifluoroacetic acid (TES/TFA) led to olefin reduction, in the case of oxazino[3,4- c][1,4]oxazine-dione with full control of the newly formed stereocenter.
- MeSH
- acylace MeSH
- alkylace MeSH
- cyklizace MeSH
- kyselina trifluoroctová chemie MeSH
- kyseliny karboxylové chemie MeSH
- molekulární struktura MeSH
- morfoliny chemická syntéza MeSH
- nitrobenzeny chemie MeSH
- oxaziny chemie MeSH
- polymery chemie MeSH
- silany chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue; however, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized. The highest rate of the drug release from the polymer carriers in presence of the lysosomal protease cathepsin B was determined for the copolymers with Val-Cit-Aba spacer. Copolymers containing pirarubicin were more cytotoxic and showed higher internalization rate than the corresponding doxorubicin counterparts. The conjugates containing GFLG and Val-Cit-Aba spacers exhibited the highest anti-tumor efficacy in vivo against murine sarcoma S-180, the highest rate of the enzymatically catalyzed drug release, and the highest cytotoxicity in vitro.
- MeSH
- doxorubicin farmakologie chemie MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory * farmakoterapie MeSH
- nanomedicína MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- protinádorové látky * farmakologie terapeutické užití chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this report, we employed the solid-phase synthetic approach to prepare variously substituted dihydropteridinones, tetrahydropyrrolopteridinones, and pyrimidodiazepinones, using a versatile building block-4,6-dichloro-5-nitropyrimidine. All these compounds are pharmacologically significant scaffolds of the great importance of medicinal chemists. The fast and efficient synthetic methodology is highly desirable for defining their structure-activity relationship (SAR) and optimizing pharmacokinetic properties. Our research efforts utilize simple synthetic methods to generate a library of analogues for future SAR studies. The efficiency of our approach was exemplified in various pteridinones as well as pyrimidodiazepinones.
- MeSH
- léčivé přípravky chemie MeSH
- polymery chemie MeSH
- pteridiny chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
In this review, we summarize synthetic approaches to preparing single or fused oxazine and thiazine derivatives using solid-phase synthesis (SPS). The literature survey revealed that diverse compounds bearing variously functionalized 1,2-oxazine, 1,3-oxazine, or 1,4-oxazine scaffolds and the corresponding thiazines are accessible by SPS. The latest contributions involving the stereoselective polymer-supported syntheses of morpholines indicate that the field is continuing to expand.
- MeSH
- cykloadiční reakce MeSH
- knihovny malých molekul chemie MeSH
- molekulární struktura MeSH
- morfoliny chemie MeSH
- oxaziny chemická syntéza MeSH
- oxidace-redukce MeSH
- polymery chemie MeSH
- pyrazoly chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi metody MeSH
- thiaziny chemická syntéza MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
