izpis_h1_title_alt

Sinteza dobro definiranih polipeptidov in polipeptidnih hibridnih polimerov z uporabo hidroksilnih skupin za iniciacijo
Gradišar, Špela (Author), Žagar, Ema (Mentor) More about this mentor... This link opens in a new window, Grošelj, Uroš (Co-mentor)

.pdfPDF - Presentation file, Download (8,64 MB)

Abstract
V okviru doktorske disertacije smo načrtovali nove sintezne poti za nadzorovano polimerizacijo z odpiranjem obroča (ROP) N-karboksianhidridov α-aminokislin (NCA) ob uporabi hidroksilnih skupin kot iniciatorjev z namenom, da bi enostavno sintetizirali dobro definirane polipeptide in predvsem polipeptidne hibridne blok kopolimere. V prvem delu doktorske disertacije smo razvili učinkovito sintezno metodo, kjer smo uspešno uporabili nizkomolekularne alkohole in hidroksi-terminirane polimere kot (makro)iniciatorje za ROP NCA. Ključna ideja pri premagovanju počasne iniciacije hidroksilne skupine je preprečiti propagacijo verig, dokler iniciacija ROP ni popolnoma zaključena, oziroma dokler nismo dosegli kvantitativne pretvorbe hidroksilnih skupin (makro)iniciatorja v primarne aminske skupine z reakcijo prvega NCA obroča. Pri tem je bistveno vlogo odigrala metansulfonska kislina (MSA) kot organokatalizator v fazi iniciacije. MSA namreč katalizira odpiranje NCA obroča s hidroksilno skupino in hkrati s protonacijo nastale aminske skupine preprečuje nadaljnjo rast polimernih verig. Propagacijo smo sprožili šele po končani iniciaciji z dodatkom baze, to je N-etildiizopropilamina, ki deprotonira nastale amonijeve skupine. Tako nastale proste primarne, aminske skupine omogočajo nadaljnjo rast verig preko običajnega normalnega aminskega mehanizma. Sintezni postopek je omogočil ne le pripravo dobro definiranih homopolipeptidov z uporabo nizkomolekularnega alkohola kot iniciatorja, ampak tudi polipeptidnih hibridnih blok kopolimerov z uporabo hidroksi-terminiranih makroiniciatorjev. V nadaljevanju smo razvili še zaporedni sintezni postopek, ki je združeval z MSA organokatalizirano ROP cikličnih estrov ali karbonatov ter v naslednji stopnji ROP NCA, iniciirano s hidroksilno skupino nastalega poliestra/polikarbonata za sintezo poliester/polikarbonat-b-polipeptid hibridnih blok kopolimerov v enem koraku. Sintezni pristop smo nadalje razširili še na ROP N-substituiranih NCA, predvsem na sarkozin NCA, za pripravo polisarkozin homopolipeptoidov. Zaradi odlične vodo-topnosti polisarkozina, smo sintetizirali tudi A-B-A amfifilne blok kopolimere, kjer je A blok predstavljal hidrofilni polisarkozin, osrednji hidrofobni B blok pa polipropilen glikol, poliester ali polikarbonat. Sintetizirani, dobro definirani amfifilni blok kopolimeri so primerni za pripravo polimernih micel ali polimersomov za potencialno uporabo v dostavnih sistemih zdravilnih učinkovin. V zadnjem delu smo raziskali tudi možnost uporabe tiosečnina-amin bifunkcionalnih organokatalizatorjev za ROP NCA z uporabo alkohola kot iniciatorja. Rezultati so pokazali, da je v prisotnosti tiosečnina-amin bifunkcionalnih organokatalizatorjev hitrost iniciacije NCA počasnejša od hitrosti propagacije verig, kar vodi do slabše definiranih polipeptidov s širšimi porazdelitvami molskih mas.

Language:Slovenian
Keywords:polimerizacija z odpiranjem obroča (ROP), N-karboksianhidridi α-aminokislin (NCA), iniciacija ROP NCA s hidroksilno skupino, dobro definirani polipeptidi, polipeptidni hibridni kopolimeri
Work type:Doctoral dissertation (mb31)
Tipology:2.08 - Doctoral Dissertation
Organization:FKKT - Faculty of Chemistry and Chemical Technology
Year:2019
COBISS.SI-ID:6771738 Link is opened in a new window
Views:251
Downloads:97
Metadata:XML RDF-CHPDL DC-XML DC-RDF
 
Average score:(0 votes)
Your score:Voting is allowed only to logged in users.
:
Share:AddThis
AddThis uses cookies that require your consent. Edit consent...

Secondary language

Language:English
Title:Synthesis of well-defined polypeptides and polypeptide hybrid polymers using hydroxyl groups for initiation
Abstract:
In this dissertation, previously unreported synthetic route for controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) using hydroxyl group as an initiatior was designed in order to simplify the synthesis of well-defined polypeptides and especially polypeptide-based hybrid block copolymers. In the first part of the work, we developed an efficient synthetic method, where we successfuly used low molecular weight alcohols and hydroxyl-terminated polymers as the (macro)initiators for ROP of NCA. The key idea in overcoming the slow initiation by the hydroxyl group is to prevent chain propagation until the initiation is completed, or in other words, until quantitative conversion of (macro)initiator hydroxyl groups into the primary amine groups is achieved. Methanesulfonic acid (MSA) plays an essential role as an organocatalyst during the initiation step. Namely, MSA efficiently catalyzes opening of the first NCA ring by a hydroxyl group, and at the same time, suppresses further chain propagation by protonation of the formed amine group. Chain propagation was started only after completion of the initiation by the addition of a base, that is N-ethyldiisopropylamine, which deprotonates the resulting ammonium groups. In this way formed free primary amino groups allow further chain growth through the normal amine mechanism. This method was successfully applied for the synthesis of not only homopolypeptides by using low molecular weight alcohol as an initiator, but also polypeptide-based hybrid block copolymers by using hydroxyl-terminated macroinitiators. We further developed a sequential synthesis procedure, combining the MSA-based organocatalyzed ROP of cyclic esters or carbonates, and in the next step, ROP of NCA initiated by the hydroxyl group of the resulting polyester/polycarbonate in order to synthesize the polyester/polycarbonate-b-polypeptide hybrid block copolymers in a one-pot manner. This synthetic approach was further extended to ROP of N-substituted NCA, especially sarcosine NCA, to prepare the polysarcosine polypeptoids. Due to excellent water-solubility of polysarcosine, the A-B-A amphiphilic block copolymers were synthesized,where A block represents hydrophilic polysarcosine and central B block hydrophobic polypropylene glycol, polyester or polycarbonate. Thus prepared amphiphilic block copolymers reveal well-defined structure and molar mass characteristics and are thus suitable for the preparation of polymeric micelles or polymersomes for potential application in drug delivery systems. In the last part, a possibility of using the thiourea-amine bifunctional organocatalysts for ROP of NCA in combination with alcohol as an initiator was investigated. The results showed that in the presence of thiourea-amine bifunctional organocatalysts, the initiation rate of NCA is slower than the chain propagation, leading to poorly defined polypeptides with broader molar mass distribution.

Keywords:ring-opening polymerization (ROP), α-amino acid N-carboxyanhydride (NCA), hydroxyl group initiated ROP NCA, well-defined polypeptides, polypeptide-based hybrid copolymers

Similar documents

Similar works from RUL:
Similar works from other Slovenian collections:

Comments

Leave comment

You have to log in to leave a comment.

Comments (0)
0 - 0 / 0
 
There are no comments!

Back