Sinteza i kompleksacijska svojstva glikokonjugata kaliks[4]arena

doctoral thesis

• Title (english): Synthesis and complexation properties of calix[4]arene glycoconjugates
• Author: Nikola Cindro
• Mentor: Vladislav Tomišić (mentor)
• Mentor: Leo Frkanec (komentor)
• Committee member: Vesna Petrović Peroković (predsjednik povjerenstva)
• Committee member: Ivo Piantanida (član povjerenstva); MBZ: 202026
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2017-12-11, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Pripravljena su tri nova, u vodi topljiva derivata kaliks[4]arena 1–3 s amidnim veznim mjestima za katione. U strukturu kaliksarena ugrađene su glukozne jedinice kao neutralni hidrofilni fragmenti koji omogućuju topljivost u vodi. Sinteza spojeva provedena je nizom reakcija, iz polaznog p-tert-butilkaliks[4]aren. Vezanje glukoznih jedinica je provedeno bakrom kataliziranom cikloadicijom alkina i azida, a amidne skupine uvedene su korištenjem standardnih sintetskih tehnika u kaliksarenskoj kemiji. Spojevi se razlikuju po vrsti amidnog veznog mjesta (sekundarni ili tercijarni) te položaju i broju glukoznih podjedinica. Provedena su istraživanja kompleksiranja alkalijskih kationa u vodi, metanolu i formamidu kako bi se stekao uvid u utjecaj solvatacije te intra- i intermolekulskih vodikovih veza na ravnoteže odgovarajućih reakcija. Konstante stabilnosti kompleksa stehiometrije 1:1 određene su pomoću UV spektrofotometrijskih i mikrokalorimetrijskih titracija, pri čemu su po prvi puta takva istraživanja provedena s neutralnim kaliksarenskim ligandima u vodi. Kalorimetrijskim mjerenjima određene su i pripadne reakcijske entalpije i entropije. Vrijednosti konstanti ravnoteže reakcija kompleksiranja smanjuju se u nizu otapala metanol > formamid > voda, što se može povezati s razlikom u jakosti solvatacije kationa u tim otapalima. Konstante stabilnosti kationskih kompleksa s priređenim spojevima uglavnom padaju u nizu Na+ > K+ > Li+ > Rb+, dok za najveći Cs+ kompleksiranje nije primijećeno. Najveće konstante stabilnosti imaju kompleksi derivata s tercijanim amidnim veznim mjestom i osam glukoznih jedinica na donjem obodu, pri čemu se taj derivat pokazao vrlo efikasnim (logK ≈ 5) i selektivnim receptorom za vezanje Na+ u vodi. Svi dobiveni rezultati detaljno su obrazloženi i raspravljeni, od sintetskih puteva za dobivanje pojedinih receptora do utjecaja njihove strukture i otapala na termodinamičku stabilnost kompleksa tih spojeva s alkalijskim kationima.

Abstract (english)

Three novel water-soluble calix[4]arene derivatives bearing amide binding sites for metal cati-ons were prepared. Glucose units were embedded in their structures as neutral hydrophilic frag-ments which enable solubility in water. Syntheses were performed through a series of reactions starting from p-tert-butylcalix[4]arene. Glycosylation was carried out using copper catalyzed alkyne azide cycloaddition, whereas amide groups were introduced using standard techniques in calixarene chemistry. The compounds differed in the type of cation-binding site (secondary or tertiary amide) as well as position and number of glucose units. Complexation of the prepared ligands with alkali metal cations in water, methanol and formamide was studied in order to get insight into the effect of solvation as well as intra- and intermolecular hydrogen bonds on the equilibria of the corresponding reactions. Stability constants of 1:1 complexes were determined by means of UV spectrophotometric and microcalorimetric titrations. Calorimetric measure-ments provided also reaction enthalpies and entropies. It should be noted that such studies were for the first time undertaken with neutral calixarens in aqueous solutions. The complexation reaction equilibrium constants decreased in the solvent order: methanol > formamide > water, which could be accounted for by considering the differences in solvation of cations in these solvents. In most cases the stability constants of the complexes decreased in the cation order: Na+ > K+ > Li+ > Rb+, whereas no complexation was observed in the case of the largest Cs+. The highest stability constants corresponded to tertiary-amide derivative bearing eight glucose units at the lower rim, and this derivative was proven to be capable of remarkably efficient (log K ≈ 5) and pronouncedly selective binding of sodium cation in water. All the obtained results were thoroughly discussed with respect to the developed synthetic routes, as well as the influ-ence of solvation and ligands structural characteristics on the thermodynamic stability of their complexes with alkali metal cations.

• Keywords: glikozilacija; ionski receptori; kaliks[4]aren; konstanta stabilnosti; voda
• Keywords (english): calix[4]arene; glicosylation; ionic receptors; stability constant; water
• Language: croatian
• URN:NBN: urn:nbn:hr:217:984774
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 147 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-12-15 11:16:46