Anion receptors: synthesis and accurate binding measurements
Kuupäev
2015-07-09
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Käesoleva doktoritöö teemaks on erinevate anioone siduvate molekulaarretseptorite süntees ning uudse kõrge täpsusega NMR-põhise mõõtemetoodika väljatöötamine seondumistasakaalude uurimiseks. Sünteesitud retseptorid kasutavad sidumistsentritena uurea, tiouurea, karbasooli, indooli ja indolokarbasooli fragmente ning nende kombinatsioone. Suhtelise seondumisaktiivsuse mõõtmine absoluutse asemel annab võimaluse saada kõrge usaldusväärsusega tulemusi, kuna paljud määramatuse allikad – näiteks ioonpaardumine ja homokonjugatsioon – taanduvad välja. Meetodit rakendati 38 sünteetilise retseptori ja nelja karboksülaataniooni – laktaat, bensoaat, atsetaat, trimetüülatsetaat – vahelise seondumise uurimisele 0.5% H2O lisandiga DMSO-d6 keskkonnas. Saadi suurepärase kooskõlalisusega (0.01 log ühikut) skaalad.
Saadud tulemused näitavad, et seondumisaktiivsuse olulisim anioonipoolne mõjutaja on aniooni aluselisus. Seondumisafiinsus kasvab aniooni aluselisuse kasvuga: laktaat < bensoaat < atsetaat trimetüülatsetaat. Siiski, mitmetel juhtudel esineb seondumisjärjekorra muutuseid, iseäranis atsetaadi ja trimetüülatsetaadi korral.
Loodud NMR-põhise seondumisafiinsuse mõõtemeetodi rakendatavus ja eelised leidsid kinnitust: puudub vajadus mõõta aniooni või retseptori kontsentratsiooni, kõrge täpsus ja usaldusväärsus, võimalus detekteerida retseptori deprotoneerumist, võimalus mõõta kuni kuus retseptorit samas lahuses.
The current dissertation focused on synthesis of different types of molecular receptors for anions, based on different binding moieties, such as urea, thiourea, carbazole, indole, indolocarbazole, as well as their combinations and on development of a novel accurate NMR-based binding affinity measurement method using the relative binding approach. Measuring the relative binding affinity instead of absolute binding affinity it is possible to obtain highly accurate result because many sources of uncertainty such as ion-pairing and homoconjugation cancel out. The method was applied to the measurement of 38 synthetic receptors towards lactate, benzoate, acetate and trimethylacetate anions in 0.5% H2O:DMSO-d6 with excellent consistency parameters around 0.01. The results indicate that on the anion side the binding affinity is largely determined by the anion basicity, higher is the anion basicity, stronger is the binding. The binding affinity orders increasing from lactate benzoate acetate trimethylacetate. Nevertheless, there are a number of occasion binding affinity order changes with changing the carboxylate anions, especially in the case of acetate and trimethylacetate anions. The applicability and advantages of the NMR method for measuring the relative binding affinity have been demonstrated: no need to measure the activity of anion and receptor concentration, high accuracy, robust, possible to see the receptor deprotonation and possible to measure up to six receptors in one solution.
The current dissertation focused on synthesis of different types of molecular receptors for anions, based on different binding moieties, such as urea, thiourea, carbazole, indole, indolocarbazole, as well as their combinations and on development of a novel accurate NMR-based binding affinity measurement method using the relative binding approach. Measuring the relative binding affinity instead of absolute binding affinity it is possible to obtain highly accurate result because many sources of uncertainty such as ion-pairing and homoconjugation cancel out. The method was applied to the measurement of 38 synthetic receptors towards lactate, benzoate, acetate and trimethylacetate anions in 0.5% H2O:DMSO-d6 with excellent consistency parameters around 0.01. The results indicate that on the anion side the binding affinity is largely determined by the anion basicity, higher is the anion basicity, stronger is the binding. The binding affinity orders increasing from lactate benzoate acetate trimethylacetate. Nevertheless, there are a number of occasion binding affinity order changes with changing the carboxylate anions, especially in the case of acetate and trimethylacetate anions. The applicability and advantages of the NMR method for measuring the relative binding affinity have been demonstrated: no need to measure the activity of anion and receptor concentration, high accuracy, robust, possible to see the receptor deprotonation and possible to measure up to six receptors in one solution.
Kirjeldus
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Märksõnad
supramolekulaarkeemia, anioonid, retseptorid, supramolecular chemistry, anions, receptors