Computational design of anion receptors and evaluation of host-guest binding
Date
2021-04-14
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Abstract
Anioon-retseptor keemia – sobivate retseptormolekulide kasutamine huvipakkuvate anioonide sisalduse või olemasolu määramiseks uuritavast keskkonnast – on kiiresti kasvav uurimisvaldkond.
Uute molekulide süntees ning eksperimentaalne uurimine on ajamahukas tegevus ja oleks kasulik, kui retseptorite omadusi oleks võimalik enne nende olemasolu ette ennustada. See, kas ja kui hästi mingi retseptor suudab teise osakese enda külge siduda (retseptor-anioon seondumistugevus), sõltub mitmest faktorist. Arvutuskeemia abil on võimalik uurida osakeste struktuuri lahuses ning hinnata geomeetrilist osakeste kokkusobivust ja seondumise efektiivsust.
Doktoritöös uuriti COSMO-RS arvutusliku meetodi rakendamisvõimalusi retseptor-anioon seondumise uurimiseks. Töö tulemusena leiti, et arvutuslikult hinnatud retseptorite seondumistugevus on märgatavalt ülehinnatud, aga meetodi abil on võimalik hinnata retseptorite kasutatavust ning vaadelda retseptor-anioon seondumise geomeetrilisi aspekte.
Retseptorite uurimisel on oluline osa ka eksperimentidel. Mikrokalorimeetriga läbi viidud isotermiline kalorimeetriline tiitrimine (reaktsiooni soojusefektide uurimine konstantsel temperatuuril tehtud tiitrimiseksperimendi kaudu) on meetodina laialdaselt kasutatud kõrge seondumistugevusega reaktsioonide uurimiseks. Selleks, et rakendada meetodit anioon-retseptor seondumise uurimiseks, mis tüüpiliselt on võrdlemisi madala seondumistugevusega, oleks vajalik meetodi kasutatavuse uurimine tema rakendusala piiri lähedal ning eksperimendi planeerimise ja läbiviimise tingimuste optimeerimine ning saadud tulemuste mõõtmistäpsuse (mõõtemääramatuse) hinnangu leidmine. Töö tulemusena leiti, et uuritud mikrokalorimeetria eksperimente saab kasutada nõrgalt seonduvate süsteemide reaktsiooniparameetrite hindamiseks ning eksperimentaalselt leitud reaktsioonientalpia hinnangu liitstandardmääramatus jääb vahemikku 1-2 kJ/mol.
Anion-receptor chemistry – using suitable receptor molecules to determine the existence or quantity of specific anions from solution environment- is a rapidly developing field of research. As the synthesis and experimental characterization of new receptor molecules is a time-consuming task, it would be useful to be able to predict the characteristics of a new molecule prior to synthesis. The efficiency (binding affinity) of receptor and anion binding depends on multiple simultaneous intramolecular interactions. Computational chemistry allows to study the structure of the chemical species in a solvent environment and estimate the spatial compatibility of the host and guest and the efficiency of binding. The doctoral study investigated the applicability of the COSMO-RS method for studying and characterization of receptor molecule and anion binding. The study found that while computational predictions for absolute values of binding affinities are overestimated by COSMO-RS, the method allows to study the usability of receptor molecules and to investigate geometric aspects of binding. In the study of receptor molecules, experimental characterization of binding is also important. Applications of microcalorimetry for isothermal titration calorimetry (ITC) experiments are commonly used for studying systems with a high binding affinity. Before the method can be applied to study anion-receptor binding – systems that typically exhibit quite low binding affinities – the method should be validated for use near the instrumental limits of application, and the measurement uncertainty should be estimated. The study determined that low volume microcalorimetry can be used to study systems of low binding affinity and the reaction enthalpy can be experimentally determined with a combined standard measurement uncertainty in the range of 1-2 kJ/mol.
Anion-receptor chemistry – using suitable receptor molecules to determine the existence or quantity of specific anions from solution environment- is a rapidly developing field of research. As the synthesis and experimental characterization of new receptor molecules is a time-consuming task, it would be useful to be able to predict the characteristics of a new molecule prior to synthesis. The efficiency (binding affinity) of receptor and anion binding depends on multiple simultaneous intramolecular interactions. Computational chemistry allows to study the structure of the chemical species in a solvent environment and estimate the spatial compatibility of the host and guest and the efficiency of binding. The doctoral study investigated the applicability of the COSMO-RS method for studying and characterization of receptor molecule and anion binding. The study found that while computational predictions for absolute values of binding affinities are overestimated by COSMO-RS, the method allows to study the usability of receptor molecules and to investigate geometric aspects of binding. In the study of receptor molecules, experimental characterization of binding is also important. Applications of microcalorimetry for isothermal titration calorimetry (ITC) experiments are commonly used for studying systems with a high binding affinity. Before the method can be applied to study anion-receptor binding – systems that typically exhibit quite low binding affinities – the method should be validated for use near the instrumental limits of application, and the measurement uncertainty should be estimated. The study determined that low volume microcalorimetry can be used to study systems of low binding affinity and the reaction enthalpy can be experimentally determined with a combined standard measurement uncertainty in the range of 1-2 kJ/mol.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
supramolecular chemistry, computational chemistry, anions, receptors, host-guest compounds