Rüütel Alo, Yrjänä Ville, Kadam Sandip A, Saar Indrek, Ilisson Mihkel, Darnell Astrid, Haav Kristjan, Haljasorg Tõiv, Toom Lauri, Bobacka Johan, Leito Ivo
Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia, https://analytical.chem.ut.ee.
Johan Gadolin Process Chemistry Centre, Laboratory of Molecular Science and Engineering, Åbo Akademi University, Biskopsgatan 8, FI-20500 Turku/Åbo, Finland.
Beilstein J Org Chem. 2020 Aug 4;16:1901-1914. doi: 10.3762/bjoc.16.157. eCollection 2020.
Carboxylate sensing solid-contact ion-selective electrodes (ISEs) were created to provide a proof-of-concept ISE development process covering all aspects from in silico ionophore design to functional sensor characterization. The biscarbazolylurea moiety was used to synthesize methylene-bridged macrocycles of different ring size aiming to fine tune selectivity towards different carboxylates. Cyclization was achieved with two separate strategies, using either amide synthesis to access up to -[CH]- macrocycles or acyl halides to access up to -[CH]- macrocycles. Seventy-five receptor-anion complexes were modelled and studied with COSMO-RS, in addition to all free host molecules. In order to predict initial selectivity towards carboxylates, H NMR relative titrations were used to quantify binding in DMSO- /HO solvent systems of two proportions - 99.5%:0.5% m/m and 90.0%:10.0% m/m, suggesting initial selectivity towards acetate. Three ionophores were selected for successful sensor prototype development and characterization. The constructed ion-selective electrodes showed higher selectivity towards benzoate than acetate, i.e., the selectivity patterns of the final sensors deviated from that predicted by the classic titration experiments. While the binding constants obtained by NMR titration in DMSO- /HO solvent systems provided important guidance for sensor development, the results obtained in this work emphasize the importance of evaluating the binding behavior of receptors in real sensor membranes.
为了提供一个从计算机辅助离子载体设计到功能传感器表征的概念验证型离子选择性电极（ISE）开发过程，创建了羧酸盐传感固体接触式离子选择性电极。使用双咔唑基脲部分合成了不同环大小的亚甲基桥连大环，旨在微调对不同羧酸盐的选择性。通过两种不同的策略实现环化，一种是使用酰胺合成法来制备多达 -[CH]- 的大环，另一种是使用酰卤来制备多达 -[CH]- 的大环。除了所有游离的主体分子外，还使用COSMO-RS对75种受体 - 阴离子配合物进行了建模和研究。为了预测对羧酸盐的初始选择性，使用1H NMR相对滴定法在两种比例的DMSO - /H2O溶剂体系（99.5%:0.5% m/m和90.0%:10.0% m/m）中定量结合，结果表明对乙酸盐具有初始选择性。选择了三种离子载体用于成功的传感器原型开发和表征。构建的离子选择性电极对苯甲酸盐的选择性高于乙酸盐，即最终传感器的选择性模式与经典滴定实验预测的不同。虽然在DMSO - /H2O溶剂体系中通过NMR滴定获得的结合常数为传感器开发提供了重要指导，但这项工作获得的结果强调了评估受体在实际传感膜中的结合行为的重要性。
