There has been a recent rapid growth in the development of chemical sensors because of the demand for simple analytical techniques that can provide continuous monitoring of analytes in a variety of matrices. [1][2][3] In the area of membrane-based ion-selective electrodes (ISEs), special emphasis has been placed on the composition of the membrane phase and on the development of new ionophores, aiming at enhancing the potentiometric response characteristics (e.g., selectivity, sensitivity, linear range and lifetime) of the ISEs.The majority of cation-selective electrodes are based on neutral carrier ionophores. In particular, the antibiotic valinomycin has proved to be an excellent ionophore in potassium-selective liquid-polymeric membrane electrodes. 4 In addition to valinomycin, several other ionophores have been used in the preparation of potassium ISEs. 5-8 Among these, bis(crown ethers) with two 15-crown-5 ethers attached via a bridge [7][8][9][10] exhibit a favorable potassium binding over sodium due to the formation of sandwich-type complexes with potassium.9,10 The observed selectivities of ISEs prepared with bis(15-crown-5 ethers) are sometimes comparable to those obtained by using valinomycin as the ionophore. 5Bis(crown ethers) can be prepared with functional groups that allow their covalent attachment on polymer matrices. This is an advantage when designing ISEs with extended lifetimes because covalent attachment of the ionophore precludes its leaching from the polymer membrane phase to the aqueous phase. 11-13 Direct attachment of a bis(crown ether) to a polymer backbone, however, may restrict the free movement of the ionophore or pose serious steric problems with the backbone of the polymer, which could lead to worsening of the response.7,14 A long flexible chain connecting the bis(crown ether) and the polymer could provide a solution to this problem. In this paper, we report on the synthesis and evaluation of a new bis(crown ether) (BCE) ionophore with a long and flexible side chain, which can serve as a precursor for the chemical immobilization to a polymer backbone. Another feature of the designed ionophore is the incorporation of a conformationally constrained bridge (an isophthalic acid derivative) between the two crown ether moieties. This isophthalic acid derivative allows each of the crown ether macrocycles to be in a parallel alignment with each other during complexation, which helps maximize their interaction with the analyte ion. ExperimentalReagents 5-Nitroisophthalic acid, 4-nitrobenzo-15-crown-5, 10% Pd/C, 97% thionyl chloride, triethylamine, aluminum oxide (neutral, Brockmann I), and stearoyl chloride were all obtained from Aldrich (Milwaukee, WI). Selectophore-grade tetrahydrofuran (THF), 2-nitrophenyloctyl ether (NPOE), tris(2-ethylhexyl)phosphate (TOP), bis(2-ethylhexyl) sebacate (DOS), bis(1- A new bis(crown ether) ionophore containing two benzo-15-crown-5 moieties connected with each other via a conformationally constrained bridge attached to a C18-lipophilic side chain was desig...