ANALYTICAL SCIENCES FEBRUARY 1998, VOL. 14 169 1998 © The Japan Society for Analytical Chemistry Synthesis and Evaluation of a Bis(crown ether) Ionophore with a Conformationally Constrained Bridge in Ion-Selective Electrodes Zhiren XIA, Ibrahim H. A. BADR, Shawn L. PLUMMER, Lawrence CULLEN, and Leonidas G. BACHAS† Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA 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 designed and synthesized. The bridge consisted of an isophthalic acid derivative, which was selected in order to enhance potassium over sodium binding. Liquid-polymeric membrane ion-selective electrodes (ISEs) based on this ionophore were prepared using different plasticizers and mole ratios of lipophilic ionic additives. Membrane electrodes with optimum composition (using o- nitrophenyloctyl ether or bis(1-butylpentyl)adipate as plasticizer and 60 mol% lipophilic borate additive) show Nernstian responses toward potassium (57 and 58 mV/decade, respectively) over a wide concentration range with a micromolar pot × –4 detection limit. These ISEs exhibit enhanced potassium over sodium selectivity (KK+,Na+=6 10 ). In addition, the + + electrodes show selectivities for potassium over Cs and NH4 that are better than those of valinomycin-based ISEs. Keywords Ion-selective electrode, cation sensor, bis(crown ether), neutral carrier, liquid-polymeric membrane, lipophilic salt There has been a recent rapid growth in the develop- the ionophore precludes its leaching from the polymer ment of chemical sensors because of the demand for membrane phase to the aqueous phase.11–13 Direct simple analytical techniques that can provide continu- attachment of a bis(crown ether) to a polymer back- ous monitoring of analytes in a variety of matrices.1–3 bone, however, may restrict the free movement of the In the area of membrane-based ion-selective electrodes ionophore or pose serious steric problems with the (ISEs), special emphasis has been placed on the com- backbone of the polymer, which could lead to worsen- position of the membrane phase and on the develop- ing of the response.7,14 A long flexible chain connect- ment of new ionophores, aiming at enhancing the ing the bis(crown ether) and the polymer could provide potentiometric response characteristics (e.g., selectivity, a solution to this problem. In this paper, we report on sensitivity, linear range and lifetime) of the ISEs. the synthesis and evaluation of a new bis(crown ether) The majority of cation-selective electrodes are based (BCE) ionophore with a long and flexible side chain, on neutral carrier ionophores. In particular, the anti- which can serve as a precursor for the chemical immo- biotic valinomycin has proved to be an excellent bilization to a polymer backbone. Another feature of ionophore in potassium-selective liquid-polymeric the designed ionophore is the incorporation of a confor- membrane electrodes.4 In addition to valinomycin, sev- mationally constrained bridge (an isophthalic acid eral other ionophores have been used in the preparation derivative) between the two crown ether moieties. This of potassium ISEs.5–8 Among these, bis(crown ethers) isophthalic acid derivative allows each of the crown with two 15-crown-5 ethers attached via a bridge7–10 ether macrocycles to be in a parallel alignment with exhibit a favorable potassium binding over sodium due each other during complexation, which helps maximize to the formation of sandwich-type complexes with their interaction with the analyte ion. potassium.9,10 The observed selectivities of ISEs pre- pared with bis(15-crown-5 ethers) are sometimes com- parable to those obtained by using valinomycin as the Experimental ionophore.5 Bis(crown ethers) can be prepared with functional Reagents groups that allow their covalent attachment on polymer 5-Nitroisophthalic acid, 4-nitrobenzo-15-crown-5, matrices. This is an advantage when designing ISEs 10% Pd/C, 97% thionyl chloride, triethylamine, alu- with extended lifetimes because covalent attachment of minum oxide (neutral, Brockmann I), and stearoyl chloride were all obtained from Aldrich (Milwaukee, † To whom correspondence should be addressed. WI). Selectophore-grade tetrahydrofuran (THF), 2- I. H.A.B.: On leave from the Department of Chemistry, Faculty nitrophenyloctyl ether (NPOE), tris(2-ethylhexyl)phos- of Science, Ain-Shams University, Cairo, Egypt. phate (TOP), bis(2-ethylhexyl) sebacate (DOS), bis(1- 170 ANALYTICAL SCIENCES FEBRUARY 1998, VOL. 14 butylpentyl) adipate (BBPA), poly(vinyl chloride) meric membrane electrodes were calculated by using (PVC), and potassium tetrakis(4-chlorophenyl)borate the matched-potential method at 2.5×10–6 M of the pri- (KTCPB) were obtained from Fluka (Ronkonkoma, mary ion concentration.15 NY). Dichloromethane, pyridine, and dimethylform- amide (DMF) were freshly distilled from bulk solvents. Synthesis of the ionophore All metal ion salts used were of analytical grade. A 16- 5-Nitroisophthaloyl chloride. An amount of 0.3039 MΩ deionized distilled water was used for the prepara- g (2.9 mmol) of 5-nitroisophthalic acid was mixed with tion of solutions. 25 ml of thionyl chloride and allowed to reflux to yield 0.35 g of 5-nitroisophthaloyl chloride (~100% yield) Apparatus that was confirmed by 1H-NMR by comparison to liter- Cell potentials were measured using a Macintosh ature data.16 Quadra 700 equipped with a MacADIOS ABO ana- 4-Aminobenzo-15-crown-5. Closely following the log/digital input/output board (GW Instruments, procedure described by Ungaro et al.17, 1 g (3.2 mmol) Somerville, MA) and a custom-built electrode interface of 4-nitrobenzo-15-crown-5 was dissolved in 50 ml of module controlled by SuperScope II software (GW anhydrous DMF. An amount of 0.10 g of 10% Pd/C Instruments). A Parr hydrogenator was used for the was then added under nitrogen. The reagents were hydrogenation reactions. allowed to react within a Parr hydrogenator under a hydrogen pressure of 30 psi to yield 0.83 g of light Membranes and cell assembly brown, viscous liquid (93% yield). The synthesis of 4- The membranes were prepared by dissolving 1 – 2 aminobenzo-15-crown-5 was confirmed by 1H-NMR. mg of bis(crown ether) (BCE; ionophore 2, Fig. 1), 33 Nitro-bis(15-crown-5 ether). 4-Aminobenzo-15- mg of PVC, varied amounts of KTCPB, and 66 mg of crown-5 (838 mg, 2.9 mmol) was dissolved in 40 ml of plasticizer in 800 µl of THF. The mixture was shaken dichloromethane (anhydrous) with one equivalent of until all components were dissolved. Then, the result- pyridine and transferred to a stirred flask under a nitro- ing homogenous solution was poured into a 16-mm gen atmosphere. Using another 50 ml of solvent, 5- glass ring sitting on a glass slide, and the solvent was nitroisophthaloyl chloride (358 mg, 2.9 mmol) was dis- allowed to evaporate at room temperature. The result- solved and kept under nitrogen. This solution was ing membrane was cut into disks with a 7-mm i.d. cork added dropwise to the reaction flask over a 1-h period. porer. A single disk was mounted on the tip of a The reaction was allowed to continue for another 5 h. Philips electrode body (Philips IS-561; Glasblaserei The product was precipitated by methanol, filtered, and Möller, Zurich). The potentiometric measurements washed first with methanol and then with chloroform. were conducted using the following setup: The product was dried in a phosphorus pentoxide desic- cator under reduced pressure for a period of one day. Ag/AgCl0.10 M lithium acetatesample solution The yield was 700 mg (85%) and the m.p. was 350 – ISE-membrane0.10 M KClAgCl/Ag 352˚C. 1H-NMR (200 MHz, DMSO): δ 3.2 – 4.1 (m, 32H), 6.95 (d, 2H), 7.80 (d, 2H), 7.95 (s, 2H), 8.92 (s, All measurements of potentials were made in beakers 2H), 8.95 (s, 1H), 10.6 (s, 2H). EI-mass spectrum: that were thermostated at 25˚C. Standard potassium molecular ion peak (741). FAB-mass spectrum: chloride solutions and the other cation solutions used M+(741), MH+(742), MNa+(764), MK+(780). for the calibration plots were obtained by serial dilution Amino-bis(15-crown-5 ether). An amount of 300 mg of 1.0 M chloride salt solutions (lithium standards were (0.40 mmol) of nitro-bis(15-crown-5 ether) was dis- made from lithium acetate). The activities of the ions solved in 50 ml of anhydrous DMF. Then, 75 mg of were calculated using the Debye–Hückel equation. 10% Pd/C was added to this solution. The nitro-bis(15- Selectivity coefficients for the BCE-based liquid poly- crown-5 ether) was hydrogenated in a Parr hydrogena- tor (25 psi) overnight. The solid catalyst was then fil- tered out, and the solvent was evaporated. The product was taken up in enough anhydrous DMF to yield a clear, golden solution, that was treated with MgSO4 and filtered. The filtrate was left under nitrogen over 4 Å molecular sieves for a week. After filtering off the sieves, the solvent was eliminated using a rotary evapo- rator. The remaining brown residue was taken up in 70 ml of anhydrous chloroform and filtered through a celite layer in a Buchner funnel. The solvent was then eliminated in a rotary evaporator yielding 184 mg of dry product (compound 1, Fig. 1). 1H-NMR (200 MHz, Fig. 1 Structure of the bis(crown ether) ionophore 2 (R= DMSO): δ 3.2 – 4.1 (m, 32H), 6.85 – 7.98 (m, 11H), CO(CH2)16CH3) prepared from the corresponding amino- 10.2 (s, 2H). EI-mass spectrum: molecular ion peak bis(15-crown-5 ether) 1 (R=H).