RESUMO
The stepwise synthesis of cone and partial cone 1,3-bridged n-propoxy-calix[4]crown ethers ("monomers" 2 and 3) with an electropolymerizable 2,2'-dithiophene-3-yl-hexylene functionality at the lower rim, is described. The potential of 2 and 3 as sensing agents for alkali metal ions was investigated by 1H NMR titration experiments with NaSCN and KSCN. The results obtained have confirmed that the presence of the heterocyclic subunit does not affect the well-known size-selectivity observed with calix[4]crowns. Monomers 2 and 3 were electropolymerized (Pt as a working electrode, CH2Cl2/CH3CN, Bu4NPF6) to produce the title chemically modified electrodes (CMEs). After coating with a PVC membrane containing a lipophylic cation exchanger, CMEs based on calix[4]-crown-5 2b (cone) and 3b (partial cone) were tested for the potentiometric recognition of alkali metal ions in aqueous solution. In agreement with NMR titration studies, a satisfactory potentiometric response in terms of K+/Na+ selectivity was obtained only with CME 2b (pK(K/Na) 1.51). The amperometric responses of PVC-uncoated CMEs were studied by cyclic voltammetry (CV) experiments in CH3CN solution. High Na- selectivity was found with the CME based on partial cone calix[4]crown-4 3a, and frequency response analysis (FRA) measurements support this finding.
RESUMO
Penta-O-alkylated p-tert-butylcalix[5]arenes 1-5 (R = benzyl, isohexyl, isopropoxyethyl, isopropoxycarbonylmethyl, and tert-butoxycarbonylmethyl, respectively) in a fixed C(5)(v) cone conformation have been studied as ionophores in liquid membrane ion-selective electrodes (ISEs) for n-butylammonium against the other branched butylammonium isomers, alkali metals, and ammonium ions, in terms of detection limits, sensitivity, and selectivity. The highest levels of potentiometric selectivity and detection limits up to 3 × 10(-)(6) M are observed with ISEs based on ionophore 2, where selectivity follows the order n-BuNH(3)(+) â« i-BuNH(3)(+) > s-BuNH(3)(+) > t-BuNH(3)(+). The lower potentiometric selectivity displayed by ISEs based on ionophores 3-5 is ascribed to their affinity for the Na(+) ion of the lipophilic salt present in the membrane, as evidenced by appropriate (1)H NMR competition experiments with Na(+) and n-BuNH(3)(+) ions. Further investigation on the selectivity mechanism of ionophore 2 by means of frequency response analysis shows that the interaction of the linear butylammonium ion with membranes containing 2 involves a lower resistance process than that occurring with the other branched isomers, thus suggesting the presence of a favorable kinetic-controlled mechanism.
RESUMO
A series of fluorinated alpha-keto acid derivatives [PhCHFCOCO2R,PhCH2CHFCOCO2R,PhCF2-COCO2R, and PhCH2CF2COCO2R (R = H, Me, and Et)] was synthesized. They were inhibitors of chymotrypsin, with Ki values ranging from 4700 to 15 microM. Benzylpyruvic derivatives were generally more potent than the corresponding phenylpyruvic analogs. Esters of the first series were also more potent than their corresponding acids, and potency increased with the number of fluorine atoms. By replacing the ethoxy group of PhCH2CF2COCO2Et (15b) with an amino acid chain (i.e., alanyl-leucyl-arginine methyl ester hydrochloride and alanyl-leucyl-valine ethyl ester), the resultant peptides PhCH2CF2COCO-Ala-Leu-Arg-OMe.HCl.H2O (20) and PhCH2CF2COCO-Ala-Leu-Val-OEt.H2O (23) were found to be slow-binding inhibitors of chymotrypsin with considerably lower Ki values (0.19 and 3.6 microM, respectively). 19F NMR studies indicate, in the case of 20, the presence of an enzyme-inhibitor complex with a hemiketal structure similar to those observed between trifluoromethyl ketones and chymotrypsin. The results illustrate that effective protease inhibitors can be designed by enhancing the electrophilic character of the reactive carbonyl group (with an electron-withdrawing group placed on each side of the carbonyl group). Their potency and/or selectivity can also be improved by taking advantage of binding interactions at S' subsites of the protease.
