ABSTRACT
A bicyclic peptide, cyclo (L-Glu(1)-D-Leu(2)-Aib(3)-L-Lys(4)-D-Leu(5)-D-Ala(6))-cyclo-(1gamma-4epsilon) (I), was designed and synthesized to provide an ammonium ion complexation site in a tetrahedral geometry. Molecular modeling, dynamics and electrostatic studies for I indicated that it exhibits some selectivity for ammonium ions over potassium and sodium ions. NMR measurements in CDCl(3)/CD(3)OD (1:1) show that for those carbonyl groups involved in cation binding, (13)C resonances shifted downfield with increasing cation concentration. The resonance that exhibited the largest change in chemical shift between uncomplexed and complexed forms was used to determine the selectivity. Selectivity values obtained were logK(NH(4) (+), Na(+) ) = - 2.4 and logK(NH(4) (+), K(+) ) = - 0.6.
Subject(s)
Magnetic Resonance Spectroscopy/methods , Peptides, Cyclic/chemistry , Quaternary Ammonium Compounds/chemistry , Carbon Isotopes , Computer Simulation , Ions/chemistry , Magnetic Resonance Spectroscopy/standards , Models, Chemical , Models, Molecular , Molecular Conformation , Peptides, Cyclic/chemical synthesis , Potassium/chemistry , Reference Standards , Reproducibility of Results , Sensitivity and Specificity , Sodium/chemistry , Solubility , Static ElectricityABSTRACT
The macrobicyclic molecule, 21-(9-anthrylmethyl)-4,17,13,16-tetraoxa-1,10,21-triazabicyclo [8.8.5]tricosane-19,23-dione, I, was designed, synthesized and characterized as a fluoroionophore for the selective, optical detection of lithium ions. Compound I is based on a bridged diazacrown structure, which provides a semirigid binding framework. Binding takes place by electrostatic interactions between the oxygen atoms of the crown and the cation and is transduced to fluorescence emission from an attached anthracene fluorophore. In a 75:25 dichloromethane/tetrahydrofuran solvent mixture, I acts as an intramolecular electron transfer "off-on" fluorescence switch, exhibiting a greater than 190-fold enhancement in fluorescence emission intensity in the presence of lithium ions. The relative selectivity of I for lithium ions over sodium, potassium and ammonium ions was found to be log K(Li+,Na+) approximately -3.36, log K(Li+,K+) approximately -1.77 and log K(Li+,NH4+) approximately -2.78.
Subject(s)
Lithium/analysis , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Indicators and Reagents , Ions , Models, Molecular , Spectrometry, FluorescenceABSTRACT
A modular technique was used to synthesize an ammonium-selective ionophore based on a cyclic depsipeptide structure. The ionophore was incorporated into a planar ion-selective electrode sensor format and the selectivity tested versus a range of metal cations in a commercial clinical diagnostic "point-of-care" instrument. Four sensor membrane formulations were tested, all of which consisted of plasticized PVC. Formulations differed as to the type of plasticizer used and whether an ionic additive was present. It was found that the membrane containing the polar plasticizer nitrophenyl octyl ether in the absence of ionic additive exhibited near-Nernstian behavior (slope, 60.1 mV/decade at 37 degrees C) and possessed high selectivity for ammonium ion over lithium and the divalent cations, calcium and magnesium (log K(POT)NH4+(j) = -7.3, -4.4, and -7.1 for lithium, calcium, and magnesium ions, respectively). The same membrane also exhibited sodium and potassium selectivity that was comparable to that reported for nonactin (log K(POT)NH4+(j) = -2.1 and -0.6 for sodium and potassium, respectively, compared to -2.4 and -0.9 in the case of nonactin). Membranes containing the less polar plasticizer, dioctyl phthalate, showed sub-Nernstian behavior (slope, <50 mV/decade at 37 degrees C). In all cases, the presence of the ionic additive potassium tetrakis(4-chlorophenyl)borate substantially reduced the selectivity observed. The flexible modular synthetic technique developed and reported here will allow the cyclic depsipeptide structure to be tuned for optimum selectivity.
