Lipophilic cations

Direct. Some radionucHdes are packaged in solution for direct sampling (qv) via a septum and injection into the patient. GalHum-67 is a marker of inflammation, infection, and various tumor types. Its half-life is 78.3 h and it is suppHed as the gallium citrate salt. Indium-111 chloride is suppHed for the labeling of white blood ceUs. The In chloride is mixed with oxine (9-hydroxyquinoline) to form a lipophilic, cationic In oxine complex, which enters the white blood ceU. The complex dissociates within the ceU, and the cationic In " ion is trapped within the ceU, owing to its charge. 

It is important to make the distinction between the multiphasic catalysis concept and transfer-assisted organometallic reactions or phase-transfer catalysis (PTC). In this latter approach, a catalytic amount of quaternary ammonium salt [Q] [X] is present in an aqueous phase. The catalyst s lipophilic cation [Q] transports the reactant s anion [Y] to the organic phase, as an ion-pair, and the chemical reaction occurs in the organic phase of the two-phase organic/aqueous mixture [2]. 

It seems that this anionic exchange would be relevant also to explain interactions of trialkyl tin (TAT) compounds (TET, tripropyltin chloride, TBT chloride) with the mitochondria. The current view of this phenomenon is that these compounds, by exploiting the Cl and OH gradient in energized mitochondria, behave as electroneutral OH /Cl exchangers. The crucial point of this new mechanism is that TATs enter the mitochondria as lipophilic cations [RsSn (rV)] and not as electroneutral compounds. The influx is followed by extrusion of the TAT compounds as electroneutral hydroxy compounds RsSnOH. ... 

Muratovska a., Lightowlers R. N., Taylor R.W., Turnbull D.M., Smith R.A. J., WiLCE J.A., Martin S.W., Murphy M.P. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res. 2001 29 1852-1863. 

Great interest in diphosphino complexes of technetium arose when Deutsch and co-workers found that lipophilic cations are able to be accumulated in heart tissue and can thus be candidates for myocardium perfusion agents [120]. Both the Tc(V) DMPE complex, [Tc02L2]+, and the [TcL2X2] + and [TcL3] + species in oxidation states +3 and +1 have been evaluated. Whereas the [Tc02L2] +... 

Fig. 4. Lipophilic-cationic( +1) myocardial perfusion imaging agents A) 99mTc-tetrofosmin R = -CH2CH,0CH,CH3 B), 9"Tc = sestamibi R=C=NCH,C (OCHJ (CH,), Q 99mTc-furifosmin R = -CH2CH2OCH2CH3...

Huet, S., Chapey, C., Robert, J., Reversal of multidrug resistance by a new lipophilic cationic molecule,... 

L neutral ligand C- charged chromo-ionophore R+ lipophilic cationic site X- analyte anion... 

FIGURE 4.6 Schematic view of the equilibria between sample, ion-selective membrane, and inner filling solution for three important classes of solvent polymeric ion-selective membranes. Top electrically neutral carrier (L) and lipophilic cation exchanger (R ) center charged carrier (L-) and anion exchanger (R+) and bottom cation exchanger (R-). 

The studies on phospholipid bilayers with defined amounts of charged component are helpful to explain the partition characteristics in biological membranes. Liposome water partition data of propranolol in lipids from kidney epithelial cells (a common model system in pharmaceutical sciences for the uptake into the gastrointestinal tract) have been successfully described with partition models developed for pure bilayers or defined mixtures [159]. Since lipophilic cations and anions can be used as probes for the membrane potential, their interaction with microbial and mitochondrial membranes has been studied... 

Complex 65 (Cardiolite), 99mTc(I)-sestamibi, is used for myocardial perfusion imaging. It was designed on the basis that lipophilic cationic complexes behave as potassium mimics and are taken up by the myocardium (281). The sequential metabolism of the six methoxy groups of 65 to hydroxyl groups in the liver leads to formation of 99mTc complexes with greater hydrophilicity which are not retained in myocardial tissues (282). 

Myoview 99mTc-tetrofosmin (67) is another clinically approved, lipophilic, cationic perfusion agent (286). The molecule contains trans-... 

In general, there are two immiscible phases in reaction mixture, viz. an aqueous phase which contains a salt (a base or nucleophile) and the other an organic phase containing the substrate which is expected to react with the salt. When a phase transfer catalyst (usually contains a lipophilic cation) is added to the reaction mixture, the lipophilic cation (which has solubility in both aqueous and organic phases), exchanges anions with the excess of anions in the salt solution. 

Smiley ST, Reers M, Mottola-Hartshom C, Lin M, Chen A, Smith TW, Steele GD Jr, Chen LB (1991) Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci USA 88 3671-3675... 

Filipovska A, Eccles MR, Smith RAJ, Murphy MP. Delivery of antisense peptide nucleic acids (PNAs) to the cytosol by disulphide conjugation to a lipophilic cation. FEES Lett 2004 556 180-186. 

A small amount of an anionic or cationic dye is added to an aqueous solution of the analyte, which is a lipophilic cationic or anionic compound. A small amount of coloured lipophilic ion pair is formed and this is extracted into a small amount of... 

This procedure is more widely used in pharmacopoeial assays than the dye extraction procedure. Excess potassium iodide is added to an aqueous solution of the analyte, which is a lipophilic cation. A lipophilic ion pair is formed between the cation and the iodide ion and is then removed by extraction into an organic phase such as chloroform. The excess iodide remaining in the aqueous phase is then titrated in concentrated HCl (> 4 M) with potassium iodate. The iodate oxidises iodide to E, which immediately reacts with Cl to give ICl resulting in the following equation ... 

Practically motivated, the aim was to develop methods for recovery and determination of amino acids in the context of analytical chemistry and biotechnology. Amino acids are hydrophilic compounds, which therefore are difficult targets for conventional solvent extraction. Extraction to an organic solvent may be enhanced by the addition of lipophilic cationic or anionic extractants, forming extractable complexes with amino acids, or by the use of macrocyclic compounds, which form stable hydrophobic host-guest complexes. The most popular reagents from the latter group are crown... 

Figure 8. Potentiometric responses to 5 -CMP (o) and 5 -AMP ( ) by PVC matrix liquid membranes (DOP/PVC = 2 1 wt/wt) containing (a) lipophilic cation 9 (3.1 wt%) and (b) lipophilic cation 9 (3.1 wt%) plus neutral cytosine derivative 10a (1.3 wt%) (150 mol% 9 relative to 10a). Measured at pH 6.8 (0.1 M HEPES-NaOH buffer) (adapted with permission from Anal. Chim. Acta 1997, 341, 134. Copyright 1997 Elsevier Science Ltd.).

The pH partition principle is a very general one, and should not be taken to imply that an ionic species will not undergo partitioning into a lipid membrane. It is probable that many highly lipophilic cations will form ion pairs with a physiological counterion such as chloride, and the ion pair will then partition into the membrane (Murthy and Zografi, 1970). 

Using both a carbocyanine dye and another lipophilic cation, triphenylmethyl-phosphonium, Seligmann and Galhn found defective changes in the membrane potential in PMNs from patients with chronic granulomatous disease in response to FMLP or PMA, In PMNs from patients with other disorders of function the responses were normal. The resting membrane potential, the response to valinomycin, (an ionophore for potassium) and the response to the ionophore for Ca, were all normal or only slightly impaired. 

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