Effect of phenyltin compounds on lipid bilayer organization

Phenyltin compounds are known to be biologically active. Their chemical structure suggests that they are likely to interact with the lipid fraction of cell membranes. Using fluorescence and NMR techniques, the effect of phenyltin compounds on selected regions of model lipid bilayers formed from phosphatidylcholine was studied. The polarization of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) dipalmitoyl-L -phosphatidylethanolamine and desorption of praseodymium ions was used to probe the polar region, whereas the polarization of 1 - (4 - trimethylammoniumphenyl) - 6 - phenyl - 1,3,5-hexatriene p-toluenesulfonate measured the hydrophobic core of the membrane. In addition, changes in the N-(5-fluoresceinthiocarbanoly)dipalmitoyl - L - α - phosphatidyl - ethanolamine fluorescence intensity indicated the amount of charge introduced by organotin compounds to the membrane surface. There were no relevant changes of measured parameters when tetraphenyltin was introduced to the vesicle suspension. Diphenyltin chloride causes changes of the hydrophobic region, whereas the triphenyltin chloride seems to adsorb in the headgroup region of the lipid bilayer. When the hemolytic activity of phenyltin compounds was measured, triphenyltin chloride was the most effective whereas diphenyltin chloride was much less effective. Tetraphenyltin causes little damage. Based on the presented data, a correlation between activity of those compounds to hemolysis (and toxicity) and the location of the compound within the lipid bilayer could be proposed. In order to inflict damage on the plasma membrane, the compound has to penetrate the lipid bilayer. Tetraphenyltin does not partition into the lipid fraction; therefore its destructive effect is negligible. The partition of the compound into the lipid phase is not sufficient enough, by itself, to change the structure of the lipid bilayer to a biologically relevant degree. The hemolytic potency seems to be dependent on the location of the compound within the lipid bilayer. Triphenyltin chloride which adsorbs on the surface of the membrane, causes a high level of hemolysis, whereas diphenyltin chloride, which penetrates much deeper, seems to have only limited potency. © 1998 John Wiley & Sons, Ltd.     

Direct or indirect influence of triphenyl‐lead on activity of Na+/K+‐ATPase

We have studied the effect of triphenyl‐lead chloride on the lipid phase of erythrocyte membranes, on lipid monomolecular layers and Na⁺/K⁺‐ATPase of the microsomal fraction of rat brain. It was found that the haemolytic effect induced by this compound occurs when its concentration exceeds 30 µM . The minimal lead concentration inducing measurable effects in monomolecular lecithin layers is about 1 µM . Inhibition of Na⁺/K⁺‐ATPase activity begins at a concentration exceeding 0.5 µM . Maximum inhibition is observed at around 40 µM —a concentration at which haemolysis also occurs. It can thus be thought that at very low lead concentrations the main (or exclusive) role in modifying membrane function is played by direct interaction between lead and the sulphydryl groups of ATPase, whereas at higher concentrations two effects seem to overlap: direct interaction between lead and enzymic proteins via their sulphydryl groups and as indirect influence on the proteins via changes in the organization of the lipid phase of the membrane. Copyright © 2000 John Wiley & Sons, Ltd.     

Fluorinated tertiary alkoxides of some lanthanides: tris-trifluorotertiarybutoxides of lanthanum, praseodymium and europium

From reactions involving M{N(SiMe₃)₂}₃ (M = La, Pr and Eu) and triflurotertiary butano[(CF₃)Me₂COH; tftb.H], the compounds [La(tftb)₃(thf)_1.5] (1), [Pr(tftb)₃ (2) and [Eu(tftb)₃] (3) have been isolated. From variable temperature ¹H and ¹⁹F NMR studies it is suggested that 1 is a mixture of [La₃(tftb)₉(thf)₂] (1a) and [La₂(tftb)₆(thf)₄] (1b). X-ray crystallography has shown that 2 is the trimer [Pr₃(tftb)₉] and variable temperature ¹H and ¹⁹F NMR suggests that 3 is also a trimer, [Eu₃(tftb)₉].     

Protection of Erythrocytes Against Organometals-Induced Hemolysis

The hemolytic toxicity of tributyllead (TBL) and triphenyllead (TPhL) chlorides and its prevention by dithiotreitol (DTT), diethylenetriaminepentamethylenephosphonic acid pentasodium (PMP) and sodium disulfide (Na2S) was studied. It was found that both TBL and TPhL efficiently hemolyzed pig erythrocytes when used in micromolar concentrations; tributyllead chloride being about twice more efficient than triphenyllead chloride. The hemolytic efficiency of these compounds was blocked by PMP, DTT and Na2S in a concentration-dependent manner. However, significant differences in anti-hemolytic efficiency of these compounds were found. Namely, DTT and Na2S were very efficiently protecting erythrocytes against the action of organoleads, while the PMP protection was weak. Also, differences between DTT and Na2S protective efficiency were found. They more efficiently prevented erythrocyte hemolysis by TPhL than by TBL. Moreover, erythrocytes were better protected against the action of TBL by Na2S than by DTT. Such differentiation may be connected with possible differences in localization of the organolead compounds and protective agents in the erythrocyte membrane. To check these possibilities a series of experiments was performed using the fluorescence technique and various fluorimetric probes. These measurements enabled to determine fluidity changes induced in erythrocyte membranes by the organoleads and the protective compounds and to formulate some remarks concerning the differences in the mechanism of interaction of the organoleads with these membranes.     

Genetic and Random Search Methods in Optimal Shape Design Problems

We describe the application of two global optimization methods, namely of genetic and random search type algorithms in shape optimization. When the so-called fictitious domain approaches are used for the numerical realization of state problems, the resulting minimized function is non-differentiable and stair-wise, in general. Such complicated behaviour excludes the use of classical local methods. Specific modifications of the above-mentioned global methods for our class of problems are described. Numerical results of several model examples computed by different variants of genetic and random search type algorithms are discussed.     

The conformation of t-butyl 2-methoxy-5, 6-dihydro-2 H-pyran-6-carboxylates and 6,6′- disubstituted 2-methoxy-5,6-dihydro-2H-pyran derivatives on the basis of 1H and 13 C NMR spectra

The ¹H and ¹³C NMR spectra of trans- and cis-tert-butyl 2-methoxy-5,6-dihydro-2H-pyran-6-carboxylates (1 and 2) and 6,6′-disubstituted 2-methoxy-5,6-dihydro-2H-pyrans (3-7) have been recorded. HH and CH coupling constants are discussed in terms of the ¹H₆?⁶H₁ conformational equilibrium. It has been found that 1 occurs exclusively in the ¹H₆ conformation, whereas its cis isomer, 2, exists in an equilibrium of both half-chair forms. 6,6′-Disubstituted 2-methoxy-5,6-dihydro-2H-pyrans 3-6 display spectral and conformational behaviour similar to that of 1, whereas 7 resembles 2 in this respect.