The water activity in dimyristoylphosphatidylcholine (DMPC) decreases by 60% when the lipid is dehydrated in the presence of trehalose concentrations higher than 0.02 M. In contrast, sucrose in concentrations 10 times higher produced only a 20% decrease in the water activity in the sample. Titrations of a DMPC solution in chloroform yielded 14 water molecules per lipid when pure water was added and seven water molecules per lipid when the titration was done with 0.025 M trehalose. The same concentrations of sucrose produced a turbid solution, which made it impossible to quantify the number of water molecules per lipid. Lipid monolayers spread on an air/water interface showed a decrease from 480 mV in pure water to 425 mV in 0.1 M trehalose. However, the same concentrations of sucrose produced an increase of less than 100 mV. Results obtained with Fourier transform infrared spectroscopy (FTIR) under the same conditions denoted that trehalose binds to the carbonyl groups, while sucrose showed no specific binding. It is concluded that per lipid molecule, 11 of 14 water molecules can be replaced by three trehalose molecules. About four are displaced by changes in the water activity of the bulk solution, and seven by specific interactions with the phospholipids. In this last case, at least two of them are linked to the carbonyls, and this appears to be the cause of the decrease in the dipole potential of the membrane. In contrast, four sucrose molecules displace only three water molecules per lipid, with no effect on the dipole potential or the carbonyl groups.

The interactions of the cryoprotective agent trehalose with a lipid membrane made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine at 323 K were studied by means of molecular dynamics simulations. It was observed that trehalose binds to the phospholipid headgroups with its main axis parallel to the membrane normal. Trehalose establishes hydrogen bonds with the carbonyl and phosphate groups and replaces water molecules from the lipid headgroup. Notably, the number of hydrogen bonds (HBs) that the membrane made with its environment was conserved after trehalose binding. The HBs between lipid and trehalose have a longer lifetime than those established between lipid and water. The binding of the sugar does not produce changes either in the lipid area or in the lipid order parameter. The effect of trehalose on the dipole potential is in agreement with experimental results. The contribution of the different components to the membrane dipole potential was analyzed. It was observed that the binding of trehalose produces changes in the different components and the sugar itself contributes to the surface potential due to the polarization of its hydroxyl in the interface.

The synthesis and chemical characterization of three new transplatinum complexes of structural formula trans-[PtCl(2)(amine)(isopropylamine)] (amine = n,n-dimethylamine, propylamine, and butylamine), 1-3, are described. Cytotoxicity tests in tumor cell lines sensitive to cis-DDP (Jurkat, Hela, and Vero) and also in tumor cell lines overexpressing ras oncogenes and resistant to cis-DDP (HL-60 and Pam 212-ras) show that complexes 1 and 3 have higher cytotoxic activity than cisplatin. Moreover, these two trans-Pt(II) complexes kill Pam 212-ras cells through apoptosis induction. These results suggest that trans-PtCl(2) complexes with asymmetric aliphatic amines may be considered a new class of biologically active trans-platinum drugs.

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Phloretin, a molecule which is known to decrease the dipole potential of lipid membranes, has a little effect on the CdO frequencies of dimyristoylphosphatidylcholine bilayers (DMPC) in comparison to that observed on the phosphates. In the first case, the frequency is displaced very slightly to higher values, while a pronounced downward shift is observed on the asymmetric vibration frequencies of the phosphates. The effect of phloretin on the phosphate groups is correlated with a decrease in the monolayer potential of DMPC in the gel and in the liquid crystalline state. From the comparison with monolayers spread on water and on 0.15 M trehalose, it is concluded that the PdO bonds of the phosphates can contribute to the dipole potential of the membrane in addition to the contribution given by the orientation of the -P-N + dipole.

Interactions of L-cysteine ethyl ester hydrochloride (CE), a bioactive cysteine derivative, with dipalmitoylphosphatidylcholine (DPPC) were investigated. To gain a deeper insight into analyzing L-cysteine ethyl ester HCl interaction with liposomes of DPPC in anhydrous and hydrated states, we performed experimental studies by infrared (Fourier transform infrared spectroscopy) and Raman spectroscopies. The results revealed that the interaction of CE with the phospholipid head groups was the same in absence or presence of water. In both states, the wavenumber of the PO 2 À group and C-N bond of the choline group decreased. This behavior can be ascribed to the replacement of hydration water and binding to the phosphate group. In the Raman spectrum results for the anhydrous and gel states, the S-H stretching band of the CE shifted to lower frequencies with a decrease in its force constant. Biologically active lipophilic molecules such as CE should be studied in terms of their interaction with lipid bilayers prior to the development of advanced lipid carrier systems such as liposomes. The results of these studies provide information on membrane integrity and physicochemical properties that are essential for the rational design of lipidic drug delivery systems.

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