Kazimierz Łątka

Interactions of Alkylphosphocholines with Model Membranes—The Langmuir Monolayer Study

Alkylphosphocholines (APCs) belong to a class of synthetic antitumor lipids, which are new-generation anticancer agents. In contrast to traditional antitumor drugs, they do not attack the cell nucleus but, rather, the cellular membrane; however, their mechanism of action is not fully understood. This work compared the interactions of selected APCs [namely, hexadecylphosphocholine (miltefosine), octadecylphosphocholine and erucylphosphocholine] with the most important membrane lipids [cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)] and examined their influence on a model membrane of tumor and normal cells. As a simple model of membranes, Langmuir monolayers prepared by mixing cholesterol either with a saturated phosphatidylcholine (DPPC), for a normal cell membrane, or with an unsaturated one (POPC), for a tumor cell membrane, have been applied. The APC–lipid interactions, based on experimental surface pressure (π) versus mean molecular area (A) isotherms, were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with the ΔGexc function). Strong attractive interactions were observed for mixtures of APCs with cholesterol, contrary to the investigated phosphatidylcholines, for which the interactions were found to be weak with a tendency to separation of film components. In ternary monolayers it has been found that the investigated model systems (cholesterol/DPPC/APC vs cholesterol/POPC/APC) differ significantly as regards the interactions between film-forming molecules. The results demonstrate stronger interactions between the components of cholesterol/POPC/APC monolayers compared to cholesterol/POPC film, mimicking tumor cell membranes. In contrast, the interactions in cholesterol/DPPC/APC films were found to be weaker than those in the cholesterol/DPPC system, serving as a model of healthy cell membranes, thus proving that the incorporation of APCs is, from a thermodynamic point of view, unfavorable for binary cholesterol/DPPC monolayers. It can be concluded that the composition of healthy cell membranes is a natural barrier preventing the incorporation of APCs into normal cells.

Structure, Chemical Bonding and 119Sn Mössbauer Spectroscopy of LaRhSn and CeRhSn

The rare earth (RE) stannides LaRhSn and CeRhSn were prepared from the elements by arcmelting or by reactions in sealed tantalum tubes in a high-frequency furnace. The structures have been refined from X-ray single crystal diffractometer data: ZrNiAl type, P6̅2̅m, a = 748.74(5), c = 422.16(3) pm, wR2 = 0.0307, 310 F2 values for LaRhSn and a = 745.8(1), c = 408.62(9) pm, wR2 = 0.0397, 354 F2 values for CeRhSn with 14 variables per refinement. The structures contain two crystallographically different rhodium sites which both have a tricapped trigonal prismatic coordination: [Rh1Sn3RE6] and [Rh2Sn6RE3]. Together the rhodium and tin atoms (280 - 288 pm Rh-Sn distances in LaRhSn and 277 - 285 pm in CeRhSn) build up three-dimensional [RhSn] networks in which the rare earth atoms fill distorted hexagonal channels. DFT band structure calculations reveal a large cerium 4 f contribution at the Fermi level and a strong mixing of cerium 5d/4 f with rhodium 4d orbitals. These results are in agreement with the short Ce-Rh bonds (304 and 309 pm) and also with the electronic and magnetic properties. 119Sn Mössbauer spectra of LaRhSn and CeRhSn show a single tin site at isomer shifts of δ = 1.98(2) (LaRhSn) and 1.79(1) mm/s (CeRhSn) subject to quadrupole splitting of Δ EQ = 0.79(4) (LaRhSn) and 1.12(3) mm/s (CeRhSn). The 1.8 K data show no transferred hyperfine field at the tin site for CeRhSn.

Electronic and Magnetic Properties of Ternary Stannides RERhSn (RE = Tb, Dy and Ho)

The results of magnetic studies and Mössbauer investigations made with 119Sn source are reviewed for the series of RERhSn (RE = Tb, Dy and Ho) compounds crystallizing in the same hexagonal ZrNiAl-type of structure. The role of crystalline electric field effects in the establishing of magnetic moment orientations observed in these compounds and their influence on the observed magnitudes of magnetic moments are discussed.

Thermodynamic Properties of RZnSn2 (R = Y, Er, Lu) Compounds with HfCuSi2 Structure Type

The results of magnetic and specific heat studies are reviewed and discussed for the series of RZnSn2 (R = Y, Er and Lu) compounds crystallizing in the same tetragonal HfCuSi2 - type of structure. A sharp peak in the specific heat of ErZnSn2 compound is indicative for magnetic ordering of Er moments at 5.0 K, being in agreement with its established antiferromagnetic nature. The estimated magnetic entropy Smagn contribution is less than that expected for the ground state J = 15/2 multiplet of Er3+.

Magnetism of ErAgSn studied by 119Sn Mössbauer spectroscopy

Antiferromagnetic ErAgSn compound was investigated in detail by 119Sn Mössbauer spectroscopy in a temperature range between 2.2 and 300 K. The 119Sn spectra recorded below 4.2 K can be well fitted with a single main magnetic component in agreement with recent neutron diffraction studies [1]. A broad distribution of magnetic hyperfine fields observed above 4.2 K and enhanced spin correlations among Er3+ ions at T > TN = 5.6 K are the remarkable features of the investigated system.

59Co nuclear magnetic resonance study in GdCo2Si2 compound

The spin echo NMR spectra of59Co for GdCo2Si2 are reported. A weak negative hyperfine field on Co nuclei was found in magnetically ordered state of the compound. The splitting of resonance lines in external magnetic field indicates on antiferromagnetic structure of Gd moments lying in thea-a plane with energetic minima in [100] and [110] directions as in GdFe2Si2 and GdNi2Si2.

Analysis of heat capacity and Mössbauer data for LuZnSn2 compound

Abstract New analysis of heat capacity data is presented for LuZnSn2 compound that takes into account anharmonic effects together with the existence of Einstein modes. 119mSn Mössbauer spectroscopy was used to monitor the hyperfine parameters at the two crystallographically inequivalent Sn sites in the studied compound. The problem of non-unique mathematical resonance spectrum description and the problem how to choose physically meaningful set of hyperfine parameters will be thoroughly discussed. Measured quadrupole interaction constants by 119mSn Mössbauer spectroscopy give estimations for Vzz component of electric field gradient tensor at both Sn sites in LuZnSn2.

Mössbauer and heat capacity studies of ErZnSn2

Abstract Heat capacity results obtained for the intermetallic compound ErZnSn2 were re-analysed to also consider, apart from the classical Debye model, the anharmonicity of the crystal lattice and the proper set of Einstein modes. The 119mSn Mössbauer technique was applied to derive the hyperfine interaction parameters characteristic of the two inequivalent crystallographic Sn sites in the compound studied. Quadrupole interaction constants, as measured by 119mSn Mössbauer spectroscopy, allowed for estimations of Vzz components of the electric field gradient tensor that exist at both Sn sites in the discussed compound.

The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer.

Abstract Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called ‘lipid rafts’, which play various biological roles, i.e., are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for selected drugs. For example alkylphosphocholines (APCs), which are new-generation antitumor agents characterized by high selectivity and broad spectrum of activity, are known to have their molecular targets located at cellular membrane and their selective accumulation in tumor cells has been hypothesized to be linked with the alternation of biophysical properties of lipid rafts. To get a deeper insight into this issue, interactions between representative APC: erucylphosphocholine, and artificial lipid raft system, modeled as Langmuir monolayer (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated. The Langmuir monolayer experiments, based on recording surface pressure-area isotherms, were complemented with Brewster angle microscopy results, which enabled direct visualization of the monolayers structure. In addition, the investigated monolayers were transferred onto solid supports and studied with AFM. The interactions between model raft system and erucylphosphocholine were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ΔGexc function). The obtained results indicate that erucylphosphocholine introduced to raft-mimicking model membrane causes fluidizing effect and weakens the interactions between cholesterol and sphingomyelin, which results in phase separation at high surface pressures. This leads to the redistribution of cholesterol molecules in model raft, which confirms the results observed in biological studies.