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The inclusion of organic molecules to different calixarenes was investigated both experimentally and theoretically. Experimental data were obtained for various calixarenes of different thicknesses interacting with perchloroethylene, chloroform, benzene and toluene at different partial pressures and temperatures. The amount of included molecules was monitored by frequency responses of mass-sensitive bulk acoustic wave devices. To estimate ‘key-lock’ binding energies, the activation energy of desorption was determined experimentally from thermodesorption spectroscopy. The host/guest interaction energies were calculated theoretically with the TRIPOS force field approach which, in contrast to current quantum chemical approaches (MOPAC/AM1, MOPAC/PM3), gave satisfactory distance-dependent energy minima. Experimentally observed changes in the binding energies for the inclusion of C 2 Cl 4 , CHCl 3 , CH 3 C 5 H 6 and C 6 H 6 molecules in calixarenes agree surprisingly well with results with theoretical calculations.

Transient membrane holes induced by sodium cholate (Schubert et al., 1986, Biochemistry 25, 5263–5269) were used to encapsulate molecules at least up to M r = 70,000 into preformed liposomes. High trapping efficiencies (TE) close to 50% were achieved with concentrated suspensions of liposomes independent of their lamellarity, which was evaluated by cryomicroscopy of cryofixated suspensions. Another suitable hole-forming detergent is n -octyl β- d -glucopyranoside. Maximum trapping efficiency was measured within a narrow concentration range of added detergent below the onset of membrane solubilization. Using pure egg yolk lecithin (egg PC) or egg PC/bovine brain phosphatidylserine (7:3 mol/mol), trapping efficiency compared with the ratio of the volume inside the liposomes to the total aqueous volume in the samples. Therefore, it is probable that solutes that have been added to the external liposomal space diffuse into the liposomes, when the membranes are opened for several minutes. TE is slightly reduced by 30 mol% cholesterol in the membrane or if highly concentrated protein solutions (insulin or hemoglobin) or molecules with elongated form (polyuridylic acid) are to be encapsulated. An especially low TE into DPPC liposomes at 25°C is indicative of suppressed hole formation in the gel phase of the membrane. The residual amount of detergent after rechromatography of the loaded liposomes and liposome alterations are negligible. Detergent-induced liposome loading (DILL) is a convenient method for entrapping small molecules, larger carbohydrates, proteins, and nucleic acids into preformed liposomes with membranes in the liquid crystal phase. In addition, the ratio of calculated to found trapping efficiency of inulin is a suitable value for the mean lamellarity of vesicles up to a diameter of 200 nm.

The synthesis of azathia-analogues of the platelet activating factor containing a methioninol backbone is reported. The preparation starts with a cylating methionine ethyl ester-HCl with palmitoyl chloride to form the amide linkage. Following ester reduction the phosphocholine part is introduced via 2-chloro-2-oxo-1,3,2-dioxaphospholane and subsequent ring opening with trimethylamine under pressure. Two related compounds, the sulfoxide and the sulfone, are obtained by oxidation with 3-chloroperbencoic acid. In addition the sulfoxide derivative is prepared starting with d - and l -methionine ethyl ester-HCl.

Various S-substituted thiosuccinimides 1a-d and thiophthalimides 2a-d were found to react with trialkylphosphites according to a Michaelis-Arbuzov type mechanism. This provides an efficient way to prepare thiophosphoric acid esters, particularly thiophospholipids, with a C-S-P bond.

A new method for the determination of lipoxins with electrochemical detection after high-performance liquid chromatography is described. The half-wave potentials of lipoxin A 4 and lipoxin B 4 at a glassy carbon electrode and a mobile phase of methanol—water (65:35, v/v) and 1 m M trifluoroacetic acid was found to be +1.14 V versus an Ag/AgCl reference electrode. The use of trifluoroacetic acid instead of sulphuric acid and lithium perchlorate led to a background current of 6–8 nA at +1.20 V. The detection limits for both lipoxins, based on a signal-to-noise ratio of 3:1, were found to be 5–10 pg (15–30 fmol). The new method was applied to an extract of human polymorphonuclear granulocytes, preincubated with 15-hydroxyeicosatetraenoic acid and stimulated with Ca 2+ ionophore A23187.

Various drugs bearing a thiol or thione function were coupled with activated lipophilic thiol derivatives to afford unsymmetrical disulfides. Synthetic methods were developed to introduce one or two long alkyl chains into drug molecules in order to obtain highly lipophilic prodrugs. These might be suitable to form bilayers or for integration into liposomes. Disulfide bond cleavage was assessed by preincubation of the 6-MP prodrug 2 in serum followed by a bioassay. The preincubation period did not increase the inhibitory potency of the prodrug on lymphocyte proliferation as compared to the parent drug. Thus disulfide bond cleavage of prodrug 2 is assumed to be an active cellular process.