Phase transitions in closed vesicles, i.e., microenvironments defined by the size of the vesicle, its contents, and permeability of its membrane are becoming increasingly important in several scientific disciplines including catalysis, growth of small crystals, cell function studies, and drug delivery. The membrane composed from lipid bilayer is in general impermeable to ions and larger hydrophilic ions. Ion transport can be regulated by ionophores while permeation of neutral and weakly hydrophobic molecules can be controlled by concentration gradients. Some weak acids or bases, however, can be transported through the membrane due to various gradients, such as electrical, ionic (pH) or specific salt (chemical potential) gradients. Upon permeation of appropriate species and reaction with the encapsulated species precipitation may occur in the vesicle interior. Alternatively, these molecules can also associate with the leaflets of the bilayer according to the transmembrane potential. Efficient liposomal therapeutics require high drug to lipid ratios and drug molecules should have, especially when associated with long circulating liposomes, low leakage rates. In this article we present very efficient encapsulation of two drugs via their intraliposomal precipitation, characterize the state of encapsulated drug within the liposome and try to fit the experimental data with a recently developed theoretical model. Nice agreement between a model which is based on chemical potential equilibration of membrane permeable species with experimental data was observed. The high loading efficiencies, however are only necessary but not sufficient condition for effective therapies. If adequate drug retention within liposomes, especially in the case of long-circulating ones, is not achieved, the therapeutic index decreases substantially. Anticancer drug doxorubicin precipitates in the liposome interior in a form of gel with low solubility product and practically does not leak out in blood circulation in the scale of days. With an antibiotic, ciprofloxacin, the high loading efficacy and test tube stability is not reproduced in in vitro plasma leakage assays and in vivo. We believe that the reasons are higher solubility product of precipitated drug in the liposome, larger fraction of neutral molecules due closer pK values of the drug with the pH conditions in the solutions and high membrane permeability of this molecule. High resolution cryoEM shows that encapsulated anticancer agent doxorubicin is precipitated in the form of bundles of parallel fibers while antibiotic ciprofloxacin shows globular precipitate. Doxorubicin gelatin also causes the change of vesicle shape.

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1‐(4‐pyridyl)pyridinium ion (C10H10N22+, (Py2)H2+) precipitates from the hydrochloric acid solution of (NH4)2MoCl5 · H2O sparingly soluble (Py2)HMoCl5 · H2O. This unreactive, air stable compound crystallizes in the orthorhombic unit cell with a = 12.895(4), b = 6.914(2), c = 16.388(7) Å, Z = 4. The ionic structure contains octahedral MoCl5 · H2O2– and (Py2)H2+. The bond lengths MoCl are between 2.406(3) to 2.446(4) Å. The bond length MoO(H2O) is 2.19(1) Å. Planar pyridine rings of the cation are rotated around the common axis by 38°. Anions are located in layers at Z = 1/4 and 3/4. Between the layers (Py2)H2+ cations are situated. (Py2)MX4Py2 (M = Mo, W; X = Cl, Br; Py = Pyridine) with deprotonated (Py2)H2+ are prepared from the solutions of (PyH)MoX4Py2 in aqueous ammonia to which (Py2)HCl2 was added. All four compounds crystallize in the triclinic crystal system. Unit cell dimensions are comparable. The stability of the compounds against oxidation and substitution could have its origin in the low solubility.

WCl4Py2 (Py = Pyridine) crystallizes in the monoclinic space group: I2/m, with a = 7.237(1), b = 7.278(2), c = 12.865(4) Å, β = 94.60(2)°, and Z = 2. WCl4Py2 has 2/m crystallographic symmetry requiring trans position of the ligands. WCl and WN bond lengths are 2.347(1) and 2.181(4) Å. WCl4Py2 is isostructural with WBr4Py2.WX4Pic2 (Pic = 4‐methylpyridine) can be obtained from WX4Py2 and 4‐methylpyridine at room temperature. Chemical and physical evidence speaks for the trans structure of WX4Pic2.