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The interaction with a model membrane, the formation of DNA nanoparticles, and the transfection ability of a homologous series of bispyridinium dihexadecyl cationic gemini surfactants, differing in the length of the alkyl spacer bridging the two pyridinium polar heads in the 1 and 1' positions (P16-n with n = 3, 4, 8, 12), have been studied by means of differential scanning calorimetry (DSC), atomic force microscopy, electrophoresis mobility shift assay, and transient transfection assay measurements. The results presented here show that their performance in gene delivery is strictly related to their structure in solution. For the first time the different transfection activities of the compounds can be explained by referring to their thermodynamic properties in solution, previously studied. The compound with a spacer formed by four carbon atoms, showing unexpected enthalpic properties vs concentration in solution, is the only one giving rise to a transfection activity comparable to that of the commercial reagent, when formulated with L-α-dioleoylphosphatidylethanolamine. We suggest that P16-4 behaves like molecular tongs able to grip basic groups near each other, allowing the formation of compact and nearly spherical DNA particles. The compound with the longest spacer gives rise to loosely condensed structures by forming a sort of bow, not able to give rise to transfection notwithstanding the double positive charge of the molecule. On the other hand, DSC measurements on synthetic membranes show that the compounds with the shortest spacers (three and four methylene groups) practically do not interact with the 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine membrane, while compounds P16-8 and, particularly, P16-12 induce the formation of surfactant-rich and surfactant-poor domains in the membrane, without showing any peculiarity for compound P16-4. This could suggest that the mechanisms involved in the interaction with the model membrane and in gene delivery are substantially different and could strike a blow for an endocytosis mechanism for the internalization in the cell of the DNA nanoparticles.

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Apparent and partial molar enthalpies at 298 K of the aqueous solutions of cationic gemini surfactants 1,1′-didodecyl-2,2′-trimethylenebispyridinium dichloride (12-Py(2)-3-(2)Py-12 Cl); 1,1′-didodecyl-2,2′-tetramethylenebispyridinium dichloride (12-Py(2)-4-(2)Py-12 Cl); 1,1′-didodecyl-2,2′-octamethylenebispyridinium dichloride (12-Py(2)-8-(2)Py-12 Cl); 1,1′-didodecyl-2,2′-dodecamethylenebispyridinium dichloride (12-Py(2)-12-(2)Py-12 Cl) were measured as a function of concentration and are here reported for the first time. The curve of the compound with the four carbon atoms spacer lies between those of the compound with spacer of 2 and 3 carbon atoms, not below the latter, as expected. This behaviour, we have already found for the same compounds here studied, but having methanesulfonate as counterion, is interpreted as an evidence of a conformation change of the molecule determined by stacking interactions between the two pyridinium rings, appearing at an optimum length of the spacer. The curves of apparent and molar enthalpies vs. concentration and surface tension measurements, here reported, show that this behaviour is independent on the counterion. On the contrary, the group contribution additivity for the counterion is respected, independently on the spacer length.Keywords. Apparent and partial molar enthalpies; cationic gemini surfactants; 1,1′-didodecyl-2,2′-trimethylenebispyridinium dichloride; 1,1′-didodecyl-2,2′-tetramethylenebispyridinium dichloride; 1,1′-didodecyl-2,2′-octamethylenebispyridinium dichloride; 1,1′-didodecyl-2,2′-dodecamethylenebispyridinium dichloride; micellization enthalpy, group contribution.Briefs. Apparent and partial molar enthalpies at 298 K of the aqueous solutions of cationic gemini surfactants 1,1′-didodecyl-2,2′-trimethylenebispyridinium dichloride (12-Py(2)-3-(2)Py-12 Cl);1,1′-didodecyl-2,2′-tetramethylenebispyridinium dichloride (12-Py(2)-4-(2)Py-12 Cl); 1,1′-didodecyl-2,2′-octamethylenebispyridinium dichloride (12-Py(2)-8-(2)Py-12 Cl); 1,1′-didodecyl-2,2′-dodecamethylenebispyridinium dichloride (12-Py(2)-12-(2)Py-12 Cl) have been measured as a function of concentration, in order to confirm the lack of methylene group additivity with respect to the enthalpic properties of the solutions, when it is added in the spacer, already found in the case of methansulfonates. The data obtained support the hypothesis of a conformation change dependent on the spacer length, but independent on the counterion.

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Blood polyamine levels have been determined in 161 healthy subjects from newborn to adult age. During the growth period spermidine concentrations are always higher than in adulthood. In the first days of life a typical pattern for spermidine and spermine appeared with an early increase in the first hours after birth and a maximum at 24 h; afterwards the levels of both amines gradually and progressively decreased. The levels reached by 10 days of life were maintained until adulthood, at which time a further decrease was evident. The high levels of polyamines during the period of body growth may suggest that also in humans these substances play a role in the process of cellular proliferation.

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