In our paper, we demonstrate several possibilities of using neutrons in pharmaceutical research with the help of examples of scientific results achieved at our University. In this first part, basic properties of neutrons and elementary principles of elastic scattering of thermal neutrons are described. Results of contrast variation neutron diffraction on oriented phospholipid bilayers with intercalated local anaesthetic or cholesterol demonstrate the potential of this method at determination of their position in bilayers. Diffraction experiments with alkan-1-ols located in the bilayers revealed their influence on bilayer thickness as a function of their alkyl chain length.
In this paper, we demonstrate several possibilities of using neutron scattering in pharmaceutical research based on examples of
scientific results achieved at our University. In this second part, elementary principles of small-angle neutron scattering and simple
methods of scattering data evaluation are described. Results of scattering on bilayers in unilamellar liposomes with intercalated
general anaesthetics, antimicrobials or cholesterol demonstrate the potential of this method at determination of structural properties
Synthesis and antimicrobial properties of binaphthyl derived quaternary ammonium bromides
(S)-N-(2-(4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepin-1-yl)ethyl)-N, N-dimethyl-N-dodecyl ammonium bromide (S)-1a and (S)-N-(2-(4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepin-1-yl)ethyl)-N, N-dimethyl-N-tetradecylammonium bromide (S)-1b have been synthesized as optically active quaternary ammonium salts starting from 1,1'-binaphthyl-2,2'-diol. Their antimicrobial activity expressed as minimal inhibition concentration (MIC) was tested against Gram-positive human pathogenic bacteria S. Aureus, Gram-negative bacteria E. coli and human fungal pathogen C. Albicans.
A group of homochiral imidazolium salts bearing hydrophobic camphor derived moiety and ester or amide functional group were synthesized and characterized. The novel imidazolium bromides were tested as antimicrobial and antifungal agents and their minimal inhibitory concentration (MIC) was evaluated and compared to clinically used benzalkonium bromide (BAB) and carbethopendecinium bromide. The MIC values of amide derivatives 2a and 2b were slightly smaller than those for BAB, indicating their good activity. None of the prepared salts was more effective than carbethopendecinium bromide. The biocidal efficacy of amide derivatives was much higher compared to the ester analogues.
The solubilisation of natural compound, (+)-usnic acid, in micellar solutions of gemini (N,N’-didecyl-N,N,N’,N’-tetramethylethane-1,2-diyldiammonium dibromide) and heterogemini (decyl 2-[decyl(dimethyl)ammonio]ethylphosphate) surfactants and their equimolar mixture has been studied. The highest solubility was found for gemini surfactant. The relationship between synergism in surface properties of mixture of surfactants and their solubilisation properties is also discussed.
The effect of ionic strength on DNA condensation by cationic liposomes prepared as a mixture of ethane-1,2-diylbis(dodecyl-dimethylammonium bromide) (C2GS12) and dioleoylphosphatidylcholine (DOPC) was studied using fluorescence spectroscopy. The DNA condensation followed by changes in emission intensity of ethidium bromide shows a strong dependence on the ionic strength of the solution. At physiologically relevant ionic strength (0.15 mol/l NaCl), the amount of DNA condensed between lipid bilayers is approximately 40% lower compared to 0.005 mol/l NaCl. The structure of formed complexes was studied using small angle X-ray diffraction (SAXD). DNA–C2GS12–DOPC complexes form a condensed lamellar phase organisation, which is partially disrupted by the increase of ionic strength. Both the lamellar repeat distance and DNA–DNA distance show dependence on C2GS12/DOPC molar ratio, temperature and also on ionic strength. We found that the method of preparation significantly affects both the quality of organisation and the structural parameters of complexes as discussed in the paper.