Challenges in Application of Langmuir Monolayer Studies To Determine the Mechanisms of Bactericidal Activity of Ruthenium Complexes.

The effects induced by antibiotics on the bacterial membrane may be correlated with their bactericidal activity, and such molecular-level interactions can be probed with Langmuir monolayers representing the cell membrane. In this study, we investigated the interaction between [Ru(mcbtz)2(PPh3)2] (RuBTZ, mcbtz = 2-mercaptobenzothiazoline) and [Ru(mctz)2(PPh3)2] (RuCTZ, mctz = 2-mercaptothiazoline) with Langmuir monolayers of a lipid extract of Escherichia coli, an extract of lipopolysaccharides (LPSs), and a zwitterionic phospholipid, dioleoylphosphatidyl choline (DOPC). RuBTZ and RuCTZ had little effects on DOPC, which is consistent with their negligible toxicity toward mammalian cells that may be approximated by a zwitterionic monolayer. Also little were their effects on LPSs. In contrast, RuBTZ and RuCTZ induced expansion in the surface pressure isotherms and decreased the compressional modulus of the E. coli lipid extract. While the more hydrophobic RuBTZ seemed to affect the hydrophobic tails of the E. coli extract monolayer to a larger extent, according to polarization modulation infrared reflection absorption spectroscopy results, evidence of a stronger RuBTZ interaction could not be confirmed unequivocally. Therefore, the interaction with the E. coli cell membrane cannot be directly correlated with the observed higher bactericidal activity of RuBTZ, in comparison to that of RuCTZ. This appears to be a case in which Langmuir monolayer studies do not suffice to determine the mechanisms responsible for the bactericidal activity.

Electrodiagnosis in compression neuropathies of the upper extremities.

Compression neuropathies may occur at several points along the course of a nerve. Electrodiagnostic studies are helpful in the evaluation of nerve compression. Nerve conduction studies are the most useful of these techniques in determining the site of compression. Compression neuropathies of the upper extremities are common, and a well planned study is important to localize the site of involvement and the severity of the nerve damage.

Correlation of [RuCl3(dppb)(VPy)] cytotoxicity with its effects on the cell membranes: an investigation using Langmuir monolayers as membrane models.

One of the major challenges in drug design is to identify compounds with potential toxicity toward target cells, preferably with molecular-level understanding of their mode of action. In this study, the antitumor property of a ruthenium complex, mer-[RuCl3(dppb)(VPy)] (dppb = 1,4-bis(diphenylphosphine)butane and VPy = 4-vinylpyridine) (RuVPy), was analyzed. Results showed that this compound led to a mortality rate of 50% of HEp-2 cell with 120 ± 10 µmol L(-1), indicating its high toxicity. Then, to prove if its mode of action is associated with its interaction with cell membranes, Langmuir monolayers were used as a membrane model. RuVPy had a strong effect on the surface pressure isotherms, especially on the elastic properties of both the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) phospholipids. These data were confirmed by polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). In addition, interactions between the positive group from RuVPy and the phosphate group from the phospholipids were corroborated by density functional theory (DFT) calculations, allowing the determination of the Ru complex orientation at the air-water interface. Although possible contributions from receptors or other cell components cannot be discarded, the results reported here represent evidence for significant effects on the cell membranes which are probably associated with the high toxicity of RuVPy.