Quantitative determination of intermolecular interactions with fluorinated aromatic rings.

The chemical double mutant cycle approach has been used to investigate substituent effects on intermolecular interactions between aromatic rings and pentafluorophenyl pi-systems. The complexes have been characterised using 1H and 19F NMR titrations, X-ray crystal structures of model compounds and molecular mechanics calculations. In the molecular zipper system used for these experiments, H-bonds and the geometries of the interacting surfaces favour the approach of the edge of the aromatic ring with the face of the pentafluorophenyl pi-system. The interactions are generally repulsive and this repulsion increases with more electron-withdrawing substituents up to a limit of +2.2 kJ mol(-1), when the complex distorts to minimise the unfavourable interaction. Strongly electron-donating groups cause a change in the geometry of the aromatic interaction and attractive stacking interactions are found (-1.6 kJ mol(-1) for NMe2). These results are generally consistent with an electrostatic model: the polarisation of the pentafluorophenyl ring leads to a partial positive charge located at the centre and this leads to repulsive interactions with the positive charges on the protons on the edge of the aromatic ring; when the aromatic ring has a high pi-electron density there is a large electrostatic driving force in favour of the stacked geometry which places this pi-electron density over the centre of the positive charge on the pentafluorophenyl group.

Selective adhesion, lipid exchange and membrane-fusion processes between vesicles of various sizes bearing complementary molecular recognition groups.

Equimolar mixtures of large unilamellar vesicles (LUVs) obtained from mixtures of egg lecithin and lipids containing complementary hydrogen bonding head groups (barbituric acid (BAR) and 2,4,6-triaminopyrimidine (TAP)) were shown to aggregate and fuse. These events have been studied in detail using electron microscopy and dynamic light scattering, and by fluorimetry using membrane or water-soluble fluorescence probes. It was shown that aggregation was followed by two competitive processes: a) lipid mixing leading to redispersion of the vesicles; b) fusion events generating much larger vesicles. In order to better understand the nature of the interaction, the effects of ionic strength and surface concentration of recognition lipids on the aggregation process were investigated by dynamic light scattering. Additionally, it was possible to inhibit the aggregation kinetics through addition of a soluble barbituric acid competitor. The study was extended to giant unilamellar vesicles (GUVs) to investigate the size effect and visualise the phenomena in situ. The interactions between complementary LUVs and GUVs or GUVs and GUVs were studied by optical microscopy using dual fluorescent labelling of both vesicle populations. A selective adhesion of LUVs onto GUVs was observed by electron and optical microscopies, whereas no aggregation took place in case of a GUV/GUV mixture. Furthermore, a fusion assay of GUV and LUV using the difference of size between GUV and LUV and calceine self-quenching showed that no mixing between the aqueous pools occured.

A supramolecular system for quantifying aromatic stacking interactions.

A supramolecular complex for investigating the thermodynamic properties of intermolecular aromatic stacking interactions has been developed. The conformation of the complex is locked in a single well-defined conformation by an array of H-bonding interactions that force two aromatic rings on one end of the complex into a stacked geometry. Chemical double-mutant cycles have been used to measure an anthracene-aniline interaction (+0.6 +/- 0.8 kJ mol(-1)) and a pentafluorophenyl-aniline interaction (-0.4 +/- 0.9 kJ mol(-1)) in this system. Although the interactions are very weak, the pentafluorophenyl interaction is attractive, whereas the anthracene interaction is repulsive: this is consistent with the dominance of pi-electron electrostatic interactions. The nitropyrrole subunits used to control the conformation of these complexes lead to problems of aggregation and multiple conformational equilibria. The implications for the thermodynamic analysis are examined in detail, and the double-mutant-cycle approach is found to be remarkably robust with respect to such effects, since systematic errors in individual experiments are removed in a pair-wise fashion when the cycle is constructed.

Cellular aggregation and trauma in cardiotomy suction systems.

Experiments in dogs showed that the high levels of cellular aggregation and trauma caused by cariodtomy suction can be considerably reduced by the avoidance of air aspiration. A hypothesis is proposed to explain this on the basis of shear stresses in the inlet cannula. Roller pump suction was also found to be slightly more traumatic than vaccum suction, but contact of the blood with the pericardium had no effect so long as the pericardium and epicardium had been previously washed with saline.

Right-sided endocarditis involving both tricuspid and pulmonary valves in a patient with ventricular septal defect.

A patient with alpha-haemolytic streptococcus endocarditis on a ventricular septal defect is described. The disease spread to involve both tricuspid and pulmonary valves which were largely destroyed. The patient developed severe right heart failure with pronounced rise in right atrial pressure. This led to right-to-left shunting through the foramen ovale with systemic embolization. She was successfully treated by operative closure of the defects and double right-sided valve replacement.

Rheumatoid pericardial effusion with heart block treated by pericardiectomy and implantation of permanent pacemaker.

A patient with long-standing seropositive erosive rheumatoid arthritis developed a pericardial effusion with chronic cardiac tamponade. He had evidence of conducting system disease and developed heart block. He was successfully treated by pericardiectomy and implantation of a demand pacemaker.

Cellular aggregation and destruction during blood circulation and oxygenation.

Platelet and leucocyte aggregation and severe haemolysis may occur in blood during the preparation of an extracorporeal circuit for open-heart surgery. Experiments with dog blood showed that both processes result from bubble oxygenation but not from circulation of diluted blood and that they appear to be inhibited by the presence of acid citrate dextrose and heparin, or citrate phosphate dextrose and heparin, but not by heparin alone.

Low-dose heparin prophylaxis against fatal pulmonary embolism.

A prospective randomised controlled trial in 500 patients over the age of 50 who were undergoing major surgery showed that low-dose subcutaneous heparin was an effective prophylactic measure against fatal pulmonary embolism. None of the 252 patients who received perioperative heparin cover died of fatal pulmonary embolism while eight of the 236 who did not receive heparin prophylaxis died of fatal pulmonary embolism. These results were statiscally significant (P less than 0.01).

Complete interruption of aortic arch, without persistent ductus arteriosus, in an adult.

A case of complete interruption of the aortic arch in an adult is presented and the previous 8 reported cases are reviewed. Obliteration of the ductus is a feature of these cases, in contrast to the more common variety found in early childhood. Comments are made on the clinical distinction between the adult type of complete interruption of the aortic arch and coarctation of the aorta.