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The core ionization energies of three strained lactams have been measured and compared with those of model lactams, amides, amines, and ketones. In general, the high values for N1s and the low values for O1s in planar amide (lactam) linkages compared to those in model amines and ketones are consistent with traditional resonance arguments. The N1s and O1s data for the distorted lactams 1,3-di-tert-butylaziridinone and 1-azabicyclo-[3.3.1]nonan-2-one are consistent with a reduced positive charge on nitrogen and a reduced negative charge on oxygen in accord with the classical resonance viewpoint

Our group has developed technology for stabilizing microbubbles with phospholipid coatings (Aerosomes®‐ImaRx Pharmaceutical Corp.). The first agent (MRX‐115) is based upon lipid‐coated microspheres filled with perfluoropropane gas and is in phase III clinical trials (October, 1997) for radiology and cardiology applications. Myocardial perfusion studies show the potential for the agent to detect ischemia in patients with myocardial infarcts. Targeting ligands have been covalently bound to lipids and incorporated into the stabilizing shells on the microbubbles. The first targeted agent planned for clinical trials is MRX‐408 (perfluorobutane gas, linear hexapeptide‐RGD analog). In vitro studies show enhanced visualization of thrombi, and in vivo studies in dogs with arterial and venous thrombi show selective enhancement, even in animals injected with heparin. In vitro studies have been performed to test sonothrombolysis comparing MRX‐115 to MRX‐408 with and without urokinase. The targeted contrast agent MRX‐408 increases the rate of clot dissolution with ultrasound. Targeted, tissue‐specific agents are feasible for ultrasound. A thrombus‐specific ultrasound contrast agent has the potential to improve clot characterization and detection as well as clot lysis.

Transfection experiments were performed in vitro in cell culture and in vivo in fish and mice using cationic liposomes with several different reporter genes. The effect of continuous‐wave 1‐MHz ultrasound on cell viability, cell permeability, and gene expression was assessed. RT‐PCR was used to monitor gene expression of cell repair genes in insonated cells. Acoustically active halocarbon‐containing liposomes were prepared for gene delivery. Ultrasound increased cell permeability and gene expression following liposomal transfection. RT‐PCR showed upregulation of repair of a number of cell repair genes after ultrasound exposure. The acoustically active gene delivery vehicles provided highly efficient transfection both with and without ultrasound in vitro and in vivo. Following IV administration of halocarbon‐containing liposomes/gene complexes, preferential gene expression was observed in the insonated tissue. Ultrasound has potentially useful applications for targeting and enhancing gene therapy.