Understanding and harnessing the interaction between energy and matter is a basic scientific endeavor. The use of high intensity ultrasound to initiate chemical reactions, as opposed to traditional energy sources such as heat and light, has opened new avenues of research. The mechanism of sonochemistry involves acoustic cavitation:​ the formation, growth, and collapse of bubbles in a liquid. New biological and inorganic materials can be synthesized using this unusual high energy source.

This thesis is divided into two parts. The first part describes the synthesis, characterization and applications of proteinaceous microspheres. Such biological materials have many medical uses including drug delivery and contrast agents for magnetic resonance imaging and echosonography. The second part of my thesis develops the use of ultrasound for the synthesis of unusual inorganic materials. Specifically, we have explored the sonochemical synthesis, characterization, and catalytic reactivity of amorphous iron. The first chapter is a detailed report on the effects of ultrasound in heterogeneous chemical reactions and is an invited review paper for Chemical Reviews.

Proteinaceous Microspheres

Microspheres have found diverse and important applications ranging from the microencapsulation of dyes, flavors and fragrances, to their use in drug delivery systems. We developed a sonochemical technique to synthesize microspheres filled with water-insoluble whose shell is composed entirely of albumin protein. Scanning electron microscopy, optical microscopy, and particle counting characterization reveals that these microcapsules are spherical with typical concentrations of 1.5 x 10⁸ microcapsule/mL. The microcapsule synthesized have a narrow Gaussian size distribution (average diameter 2.5 ± 1.0 μm). Microcapsule formation is strongly inhibited by free radical traps, by superoxide dismutase (but not by catalase), by an absence of 0 2, and by a lack of free cysteine residues in the protein. The microcapsules are held together by disulfide bonds between protein cysteine residues, and superoxide (sonochemically produced during acoustic cavitation) is the oxidizing agent that cross-links the proteins.

In addition to producing liquid-filled microcapsules, air-filled microbubbles have also been synthesized. These proteinaceous microbubbles are currently in clinical use as contrast agents for echosonography. Two dimensional contrast echosonography has become a valuable and routine procedure in diagnosing cardiac diseases. This diagnostic method is especially useful in monitoring myocardial perfusion and ventricular hemodynamics. To enhance image quality, a solution containing microbubbles may be injected intravenously to perfuse the cardiovascular system;​ these microbubbles change the acoustic impedance of the blood flow, resulting in dramatically improved echo contrast with the surrounding tissues. The sonochemically synthesized proteinaceous microbubbles are non-toxic, stable, and micron size.

Another application of sonochemically produced microspheres involves their use for drug delivery of hydrophobic compounds. Present drug delivery methods primarily focus on water soluble drugs. Currently, there are methods of introducing water soluble drugs into liposomes and of attaching drugs to solid microspheres. We have discovered a new method that can be used to encapsulate water-insoluble or hydrophobic drugs in a microsphere of albumin protein. For example, aqueous solutions of spherical proteinaceous microcapsule filled with a-methyl-4-(2-propyl)phenyl-acetic acid (i.e., ibuprofen) can be synthesized. These microcapsule have an average diameter of ≈ 2.5 μm with concentrations of ≈ 2.6 x 10⁸ microcapsule/mL. Ibuprofen (trade names:​ Motrin IB™ , Advil™) was released over a 6 hour period at 38°C. Ibuprofen was encapsulated at a concentration of ≈1 x 10⁻¹¹ gram/microcapsule.

The use of microcapsule for medical imaging also shows great promise. The development of a non-invasive technique for in vivo temperature measurement has many potential clinical applications. Microcapsules containing a stable nitroxide radical and a solid fatty acid have been synthesized. The fatty acid core undergoes a reversible phase change (solid/liquid) inside the microcapsule upon heating and cooling. The nitroxide free radical electron paramagnetic resonance (EPR) signal is dramatically dependent on its environment, and consequently the temperature can be determined from a calibrated line-width. The current microcapsule have a temperature range from 37 to 42°C with a temperature sensitivity of = 0.3°C. These microcapsule are designed especially for optimizing the treatment of cancer in vivo with hypothermia.

Another application involves chemoselective medical imaging. Oxygen plays a critical role in physiological, pathophysiological, and therapeutic processes. We lack, however, techniques for the direct measurement of O₂ concentration in vivo. Low concentrations of O₂ are associated with a variety of normal and pathological processes in tissues but are difficult to measure. EPR has been previously been used for the determination of O₂ even at low concentrations (< 10⁻⁴). We have developed an EPR technique for non-invasive in vivo oxygen measurement that uses nitroxide free radicals inside our proteinaceous microcapsule. Encapsulation of a nitroxide free radical dissolved in cyclohexane was accomplished. These microcapsule are easily penetrated by gases, and the O₂ concentration can be quantitatively

determined from the observed EPR Iine-width. An EPR spectrum from the lower back of an injected mouse was obtained. Injection of Ketamine [2-(2-chlorophenyl)-2-(methylamino)cyclohexanone], a local anaesthetic that reduces O₂ consumption, produced a decrease in line-width. Thus, a reduction in local physiological activity in the mouse was observed using this technique.

Amorphous Iron

Amorphous metallic alloys ("metallic glasses") lack long range crystalline order and have unique electronic, magnetic, and corrosion-resistant properties. The production of metallic glasses is difficult because extremely rapid cooling of molten metals is necessary to prevent crystallization. Cooling rates of « 107 K/sec are required for the formation of most metallic glasses;​ for comparison, plunging red hot steel into water produces cooling at only = 2500 K/sec. Enormous heating and cooling rates of between 10⁹ to 10¹³ K/sec are produced during acoustic cavitation. Ultrasonic irradiation of iron pentacarbonyl, a volatile inorganic compound, produces nearly pure amorphous iron.

Several physical techniques were used to characterize the sonochemically synthesized iron powder. X-ray powder diffraction and electron microdiffraction show the iron to be amorphous. An exothermic transition (corresponding to crystallization) in the differential scanning calorimeter profile is observed at 310°C for the amorphous iron powder. Scanning electron and transmission electron microscopy show that this powder is composed of many smaller iron particles (< 0 .0 3 /*m).

The amorphous iron powder is a soft ferromagnet, that is, it does not retain memory of prior magnetization. The coercivity at 5 K is » 190 gauss and decreases to = 10 gauss by room temperature. The saturation magnetization of the amorphous iron is =160 emu/g and is slightly less than crystalline iron (217 emu/g).

The amorphous iron powder is an active catalyst for the Fischer-Tropsch hydrogenation of CO and for hydrogenolysis and dehydrogenation of saturated hydrocarbons. The amorphous iron catalyst is ~ 150 times more reactive than commercially available crystalline iron. This increase in catalytic activity is attributed to its larger surface area ( ~ 120 m²/g) compared to crystalline iron (0.8 m²/g).

We have also observed the atomic emission lines o f iron during the ultrasonic irradiation of iron pentacarbonyl. Spectrally resolved sonoluminescence spectra have also been obtained from other metal carbonyls such as Cr(CO)6 and Mo(CO)6. The high temperatures and pressures created during acoustic cavitation strip carbon monoxide from the metal atom and thermally populate the excited states. The sonoluminescence confirms the formation of iron atoms produced by the extreme conditions generated by high intensity ultrasound