Picosecond phase-grating spectroscopy is highly sensitive to density changes and provides a new holographic approach to the study of protein dynamics. Photodissociation of carbon monoxide from heme proteins induces a well-defined transition from a ligated to a deoxy structure that is important to hemoglobin and myoglobin functionality. Grating spectroscopy was used to observe protein-driven density waves on a picosecond time scale after carbon monoxide dissociation. This result demonstrates that global tertiary structure changes of proteins occur on an extremely fast time scale and provides new insight into the biomechanics of deterministic protein motion.

Phase grating spectroscopy has been used to follow the optically triggered tertiary structural changes of carboxymyoglobin (MbCO) and carboxyhemoglobin (HbCO). Probe wavelength and temperature dependencies have shown that the grating signal arises from nonthermal density changes induced by the protein structural changes. The material displaced through the protein structural changes leads to the excitation of coherent acoustic modes of the surrounding water. The coupling of the structural changes to the fluid hydrodynamics demonstrates that a global change in the protein structure is occurring in less than 30 ps. The global relaxation is on the same time scale as the local changes in structure in the vicinity of the heme pocket. The observed dynamics for global relaxation and correspondence between the local and global structural changes provides evidence for the involvement of collective modes in the propagation of the initial tertiary conformational changes. The energetics can also be derived from the acoustic signal. For MbCO, the photodissociation process is endothermic by 21 +/- 2 kcal/mol, which corresponds closely to the expected Fe-CO bond enthalpy. In contrast, HbCO dissipates approximately 10 kcal/mol more energy relative to myoglobin during its initial tertiary structural relaxation. The difference in energetics indicates that significantly more energy is stored in the hemoglobin structure and is believed to be related to the quaternary structure of hemoglobin not present in the monomeric form of myoglobin. These findings provide new insight into the biomechanics of conformational changes in proteins and lend support to theoretical models invoking stored strain energy as the driving force for large amplitude correlated motions.

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However, bioavailability considerations seem to suggest that the reactive surface, S, is of greater relevance.34 The dissolution of some drugs is summarized in 26-29: The Z>R -2 values for all indicate that the dissolution occurs at the outer exposed regions of the drug crystal.Summary. The reactive regions of many heterogeneous reactions have a characteristic reaction dimension, Z)R. Z)R may be larger, smaller, or equal to the surface fractal dimension, D (see the recently suggested mutlifractal concept35). Z)R is sensitive to reaction conditions (compare the following pairs: 1, 2; 3, 4; 15, 16; 23, 24). The absolute and the relative values of Z)R add to the understanding of the reaction mechanism. An important conclusion made is that the reaction efficiency can be increased by reducing the particle size for DK < D, m > 1 cases and increasing particle size for Z)R > D, m < 1 reactions. This can be analyzed by the generalized Wenzel law (eq 5).The ideas presented in this report have been already utilized successfully by other groups, e.g., in coal gasification (30).36 We •