Direct imaging of transient molecular structures with ultrafast diffraction.

Ultrafast electron diffraction (UED) has been developed to study transient structures in complex chemical reactions initiated with femtosecond laser pulses. This direct imaging of reactions was achieved using our third-generation apparatus equipped with an electron pulse (1.07 +/- 0.27 picoseconds) source, a charge-coupled device camera, and a mass spectrometer. Two prototypical gas-phase reactions were studied: the nonconcerted elimination reaction of a haloethane, wherein the structure of the intermediate was determined, and the ring opening of a cyclic hydrocarbon containing no heavy atoms. These results demonstrate the vastly improved sensitivity, resolution, and versatility of UED for studying ultrafast structural dynamics in complex molecular systems.

Evidence of nonspecific surface interactions between laser-polarized xenon and myoglobin in solution.

The high sensitivity of the magnetic resonance properties of xenon to its local chemical environment and the large (129)Xe NMR signals attainable through optical pumping have motivated the use of xenon as a probe of macromolecular structure and dynamics. In the present work, we report evidence for nonspecific interactions between xenon and the exterior of myoglobin in aqueous solution, in addition to a previously reported internal binding interaction. (129)Xe chemical shift measurements in denatured myoglobin solutions and under native conditions with varying xenon concentrations confirm the presence of nonspecific interactions. Titration data are modeled quantitatively with treatment of the nonspecific interactions as weak binding sites. Using laser-polarized xenon to measure (129)Xe spin-lattice relaxation times (T(1)), we observed a shorter T(1) in the presence of 1 mM denatured apomyoglobin in 6 M deuterated urea (T(1) = 59 +/- 1 s) compared with that in 6 M deuterated urea alone (T(1) = 291 +/- 2 s), suggesting that nonspecific xenon-protein interactions can enhance (129)Xe relaxation. An even shorter T(1) was measured in 1 mM apomyoglobin in D(2)O (T(1) = 15 +/- 0.3 s), compared with that in D(2)O alone (T(1) = 506 +/- 5 s). This difference in relaxation efficiency likely results from couplings between laser-polarized xenon and protons in the binding cavity of apomyoglobin that may permit the transfer of polarization between these nuclei via the nuclear Overhauser effect.

Ultrafast diffraction and structural dynamics: the nature of complex molecules far from equilibrium.

Studies of molecular structures at or near their equilibrium configurations have long provided information on their geometry in terms of bond distances and angles. Far-from-equilibrium structures are relatively unknown-especially for complex systems-and generally, neither their dynamics nor their average geometries can be extrapolated from equilibrium values. For such nonequilibrium structures, vibrational amplitudes and bond distances play a central role in phenomena such as energy redistribution and chemical reactivity. Ultrafast electron diffraction, which was developed to study transient molecular structures, provides a direct method for probing the nature of complex molecules far from equilibrium. Here we present our ultrafast electron diffraction observations of transient structures for two cyclic hydrocarbons. At high internal energies of approximately 4 eV, these molecules display markedly different behavior. For 1,3,5-cycloheptatriene, excitation results in the formation of hot ground-state structures with bond distances similar to those of the initial structure, but with nearly three times the average vibrational amplitude. Energy is redistributed within 5 ps, but with a negative temperature characterizing the nonequilibrium population. In contrast, the ring-opening reaction of 1,3-cyclohexadiene is shown to result in hot structures with a CC bond distance of over 1.7 A, which is 0.2 A away from any expected equilibrium value. Even up to 400 ps, energy remains trapped in large-amplitude motions comprised of torsion and asymmetric stretching. These studies promise a new direction for studying structural dynamics in nonequilibrium complex systems.

NMR of laser-polarized xenon in human blood.

By means of optical pumping with laser light it is possible to enhance the nuclear spin polarization of gaseous xenon by four to five orders of magnitude. The enhanced polarization has allowed advances in nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI), including polarization transfer to molecules and imaging of lungs and other void spaces. A critical issue for such applications is the delivery of xenon to the sample while maintaining the polarization. Described herein is an efficient method for the introduction of laser-polarized xenon into systems of biological and medical interest for the purpose of obtaining highly enhanced NMR/MRI signals. Using this method, we have made the first observation of the time-resolved process of xenon penetrating the red blood cells in fresh human blood-the xenon residence time constant in the red blood cells was measured to be 20.4 +/- 2 ms. The potential of certain biologically compatible solvents for delivery of laser-polarized xenon to tissues for NMR/MRI is discussed in light of their respective relaxation and partitioning properties.

In vivo NMR and MRI using injection delivery of laser-polarized xenon.

Because xenon NMR is highly sensitive to the local environment, laser-polarized xenon could be a unique probe of living tissues. Realization of clinical and medical science applications beyond lung airspace imaging requires methods of efficient delivery of laser-polarized xenon to tissues, because of the short spin-lattice relaxation times and relatively low concentrations of xenon attainable in the body. Preliminary results from the application of a polarized xenon injection technique for in vivo 129Xe NMR/MRI are extrapolated along with a simple model of xenon transit to show that the peak local concentration of polarized xenon delivered to tissues by injection may exceed that delivered by respiration by severalfold.