Ultrafast X-ray Absorption Spectroscopy Reveals Excited-State Dynamics of B12 Coenzymes Controlled by the Axial Base.

Polarized time-resolved X-ray absorption spectroscopy at the Co K-edge is used to probe the excited-state dynamics and photolysis of base-off methylcobalamin and the excited-state structure of base-off adenosylcobalamin. For both molecules, the final excited-state minimum shows evidence for an expansion of the cavity around the Co ion by ca. 0.04 to 0.05 Å. The 5-coordinate base-off cob(II)alamin that is formed following photodissociation has a structure similar to that of the 5-coordinate base-on cob(II)alamin, with a ring expansion of 0.03 to 0.04 Å and a contraction of the lower axial bond length relative to that in the 6-coordinate ground state. These data provide insights into the role of the lower axial ligand in modulating the reactivity of B12 coenzymes.

Watching Excited State Dynamics with Optical and X-ray Probes: The Excited State Dynamics of Aquocobalamin and Hydroxocobalamin.

Femtosecond time-resolved X-ray absorption (XANES) at the Co K-edge, X-ray emission (XES) in the Co Kß and valence-to-core regions, and broadband UV-vis transient absorption are combined to probe the femtosecond to picosecond sequential atomic and electronic dynamics following photoexcitation of two vitamin B12 compounds, hydroxocobalamin and aquocobalamin. Polarized XANES difference spectra allow identification of sequential structural evolution involving first the equatorial and then the axial ligands, with the latter showing rapid coherent bond elongation to the outer turning point of the excited state potential followed by recoil to a relaxed excited state structure. Time-resolved XES, especially in the valence-to-core region, along with polarized optical transient absorption suggests that the recoil results in the formation of a metal-centered excited state with a lifetime of 2-5 ps. This combination of methods provides a uniquely powerful tool to probe the electronic and structural dynamics of photoactive transition-metal complexes and will be applicable to a wide variety of systems.

Time-resolved spectroscopy: Advances in understanding the electronic structure and dynamics of cobalamins.

Time resolved spectroscopy provides unique insight into the structure and function of cobalamins. In these experiments, the cobalamin is initially excited by a short "pump" pulse in the UV-visible region and then characterized at some later time using a short "probe" pulse. The emphasis in this chapter is on both UV-visible and X-ray probe pulses, with a particular focus on the unique information provided by the latter. The principles of time-resolved spectroscopy are reviewed, with an emphasis on ultrafast measurements (time scales less than ~10ps) to characterize short-lived cobalamin excited states. Several practical considerations are discussed, with a focus on the technical details that are necessary to obtain high quality, interpretable data. These include sample delivery, polarization, and excitation power. Some of the theoretical approaches to interpreting data are discussed.

Triaging patients at risk of influenza using a patient portal.

Vanderbilt University has a widely adopted patient portal, MyHealthAtVanderbilt, which provides an infrastructure to deliver information that can empower patient decision making and enhance personalized healthcare. An interdisciplinary team has developed Flu Tool, a decision-support application targeted to patients with influenza-like illness and designed to be integrated into a patient portal. Flu Tool enables patients to make informed decisions about the level of care they require and guides them to seek timely treatment as appropriate. A pilot version of Flu Tool was deployed for a 9-week period during the 2010-2011 influenza season. During this time, Flu Tool was accessed 4040 times, and 1017 individual patients seen in the institution were diagnosed as having influenza. This early experience with Flu Tool suggests that healthcare consumers are willing to use patient-targeted decision support. The design, implementation, and lessons learned from the pilot release of Flu Tool are described as guidance for institutions implementing decision support through a patient portal infrastructure.