The photochemically induced electrocyclic ring-opening reaction of 1,3-cyclohexadiene to 1,3,5-hexatriene serves as a prototype for many important reactions in chemistry and in biological systems. Based on experimental and computational studies, a detailed picture of the reaction has now emerged: Excitation to the Franck-Condon region places the molecule on a steeply repulsive part of the 1B potential energy surface, which propels the molecule in exactly the conrotatory direction that conforms to the Woodward-Hoffmann rules of orbital symmetry. Bypassing a cusp in a symmetry-breaking direction, the wave packet enters the 2A state within 55 fs. It continues to move directly toward the 2A/1A conical intersection, where it crosses in approximately 80 fs to the ground state. This article summarizes the published experimental and theoretical work to describe the current understanding of the reaction while pointing to important questions that remain to be addressed.

Two identical ionization centers, one on each nitrogen atom, make N,N′dimethylpiperazine an important model to explore how the transfer of a (partial) charge is linked to the structural deformations of the molecular skeleton. Time-resolved photoelectron spectroscopy uncovered that upon excitation to the 3p Rydberg level at 207 nm only one of the initially symmetry-equivalent nitrogen atoms acquires the charge, creating an asymmetric molecular structure with a localized charge. Rapid internal conversion to 3s leads to a multitude of conformeric structures with the charge localized on one nitrogen atom (230 fs time constant) and a rigid structure with the charge delocalized over both nitrogen atoms (480 fs time constant). Structural motions continue while the molecule samples the 3s potential energy landscape, leading to an equilibrium between charge-localized and charge-delocalized conformeric structures that is approached with a 2.65 ps time constant.

Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pumpprobe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct "dusty" quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.

Time-resolved Rydberg fingerprint spectroscopy and quantum calculations reveal the structure dependent electron lone pair interaction and charge delocalization in real time.

We have observed time-resolved, structural dynamics of a coherent vibrational wavepacket in Rydberg-excited N-methyl morpholine, a molecule with 48 internal degrees of freedom. The molecular structure was established by associating the time-dependent Rydberg electron binding energy, obtained from time-resolved photoionization-photoelectron spectroscopy, to the molecular structure using self-interaction corrected density functional calculations. Optical excitation at 226 nm launches an oscillatory wavepacket in the amine umbrella coordinate with a 650 fs period. Even though the Franck-Condon excitation is at an angle of 17°, the wavepacket settles into an oscillation between 4° and -10° within a fraction of a vibrational period and then dephases with a time constant of 750 fs.

Rotations about its three carbon-nitrogen bonds give triethylamine a complex, 3-dimensional potential energy landscape of conformeric structures. Electronic excitation to Rydberg states prepares the molecule in a high-energy, nonequilibrium distribution of such conformers, initiating ultrafast transitions between them. Time-resolved Rydberg electron binding energy spectra, observed using photoionization-photoelectron spectroscopy with ultrashort laser pulses, reveal these time-evolving structures. The time-dependent structural fingerprint spectra are assigned with the aid of a computational analysis of the potential energy landscape. Upon 209 nm electronic excitation to the 3p Rydberg state, triethylamine decays to 3s with a 200 fs time constant. The initially prepared conformer reacts to a mixture of structures with a time constant of 232 fs and settles into a final geometry distribution on a further subpicosecond time scale. The binding energy of the Rydberg electron is found to be an important determinant of the conformeric energy landscape.

The aggregation of the amyloid beta (Aβ) protein into plaques is a pathological feature of Alzheimer's disease (AD). While amyloid aggregates have been extensively studied in vitro, their structural aspects and associated chemistry in the brain are not fully understood. In this report, we demonstrate, using infrared spectroscopic imaging, that Aβ plaques exhibit significant heterogeneities in terms of their secondary structure and phospholipid content. We show that the capabilities of discrete frequency infrared imaging (DFIR) are ideally suited for characterization of amyloid deposits in brain tissues and employ DFIR to identify nonplaque β-sheet aggregates distributed throughout brain tissues. We further demonstrate that phospholipid-rich β-sheet deposits exist outside of plaques in all diseased tissues, indicating their potential clinical significance. This is the very first application of DFIR toward a characterization of protein aggregates in an AD brain and provides a rapid, label-free approach that allows us to uncover β-sheet heterogeneities in the AD, which may be significant for targeted therapeutic strategies in the future.

In molecular beams, the tertiary amine N,N-dimethylisopropyl amine can form molecular clusters that are evident in photoelectron and mass spectra obtained upon resonant multiphoton ionization via the 3p and 3s Rydberg states. By delaying the ionization pulse from the excitation pulse we follow, in time, the ultrafast energy relaxation dynamics of the 3p to 3s internal conversion and the ensuing cluster evaporation, proton transfer, and structural dynamics. While evaporation of the cluster occurs in the 3s Rydberg state, proton transfer dominates on the ion surface. The mass-spectrum shows protonated species that arise from a proton transfer from the alpha-carbon of the neutral parent molecule to the N-atom of its ionized partner in the dimer. DFT calculations support the proton transfer mechanism between tightly bonded cluster components. The photoelectron spectrum shows broad peaks, ascribed to molecular clusters, which have an instantaneous shift of about 0.5 eV toward lower binding energies. That shift is attributed to the charge redistribution associated with the induced dipoles in surrounding cluster molecules. A time-dependent shift that decreases the Rydberg electron binding energy by a further 0.4 eV arises from the structural reorganization of the cluster solvent molecules as they react to the sudden creation of a charge.