Three-Photon Spectroscopy of Porphyrins.

Recent advances in laser technology have made three-photon (3P) microscopy a real possibility, raising interest in the phenomenon of 3P absorption (3PA). Understanding 3PA of organic chromophores is especially important in view of those imaging applications that rely on exogenous probes, whose optical properties can be manipulated and optimized. Here, we present measurements and theoretical analysis of the degenerate 3PA spectra of several phosphorescent metalloporphyrins, which are used in the construction of biological oxygen probes. The effective 3PA cross sections (σ(3)) of these porphyrins near 1700 nm, a new promising biological optical window, were found to be on the order of 1000 GM3 (1 GM3 = 10-83 cm6 s2), therefore being among the highest values reported to date for organic chromophores. To interpret our data, we developed a qualitative four-state model specific for porphyrins and used it in conjunction with quantitative analysis based on the time-dependent density functional theory (TDDFT)/a posteriori Tamm-Dancoff approximation (ATDA)/sum-over-states (SOS) formalism. The analysis revealed that B (Soret) state plays a key role in the enhancement of 3PA of porphyrins in the Q band region, while the low-lying two-photon (2P)-allowed gerade states interfere negatively and diminish the 3PA strength. This study features the first systematic examination of 3PA properties of porphyrins, suggesting ways to improve their performance and optimize them for imaging and other biomedical applications.

Ultrafast Solvation Dynamics and Vibrational Coherences of Halogenated Boron-Dipyrromethene Derivatives Revealed through Two-Dimensional Electronic Spectroscopy.

Boron-dipyrromethene (BODIPY) chromophores have a wide range of applications, spanning areas from biological imaging to solar energy conversion. Understanding the ultrafast dynamics of electronically excited BODIPY chromophores could lead to further advances in these areas. In this work, we characterize and compare the ultrafast dynamics of halogenated BODIPY chromophores through applying two-dimensional electronic spectroscopy (2DES). Through our studies, we demonstrate a new data analysis procedure for extracting the dynamic Stokes shift from 2DES spectra revealing an ultrafast solvent relaxation. In addition, we extract the frequency of the vibrational modes that are strongly coupled to the electronic excitation, and compare the results of structurally different BODIPY chromophores. We interpret our results with the aid of DFT calculations, finding that structural modifications lead to changes in the frequency, identity, and magnitude of Franck-Condon active vibrational modes. We attribute these changes to differences in the electron density of the electronic states of the structurally different BODIPY chromophores.

Drug-Free Noninvasive Thermal Nerve Block: Validation of Sham Devices.

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were offered for patients to use daily at-home for one week to assess the durability of sham placebo effects before participants were given active treatment in a second office visit followed by another optional week of self-administered active treatment at-home use. Sham treatments reduced pain scores by an average of 31% from 6.0 ± 2.3 to 4.3 ± 3.3, including two participants who fell asleep during the in-office treatment and woke up with no pain, but whose pain recurred after returning home during at-home use of the sham system. In-office active treatments reduced pain scores by 52% from 6.7 ± 2.1 to 3.3 ± 2.9 with sustained pain relief during optional at-home use. Successful blinding for the study was confirmed with an ideal Bang's Blinding Index of 0 and an ideal James' Blinding Index of 1. Both the sham and active treatments were viewed by participants as highly credible, and credibility increased from the beginning to end of sham treatments on average.

Resolving the Impact of Hydrogen Bonding on the Phylloquinone Cofactor through Two-Dimensional Infrared Spectroscopy.

Two-dimensional infrared spectroscopy (2DIR) was applied to phylloquinone (PhQ), an important biological cofactor, to elucidate the impact of hydrogen bonding on the ultrafast dynamics and energetics of the carbonyl stretching modes. 2DIR measurements were performed on PhQ dissolved in hexanol, which served as the hydrogen bonding solvent, and hexane, which served as a non-hydrogen bonding control. Molecular dynamics simulations and quantum chemical calculations were performed to aid in spectral assignment and interpretation. From the position of the peaks in the 2DIR spectra, we extracted the transition frequencies for the fundamental, overtone, and combination bands of hydrogen bonded and non-hydrogen bonded carbonyl groups of PhQ in the 1635-1680 cm-1 region. We find that hydrogen bonding to a single carbonyl group acts to decouple the two carbonyl units of PhQ. Through analysis of the time-resolved 2DIR data, we find that hydrogen bonding leads to faster vibrational relaxation as well as an increase in the inhomogeneous broadening of the carbonyl groups. Overall, this work demonstrates how hydrogen bonding to the carbonyl groups of PhQ presents in the 2DIR spectra, laying the groundwork to use PhQ as a 2DIR probe to characterize the ultrafast fluctuations in the local environment of natural photosynthetic complexes.

Unraveling Confined Dynamics of Guests Trapped in Self-Assembled Pd6L4 Nanocages by Ultrafast Mid-IR Polarization-Dependent Spectroscopy.

Self-assembled coordination cages form host-guest complexes through weak noncovalent interactions. Knowledge of how these weak interactions affect the structure, reactivity, and dynamics of guest molecules is important to further the design principles of current systems and optimize their specific functions. We apply ultrafast mid-IR polarization-dependent pump-probe spectroscopy to probe the effects of two Pd6L4 self-assembled nanocages on the properties and dynamics of fluxional group-VIII metal carbonyl guest molecules. We find that the interactions between the Pd6L4 nanocages and guest molecules act to alter the ultrafast dynamics of the guests, restricting rotational diffusional motion and decreasing the vibrational lifetime.