Probing the photodynamics of photoprotective molecules and two-photon activated metal complexes

The work presented in this thesis consists of three distinct areas, each of which is explored using solution-phase femtosecond transient electronic (ultraviolet/visible) absorption spectroscopy. The first area is the effects of the environmental surroundings on the intrinsic photodynamics of a molecule. The second area is the photodynamics responsible for the apparent photostability of a pair of photoprotective molecules. Finally, we explore the effects of two-photon excitation on a ruthenium metal complex. The overarching link between these areas, which at face value appear disconnected, is the idea of the protection of biological systems from the deleterious effects of exposure to solar ultraviolet. The first experiment studies the solvation effects on the photodynamics of 4-tert-butyl-1,2-dihydroxybenzene, a motif of an ultraviolet radiation absorbing chromophore subunit of eumelanin, which serves in the body’s natural photoprotection mechanisms. This work demonstrates that the level of solvent interaction can have a drastic effect on the inherent photodynamics. In the case of a weakly interacting solvent the observed dynamics display a similarity to those observed of the molecule in the isolated environment of the gas-phase, which consist of an ultrafast O–H bond dissociation. However, when placed in a strongly interacting solvent, the dynamics change significantly. Rather than an ultrafast dissociation, a multitude of decay pathways occur instead and take place on the order of nanoseconds. The second experiment studies the ultrafast deactivation route for a pair of sunscreening agents, 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid and 3-(3,4-dihydroxyphenyl)-2-propenoic acid. In this work, we highlight an ultrafast photoisomerization pathway between the trans- and cis-isomers. This involves a population transfer between two excited states, aided by a conical intersection and subsequently through a second conical intersection between an excited state and ground state along the isomerization coordinate, to regenerate the original trans-isomer or the cis-isomer. The third experiment studies the role of two-photon activation on a ruthenium poly-pyridyl complex and compares this to the one-photon activation process. In this work we demonstrate that both methods of activation result in the same photoproduct and on comparable timescales and yields. In doing so, we demonstrate that the observed excited state dynamics appear to be independent of the excitation method, which may have repercussions in the design of next generation photochemotherapy drugs

Unravelling the photoprotection properties of mycosporine amino acid motifs

Photoprotection from harmful ultraviolet (UV) radiation exposure is a key problem in modern society. Mycosporine like amino acids found in fungi, cyanobacteria, macroalgae, phytoplankton and humans, are already presenting a promising form of natural photoprotection in sunscreen formulations. Using time-resolved transient electronic absorption spectroscopy and guided by complementary ab initio calculations, we help to unravel how the core structures of these molecules perform under UV irradiation. Through such detailed insight into the relaxation mechanisms of these ubiquitous molecules, we hope to inspire new thinking in developing next generation sun protecting molecules

Determination of secondary species in solution through pump-selective transient absorption spectroscopy and explicit-solvent TDDFT

The measured electronic excitations of a given species in solution are often a composite of the electronic excitations of various equilibrium species of that molecule. It is common for a proportion of a species to deprotonate in solution, or form a tautomeric equilibrium, producing new peaks corresponding to the electronic excitations of the new species. One prominent example is alizarin in methanol, which at different temperatures, and in solutions with differing pH, has an isosbestic point between the two dominant excitations at 435 and 540 nm. The peak at 435 nm has been attributed to alizarin; the peak at 540 nm, however, more likely results from a species in equilibrium with alizarin. In this work, we were able to use both experimental and computational techniques to selectively examine electronic properties of both alizarin and its secondary species in equilibrium. This was achieved through use of transient electronic absorption spectroscopy, following selective photoexcitation of a specific species in equilibrium. The resulting transient electronic absorption spectra were compared to the known transient absorption spectra of potential secondary equilibrium species. The ground state absorption spectra associated with each species in equilibrium were predicted using linear-scaling time-dependent density functional theory with an explicitly modeled solvent and compared to the experimental result. This evidence from both techniques combines to suggest that the excitation at 540 nm arises from a specific monoanionic form of alizarin

Bridging the gap between the gas and solution phase : solvent specific photochemistry in 4-tert-butylcatechol

Eumelanin is a naturally synthesized ultraviolet light absorbing biomolecule, possessing both photoprotective and phototoxic properties. We infer insight into these properties of eumelanin using a bottom-up approach, by investigating a subunit analogue, 4-tert-butylcatechol. Utilizing a combination of femtosecond transient electronic absorption spectroscopy and time-re-solved velocity map ion imaging, our results suggest an environmental-dependent relaxation pathway, following irradiation at 267 nm to populate the S1 (1ππ*) state. Gas-phase and non-polar solution-phase measurements reveal that the S1 state decays through coupling onto the S2 (1πσ*) state that is dissociative along the non-intramolecular hydrogen bonded ‘free’ O–H bond. This process is mediated by tunneling beneath an S1/S2 conical intersection and occurs in 4.9 ± 0.6 ps in the gas-phase and 27 ± 7 ps in the non-polar cyclohexane solution. Comparative studies on the deuterated isotopologue of 4-tert-butylcatechol in both the gas- and solution-phase (cyclohexane) reveals an average kinetic isotope effect of ~19 and ~7, respectively, supportive of O–H dissociation mediated by a quantum tunneling mechanism. In contrast, in the polar acetonitrile, the S1 state decays on a much longer timescale of 1.7 ± 0.1 ns. We propose that the S1 decay is now multicomponent, likely driven by internal conversion, intersystem crossing and fluorescence, as well as O–H dissociation. The attribution of conformer driven excited state dynamics to explain how the S1 state decays in the gas- and non-polar solution-phase versus the polar solution-phase, elegantly demonstrates the influence the environment has on the ensuing excited state dynamics

Excited-state dynamics of a two-photon-activatable ruthenium prodrug

We present a new approach to investigate how the photodynamics of an octahedral ruthenium(II) complex activated through two-photon absorption (TPA) differ from the equivalent complex activated through one-photon absorption (OPA). We photoactivated a RuII polypyridyl complex containing bioactive monodentate ligands in the photodynamic therapy window (620–1000 nm) by using TPA and used transient UV/Vis absorption spectroscopy to elucidate its reaction pathways. Density functional calculations allowed us to identify the nature of the initially populated states and kinetic analysis recovers a photoactivation lifetime of approximately 100 ps. The dynamics displayed following TPA or OPA are identical, showing that TPA prodrug design may use knowledge gathered from the more numerous and easily conducted OPA studies

Spectroscopic studies on photoinduced reactions of the anticancer prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]

The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py = pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption and UV-Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and multi-curve resolution alternating least squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans [Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a -10 cm-1 shift to the anti-symmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, where at least one hydroxyl radical is formed in the reduction of Pt(IV) to Pt(II). Additionally, the photoinduced reaction of 1 with 5'-guanosine monophosphate was studied, and the identity of key photoproducts was assigned with the help of ATR FTIR spectroscopy, mass spectrometry and DFT calculations. The identification of marker bands for photoproducts, e.g. trans-[Pt(N3)(py)2(5'-GMP)] and trans-[Pt(py)2(5'-GMP)2], will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes

Probing the ultrafast energy dissipation mechanism of the sunscreen oxybenzone after UVA irradiation

Oxybenzone is a common constituent of many commercially available sunscreens providing photoprotection from ultraviolet light incident on the skin. Femtosecond transient electronic and vibrational absorption spectroscopies have been used to investigate the non-radiative relaxation pathways of oxybenzone in cyclohexane and methanol after excitation in the UVA region. The present data suggest that the photoprotective properties of oxybenzone can be understood in terms of an initial ultrafast excited state enol -> keto tautomerization, followed by efficient internal conversion and subsequent vibrational relaxation to the ground state (enol) tautomer

Combatting AMR : photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid selective antimycobacterial activity

The novel photoactive ruthenium(II) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1·2PF6, INH = isoniazid) was designed to incorporate the anti-tuberculosis drug, isoniazid, that could be released from the Ru(II) cage by photoactivation with visible light. In aqueous solution, 1 rapidly released two equivalents of isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2]2+ upon irradiation with 465 nm blue light. We screened for activity against bacteria containing the three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and multi-colored LED multi-well arrays. Complex 1 is inactive in the dark, but when photoactivated is 5.5× more potent towards M. smegmatis compared to the clinical drug isoniazid alone. Complementary pump-probe spectroscopy measurements along with density functional theory calculations reveal that the mono-aqua product is formed in <500 ps, likely facilitated by a 3MC state. Importantly, complex 1 is highly selective in killing mycobacteria versus normal human cells, towards which it is relatively non-toxic. This work suggests that photoactivatable prodrugs such as 1 are potentially powerful new agents in combatting the global problem of antibiotic resistance

Liquid-Crystal-Based Controllable Attenuators Operating in the 1-4 Terahertz Band

Liquid-crystal devices (LCDs) offer a potential route toward adaptive optical components for use in the < 2 THz band of the electromagnetic spectrum. We demonstrate LCDs using a commercially available material (E7), with unbiased birefringence values of 0.14-0.18 in the 0.3-4 THz band. We exploit the linear dichroism of the material to modulate the emission from a 3.4-THz quantum cascade laser by up to 40%, dependent upon both the liquid-crystal layer thickness and the bias voltage applied.Comment: 10 pages, 6 figure

Switchbacks, microstreams, and broadband turbulence in the solar wind

Switchbacks are a striking phenomenon in near-Sun coronal hole flows, but their origins, evolution, and relation to the broadband fluctuations seen farther from the Sun are unclear. We use the near-radial lineup of Solar Orbiter and Parker Solar Probe during September 2020 when both spacecraft were in wind from the Sun's Southern polar coronal hole to investigate if switchback variability is related to large scale properties near 1 au. Using the measured solar wind speed, we map measurements from both spacecraft to the source surface and consider variations with source Carrington longitude. The patch modulation of switchback amplitudes at Parker at 20 solar radii was associated with speed variations similar to microstreams and corresponds to solar longitudinal scales of around 5°–10°. Near 1 au, this speed variation was absent, probably due to interactions between plasma at different speeds during their propagation. The alpha particle fraction, which has recently been shown to have spatial variability correlated with patches at 20 solar radii, varied on a similar scale at 1 au. The switchback modulation scale of 5°–10°, corresponding to a temporal scale of several hours at Orbiter, was present as a variation in the average deflection of the field from the Parker spiral. While limited to only one stream, these results suggest that in coronal hole flows, switchback patches are related to microstreams, perhaps associated with supergranular boundaries or plumes. Patches of switchbacks appear to evolve into large scale fluctuations, which might be one driver of the ubiquitous turbulent fluctuations in the solar wind