Influence of Vibrational Excitation and Nuclear Dynamics in Multiphoton Photoelectron Circular Dichroism of Fenchone.

We report photoelectron circular dichroism of S-(+)-fenchone enantiomers recorded with state-state vibrational level resolution using picosecond laser (2 + 1) resonance enhanced multiphoton ionization via 3s and 3p Rydberg intermediate states. The 3p state decays to the 3s state on a picosecond time scale so that, above the 3p Rydberg excitation threshold, ionization of vibrationally hot 3s states competes with direct 3p-1 ionization. Complex vibronic dynamics of the 3p → 3s internal conversion weaken the Rydberg Δv = 0 propensity rule in both the 3p-1 and 3s-1 ionization channels. Large variations of the forward-backward chiral asymmetry factors are observed between the Δv = 0 and Δv > 0 vibrational transitions, including dramatic swings from up to ±17%. Such changes of sign indicate complete reversal of the preferred direction for photoelectron emission in the laboratory frame, associated with vibrational motion. These asymmetry switches easily exceed the amplitude and frequency of such vibrationally induced flips previously observed in single photon ionization.

Dynamics of electronically excited states in the eumelanin building block 5,6-dihydroxyindole.

We report the first excited state dynamics study of gas-phase 5,6-dihydroxyindole (5,6-DHI), a key building block of eumelanin pigments that are found throughout nature and serve as important photo-protective compounds. Time-resolved ion-yield measurements over the 241-296 nm ultraviolet photoexcitation region revealed non-adiabatic processes occurring on up to three distinct timescales. These reflect ultrafast (i.e. sub-picosecond) internal conversion within the excited state singlet manifold, and much longer-lived processes ranging from 10 ps to in excess of 1 ns. Our investigation paves the way for precisely targeted future studies of 5,6-DHI that exploit more differential measurement techniques. The work was facilitated by the use of soft laser-based thermal desorption to introduce 5,6-DHI samples into the gas phase. This approach, based on low-cost, readily available diode lasers, is straightforward, easily controllable and potentially applicable to a wide range of non-volatile molecular species.

Imaging the Photodissociation Dynamics of Nitrous Acid (HONO): The Role of Torsion.

We present the findings of the first imaging study of trans-HONO and cis-HONO photodissociation through the [Formula: see text] band and [Formula: see text] band of the Ã1A″-X̃1A' transition. The NO photofragment was probed by (1 + 1) resonance-enhanced multiphoton ionization and studied using the direct-current slice imaging technique with our finite slice reconstruction method. The NO state-specific translational energy distributions show some rotational structure corresponding to the internal state distribution in the OH cofragment. All images showed a perpendicular angular distribution with a recoil anisotropy parameter from ca. -0.6 to -0.8. In both bands, cis-HONO showed greater anisotropy than trans-HONO. Deviation from the limiting value expected for a pure perpendicular dissociation is ascribed to deviation of the transition moment from normal to the heavy atom plane owing to OH torsion, rather than lifetime effects assumed in the large body of previous work.

Imaging diffraction oscillations for inelastic collisions of NO radicals with He and D2.

We present state-to-state differential cross sections for collisions of NO molecules (X2Π1/2,j=1/2,f) with He atoms and ortho-D2 (j = 0) molecules as a function of collision energy. A high angular resolution obtained using the combination of Stark deceleration and velocity map imaging allows for the observation of diffraction oscillations in the angular scattering distributions. Differences in the differential cross sections and, in particular, differences in the angular spacing between individual diffraction peaks are observed. Since the masses of D2 and He are almost equal and since D2(j = 0) may be considered as a pseudo-atom, these differences directly reflect the larger size of D2 as compared to He. The observations are in excellent agreement with the cross sections obtained from quantum close-coupling scattering calculations based on accurate ab initio NO-He and NO-D2 potential energy surfaces. For the latter, we calculated a new NO-D2 potential energy surface.

Caveats in the interpretation of time-resolved photoionization measurements: A photoelectron imaging study of pyrrole.

We report time-resolved photoelectron imaging studies of gas-phase pyrrole over the 267-240 nm excitation region, recorded in conjunction with a 300 nm probe. Of specific interest is the lowest-lying (3s/πσ*) state, which exhibits very weak oscillator strength but is thought to be excited directly at wavelengths ≤254 nm. We conclude, however, that the only significant contribution to our photoelectron data at all wavelengths investigated is from non-resonant ionization. Our findings do not rule out (3s/πσ*) state excitation (as appears to be confirmed by supporting time-resolved ion-yield measurements) but do potentially highlight important caveats regarding the use and interpretation of photoreactant ionization measurements to interrogate dynamical processes in systems exhibiting significant topological differences between the potential energy surfaces of the neutral and cation states.

Ultrafast relaxation dynamics of electronically excited piperidine: ionization signatures of Rydberg/valence evolution.

We have investigated the electronic relaxation dynamics of gas-phase piperidine (a secondary aliphatic amine) using time-resolved photoelectron imaging. Following 200 nm excitation, spectrally sharp and highly anisotropic photoelectron data reveal ultrafast (60 fs) internal conversion between the initially excited 3px Rydberg state and the lower-lying 3s Rydberg state, mediated by the evolution of nσ* valence character along the 3px N-C bond. This behaviour is in good agreement with previously reported findings for several tertiary aliphatic amines. In contrast to the these systems, however, much broader photoelectron signals exhibiting only very small angular anisotropy and two distinct decay timescales (180 fs and 1.7 ps) were also observed. As confirmed by our supporting calculations, this is attributable to nσ* valence character now evolving along the N-H stretching coordinate within the 3s Rydberg state as the molecule starts dissociating to yield H atom photoproducts in conjunction with ground state piperidinyl radicals. By analogy with systems such as ammonia and morpholine, we conclude this event may occur either promptly or, alternatively, via a "frustrated" process where the system repeatedly traverses the upper cone of a conical intersection with the ground state until the required region of phase space is sampled to facilitate non-adiabatic population transfer. Our findings reveal the role of several different nuclear coordinate motions in driving stepwise internal conversion across multiple potential energy surfaces and the distinct photoionization signatures that are associated with these processes.

The role of novel Rydberg-valence behaviour in the non-adiabatic dynamics of tertiary aliphatic amines.

Time-resolved photoelectron imaging was used to study non-adiabatic relaxation dynamics in N,N-dimethylisopropylamine, N,N-dimethylpropylamine and N-methylpyrrolidine following excitation at 200 nm. This series of tertiary aliphatic amines are all of similar chemical makeup, but exhibit differences in their structure - being branched, straight-chain and cyclic, respectively. Our experimental investigation, supported by extensive theoretical calculations, provides considerable new insight into the nature of the internal conversion processes that mediate dynamical evolution between electronic states of predominantly Rydberg character in this important class of model photochemical systems. In particular, the angle-resolved data afforded by the imaging approach (something not previously reported for tertiary aliphatic amines) offers novel and highly-detailed mechanistic information about the overall relaxation pathway. Strikingly, both the experimental and theoretical findings suggest that a critical factor driving the non-adiabatic dynamics is the evolution of valence character along an N-C stretching coordinate within a member of the 3p manifold. This is in stark contrast to primary and secondary amines, as well as many other small hetero-atom containing organic species, where evolution of valence character within the 3s state is now a well-established phenomenon implicated in mediating ultrafast non-adiabatic photochemistry.

Relative Photoionization Cross Sections of Super-Atom Molecular Orbitals (SAMOs) in C60.

The electronic structure and photoinduced dynamics of fullerenes, especially C60, is of great interest because these molecules are model systems for more complex molecules and nanomaterials. In this work we have used Rydberg Fingerprint Spectroscopy to determine the relative ionization intensities from excited SAMO (Rydberg-like) states in C60 as a function of laser wavelength. The relative ionization intensities are then compared to the ratio of the photoionization widths of the Rydberg-like states, computed in time-dependent density functional theory (TD-DFT). The agreement is remarkably good when the same photon order is required to energetically access the excited states. This illustrates the predictive potential of quantum chemistry for studying photoionization of large, complex molecules as well as confirming the assumption that is often made concerning the multiphoton excitation and rapid energy redistribution in the fullerenes.

Time-resolved photoionization spectroscopy of mixed Rydberg-valence states: indole case study.

Time-resolved photoelectron imaging was used to study non-adiabatic relaxation dynamics in gas-phase indole following photo-excitation at 267 nm and 258 nm. Our data analysis was supported by various ab initio calculations using both coupled cluster and density functional methods. The highly differential energy- and angle-resolved information provided by our experimental approach provides extremely subtle details of the complex interactions occurring between several low-lying electronically excited states. In particular, new insight into the role and fate of the mixed Rydberg-valence 3s/πσ* state is revealed. This includes population residing on the excited state surface at large N-H separations for a relatively long period of time (∼1 ps) prior to dissociation and/or internal conversion. Our findings may, in part, be rationalized by considering the rapid evolution of this state's electronic character as the N-H stretching coordinate is extended - as extensively demonstrated in the supporting theory. Overall, our findings highlight a number of important general caveats regarding the nature of mixed Rydberg-valence excited states, their spectral signatures and detection sensitivity in photoionization measurements, and the evaluation of their overall importance in mediating electronic relaxation in a wide range of small model-chromophore systems providing bio-molecular analogues - a topic of considerable interest within the chemical dynamics community over the last decade.

Ultraviolet relaxation dynamics of aniline, N, N-dimethylaniline and 3,5-dimethylaniline at 250 nm.

Time-resolved photoelectron imaging was used to investigate the electronic relaxation dynamics of gas-phase aniline, N, N-dimethylaniline, and 3,5-dimethylaniline following ultraviolet excitation at 250 nm. Our analysis was supported by ab initio coupled-cluster calculations evaluating excited state energies and (in aniline) the evolution of a range of excited state physical properties as a function of N-H bond extension. Due to a lack of consistency between several earlier studies undertaken in aniline, the specific aim of this present work was to gain new insight into the previously proposed non-adiabatic coupling interaction between the two lowest lying singlet excited states S1(ππ(∗)) and S2(3s/πσ(∗)). The methyl-substituted systems N, N-dimethylaniline and 3,5-dimethylaniline were included in order to obtain more detailed dynamical information about the key internal molecular coordinates that drive the S1(ππ(∗))/S2(3s/πσ(∗)) coupling mechanism. Our findings suggest that in all three systems, both electronic states are directly populated during the initial excitation, with the S2(3s/πσ(∗)) state then potentially decaying via either direct dissociation along the N-X stretching coordinate (X = H or CH3) or internal conversion to the S1(ππ(∗)) state. In aniline and N, N-dimethylaniline, both pathways most likely compete in the depletion of S2(3s/πσ(∗)) state population. However, in 3,5-dimethylaniline, only the direct dissociation mechanism appears to be active. This is rationalized in terms of changes in the relative rates of the two decay pathways upon methylation of the aromatic ring system.

Solvent induced conformer specific photochemistry of guaiacol.

Using a combination of ultrafast solution- and gas-phase spectroscopies, together with high-level theory calculations, we demonstrate that we are able to track conformer-specific photodissociation dynamics in solution through solvent choice. We reveal this phenomenon in guaiacol (2-methoxyphenol), a key subunit of the natural biopolymer lignin. In cyclohexane, the first electronically excited (1)ππ* (S1) state in guaiacol relaxes with a time-constant of τ = 4.5 ± 0.2 ns, mediated through intersystem crossing to lower lying triplet (Tn) states and internal conversion and fluorescence back to the ground state (S0). In contrast, in methanol, a further relaxation channel is also present; the S1 state relaxes with a time-constant of τ = 2.9 ± 0.1 ns, which is now additionally mediated through coupling onto a dissociative (1)πσ* (S2) state and subsequent O-H bond fission, evidenced through the appearance of a spectral signature for the guaiacoxyl radical after ∼250 ps. With the aid of complementary calculations, we attribute this to the now absent intramolecular H-bond between OH and OMe moieties, which now favours intermolecular H-bonding to methanol, lowering the barrier to O-H dissociation and facilitating H-atom loss via tunnelling.

Following the relaxation dynamics of photoexcited aniline in the 273-266 nm region using time-resolved photoelectron imaging.

Time-resolved photoelectron imaging was used to investigate the relaxation dynamics of electronically excited aniline in the gas-phase following ultraviolet irradiation in the 273-266 nm region. We find that at all wavelengths studied, excitation is predominantly to the long-lived (>1 ns) S1(ππ(*)) state, which exhibits ultrafast intramolecular vibrational redistribution on a <1 ps timescale. At excitation wavelengths centred on resonant transitions in the aniline absorption spectrum that have previously been assigned to the higher lying S2(3s∕πσ(*)) state, we also see clear evidence of this state playing a role in the dynamics. However, we see no indication of any non-adiabatic coupling between the S1(ππ(*)) and S2(3s∕πσ(*)) states over the range of excitation wavelengths studied.

Time-resolved photoelectron imaging of excited state relaxation dynamics in phenol, catechol, resorcinol, and hydroquinone.

Time-resolved photoelectron imaging was used to investigate the dynamical evolution of the initially prepared S(1) (ππ*) excited state of phenol (hydroxybenzene), catechol (1,2-dihydroxybenzene), resorcinol (1,3-dihydroxybenzene), and hydroquinone (1,4-dihydroxybenzene) following excitation at 267 nm. Our analysis was supported by ab initio calculations at the coupled-cluster and CASSCF levels of theory. In all cases, we observe rapid (<1 ps) intramolecular vibrational redistribution on the S(1) potential surface. In catechol, the overall S(1) state lifetime was observed to be 12.1 ps, which is 1-2 orders of magnitude shorter than in the other three molecules studied. This may be attributed to differences in the H atom tunnelling rate under the barrier formed by a conical intersection between the S(1) state and the close lying S(2) (πσ*) state, which is dissociative along the O-H stretching coordinate. Further evidence of this S(1)/S(2) interaction is also seen in the time-dependent anisotropy of the photoelectron angular distributions we have observed. Our data analysis was assisted by a matrix inversion method for processing photoelectron images that is significantly faster than most other previously reported approaches and is extremely quick and easy to implement.

Case-control studies of risk factors for primary biliary cirrhosis in two United Kingdom populations.

OBJECTIVE: The aetiology of primary biliary cirrhosis (PBC) is largely unknown. Previous studies have indicated that both environmental and genetic risk factors may be important. DESIGN: We undertook a large case-control study to study possible risk factors in more detail. All patients were sent postal questionnaires on risk factors. PATIENTS: We identified two sets of PBC cases from a geographically defined epidemiology study (epidemiological cases) and from a survey of the national patient support group (Foundation cases). Controls were selected from the electoral roll in strata matched to epidemiological cases by quartiles of age and sex. RESULTS: Analysable questionnaires were received from 318 epidemiological cases, 2258 Foundation cases and 2438 controls. Statistically significant associations were seen with smoking (OR=1.63 (95% CI, 1.27 to 2.09)), epidemiological cases versus controls (1.57 (1.39 to 1.78)), Foundation cases versus controls, hair dye use (1.37 (0.98 to 1.80)), 1.25 (1.07 to 1.46)), and with previous histories of psoriasis (1.90 (1.21 to 1.91), 2.33 (1.03 to 1.73)), urinary infections (2.06 (1.56 to 0.1.73), 1.80 (1.54 to 2.11)), and shingles (2.38 (1.82 to 3.11), 1.23 (1.08 to 1.43)) and previous autoimmune diseases. Alcohol consumption was negatively associated with PBC (0.57 (0.39 to 0.83), 0.73 (0.61 to 0.79)). We did not identify any associations with obstetric risk factors except a previous history of obstetric cholestasis (2.13 (1.25 to 3.59), 2.20 (1.61 to 3.03)). CONCLUSION: We have confirmed that among environmental risk factors, smoking and the use of some cosmetics as well as urinary infections appear important. Among possible genetic risk factors a family history of PBC is a strong association and that a previous history of obstetric cholestasis as another putative 'genetic' risk.

Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis.

BACKGROUND AND AIMS: Study of health related quality of life (HRQOL) and the factors responsible for its impairment in primary biliary cirrhosis (PBC) has, to date, been limited. There is increasing need for a HRQOL questionnaire which is specific to PBC. The aim of this study was to develop, validate, and evaluate a patient based PBC specific HRQOL measure. SUBJECTS AND METHODS: A pool of potential questions was derived from thematic analysis of indepth interviews carried out with 30 PBC patients selected to represent demographically the PBC patient population as a whole. This pool was systematically reduced, pretested, and cross validated with other HRQOL measures in national surveys involving a total of 900 PBC patients, to produce a quality of life profile measure, the PBC-40, consisting of 40 questions distributed across six domains. The PBC-40 was then evaluated in a blinded comparison with other HRQOL measures in a further cohort of 40 PBC patients. RESULTS: The six domains of PBC-40 relate to fatigue, emotional, social, and cognitive function, general symptoms, and itch. The highest mean domain score was seen for fatigue and the lowest for itch. The measure has been fully validated for use in PBC and shown to be scientifically sound. PBC patient satisfaction, measured in terms of the extent to which a questionnaire addresses the problems that they experience, was significantly higher for the PBC-40 than for other HRQOL measures. CONCLUSION: The PBC-40 is a short easy to complete measure which is acceptable to PBC patients and has significantly greater relevance to their problems than other frequently used HRQOL measures. Its scientific soundness, shown in extensive testing, makes it a valuable instrument for future use in clinical and research settings.

The diurnal profile of gastric pepsin activity is reduced with Helicobacter pylori infection.

Both Helicobacter pylori and pepsin are proven mucosal damaging agents and implicated in the aetiology of peptic ulcer disease. Historically studies of pepsin over time have proved methodologically difficult, and as a result little work has been done on the effect of H. pylori on luminal pepsin secretion. Our objectives were to determine pepsin activity over 24 hr in normal human subjects and to examine luminal pepsin activity in relation to H. pylori infection. Twenty-seven healthy volunteers had gastric juice samples aspirated every 2 hr for 24 hr. All subjects had H. pylori status determined by C13 urea breath test and serology. Meals were standardized throughout the study period. Gastric juice samples were measured for pH, diluted, and frozen in acetate buffer pH 4.1 for up to 1 month, conditions shown to cause no loss of activity. Individual samples were measured for pepsin activity by assaying for new N-terminal peptide formation. Mean pepsin activity (microg enzyme/ml) in 21 normal H. pylori-negative subjects ranged from 114 to 1030 microg/ml, with a characteristic diurnal profile of increasing activity to maximum after the evening meal. Mean pepsin activity in subjects with H. pylori was consistently below that for age-matched H. pylori-negative subjects at each time point. Overall mean pepsin activity was significantly lower in those with H. pylori compared to those without (P < 0.001). There is significant pepsin activity in the stomach throughout the 24-hr period, with a trend for the highest activity through the night. Subjects with H. pylori infection have lower luminal pepsin activity.

Tamoxifen: a novel treatment for primary biliary cirrhosis?

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, which predominantly affects women. It is characterised histologically by necroinflammation of small intrahepatic bile ducts and biochemically by elevated serum alkaline phosphatase, levels of which at diagnosis predict survival. Ursodeoxycholic acid (UDCA) is the only treatment shown to improve liver biochemistry and survival. We report two patients with PBC who show a fall in serum alkaline phosphates levels whilst receiving tamoxifen therapy. Tamoxifen may exert this effect, which warrants further study, either via cholangiocyte estrogen receptors, inhibiting cholangiocyte proliferation and inducing apoptosis or by activating pregnane X receptor, analogous to the mode of action of UDCA.

Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study.

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic liver disease with autoimmune features but uncertain aetiology. Increased risk of PBC among relatives of patients may reflect common environmental factors, or inherited immunogenetic susceptibility. Associations between PBC and other autoimmune diseases have been reported, but their true extent and pattern is unknown. AIM: To examine the prevalence and association patterns of autoimmune disease in a representative group of PBC patients. DESIGN: Clinical cohort study. METHODS: We clinically assessed members of a geographically-based PBC patient cohort (n = 160) for the presence of additional autoimmune disease, using established specific diagnostic criteria. RESULTS: Some 53% of patients had at least one additional autoimmune condition, and 63% had serum autoantibodies other than AMA or ANA. AMA+ patients had a significantly lower prevalence of additional autoimmunity than AMA- patients (49% vs. 79%; p < 0.01). The greatest relative increase in disease prevalence was for scleroderma (8% of patients). Autoimmune disease was present in 14% of first-degree relatives. DISCUSSION: PBC patients and their families have a wide susceptibility to autoimmunity. This observation supports an autoimmune aetiology and suggests that the genetic basis of PBC is likely to be expressed, at least in part, through factors controlling immune tolerance in general.

Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort.

BACKGROUND: Many patients with primary biliary cirrhosis (PBC) are asymptomatic at the time of diagnosis. However, because most studies of asymptomatic PBC have been small and from tertiary centres, asymptomatic PBC remains poorly characterised. AIMS: To describe the features and progression of initially asymptomatic PBC patients. METHODS: Follow up by interview and note review of a large geographically and temporally defined cohort of patients with PBC, collected by multiple methods. RESULTS: Of a total of 770 patients, 469 (61%) were asymptomatic at diagnosis. These patients had biochemically and histologically less advanced disease than initially symptomatic patients. Median survival was similar in both groups (9.6 v 8.0 years, respectively) possibly due to excess of non-liver related deaths in asymptomatic patients (31% v 57% of deaths related to liver disease). Survival in initially asymptomatic patients was not affected by subsequent symptom development. By the end of follow up, 20% of initially asymptomatic patients had died of liver disease or required liver transplantation. The majority of initially asymptomatic patients developed symptoms of liver disease if they were followed up for long enough (Kaplan-Meier estimate of proportion developing symptoms: 50% after five years, 95% after 20 years). However, 45% of patients remained asymptomatic at the time of death. CONCLUSIONS: Although asymptomatic PBC is less severe at diagnosis than symptomatic disease, it is not associated with a better prognosis, possibly due to an increase in non-hepatic deaths. The reasons for this are unclear but may reflect confounding by other risk factors or surveillance bias. These findings have important implications for future treatment strategies.

Snoring, daytime sleepiness and stroke: a case-control study of first-ever stroke.

Previous reports have shown an association between snoring and stroke but it is not clear whether this reflects confounding factors nor whether the association is attributable to obstructive sleep apnoea (OSA). We performed a case-control study of 181 patients admitted to hospital with first-ever stroke and community control subjects matched individually for age, sex and general practitioner. Subjects were interviewed with a structured questionnaire to identify snoring, daytime sleepiness and stroke risk factors. The association between snoring alone and stroke was not statistically significant: odds ratio (95% CI) 1.44 (0.88, 2.41). Daytime sleepiness was, however, significantly associated with stroke: odds ratio 3.07 (1.65, 6.08). Multiple logistic regression showed that hypertension, current smoking, taking alcohol regularly (negatively) and a higher Epworth sleepiness score were independently associated with stroke. The results suggest that the previously reported association between 'simple' snoring and stroke might have been due to poor controlling for confounding variables. Our study suggests an association with greater sleepiness prestroke, the cause of which is unclear, although OSA is a possible candidate.