Capturing electron-driven chiral dynamics in UV-excited molecules.

Chiral molecules, used in applications such as enantioselective photocatalysis1, circularly polarized light detection2 and emission3 and molecular switches4,5, exist in two geometrical configurations that are non-superimposable mirror images of each other. These so-called (R) and (S) enantiomers exhibit different physical and chemical properties when interacting with other chiral entities. Attosecond technology might enable influence over such interactions, given that it can probe and even direct electron motion within molecules on the intrinsic electronic timescale6 and thereby control reactivity7-9. Electron currents in photoexcited chiral molecules have indeed been predicted to enable enantiosensitive molecular orientation10, but electron-driven chiral dynamics in neutral molecules have not yet been demonstrated owing to the lack of ultrashort, non-ionizing and perturbative light pulses. Here we use time-resolved photoelectron circular dichroism (TR-PECD)11-15 with an unprecedented temporal resolution of 2.9 fs to map the coherent electronic motion initiated by ultraviolet (UV) excitation of neutral chiral molecules. We find that electronic beatings between Rydberg states lead to periodic modulations of the chiroptical response on the few-femtosecond timescale, showing a sign inversion in less than 10 fs. Calculations validate this and also confirm that the combination of the photoinduced chiral current with a circularly polarized probe pulse realizes an enantioselective filter of molecular orientations following photoionization. We anticipate that our approach will enable further investigations of ultrafast electron dynamics in chiral systems and reveal a route towards enantiosensitive charge-directed reactivity.

Far-Field Petahertz Sampling of Plasmonic Fields.

The response of metal nanostructures to optical excitation leads to localized surface plasmon (LSP) generation with nanoscale field confinement driving applications in, for example, quantum optics and nanophotonics. Field sampling in the terahertz domain has had a tremendous impact on the ability to trace such collective excitations. Here, we extend such capabilities and introduce direct sampling of LSPs in a more relevant petahertz domain. The method allows to measure the LSP field in arbitrary nanostructures with subcycle precision. We demonstrate the technique for colloidal nanoparticles and compare the results to finite-difference time-domain calculations, which show that the build-up and dephasing of the plasmonic excitation can be resolved. Furthermore, we observe a reshaping of the spectral phase of the few-cycle pulse, and we demonstrate ad-hoc pulse shaping by tailoring the plasmonic sample. The methodology can be extended to single nanosystems and applied in exploring subcycle, attosecond phenomena.

Site-dependent nuclear dynamics in core-excited butadiene.

Symmetry breaking and competition between electronic decay and nuclear dynamics are major factors determining whether the memory of the initial core-hole localisation in a molecule is retained long enough to affect fragmentation. We investigate the fate of core holes localised at different sites in the free 1,3 trans butadiene molecule by using synchrotron radiation to selectively excite core electrons from different C 1s sites to π* orbitals. Fragmentation involving bonds localised at the site of the core hole provides clear evidence for preferential bond breaking for a core hole located at the terminal carbon site, while the signature of localisation is weak for a vacancy on the central carbon site. The origin of this difference is attributed to out-of-plane vibrations, and statistical evaporation of protons for vacancies located at the central carbon sites.

Real-time observation of a correlation-driven sub 3 fs charge migration in ionised adenine.

Sudden ionisation of a relatively large molecule can initiate a correlation-driven process dubbed charge migration, where the electron density distribution is expected to rapidly move along the molecular backbone. Capturing this few-femtosecond or attosecond charge redistribution would represent the real-time observation of electron correlation in a molecule with the enticing prospect of following the energy flow from a single excited electron to the other coupled electrons in the system. Here, we report a time-resolved study of the correlation-driven charge migration process occurring in the nucleic-acid base adenine after ionisation with a 15-35 eV attosecond pulse. We find that the production of intact doubly charged adenine - via a shortly-delayed laser-induced second ionisation event - represents the signature of a charge inflation mechanism resulting from many-body excitation. This conclusion is supported by first-principles time-dependent simulations. These findings may contribute to the control of molecular reactivity at the electronic, few-femtosecond time scale.

Fission of charged nano-hydrated ammonia clusters - microscopic insights into the nucleation processes.

While largely studied on the macroscopic scale, the dynamics leading to nucleation and fission processes in atmospheric aerosols are still poorly understood at the molecular level. Here, we present a joint experimental-theoretical study of a model system consisting of hydrogen-bonded ammonia and water molecules. Experimentally, the clusters were produced via adiabatic co-expansion. Double ionization ionic products were prepared using synchrotron radiation and analyzed with coincidence mass- and 3D momentum spectroscopy. Calculations were carried out using ab initio molecular dynamics to understand the fragmentation within the first ∼500 fs. Further exploration of the potential energy surfaces was performed at a DFT level of theory to gain information on the energetics of the processes. Water was identified as an efficient nano-droplet stabilizer, and is found to have a significant effect even at low water content. On the molecular level, the stabilizing role of water can be related to an increase in the dissociation energy between ammonia molecules and the water enriched environment at the cluster surface. Furthermore, our results support the role of ammonium as a charge carrier in the solution, preferentially bound to surrounding ammonia molecules, which can influence the atmospheric nucleation process.

Generation of deep ultraviolet sub-2-fs pulses.

We demonstrate the generation of few-cycle deep ultraviolet pulses via frequency upconversion of 5-fs near-infrared pulses in argon using a laser-fabricated gas cell. The measured spectrum extends from 210 to 340 nm, corresponding to a transform-limited pulse duration of 1.45 fs. We extract from a dispersion-free second-order cross-correlation measurement a pulse duration of 1.9 fs, defining a new record in the deep ultraviolet spectral range.

The role of charge and proton transfer in fragmentation of hydrogen-bonded nanosystems: the breakup of ammonia clusters upon single photon multi-ionization.

The charge and proton dynamics in hydrogen-bonded networks are investigated using ammonia as a model system. The fragmentation dynamics of medium-sized clusters (1-2 nm) upon single photon multi-ionization is studied, by analyzing the momenta of small ionic fragments. The observed fragmentation pattern of the doubly- and triply-charged clusters reveals a spatial anisotropy of emission between fragments (back-to-back). Protonated fragments exhibit a distinct kinematic correlation, indicating a delay between ionization and fragmentation (fission). The different kinematics observed for channels containing protonated and unprotonated species provides possible insights into the prime mechanisms of charge and proton transfer, as well as proton hopping, in such a nanoscale system.

Dissociation of cyclopropane in double ionization continuum.

Dissociative double photoionization of cyclopropane is studied in the inner-valence region using tunable synchrotron radiation. With the aid of ab initio quantum chemical calculations the energies of dication states and their favoured fragmentation pathways are determined. These are compared to the experimental appearance energies of two-body fragmentation processes and to the kinetic energy released upon dissociation. Photon energy dependent state-selective dissociation in the 25-35 eV range is found. Calculations of dissociation pathways suggest that cyclopropane ring-deformation is selectively triggered at certain photon energies. The calculations suggest that initial ring deformation essentially determines the population of different dication states that function as gateways for particular dissociation channels. The measurements show that stepwise ionization processes populate dissociative 3e'-2 states via ring-opening and Jahn-Teller active states at photon energies below the double-ionization threshold. For energies above the double-ionization threshold the kinematics indicate that double ionization takes place predominantly within the Franck-Condon region populating 3e'-1 1e''-1 states.

Dissociative double-photoionization of butadiene in the 25-45 eV energy range using 3-D multi-coincidence ion momentum imaging spectrometry.

Dissociative double-photoionization of butadiene in the 25-45 eV energy range has been studied with tunable synchrotron radiation using full three-dimensional ion momentum imaging. Using ab initio calculations, the electronic states of the molecular dication below 33 eV are identified. The results of the measurement and calculation show that double ionization from π orbitals selectively triggers twisting about the terminal or central C-C bonds. We show that this conformational rearrangement depends upon the dication electronic state, which effectively acts as a gateway for the dissociation reaction pathway. For photon energies above 33 eV, three-body dissociation channels where neutral H-atom evaporation precedes C-C charge-separation in the dication species appear in the correlation map. The fragment angular distributions support a model where the dication species is initially aligned with the molecular backbone parallel to the polarization vector of the light, indicating a high probability for double-ionization to the "gateway states" for molecules with this orientation.

Molecular dynamics of NH3 induced by core-electron excitation.

Nuclear motion in the N1s(-1)4a core-excited state of ammonia is investigated by studying the angular anisotropy of fragments produced in the decay of the highly excited molecule and compared with predictions from ab initio calculations. Two different fragmentation channels (H(+)/NH2(+) and H(+)/NH(+)/H) reveal complex nuclear dynamics as the excitation photon energy is tuned through the 4a1 resonance. The well-defined angular anisotropy of the fragments produced in the dissociation of the molecular dication species suggests a very rapid nuclear motion and the time scale of the nuclear dynamics is limited to the low fs timescale.

Multi-purpose two- and three-dimensional momentum imaging of charged particles for attosecond experiments at 1 kHz repetition rate.

We report on the versatile design and operation of a two-sided spectrometer for the imaging of charged-particle momenta in two dimensions (2D) and three dimensions (3D). The benefits of 3D detection are to discern particles of different mass and to study correlations between fragments from multi-ionization processes, while 2D detectors are more efficient for single-ionization applications. Combining these detector types in one instrument allows us to detect positive and negative particles simultaneously and to reduce acquisition times by using the 2D detector at a higher ionization rate when the third dimension is not required. The combined access to electronic and nuclear dynamics available when both sides are used together is important for studying photoreactions in samples of increasing complexity. The possibilities and limitations of 3D momentum imaging of electrons or ions in the same spectrometer geometry are investigated analytically and three different modes of operation demonstrated experimentally, with infrared or extreme ultraviolet light and an atomic/molecular beam.

Rapid bond rearrangement in core-excited molecular water.

The angular anisotropy of fragments created in the dissociation of core-electron excited water molecules is studied to probe the correlation between fragmentation channels, kinematics and molecular geometry. We present fragment kinetic measurements for water molecules where the inner-shell oxygen electron is excited to the unoccupied 4a1 and 2b2 valence molecular orbitals. The kinematics of individual fragmentation channels are measured using fully three-dimensional momentum imaging of fragments. The results show that the geometry of the molecule and the kinetic energy of fragments are strongly coupled in the atomisation process. In addition we identify a fragmentation process arising from bond rearrangement evidenced by the H2(+)-O(+) ion pair which is accessible for resonant excitation of the 1s electron. In all of the two-body fragmentation processes the dissociation takes place along the potential-energy surface, while atomisation reveals both dissociation along the potential surface and Coulomb explosion. The angular distribution of fragments suggests that the bond rearrangement is very rapid; likely on a sub 10 fs time scale.

Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the kappa opioid receptor.

A series of 2-substituted sulfamoyl arylacetamides of general structure 2 were prepared as potent kappa opioid receptor agonists and the affinities of these compounds for opioid and chimeric receptors were compared with those of dynorphin A. Compounds 2e and 2i were identified as non-peptide small molecules that bound to chimeras 3 and 4 with high affinities similar to dynorphin A, resulting in K(i) values of 1.5 and 1.2 nM and 1.3 and 2.2 nM, respectively.

Pharmacological characterization of human kappa/mu opioid receptor chimeras that retain high affinity for dynorphin A.

Arylacetamide analgesics that stimulate kappa opioid receptors in the central nervous system mediate dysphoria and psychosis as well as analgesia. However, the naturally occurring peptide agonist, dynorphin A, is analgesic in the absence of dysphoria and psychosis, indicating that the therapeutic effects of kappa opioid agonists may be separated from their side effects. As part of our effort to discover kappa opioid receptor analgesics lacking side effects, we designed and constructed two mu/kappa chimeric receptors, composed primarily of amino acid residues derived from the mu opioid receptor, that were expected to bind dynorphin A with high affinity. In one, extracellular loop 2 and transmembrane domain 4 were derived from the kappa opioid receptor and in the other, only extracellular loop 2 was derived from the kappa opioid receptor. Most competitors of [(3)H]diprenorphine binding from a variety of structural classes bound to the chimeras with affinities similar to those with which they bound to the mu opioid receptor. In contrast, dynorphin A analogs bound to the chimeras with affinities similar to those with which they bound to the kappa opioid receptor. Pharmacological characterization of [(35)S]GTPgammaS binding mediated by the chimera with extracellular loop 2 derived from the kappa opioid receptor showed that it behaved as if it were mu opioid receptor with high affinity for dynorphin A analogs. These chimeras may be useful in identifying novel kappa receptor agonists that bind to the second extracellular loop of the receptor and share the desirable therapeutic profile of dynorphin A.

Synthesis and evaluation of novel peripherally restricted kappa-opioid receptor agonists.

A series of 3-substituted analogs (3) of the parent kappa agonist, 1, were prepared to limit access to the central nervous system. With the exception of compound 3j, all other compounds bound to the human kappa opioid receptor with high affinity (K(i)=0.31-9.5 nM) and were selective for kappa over mu and delta opioid receptors. Compounds 3c, d, and 3g-i produced potent antinociceptive activity in the rat formalin assay (i.paw) and the mouse acetic acid-induced writhing assay (s.c.), with weak activity in the mouse platform sedation test. The peripheral restriction indices of 3c, d, 3g, and 3i were improved 2- to 7-fold compared to the parent compound 1, and these compounds were approximately 2- to 5-fold more potent than the peripheral kappa agonist ICI 204448.

Amino acid conjugates as kappa opioid receptor agonists.

A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.6 nM), 3l (Ki = 4.6 nM), 3m (Ki = 0.83 nM) and 3o (Ki = 2 nM) possessed potent affinities for the kappa opioid receptor in vitro with reasonable selectivity over other opioid receptors.