Formation of Doubly and Triply Charged Fullerene Dimers in Superfluid Helium Nanodroplets.

Sequential ionization of fullerene cluster ions (C_{60})_{n}^{+} within multiply charged helium nanodroplets leads to the intriguing phenomenon of forming and stabilizing doubly and triply charged fullerene oligomers. While the formation of doubly charged dimers (C_{60})_{2}^{2+} has been predicted in earlier studies, the observation of even triply charged ones (C_{60})_{2}^{3+} is highly surprising. This remarkable resilience against Coulomb explosion is achieved through efficient cooling within the superfluid environment of helium nanodroplets and a sequential ionization scheme that populates covalently bound or physisorbed fullerene dimers. Calculations support the stability of four differently bonded (C_{60})_{2}^{2+} and (C_{60})_{2}^{3+} isomers and predict a low Coulomb barrier (<0.4 eV) preventing even dissociation of cold van der Waals complexes.

Size limits and fission channels of doubly charged noble gas clusters.

Small, highly charged liquid droplets are unstable with respect to spontaneous charge separation when their size drops below the Rayleigh limit or, in other words, their fissility parameter X exceeds the value 1. The absence of small doubly charged atomic cluster ions in mass spectra below an element-specific appearance size na has sometimes been attributed to the onset of barrierless fission at X = 1. However, more realistic models suggest that na marks the size below which the rate of fission surpasses that of competing dissociative channels, and the Rayleigh limit of doubly charged van der Waals clusters has remained unchartered. Here we explore a novel approach to form small dicationic clusters, namely by Penning ionization of singly charged noble gas (Ng) clusters that are embedded in helium nanodroplets; the dications are then gently extracted from the nanodroplets by low-energy collisions with helium gas. We observe Ngn2+ ions that are about 40% smaller than previously reported for xenon and krypton and about 20% for argon. These findings suggest that fission barriers have been underestimated in previous theoretical work. Furthermore, we measure the size distributions of fragment ions that are produced by collisional excitation of mass-selected dications. At lowest collision gas pressure, dicationic Kr and Xe clusters that are smaller than previously observed are found to evaporate an atom before they undergo highly symmetric fission. The distribution of fragments resulting from fission of small dicationic Ar clusters is bimodal.

Doubly charged dimers and trimers of heavy noble gases.

Many doubly charged heteronuclear dimers are metastable or even thermodynamically stable with respect to charge separation. Homonuclear dicationic dimers, however, are more difficult to form. He22+ was the first noble gas dimer predicted to be metastable and, decades later, observed. Ne22+ is the only other dicationic noble gas dimer that has been detected so far. Here, we present a novel approach to form fragile dicationic species, by post-ionization of singly charged ions that are embedded in helium nanodroplets (HNDs). Bare ions are then extracted by colliding the HNDs with helium gas. We detect homonuclear doubly charged dimers and trimers of krypton and xenon, but not argon. Our multi-reference ab initio calculations confirm the stability of Kr22+, Kr32+, Xe22+, Xe32+, and Ar22+, but put the stability of Ar32+ towards dissociation to Ar+ + Ar2+ into question.

Chemistry and physics of dopants embedded in helium droplets.

Helium droplets represent a cold inert matrix, free of walls with outstanding properties to grow complexes and clusters at conditions that are perfect to simulate cold and dense regions of the interstellar medium. At sub-Kelvin temperatures, barrierless reactions triggered by radicals or ions have been observed and studied by optical spectroscopy and mass spectrometry. The present review summarizes developments of experimental techniques and methods and recent results they enabled.

Spectroscopy of C60+ and C120+ in the mid-infrared.

Infrared spectra of C60+ and C120+, obtained via helium messenger spectroscopy, are reported. For C60+, new absorption features have been found just above the discrete vibrational spectrum of the ion. The absorption profile, which is broad and contains little structure, is assigned to one or more electronic absorption transitions and is in good agreement with predictions from time-dependent density functional theory. It seems likely that the transitions observed correspond to excitation from the 2A1u electronic ground state to one or both of the low-lying 2E1u and 2E2u electronic states previously identified as dark states of C60+. These states presumably become optically bright through vibronic coupling and specifically the Jahn-Teller effect. In the case of C120+, the simplest positively charged oligomer of C60, we present the first vibrational spectrum of this ion. Through a comparison with theory, vibrational features are best explained by a peanut-shaped structure for C120+, maintained by covalent bonding between the two C60 units. We have also discovered electronic transitions for C120+, which, similar to C60+, lie just above the vibrational spectrum.

A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer.

OBJECTIVE: Molecular taxonomy of tumours is the foundation of personalised medicine and is becoming of paramount importance for therapeutic purposes. Four transcriptomics-based classification systems of pancreatic ductal adenocarcinoma (PDAC) exist, which consistently identified a subtype of highly aggressive PDACs with basal-like features, including ΔNp63 expression and loss of the epithelial master regulator GATA6. We investigated the precise molecular events driving PDAC progression and the emergence of the basal programme. DESIGN: We combined the analysis of patient-derived transcriptomics datasets and tissue samples with mechanistic experiments using a novel dual-recombinase mouse model for Gata6 deletion at late stages of KRasG12D-driven pancreatic tumorigenesis (Gata6LateKO). RESULTS: This comprehensive human-to-mouse approach showed that GATA6 loss is necessary, but not sufficient, for the expression of ΔNp63 and the basal programme in patients and in mice. The concomitant loss of HNF1A and HNF4A, likely through epigenetic silencing, is required for the full phenotype switch. Moreover, Gata6 deletion in mice dramatically increased the metastatic rate, with a propensity for lung metastases. Through RNA-Seq analysis of primary cells isolated from mouse tumours, we show that Gata6 inhibits tumour cell plasticity and immune evasion, consistent with patient-derived data, suggesting that GATA6 works as a barrier for acquiring the fully developed basal and metastatic phenotype. CONCLUSIONS: Our work provides both a mechanistic molecular link between the basal phenotype and metastasis and a valuable preclinical tool to investigate the most aggressive subtype of PDAC. These data, therefore, are important for understanding the pathobiological features underlying the heterogeneity of pancreatic cancer in both mice and human.

Light Driven Ultrafast Bioinspired Molecular Motors: Steering and Accelerating Photoisomerization Dynamics of Retinal.

Photoisomerization of retinal protonated Schiff base in microbial and animal rhodopsins are strikingly ultrafast and highly specific. Both protein environments provide conditions for fine-tuning the photochemistry of their chromophores. Here, by combining time-resolved action absorption spectroscopy and high-level electronic structure theory, we show that similar control can be gained in a synthetically engineered retinal chromophore. By locking the dimethylated retinal Schiff base at the C11═C12 double bond in its trans configuration (L-RSB), the excited-state decay is rendered from a slow picosecond to an ultrafast subpicosecond regime in the gas phase. Steric hindrance and pretwisting of L-RSB are found to be important for a significant reduction in the excited-state energy barriers, where isomerization of the locked chromophore proceeds along C9═C10 rather than the preferred C11═C12 isomerization path. Remarkably, the accelerated excited-state dynamics also becomes steered. We show that L-RSB is capable of unidirectional 360° rotation from all-trans to 9-cis and from 9-cis to all-trans in only two distinct steps induced by consecutive absorption of two 600 nm photons. This opens a way for the rational design of red-light-driven ultrafast molecular rotary motors based on locked retinal chromophores.

Phenanthrene: establishing lower and upper bounds to the binding energy of a very weakly bound anion.

Quite a few molecules do not form stable anions that survive the time needed for their detection; their electron affinities (EA) are either very small or negative. How does one measure the EA if the anion cannot be observed? Or, at least, can one establish lower and upper bounds to their EA? We propose two approaches that provide lower and upper bounds. We choose the phenanthrene (Ph) molecule whose EA is controversial. Through competition between helium evaporation and electron detachment in HenPh- clusters, formed in helium nanodroplets, we estimate the lower bound of the vertical detachment energy (VDE) of Ph- as about -3 meV. In the second step, Ph is complexed with calcium whose electron affinity is just 24.55 meV. When CaPh- ions are collided with a thermal gas of argon, one observes Ca- product ions but no Ph-, suggesting that the EA of Ph is below that of Ca.

Stabilization of phenanthrene anions in helium nanodroplets.

It has been debated for years if the polycyclic aromatic hydrocarbon phenanthrene exists in its anionic form, or, in other words, if its electron affinity (EA) is positive or negative. In this contribution we confirm that the bare phenanthrene anion Ph- created in a binary collision with an electron at room temperature has a lifetime shorter than microseconds. However, the embedding of neutral phenanthrene molecules in negatively charged helium nanodroplets enables the formation of phenanthrene anions by charge transfer processes and the stabilization of the latter in the ultracold environment. Gentle shrinking of the helium matrix of phenanthrene-doped HNDs by collisions with helium gas makes the bare Ph- visible by high-resolution mass spectrometry. From these and previous measurements we conclude, that the EA of phenanthrene is positive and smaller than 24.55 meV.

Helium structures around SF5+ and SF6+: novel intermolecular potential and mass spectrometry experiments.

Helium clusters around the recently experimentally observed sulphur hexafluoride SF6+ and sulphur pentafluoride SF5+ ions are investigated using a combined experimental and theoretical effort. Mass spectrometry ion yields are obtained and the energetics and structure of the corresponding HeN-SF6+ and HeN-SF5+ clusters are analyzed using path integral molecular dynamics calculations as a function of N, the number of He atoms, employing a new intermolecular potential describing the interaction between the dopant and the surrounding helium. The new force field is optimized on benchmark potential energy ab initio calculations and represented by improved Lennard-Jonnes analytical expressions. This procedure improves the previous potentials employed in similar simulations for neutral SF6 attached to helium nanodroplets. The theoretical analysis explains the characteristic features observed in the experimental ion yields which suggest the existence of stable configurations at specific sizes.

Adsorption of Helium and Hydrogen on Triphenylene and 1,3,5-Triphenylbenzene.

The adsorption of helium or hydrogen on cationic triphenylene (TPL, C18H12), a planar polycyclic aromatic hydrocarbon (PAH) molecule, and of helium on cationic 1,3,5-triphenylbenzene (TPB, C24H18), a propeller-shaped PAH, is studied by a combination of high-resolution mass spectrometry and classical and quantum computational methods. Mass spectra indicate that HenTPL+ complexes are particularly stable if n = 2 or 6, in good agreement with the quantum calculations that show that for these sizes, the helium atoms are strongly localized on either side of the central carbon ring for n = 2 and on either side of the three outer rings for n = 6. Theory suggests that He14TPL+ is also particularly stable, with the helium atoms strongly localized on either side of the central and outer rings plus the vacancies between the outer rings. For HenTPB+, the mass spectra hint at enhanced stability for n = 2, 4 and, possibly, 11. Here, the agreement with theory is less satisfactory, probably because TPB+ is a highly fluxional molecule. In the global energy minimum, the phenyl groups are rotated in the same direction, but when the zero-point harmonic correction is included, a structure with one phenyl group being rotated opposite to the other two becomes lower in energy. The energy barrier between the two isomers is very small, and TPB+ could be in a mixture of symmetric and antisymmetric states, or possibly even vibrationally delocalized.

Solvation of Large Polycyclic Aromatic Hydrocarbons in Helium: Cationic and Anionic Hexabenzocoronene.

The adsorption of helium on charged hexabenzocoronene (Hbc, C42H18), a planar polycyclic aromatic hydrocarbon (PAH) molecule of D6h symmetry, was investigated by a combination of high-resolution mass spectrometry and classical and quantum computational methods. The ion abundance of HenHbc+ complexes versus size n features prominent local anomalies at n = 14, 38, 68, 82, and a weak one at 26, indicating that for these "magic" sizes, the helium evaporation energies are relatively large. Surprisingly, the mass spectra of anionic HenHbc- complexes feature a different set of anomalies, namely at n = 14, 26, 60, and 62, suggesting that the preferred arrangement of the adsorbate atoms depends on the charge of the substrate. The results of our quantum calculations show that the adsorbate layer grows by successive filling of concentric rings that surround the central benzene ring, which is occupied by one helium atom each on either side of the substrate. The helium atoms are fairly localized in filled rings and they approximately preserve the D6h symmetry of the substrate, but helium atoms in partially filled rings are rather delocalized. The first three rings contain six atoms each; they account for magic numbers at n = 14, 26, and 38. The size of the first ring shrinks as atoms are filled into the second ring, and the position of atoms in the second ring changes from hollow sites to bridge sites as atoms are filled into the third ring. Beyond n = 38, however, the arrangement of helium atoms in the first three rings remains essentially frozen. Presumably, another ring is filled at n = 68 for cations and n = 62 for anions. The calculated structures and energies do not account for the difference between charge states, although they agree with the measurements for the cations and show that the first solvation shell of Hbc± is complete at n = 68. Beyond that size, the adsorbate layer becomes three-dimensional, and the circular arrangement of helium changes to hexagonal.

Controlling Light-Induced Proton Transfer from the GFP Chromophore.

The front cover artwork is provided by the groups of Assoc. Prof. Anastasia V. Bochenkova (Lomonosov Moscow State University) and Prof. Lars H. Andersen (Aarhus University). The image shows the quantum nature of wavelength-dependent excited-state proton transfer in gas-phase H-bonded complexes of the GFP chromophore with an anionic proton acceptor. Read the full text of the Article at 10.1002/cphc.202100068.

Controlling Light-Induced Proton Transfer from the GFP Chromophore.

Green Fluorescent Protein (GFP) is known to undergo excited-state proton transfer (ESPT). Formation of a short H-bond favors ultrafast ESPT in GFP-like proteins, such as the GFP S65T/H148D mutant, but the detailed mechanism and its quantum nature remain to be resolved. Here we study in vacuo, light-induced proton transfer from the GFP chromophore in hydrogen-bonded complexes with two anionic proton acceptors, I- and deprotonated trichloroacetic acid (TCA- ). We address the role of the strong H-bond and the quantum mechanical proton-density distribution in the excited state, which determines the proton-transfer probability. Our study shows that chemical modifications to the molecular network drastically change the proton-transfer probability and it can become strongly wavelength dependent. The proton-transfer branching ratio is found to be 60 % for the TCA complex and 10 % for the iodide complex, being highly dependent on the photon energy in the latter case. Using high-level ab initio calculations, we show that light-induced proton transfer takes place in S1 , revealing intrinsic photoacid properties of the isolated GFP chromophore in strongly bound H-bonded complexes. ESPT is found to be very sensitive to the topography of the highly anharmonic potential in S1 , depending on the quantum-density distribution upon vibrational excitation. We also show that the S1 potential-energy surface, and hence excited-state proton transfer, can be controlled by altering the chromophore microenvironment.

Tuning fast excited-state decay by ligand attachment in isolated chlorophyll a.

Excited-state dynamics plays a key role for light harvesting and energy transport in photosynthetic proteins but it is nontrivial to separate the intrinsic photophysics of the light-absorbers (chlorophylls) from interactions with the protein matrix. Here we study chlorophyll a (4-coordinate complex) and axially ligated chlorophyll a (5-coordinate complex) isolated in vacuo applying mass spectrometry to shed light on the intrinsic dynamics in the absence of nearby chlorophylls, carotenoids, amino acids, and water molecules. The 4-coordinate complexes are tagged by quaternary ammonium ions while the charge is provided by a formate ligand in the case of 5-coordinate complexes. Regardless of excitation to the Soret band or the Q band, a fast ps decay is observed, which is ascribed to the decay of the lowest excited singlet state either by intersystem crossing (ISC) to nearby triplet states or by excited-state relaxation on the excited-state potential-energy surface. The lifetime of the first excited state is 15 ps with Mg2+ at the chlorophyll center, but only 1.7 ps when formate is attached to Mg2+. When the Soret band is excited, an initial sup-ps relaxation is observed which is ascribed to fast internal conversion to the first excited state. With respect to ISC, two factors seem to play a role for the reduced lifetime of the formate-chlorophyll complex: (i) The Mg ion is pulled out of the porphyrin plane thus reducing the symmetry of the chromophore, and (ii) the first excited state (Q band) and T3 are tuned almost into resonance by the ligand, which increases the singlet-triplet mixing.

Spectroscopy and photoisomerization of protonated Schiff-base retinal derivatives in vacuo.

The protonated Schiff-base retinal acts as the chromophore in bacteriorhodopsin as well as in rhodopsin. In both cases, photoexcitation initializes fast isomerization which eventually results in storage of chemical energy or signaling. The details of the photophysics for this important chromophore is still not fully understood. In this study, action-absorption spectra and photoisomerization dynamics of three retinal derivatives are measured in the gas phase and compared to that of the protonated Schiff-base retinal. The retinal derivatives include C9C10trans-locked, C13C14trans-locked and a retinal derivative without the ß-ionone ring. The spectroscopy as well as the isomerization speed of the chromophores are altered significantly as a consequence of the steric constraints.

Complexes with Atomic Gold Ions: Efficient Bis-Ligand Formation.

Complexes of atomic gold with a variety of ligands have been formed by passing helium nanodroplets (HNDs) through two pickup cells containing gold vapor and the vapor of another dopant, namely a rare gas, a diatomic molecule (H2, N2, O2, I2, P2), or various polyatomic molecules (H2O, CO2, SF6, C6H6, adamantane, imidazole, dicyclopentadiene, and fullerene). The doped HNDs were irradiated by electrons; ensuing cations were identified in a high-resolution mass spectrometer. Anions were detected for benzene, dicyclopentadiene, and fullerene. For most ligands L, the abundance distribution of AuLn+ versus size n displays a remarkable enhancement at n = 2. The propensity towards bis-ligand formation is attributed to the formation of covalent bonds in Au+L2 which adopt a dumbbell structure, L-Au+-L, as previously found for L = Xe and C60. Another interesting observation is the effect of gold on the degree of ionization-induced intramolecular fragmentation. For most systems gold enhances the fragmentation, i.e., intramolecular fragmentation in AuLn+ is larger than in pure Ln+. Hydrogen, on the other hand, behaves differently, as intramolecular fragmentation in Au(H2)n+ is weaker than in pure (H2)n+ by an order of magnitude.

Correction to: The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection.

In the original article there are errors in the authors' affiliations.

The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection.

BACKGROUND: Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI's strength for prognostication. METHODS: Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis. RESULTS: Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7-27.0), compared with 18.7 months (10.2-35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032). CONCLUSIONS: The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.

Color tuning of chlorophyll a and b pigments revealed from gas-phase spectroscopy.

Chlorophyll (Chl) pigments are responsible for vital mechanisms in photosynthetic proteins: light harvesting, energy transfer and charge separation. A complex interplay between the Chl molecule and its microenvironment determines its transition energy. Interactions such as excitonic coupling with one or more pigments (Chls or carotenoids), axial ligation to the magnesium center, or electrostatic interactions between Chl and nearby amino-acid residues all influence the photophysical properties. Here we use time-resolved photodissociation action spectroscopy to determine transition energies of Chla/b complexes in vacuo to directly compare the impact of a negatively charged axial ligand (formate) to that of exciton coupling between two Chls. Experiments carried out at the electrostatic ion storage ring ELISA allow dissociation to be sampled on hundreds of milliseconds time scale. Absorption-band maxima of Chla-formate complexes are found at 433 ± 4 nm/2.86 ± 0.03 eV (Soret band) and in the region 654-675 nm/1.84-1.90 eV (Q band) and those of Chla dimers tagged by a quaternary ammonium ion at 419 ± 5 nm/2.96 ± 0.04 eV (Soret band) and 647 nm/1.92 eV (Q band). The axial ligand strongly affects the Chla transition energies causing redshifts of 0.21 eV of the Soret band and 0.04-0.1 eV of the Q band compared to Chla tagged by a quaternary ammonium. Slightly smaller shifts were found in case of Chlb. The redshifts are approximately twice that induced by excitonic coupling between two Chlas, also tagged by a quaternary ammonium ion. Axial ligation brings the absorption by isolated Chls very close to that of photosynthetic proteins.