| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ashworth, Eleanor K., et al.
(författare)
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Protomers of the green and cyan fluorescent protein chromophores investigated using action spectroscopy
- 2023
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - 1463-9076 .- 1463-9084. ; 25:30, s. 20405-20413
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Tidskriftsartikel (refereegranskat)abstract
- The photophysics of biochromophore ions often depends on the isomeric or protomeric distribution, yet this distribution, and the individual isomer contributions to an action spectrum, can be difficult to quantify. Here, we use two separate photodissociation action spectroscopy instruments to record electronic spectra for protonated forms of the green (pHBDI(+)) and cyan (Cyan(+)) fluorescent protein chromophores. One instrument allows for cryogenic (T = 40 & PLUSMN; 10 K) cooling of the ions, while the other offers the ability to perform protomer-selective photodissociation spectroscopy. We show that both chromophores are generated as two protomers when using electrospray ionisation, and that the protomers have partially overlapping absorption profiles associated with the S-1 & LARR; S-0 transition. The action spectra for both species span the 340-460 nm range, although the spectral onset for the pHBDI(+) protomer with the proton residing on the carbonyl oxygen is red-shifted by & AP;40 nm relative to the lower-energy imine protomer. Similarly, the imine and carbonyl protomers are the lowest energy forms of Cyan(+), with the main band for the carbonyl protomer red-shifted by & AP;60 nm relative to the lower-energy imine protomer. The present strategy for investigating protomers can be applied to a wide range of other biochromophore ions.
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| 3. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 4. |
- Lee, Jason W. L., et al.
(författare)
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Cooling dynamics of energized naphthalene and azulene radical cations
- 2023
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Ingår i: Journal of Chemical Physics. - 0021-9606 .- 1089-7690. ; 158:17
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Tidskriftsartikel (refereegranskat)abstract
- Naphthalene and azulene are isomeric polycyclic aromatic hydrocarbons (PAHs) and are topical in the context of astrochemistry due to the recent discovery of substituted naphthalenes in the Taurus Molecular Cloud-1 (TMC-1). Here, the thermal- and photo-induced isomerization, dissociation, and radiative cooling dynamics of energized (vibrationally hot) naphthalene (Np+) and azulene (Az(+)) radical cations, occurring over the microsecond to seconds timescale, are investigated using a cryogenic electrostatic ion storage ring, affording molecular cloud in a box conditions. Measurement of the cooling dynamics and kinetic energy release distributions for neutrals formed through dissociation, until several seconds after hot ion formation, are consistent with the establishment of a rapid (sub-microsecond) Np+ reversible arrow Az(+) quasi-equilibrium. Consequently, dissociation by C2H2-elimination proceeds predominantly through common Az(+) decomposition pathways. Simulation of the isomerization, dissociation, recurrent fluorescence, and infrared cooling dynamics using a coupled master equation combined with high-level potential energy surface calculations [CCSD(T)/cc-pVTZ], reproduce the trends in the measurements. The data show that radiative cooling via recurrent fluorescence, predominately through the Np+ D-0 <- D-2 transition, efficiently quenches dissociation for vibrational energies up to approximate to 1 eV above dissociation thresholds. Our measurements support the suggestion that small cations, such as naphthalene, may be more abundant in space than previously thought. The strategy presented in this work could be extended to fingerprint the cooling dynamics of other PAH ions for which isomerization is predicted to precede dissociation.
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| 5. |
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| 6. |
- Ashworth, Eleanor K., et al.
(författare)
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Complexation of Green and Red Kaede Fluorescent Protein Chromophores by a Zwitterion to Probe Electrostatic and Induction Field Effects
- 2022
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 126:7, s. 1158-1167
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Tidskriftsartikel (refereegranskat)abstract
- The photophysics of green fluorescent protein (GFP) and red Kaede fluorescent protein (rKFP) are defined by the intrinsic properties of the light-absorbing chromophore and its interaction with the protein binding pocket. This work deploys photodissociation action spectroscopy to probe the absorption profiles for a series of synthetic GFP and rKFP chromophores as the bare anions and as complexes with the betaine zwitterion, which is assumed as a model for dipole microsolvation. Electronic structure calculations and energy decomposition analysis using Symmetry-Adapted Perturbation Theory are used to characterize gas-phase structures and complex cohesion forces. The calculations reveal a preponderance for coordination of betaine to the phenoxide deprotonation site predominantly through electrostatic forces. Calculations using the STEOM-DLPNO-CCSD method are able to reproduce absolute and relative vertical excitation energies for the bare anions and anion–betaine complexes. On the other hand, treatment of the betaine molecule with a point-charge model, in which the charges are computed from some common electron density population analysis schemes, show that just electrostatic and point-charge induction interactions are unable to account for the betaine-induced spectral shift. The present methodology could be applied to investigate cluster forces and optical properties in other gas-phase ion–zwitterion complexes.
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| 7. |
- Ashworth, Eleanor K., et al.
(författare)
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Cryogenic Fluorescence Spectroscopy of Ionic Fluorones in Gaseous and Condensed Phases : New Light on Their Intrinsic Photophysics
- 2022
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 126:51, s. 9553-9563
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence spectroscopy of gas-phase ions generated through electrospray ionization is an emerging technique able to probe intrinsic molecular photophysics directly without perturbations from solvent interactions. While there is ample scope for the ongoing development of gas-phase fluorescence techniques, the recent expansion into low-temperature operating conditions accesses a wealth of data on intrinsic fluorophore photophysics, offering enhanced spectral resolution compared with room-temperature measurements, without matrix effects hindering the excited-state dynamics. This perspective reviews current progress on understanding the photophysics of anionic fluorone dyes, which exhibit an unusually large Stokes shift in the gas phase, and discusses how comparison of gas- and condensed-phase fluorescence spectra can fingerprint structural dynamics. The capacity for temperature-dependent measurements of both fluorescence emission and excitation spectra helps establish the foundation for the use of fluorone dyes as fluorescent tags in macromolecular structure determination. We suggest ideas for technique development.
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| 8. |
- Bull, James N., et al.
(författare)
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Action spectroscopy of deprotomer-selected hydroxycinnamate anions
- 2021
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Ingår i: European Physical Journal D. - : Springer Science and Business Media LLC. - 1434-6060 .- 1434-6079. ; 75:2
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Tidskriftsartikel (refereegranskat)abstract
- Tandem ion mobility mass spectrometry-coupled laser excitation is used to record photodetachment, photoisomerization and photodepletion action spectra for a series of deprotomer-selected hydroxycinnamate anions, including deprotonated caffeic, ferulic and sinapinic acids. This molecular series accounts for most hydroxycinnainic moieties found in nature. Phenoxide deprotomers for para and ortho structural isomers have similar photodetachment action spectra that span the 350-460nm range with the maximum response occurring between 420 and 440 nm. None of the phenoxide deprotomers showed evidence for E -> Z photoisomerization. In contrast, photoexcitation of the carboxylate deprotomers of caffeic and ferulic acids and the meta-phenoxide deprotomer of caffeic acid initiates intramolecular proton transfer to give the para-phenoxide deprotomer. Photoexcitation of the carboxylate deprotomer of sinapinic acid and ortho-coumaric acid does not result in intramolecular proton transfer, presumably due to substantial barriers for rearrangement. For deprotonated meta-coumaric acid, interconversion between the phenoxide and carboxylate deprotomers occurs in the ion mobility spectrometer drift region where the effective ion temperature is T-eff approximate to 299 K.
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| 9. |
- Bull, James N., et al.
(författare)
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Autoionization from the plasmon resonance in isolated 1-cyanonaphthalene
- 2023
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Ingår i: Journal of Chemical Physics. - 0021-9606 .- 1089-7690. ; 158:24
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons have widely been conjectured to be ubiquitous in space, as supported by the recent discovery of two isomers of cyanonaphthalene, indene, and 2-cyanoindene in the Taurus molecular cloud-1 using radioastronomy. Here, the photoionization dynamics of 1-cyanonaphthalene (1-CNN) are investigated using synchrotron radiation over the hν = 9.0–19.5 eV range, revealing that prompt autoionization from the plasmon resonance dominates the photophysics for hν = 11.5–16.0 eV. Minimal photo-induced dissociation, whether originating from an excited state impulsive bond rupture or through internal conversion followed by a statistical bond cleavage process, occurs over the microsecond timescale (as limited by the experimental setup). The direct photoionization cross section and photoelectron angular distributions are simulated using an ezDyson model combining Dyson orbitals with Coulomb wave photoejection. When considering these data in conjunction with recent radiative cooling measurements on 1-CNN+, which showed that cations formed with up to 5 eV of internal energy efficiently stabilize through recurrent fluorescence, we conclude that the organic backbone of 1-CNN is resilient to photodestruction by VUV and soft XUV radiation. These dynamics may prove to be a common feature for the survival of small polycyclic aromatic hydrocarbons in space, provided that the cations have a suitable electronic structure to support recurrent fluorescence.
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| 10. |
- Bull, James N., et al.
(författare)
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Ion mobility action spectroscopy of flavin dianions reveals deprotomer-dependent photochemistry
- 2018
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:29, s. 19672-19681
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Tidskriftsartikel (refereegranskat)abstract
- The intrinsic optical properties and photochemistry of flavin adenine dinucleotide (FAD) dianions are investigated using a combination of tandem ion mobility spectrometry and action spectroscopy. Two principal isomers are observed, the more stable form being deprotonated on the isoalloxazine group and a phosphate (N-3,PO4 deprotomer), and the other on the two phosphates (PO4,PO4 deprotomer). Ion mobility data and electronic action spectra suggest that photo-induced proton transfer occurs from the isoalloxazine group to a phosphate group, converting the PO4,PO4 deprotomer to the N-3,PO4 deprotomer. Comparisons of the isomer selective action spectra of FAD dianions and flavin monoanions with solution spectra and gas-phase photodissociation action spectra suggests that solvation shifts the electronic absorption of the deprotonated isoalloxazine group to higher energy. This is interpreted as evidence for significant charge transfer in the lowest optical transition of deprotonated isoalloxazine. Overall, this work demonstrates that the site of deprotonation of flavin anions strongly affects their electronic absorptions and photochemistry.
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