| 1. |
- Borg, O. Anders, et al.
(författare)
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A Computational Study on the Lowest Triplet State of Ruthenium Polypyridyl Complexes used in Artificial Photosynthesis
- 2008
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 112:19, s. 4470-4476
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Tidskriftsartikel (refereegranskat)abstract
- The potential energy surfaces of the first excited triplet state of some ruthenium polypyridyl complexes were investigated by means of density functional theory. Focus was placed on the interaction between the geometrical changes accompanying the photoactivity of these complexes when used as antenna complexes in artificial photosynthesis and dye-sensitized solar cells and the accompanying changes in electronic structure. The loss process (3)MLCT --> (3)MC can be understood by means of ligand-field splitting, traced down to the coordination of the central ruthenium atom.
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| 2. |
- Borg, O. Anders, et al.
(författare)
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Electron-transfer induced repair of 6-4 photoproducts in DNA : a computational study.
- 2007
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Ingår i: Journal of Physical Chemistry A. - Washington, DC : American Chemical Society. - 1089-5639 .- 1520-5215. ; 111:12, s. 2351-2361
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism employed by DNA photolyase to repair 6-4 photoproducts in UV-damaged DNA is explored by means of quantum chemical calculations. Considering the repair of both oxetane and azetidine lesions, it is demonstrated that reduction as well as oxidation enables a reversion reaction by creating anionic or cationic radicals that readily fragment into monomeric pyrimidines. However, on the basis of calculated reaction energies indicating that electron transfer from the enzyme to the lesion is a much more favorable process than electron transfer in the opposite direction, it is suggested that the photoenzymic repair can only occur by way of an anionic mechanism. Furthermore, it is shown that reduction of the oxetane facilitates a mechanism involving cleavage of the C−O bond followed by cleavage of the C−C bond, whereas reductive fragmentation of the azetidine may proceed with either of the intermonomeric C−N and C−C bonds cleaved as the first step. From calculations on neutral azetidine radicals, a significant increase in the free-energy barrier for the initial fragmentation step upon protonation of the carbonylic oxygens is predicted. This effect can be attributed to protonation serving to stabilize reactant complexes more than transition structures.
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| 3. |
- Borg, O Anders, et al.
(författare)
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Photochemistry of bromofluorobenzenes.
- 2006
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Ingår i: J Phys Chem A Mol Spectrosc Kinet Environ Gen Theory. - 1089-5639. ; 110, s. 7045-
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Borg, O. Anders, et al.
(författare)
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Predissociation of Chlorobenzene, beyond the pseudo-diatomic model
- 2008
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 456:4-6, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of chlorobenzene via the lowest singlet excited state has been investigated by means of pump-probe femtosecond spectroscopy and spin-orbit corrected ab initio quantum chemistry. We have found that the so far accepted model with a (1)pi pi* -> (3)pi/n sigma* reaction mechanism has to be amended. We suggest that the mechanism goes via a transition from (1)pi pi* to a pi sigma* state that is to 90% a singlet. Further, three nuclear degrees of freedom required to describe the dissociation have been defined.
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| 5. |
- Borg, O. Anders, et al.
(författare)
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Relative ground and excited-state pKa values of phytochromobilin in the photoactivation of phytochrome : a computational study
- 2007
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:39, s. 11554-11565
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Tidskriftsartikel (refereegranskat)abstract
- The conversion of the plant photoreceptor phytochrome from an inactive (Pr) to an active form (Pfr) is accomplished by a red-light induced Z E photoisomerization of its phytochromobilin chromophore. In recent years, the question whether the photoactivation involves a change in chromophore protonation state has been the subject of many experimental studies. Here, we have used quantum chemical methods to calculate relative ground and excited-state pKa values of the different pyrrole moieties of phytochromobilin in a protein-like environment. Assuming (based on experimental data) a Pr ZaZsZa chromophore and considering isomerizations at C15 and C5, it is found that moieties B and C are the strongest acids both in the ground state and in the bright first singlet excited state, which is rationalized in simple geometric and electronic terms. It is also shown that neither light absorption nor isomerization increases the acidity of phytochromobilin relative to the reference Pr state with all pyrrolenic nitrogens protonated. Hence, provided that the subset of chromophore geometries under investigation is biologically relevant, there appears to be no intrinsic driving force for a proton-transfer event. In a series of benchmark calculations, the performance of ab initio and time-dependent density functional theory methods for excited-state studies of phytochromobilin is evaluated in light of available experimental data.
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| 6. |
- Borg, O. Anders, et al.
(författare)
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Relative Ground and Excited-State pKa Values of Phytochromobilin in the Photoactivation of Phytochrome : A Computational StudyRelative Ground and Excited-State pKa Values of Phytochromobilin in the Photoactivation of Phytochrome: A Computational Study
- 2007
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:39, s. 11554-11565
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Tidskriftsartikel (refereegranskat)abstract
- The conversion of the plant photoreceptor phytochrome from an inactive (Pr) to an active form (Pfr) is accomplished by a red-light induced Z→ E photoisomerization of its phytochromobilin chromophore. In recent years, the question whether the photoactivation involves a change in chromophore protonation state has been the subject of many experimental studies. Here, we have used quantum chemical methods to calculate relative ground and excited-state pKa values of the different pyrrole moieties of phytochromobilin in a protein-like environment. Assuming (based on experimental data) a Pr ZaZsZa chromophore and considering isomerizations at C15 and C5, it is found that moieties B and C are the strongest acids both in the ground state and in the bright first singlet excited state, which is rationalized in simple geometric and electronic terms. It is also shown that neither light absorption nor isomerization increases the acidity of phytochromobilin relative to the reference Pr state with all pyrrolenic nitrogens protonated. Hence, provided that the subset of chromophore geometries under investigation is biologically relevant, there appears to be no intrinsic driving force for a proton-transfer event. In a series of benchmark calculations, the performance of ab initio and time-dependent density functional theory methods for excited-state studies of phytochromobilin is evaluated in light of available experimental data.
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| 7. |
- Borg, O. Anders, et al.
(författare)
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Which factors determine the acidity of the phytochromobilin chromophore of plant phytochrome?
- 2008
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 10:18, s. 2528-2537
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Tidskriftsartikel (refereegranskat)abstract
- Quantum chemical calculations aimed at identifying the factors controlling the acidity of phytochromobilin, the tetrapyrrole chromophore of the plant photoreceptor phytochrome, are reported. Phytochrome is converted from an inactive (Pr) to an active form (Pfr) through a series of events initiated by a Z E photoisomerization of phytochromobilin, forming the Lumi-R intermediate, and much controversy exists as to whether the protonation state of the chromophore (cationic in Pr with all nitrogens protonated) changes during the photoactivation. Here, relative ground (S0) and excited-state (S1) pKas of all four pyrrole moieties of phytochromobilin in all 64 possible configurations with respect to the three methine bridges are calculated in a protein-like environment, using a recently benchmarked level of theory. Accordingly, the relationships between acidity and chromophore geometry and charge distribution, hydrogen bonding, and light absorption are investigated in some detail, and discussed in terms of possible mechanisms making a proton transfer reaction more probable along the Pr Pfr reaction than in the parent cationic Pr state. It is found that charge distribution in the cationic species, intra-molecular hydrogen bonding in the neutral, and hydrogen bonding with two highly conserved aspartate and histidine residues have a significant effect on the acidity, while overall chromophore geometry and electronic state are less important factors. Furthermore, based on the calculations, two processes that may facilitate a proton transfer by substantially lowering the pKas relative to their Pr values are identified: (i) a thermal Z,anti Z,syn isomerization at C5, occurring after formation of Lumi-R; (ii) a perturbation of the hydrogen bonding network which in Pr comprises the nitrogens of pyrroles A, B and C and the two aspartate and histidine residues.
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| 8. |
- Durbeej, Bo, et al.
(författare)
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Computational evidence in favor of a protonated chromophore in the photoactivation of phytochrome
- 2005
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Ingår i: Chemical Physics Letters. - : Elsevier. - 0009-2614 .- 1873-4448. ; 416:1-3, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- The photoactivation of the plant photoreceptor phytochrome is governed by a red-light-induced C15-Z C15-E isomerization of the tetrapyrrolic chromophore phytochromobilin. From the viewpoint of experimental studies, ambiguity prevails as to whether the photoactivation involves a proton transfer from the chromophore to the surrounding protein. Here, we report a theoretical study addressing the effect of phytochromobilin protonation state on its photoisomerization by means of quantum chemical calculations. It is found that neutral forms of the chromophore are much less likely to photoisomerize than the parent, protonated form − a finding which supports the view that phytochromobilin remains protonated during phytochrome photoactivation.
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| 9. |
- Durbeej, Bo, et al.
(författare)
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Phytochromobilin C15-Z,syn → C15-E,anti isomerization: concerted or stepwise?
- 2004
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 6:21, s. 5066-5073
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Tidskriftsartikel (refereegranskat)abstract
- The C15-Z,syn C15-E,anti isomerization of phytochromobilin that underlies the photoactivation of phytochrome, the plant photoreceptor responsive to red and far-red light, is investigated by means of quantum chemical methods. By calculating ground and excited-state potential energy surfaces for a phytochromobilin model comprising the full tetrapyrrolic skeleton, and taking into consideration rotations around the C14–C15 and C15=C16 bonds constituting the methine bridge between pyrrole rings C and D, it is found that a stepwise Z E, syn anti mechanism is energetically preferable over a concerted Z,syn E,anti mechanism. In particular, on the basis of the calculated potential energy surfaces, it is proposed that the primary photochemical reaction involves a Z E isomerization only, and that the subsequent syn anti isomerization proceeds thermally.
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| 10. |
- Karlsson, Daniel, et al.
(författare)
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Experimental and theoretical study of the photodissociation of bromo-3-fluorobenzene
- 2008
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:3, s. 034307-
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Tidskriftsartikel (refereegranskat)abstract
- The UV photodissociation of bromo-3-fluorobenzene under collisionless conditions has been studied as a function of the excitation wavelength between 255 and 265 nm. The experiments were performed using ultrafast pump-probe laser spectroscopy. To aid in the interpretation of the results, it was necessary to extend the theoretical framework substantially compared to previous studies, to also include quantum dynamical simulations employing a two-dimensional nuclear Hamiltonian. The nonadiabatic potential energy surfaces (PES) were parameterized against high-level MS-CASTP2 quantum chemical calculations, using both the C–Br distance and the out-of-plane bending of the bromine as nuclear parameters. We show that the wavelength dependence of the photodissociation via the S0→1ππ*→1πσ* channel, accessible with a ∼ 260 nm pulse, is captured in this model. We thereby present the first correlation between experiments and theory within the quantitative regime.
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| 11. |
- Micke, Patrick, et al.
(författare)
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The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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| 12. |
- Wadt, Karin A W, et al.
(författare)
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Molecular characterization of melanoma cases in denmark suspected of genetic predisposition.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.
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| 13. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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