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1.
Dr. Nicoló Zuin Fantoni Dr. Zara Molphy Sinéad O'Carroll Dr. Georgia Menounou Dr. George Mitrikas Dr. Marios G. Krokidis Dr. Chryssostomos Chatgilialoglu Dr. John Colleran Dr. Anna Banasiak Prof. Martin Clynes Dr. Sandra Roche Suainibhe Kelly Prof. Vickie McKee Prof. Andrew Kellett 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(3):971-983
We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (Kapp) rising from 105 to 107 m −1 with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin. 相似文献
2.
Requejo-Isidro J McGinty J Munro I Elson DS Galletly NP Lever MJ Neil MA Stamp GW French PM Kellett PA Hares JD Dymoke-Bradshaw AK 《Optics letters》2004,29(19):2249-2251
We report the development of a high-speed wide-field fluorescence-lifetime imaging (FLIM) system that provides fluorescence-lifetime images at rates of as many as 29 frames/s. A FLIM multiwell plate reader and a potentially portable FLIM endoscopic system operating at 355-nm excitation have been demonstrated. 相似文献
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Teresa Lauria Dr. Creina Slator Prof. Vickie McKee Dr. Markus Müller Samuele Stazzoni Antony L. Crisp Prof. Thomas Carell Prof. Andrew Kellett 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(70):16782-16792
Nucleic acid click chemistry was used to prepare a family of chemically modified triplex forming oligonucleotides (TFOs) for application as a new gene-targeted technology. Azide-bearing phenanthrene ligands—designed to promote triplex stability and copper binding—were ‘clicked’ to alkyne-modified parallel TFOs. Using this approach, a library of TFO hybrids was prepared and shown to effectively target purine-rich genetic elements in vitro. Several of the hybrids provide significant stabilisation toward melting in parallel triplexes (>20 °C) and DNA damage can be triggered upon copper binding in the presence of added reductant. Therefore, the TFO and ‘clicked’ ligands work synergistically to provide sequence-selectivity to the copper cutting unit which, in turn, confers high stabilisation to the DNA triplex. To extend the boundaries of this hybrid system further, a click chemistry-based di-copper binding ligand was developed to accommodate designer ancillary ligands such as DPQ and DPPZ. When this ligand was inserted into a TFO, a dramatic improvement in targeted oxidative cleavage is afforded. 相似文献
5.
Prisecaru A Devereux M Barron N McCann M Colleran J Casey A McKee V Kellett A 《Chemical communications (Cambridge, England)》2012,48(55):6906-6908
The di-copper(II) cation, [Cu(2)(μ-terephthalate)(1,10-phen)(4)](2+), is a powerful, non-sequence-specific, minor-groove oxidizer of duplex DNA which, unlike copper(II) bis-1,10-phenanthroline chloride, operates independently of exogenous reagents. The agent displays excellent in vitro cytoxicity towards cisplatin-resistant ovarian cancer cells, producing intracellular reactive oxygen species upon nano-molar exposure. 相似文献
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K. Kellett S. A. Kantonen B. M. Duggan M. K. Gilson 《Journal of solution chemistry》2018,47(10):1597-1608
Researchers developing software to predict the binding constants of small molecules for proteins have, in recent years, turned to host–guest systems as simple, computationally tractable model systems to test and improve these computational methods. However, taking full advantage of this strategy requires aqueous host–guest systems that probe a greater diversity of chemical interactions. Here, we advance the development of an experimental platform to generate such systems by building on the cyclodextrin (CD) class of hosts. The secondary face derivative mono-3-carboxypropionamido-β-cyclodextrin (CP-β-CD) was synthesized in a one-pot strategy with 87% yield, and proved to have much greater aqueous solubility than native β-CD. The complexation of anionic CP-β-CD with the cationic drug rimantadine hydrochloride was explored using one- and two-dimensional nuclear magnetic resonance; NOESY analysis showed secondary face binding of the ammonium moiety of the guest, based on cross-correlations between the amic acid functionality and the side-chain of rimantadine. Isothermal titration calorimetry was furthermore used to determine the standard Gibbs energy and enthalpy for this binding reaction, and the results were compared with those of rimantadine with native β-CD. 相似文献
7.
Andrew Kellett Georgina Rosair Michael Devereux Mary McNamara Malachy McCann 《Acta Crystallographica. Section C, Structural Chemistry》2010,66(11):m358-m362
The structures of [Cu(AA)6](ClO4)2, (I), and [Mn(AA)6](ClO4)2, (II) (AA is acrylamide, also known as prop‐2‐enamide; C3H5NO), display both intra‐ and intermolecular N—H...O hydrogen bonding. A three‐dimensional network is propagated via the perchlorate counter‐ions. There are two crystallographically independent molecules in the copper complex, with the most significant difference between them being the conformation of one symmetry‐related pair of AA ligands which are in the unusual syn conformation. The copper complex exhibits syn/anti disorder of the =CH2 group in one pair of symmetry‐related AA ligands. The CuII and MnII centres are both situated on centres of inversion. The copper complex cation has octahedral coordination geometry with typical Jahn–Teller distortions. 相似文献
8.
B.H Kellett 《Annals of Physics》1974,87(1):60-94
The Bethe-Salpeter equation for the relativistic three quark bound state is solved for an instantaneous interaction in the ladder approximation. The particular solution obtained is valid for simple potentials in both the weak and strong binding situations. The general method for calculating matrix elements for the interaction of the bound state with an external electromagnetic field is presented. Particular attention is paid to the emergence of the nonrelativistic quark model interaction as the lowest order approximation in a perturbative expansion in the inverse quark mass. Relativistic corrections to this approximation are investigated, and their importance is seen to depend on the quark mass. For light quarks these corrections can be large, and to reproduce the proton magnetic moment, for instance, a substantial anomalous moment is necessary. The model has several encouraging features. The form factors with a harmonic potential have an asymptotic k?2 behavior, and the relativistic corrections to the SU(6) results for the form factors are of the correct order of magnitude. 相似文献
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B. H. Kellett 《Foundations of Physics》1977,7(9-10):735-757
The Einstein-Podolsky-Rosen paradox as formulated in their original paper is critically examined. Their argument that quantum mechanics is incomplete is shown to be unsatisfactory on two important grounds. (i) The gedanken experiment proposed by Einstein, Podolsky, and Rosen is physically unrealizable, and consequently their argument is invalid as it stands. (ii) The basic assumptions of their argument are equivalent to the assumption that quantum mechanical systems are in fact describable by unique eigenfunctions of the operators corresponding to physical observables, independent of any observation or measurement. Following an argument due to Furry, it is shown that this interpretation of quantum mechanics must lead to some physical predictions at variance with those of conventional quantum mechanics. A decisive experiment has been performed by Freedman and Clauser, which rules out this interpretation, and imposes severe restrictions on any alternative theory which incorporates the Einstein, Podolsky, and Rosen concept of physical reality. 相似文献
10.
A value of or less for the ratio of the P level splittings in approximate agreement with the assignment of the states at 3.41, 3.50 and 3.55 to the 0++,and 2++ P-wave levels, is obtained with a short-range Coulomb (Lorentz vector) potential together with a long-range linear (Lorentz scalar) confining potential. The radiative transition widths Γ(ψ′ → 3.41 + γ), Γ(ψ′ → 3.50 + γ), Γ(χ′ → 3.55 + γ) are significantly smaller than those obtained in previous (one-channel) charmonium calculations. The best results were obtained by allowing the Coulomb coupling constant αs to have a momentum dependence suggested by asymptotic freedom formulae. 相似文献