Hall, James P.

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Hall, James P.
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Hall, James P.

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  • Publication
    Monitoring guanine photo-oxidation by enantiomerically resolved Ru(II) dipyridophenazine complexes using inosine-substituted oligonucleotides
    (Royal Society of Chemistry, 2015-10-01)
    Keane, Páraic M. 
    ;
    Poynton, Fergus E. 
    ;
    Hall, James P. 
    ;
    Quinn, Susan J. 
    ;
    et al. 
    The intercalating [Ru(TAP)2(dppz)]2+ complex can photo-oxidise guanine in DNA, although in mixed-sequence DNA it can be difficult to understand the precise mechanism due to uncertainties in where and how the complex is bound. Replacement of guanine with the less oxidisable inosine (I) base can be used to understand the mechanism of electron transfer (ET). Here the ET has been compared for both Λ- and Δ-enantiomers of [Ru(TAP)2(dppz)]2+ in a set of sequences where guanines in the readily oxidisable GG step in {TCGGCGCCGA}2 have been replaced with I. The ET has been monitored using picosecond and nanosecond transient absorption and picosecond time-resolved IR spectroscopy. In both cases inosine replacement leads to a diminished yield, but the trends are strikingly different for Λ- and Δ-complexes.
      184Scopus© Citations 13
  • Publication
    Enantiomeric conformation controls rate and yield of photoinduced electron transfer in DNA sensitized by Ru(II) dipyridophenazine complexes
    (American Chemical Society, 2015-02-05)
    Keane, Páraic M. 
    ;
    Poynton, Fergus E. 
    ;
    Hall, James P. 
    ;
    Quinn, Susan J. 
    ;
    et al. 
    Photosensitized oxidation of guanine is an important route to DNA damage. Ruthenium polypyridyls are very useful photosensitizers, as their reactivity and DNA-binding properties are readily tunable. Here we show a strong difference in the reactivity of the two enantiomers of [Ru(TAP)2(dppz)]2+, by using time-resolved visible and IR spectroscopy. This reveals that the photosensitized one-electron oxidation of guanine in three oligonucleotide sequences proceeds with similar rates and yields for bound Δ-[Ru(TAP)2(dppz)]2+, whereas those for the λ enantiomer are very sensitive to base sequence. It is proposed that these differences are due to preferences of each enantiomer for different binding sites in the duplex.
      174Scopus© Citations 27
  • Publication
    Inosine Can Increase DNA′s Susceptibility to Photo‐oxidation by a RuII Complex due to Structural Change in the Minor Groove
    (Wiley, 2017-08-01)
    Keane, Páraic M. 
    ;
    Hall, James P. 
    ;
    Poynton, Fergus E. 
    ;
    Quinn, Susan J. 
    ;
    et al. 
    Weinheim Key to the development of DNA-targeting phototherapeutic drugs is determining the interplay between the photoactivity of the drug and its binding preference for a target sequence. For the photo-oxidising lambda-[Ru(TAP)2(dppz)]2+ (Λ-1) (dppz=dipyridophenazine) complex bound to either d{T1C2G3G4C5G6C7C8G9A10}2 (G9) or d{TCGGCGCCIA}2 (I9), the X-ray crystal structures show the dppz intercalated at the terminal T1C2;G9A10 step or T1C2;I9A10 step. Thus substitution of the G9 nucleobase by inosine does not affect intercalation in the solid state although with I9 the dppz is more deeply inserted. In solution it is found that the extent of guanine photo-oxidation, and the rate of back electron-transfer, as determined by pico- and nanosecond time-resolved infrared and transient visible absorption spectroscopy, is enhanced in I9, despite it containing the less oxidisable inosine. This is attributed to the nature of the binding in the minor groove due to the absence of an NH2 group. Similar behaviour and the same binding site in the crystal are found for d{TTGGCGCCAA}2 (A9). In solution, we propose that intercalation occurs at the C2G3;C8I9 or T2G3;C8A9 steps, respectively, with G3 the likely target for photo-oxidation. This demonstrates how changes in the minor groove (in this case removal of an NH2 group) can facilitate binding of RuIIdppz complexes and hence influence any sensitised reactions occurring at these sites. No similar enhancement of photooxidation on binding to I9 is found for the delta enantiomer.
      149Scopus© Citations 18
  • Publication
    Reversal of a Single Base-Pair Step Controls Guanine Photo-Oxidation by an Intercalating Ruthenium(II) Dipyridophenazine Complex
    (Wiley, 2015-07-13)
    Keane, Páraic M. 
    ;
    Poynton, Fergus E. 
    ;
    Hall, James P. 
    ;
    Quinn, Susan J. 
    Small changes in DNA sequence can often have major biological effects. Here the rates and yields of guanine photo-oxidation by Λ-[Ru(TAP)2(dppz)]2+ have been compared in 5′-{CCGGATCCGG}2 and 5′-{CCGGTACCGG}2 using pico/nanosecond transient visible and time-resolved IR (TRIR) spectroscopy. The inefficiency of electron transfer in the TA sequence is consistent with the 5′-TA-3′ versus 5′-AT-3′ binding preference predicted by X-ray crystallography. The TRIR spectra also reveal the differences in binding sites in the two oligonucleotides.
      252Scopus© Citations 30