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CONCLUSIONS
Spatial proximity of two arylethynyl groups is not required for
efficient DNA photocleavage by enediyne-lysine conjugates.
Newly prepared meta-bis-alkyne chromophores are able to
induce DNA ds-photocleavage upon UV irradiation at different
pH conditions. Translocation of p-alkyne in m,p-enediyne
hybrids to the meta position, alleviates the acidifying effect of
the acceptor TFP group, rendering the a-amino group of lysine
residues to have similar basicity in the two conjugates. The
intrinsic DNA-binding constants of the conjugates from UV titra-
tions suggest intercalative DNA binding for phenyl substituted
conjugate (1) and groove binding for TFP substituted conjugate
(2). The difference of the DNA photocleavage activity of the
conjugates stems from protonation states of lysine amino groups,
responsible for intramolecular PET quenching of excited state of
molecules. Scavenger experiments for ROS has shown that gen-
eration of singlet oxygen is an important contributor to the
observed DNA ds-damage.
Acknowledgements—This work was supported by the Natural Science
Foundation (Grant CHE-1152491). The paper is dedicated to the memory
of Professor Michael Kasha, an esteemed colleague whose intellectual
generosity and quick wit illuminated so many discussions at the faculty
coffee table in the Dittmer Chemistry Building at the Florida State
University.
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SUPPORTING INFORMATION
Additional Supporting Information may be found in the online
version of this article:
Figure S1. Fluorescence titration spectra of the compound 1
(15 lM) with ct DNA (0–10.8 lM bpꢀ1) at pH 7 (excitation at
307 nm).
Figure S2. Fluorescence titration spectra of the compound 1
(15 lM) with ct DNA (0–10.8 lM bpꢀ1) at pH 8 (excitation at
307 nm).
Data S1. Synthesis of compounds.
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