Synthesis of analogues of a flexible thiopyrylium photosensitizer for purging blood-borne pathogens and binding mode and affinity studies of their complexes with DNA.
A series of thio- and selenopyrylium analogues of 2,4-di(4-dimethylaminophen-yl)-6-methylthiopyrylium iodide were prepared in five steps from 4-dimethylaminophenyl-propargyl aldehyde and the corresponding lithium acetylide. When bound to DNA, all of the dyes absorb at wavelengths >600nm, which avoids the hemoglobin band I maximum at 575nm. The binding of the series of dyes to double-stranded DNA was examined spectrophotometrically and by isothermal titration calorimetry to determine binding constants, by a topoisomerase I DNA unwinding assay, by competition dialysis with [poly(dGdC)](2) and [poly(dAdT)](2), and by ethidium bromide displacement studies to examine propensities for intercalation, and by circular dichroism studies. The dyes were found to show mixed binding modes.
McKnight
Ruel E
RE
Department of Chemistry, State University of New York at Geneseo, 1 College Circle, Geneseo, NY 14454, USA. mcknight@geneseo.edu
Ye
Mao
M
Ohulchanskyy
Tymish Y
TY
Sahabi
Sadia
S
Wetzel
Bryan R
BR
Wagner
Stephen J
SJ
Skripchenko
Andrey
A
Detty
Michael R
MR
D001667:Binding, Competitive / Q000187:drug effects; D017848:Blood-Borne Pathogens; D002151:Calorimetry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D004269:DNA, Bacterial / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D003956:Dialysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004996:Ethidium / Q000378:metabolism; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors
D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D017319:Photosensitizing Agents; D013876:Thiophenes; D059004:Topoisomerase I Inhibitors; C521680:thiopyrylium; D004996:Ethidium