The interaction of Chlorophyll derivative photosensitizer CPD3 with mouse lung cancer DNA

Abstract

CPD 3 is a new kind of photosensitizer (PS) with promising applications in photodynamic therapy (PDT) for anticancer treatment. The binding properties of CPD 3 to mouse lung cancer cell DNA have been investigated by using absorption spectroscopy. In neutral CPD 3 -DNA mix solution in NS, the peak wavelengths of absorption bands of CPD 3 (B and Q band) do not change basically but the intensities of them do decrease with increase of the concentration of the DNA, in addition, some new red-shifted absorption bands appear in the spectra and become stronger with increasing the concentration of the DNA and with prolonging incubation period of the sample solution. In basic mix solution (pH=8.0), the situation above is not observed and absorption bands of CPD 3 are not yet changed in the peak position and intensity even though the concentration of DNA in the solution is high enough to 1.75×10 -5 mg/l. The study shows that some free CPD 3 molecules bind to DNA to form a "complex" through intensive groove and hydrogen bonding interaction between them in a proper time period. However, the electrostatic interaction between CPD 3 and the DNA is not important for formation of the "complex". The intercalative binding model included groove, hydrogen bonding, and spatial obstacle interaction would be preferable. The photobleaching (PB) properties of the CPD 3 solution with and without the DNA are investigated under irradiating with LD at 674nm and 20mW. For the former, PB lifetime of CPD 3 is 49.3 seconds, for the latter, 96.2 seconds. Both the decay curves obey single exponential drop rule exactly. The results show that the PB of CPD 3 is a single excited state reaction; the intercalative binding between CPD 3 and DNA can increase the rate constant for PB reaction. The electrophoresis graph of the bleached solution indicates that the DNA is destroyed basically. The study indicates the CPD 3 is an efficient and stable PS for PDT. Ⅰ. INTRODUCTIONIn resent years, the study of the interactions of various small organic molecules with DNA has been of great interest because their importance in understanding the effects of the drug on DNA and the consequent designs of new efficient drugs targeted to DNA [1][2][3][4] . As well known, there are mainly three interaction models about of organic molecules and the DNA double helix: electrostatic binding, groove (or surface) binding and intercalative binding. Electrostatic binding interactions between cationic species and the negatively charged DNA phosphate backbone occur usually along the exterior of the helix. Groove binding generally involves direct hydrogen bonding, Van der Waals interactions with the nucleic acid bases in the deep minor groove or the wide shallow major groove of the DNA helix. The intercalative binding and groove binding are related to the grooves in the DNA double helix, but the electrostatic binding can take place out of the groove.Chlorophyll derivatives (CPD s ) are a new class of potential photosensitizer (PS) in photodynamic therapy (PDT) of the tumors. Some researc...