Light-induced interaction of anthraquinone derivative with Guanosine monophosphate: molecular mechanism and...

Photoinduced reactions between photosensitizers and nucleic acids represent a fundamental mechanism in photodynamic therapy (PDT), primarily involving light-mediated oxidative damage to DNA. This study elucidates the interaction of a novel anthraquinone derivative, 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Q1), with nucleotides using a combination of NMR spectroscopy, chemically induced dynamic nuclear polarization (CIDNP), and molecular dynamics simulations. We demonstrate that Q1 forms complexes with guanosine (GMP), adenosine (AMP), and cytidine (CMP) monophosphates in the dark, with the highest stability constant observed for the Q1/GMP complex. Upon photoexcitation, electron transfer occurs exclusively from GMP to Q1, generating a semiquinone radical anion and a neutral guanyl radical. The CIDNP data allowed for an estimation of the triplet state energy of Q1, E_T(Q1) = 2.1 ± 0.1 eV. Also, irradiation at 520 nm enhances the cytotoxicity of Q1 against MDA-MB-231 (human breast adenocarcinoma) and A549 (lung carcinoma) cell lines. We conclude that the specific photoinduced radical reaction between Q1 and guanine bases is a component of its cytotoxic mechanism, establishing Q1 as a promising candidate for further development in PDT applications.