Quantum mechanical SCS(MI)-MP2/cc-pVTZ calculations predict the strength of proflavine, ellipticine and 1-pyrenemethylamine intercalation into single-stranded (ss) and double-stranded (ds) DNA. The results were compared with experimental results obtained from electrochemical impedance spectroscopy (EIS). Similar interaction energies of ellipticine with the guanine-cytosine base pair compared to the individual nucleobases guanine and cytosine suggested non-specific binding also to ssDNA. Accordingly, EIS identified ellipticine as being non-selective and therefore unsuitable for the detection of DNA hybridisation. The interaction energy of proflavine is significantly higher than the minimum required energy for a single intercalation site, and substantially lower with respect to the minimum energy needed for binding with ssDNA. In EIS studies, proflavine did not show any change in the charge-transfer resistance with respect to ssDNA and a decrease with respect to dsDNA. Calculations showed that 1-pyrenemethylamine has sufficiently high interaction energy to intercalate into dsDNA, however, the interaction energy towards ssDNA is close to the minimum required value, suggesting a weak interaction with ssDNA. EIS measurements support the calculations. A method for the calculation of interaction energies is provided, which can be used to characterise the interaction strength between new intercalators and DNA before being synthesised.
Keywords: DNA intercalation; electrochemical impedance spectroscopy; molecular modelling; post-Hartree-Fock; quantum mechanical interaction energy.
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