The electric regulation mechanism of drug molecules intercalating with DNA

The insertion of small drug molecules into DNA can change its electrical properties, thereby controlling the probability of its electrical transmission. This characteristic has enabled its widespread application in molecular electronics. However, the current understanding of the intercalation properties and electronic transmission mechanisms is still not deep enough, which severely restricts its practical application. In this paper, the density functional theory and the non-equilibrium Green's function formula are combined to bind three different small drug molecules to the same sequence of DNA through intercalation, in order to discuss the impact of intercalation and molecular structure on the electrical properties of DNA. After inserting two MAR70 molecules, the conductivity decreased from 2.38 × 10⁻⁵ G₀ to 3.37 × 10⁻⁷ G₀. Upon the insertion of Nogalamycin, the conductivity dropped to 2.01 × 10⁻⁵ G₀, only slightly lower than that of bare B-DNA. However, when cyanomorpholinodoxorubicin was inserted, the conductivity was 2.65 × 10⁻⁶ G₀. In our study, we observed some common characteristics. After intercalating with drug molecules, new energy levels were induced, altering the positions of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels, resulting in a narrowed bandgap and consequently reduced conductivity of the complex. Furthermore, the conductivity was also related to the number of inserted drug molecules, fewer inserted molecules led to a decrease in conductivity. The results of this study indicate that embedding drug molecules can reduce or regulate the conductivity of DNA, providing new insights for its application in the field of nanoelectronics.