Physical properties of over 8000 intramolecular hydrogen bonds (iHBs), including 2901 ones of the types OH⋯O, OH⋯N, NH⋯O and OH⋯C, in 4244 conformers of the DNA-related molecules (four canonical 2′-deoxyribonucleotides, 1,2-dideoxyribose-5-phosphate, and 2-deoxy-D-ribose in its furanose, pyranose and linear forms) have been investigated using quantum theory of atoms in molecules (QTAIM) and vibrational analysis. It has been found that for all iHBs with positive red-shift of the proton donating group stretching frequency the shift value correlates with ρ^cp—the electron charge density at the (3,−1)-type bond critical point. Combining QTAIM and spectroscopic data new relationships for estimation of OH⋯O, OH⋯N, NH⋯O and OH⋯C iHB enthalpy of formation (kcal mol⁻¹) with RMS error below 0.8 kcal mol⁻¹ have been established: E_OH⋯O = −3.09 + 239·ρ^cp, E_OH⋯N = 1.72 + 142·ρ^cp, E_NH⋯O = −2.03 + 225·ρ^cp, E_OH⋯C = −0.29 + 288·ρ^cp, where ρ^cp is in e a₀ ⁻³ (a₀ – the Bohr radius). It has been shown that XH⋯Y iHBs with red-shift values over 40 cm⁻¹ are characterized by the following minimal values of the XHY angle, ρ^cp and ∇²ρ^cp: 112°, 0.005 e a₀ ⁻³ and 0.016 e a₀ ⁻⁵, respectively. New relationships have been used to reveal the strongest iHBs in canonical 2′-deoxy- and ribonucleosides and the O_5′H⋯N₃ H-bond in ribonucleoside guanosine was found to have the maximum energy (8.1 kcal mol⁻¹).

We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C₆₀ fullerene (C₆₀+Cis complex) and showed its higher toxicity toward tumor cell lines in vitro when compared to Cis alone. The highest toxicity of the complex was observed in HL-60/adr and HL-60/vinc chemotherapy-resistant human leukemia cell sublines (resistant to Adriamycin and Vinculin, respectively). We discovered that the action of the C₆₀+Cis complex is associated with overcoming the drug resistance of the tumor cell lines through observing an increased number of apoptotic cells in the Annexin V/PI assay. Moreover, in vivo assays with Lewis lung carcinoma (LLC) C57BL/6J male mice showed that the C₆₀+Cis complex increases tumor growth inhibition, when compared to Cis or C₆₀ fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C₆₀ fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP-1), and multidrug resistance protein 2 (MRP-2) molecules. The observed phenomenon revealed a possible mechanism to bypass tumor cell drug resistance by the C₆₀+Cis complex. Additionally, the results of the Ames test show that the formation of such a complex diminishes the Cis mutagenic activity and may reduce the probability of secondary neoplasm formation. In conclusion, the C₆₀+Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo, overcoming drug resistance likely by the potential of the C₆₀ fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C₆₀+Cis complex might be a potential novel chemotherapy modification.