Modeling of carbon nanoparticles, biomolecules and drugs intermolecular interaction

Plastun I.L., Bokarev A.N., Zakharov A.A., Naumov A.A.

Saratov State Technical University named after Yuri Gagarin, 77 Politechnicheskaya str., Saratov, Russia

By molecular modeling based on density functional theory (DFT) features of intermolecular interaction and complexation based on hydrogen bonds between carbon nanoparticles, biomolecules and drugs are investigated. Modeling of molecular structures and their ensembles is performed using the B3LYP functional with the base set 6-31G(d) using the Gaussian 09 software package.

Molecular mechanisms underlying the interaction of modified carbon nanoparticles with biomolecules and drugs are described on the basis of calculation of molecular structures and IR spectra of individual molecules and their ensembles with subsequent analysis of the hydrogen bonds formed.

Theoretical substantiation of therapeutic activity significant increasing and reduction of side effects was obtained when using carboxylated nanodiamonds together with highly toxic drugs doxorubicin and mitoxantrone used in the course of antitumor therapy. Presence of modified nanodiamonds contributes to the retention of these drugs in the affected cells due to the formation of supramolecular ensembles based on hydrogen bonds, which leads to the retention of molecular complexes in cells for a longer period, and, as a consequence, - to increasing the therapeutic activity and reduce side effects. Comparison of calculated IR spectra revealed a good agreement with experimental data.

Biocompatibility and possibility of using oxidized graphene as a means of retaining drugs in cells are analyzed. It was found that, as in case of modified nanodiamonds, interaction of oxidized graphene with drugs and biomolecules is caused by the formation of numerous medium-strength hydrogen bonds, which indicates the manifestation of supramolecular interaction.

Interaction of modified carbon structures with biomolecules based on the formation of hydrogen bonds also underlies the process of single-molecule DNA sequencing in real time, based on the polymerization reaction. On the basis of molecular modeling, the parameters of hydrogen bonds in a multicomponent mixture were analyzed: nucleotide-carbon structure (alkane) enriched with maleimide (sequencer sensor) – molecules of substances of the working solution of the sequencer. In addition, the electron density of molecules of substances involved in the sequencing process and their complexes were estimated using THE dftb+software package. Based on the performed calculations, recommendations for the selection of optimal sequencing conditions are given.

All calculations were performed using the simulation of macromolecular carbon structures on the basis of their small-sized counterparts having the same parameters of the interaction. Admissibility of such estimates is justified by good agreement with experimental results.

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