Adduct of fullerene C₆₀ with l-arginine: interaction with DNA, genotoxic and mutagenic properties

Abstract

The paper presents a physicochemical study of the water-soluble adduct of C₆₀ with l-arginine, including a quantum chemical determination of the stability of isomers, measurement of antiradical activity towards the ABTS radical, determination of the lipophilicity coefficient, particle size distribution in aqueous solutions and calculation of ζ-potentials. A separate part of the article is devoted to the study of the effect of the C₆₀ adduct with l-arginine on DNA in in vitro experiments (determination of the binding constant using isothermal titration calorimetry, study of genotoxicity, DNA melting temperature, effect on DNA circular dichroism spectra). Data are also presented on the biodistribution of the C₆₀ adduct with l-arginine in the organs and tissues of animals and its effect on clinical and biochemical blood parameters. The mutagenic effect of the C₆₀ adduct with l-arginine was determined in vivo on a model of mice abnormal sperm heads. It was shown that the adduct is in a neutral state in physiological solution, has an affinity to both aqueous and lipid phases (logP_ow = 0.23), and forms a complex with DNA (K_a = 4.59 10⁶ M ⁻¹), while it does not have cyto- and genotoxicity in vitro and mutagenicity in vivo.

Keywords:

• Fullerene
• genotoxicity
• cytotoxicity
• mutagenicity
• biodistribution

Acknowledgments

The work was carried out with the financial support of the Ministry of Health of the Russian Federation ‘Development of a radioprotector based on water-soluble forms of nanocarbon modified with l-amino acids’ EGISU: 123020800170-8. The equipment of the following Resource Centres of the Research Park of Saint Petersburg State University was used: Computing Centre, the Centre for Diagnostics of Functional Materials for Medicine, Pharmacology and Nanoelectronics, Magnetic Resonance Research Centre, Centre for Chemical Analysis and Materials Research, Thermogravimetric and Calorimetric Research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was carried out with the financial support of the Ministry of Health of the Russian Federation ‘Development of a radioprotector based on water-soluble forms of nanocarbon modified with l-amino acids’ EGISU: 123020800170-8. The equipment of the following Resource Centres of the Research Park of Saint Petersburg State University was used: Computing Centre, the Centre for Diagnostics of Functional Materials for Medicine, Pharmacology and Nanoelectronics, Magnetic Resonance Research Centre, Centre for Chemical Analysis and Materials Research, Thermogravimetric and Calorimetric Research.