N,N',N''-Trisubstituted guanidine derivatives as DNA-intercalators: synthesis, crystal structures and biophysical investigations

• Published in: New journal of chemistry Vol. 47; no. 30; pp. 14185 - 14194
• Main Authors: Priyadharshini, R. Durga, Sathishkumar, P. N., Bensingh, M., Bhuvanesh, N., Vennila, K. N., Karvembu, R., Elango, Kuppanagounder P.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 31.07.2023; Royal Society of Chemistry
• Subjects: Binding; Chemistry; Chemistry, Multidisciplinary; Dichroism; Hydrophobicity; In vitro methods and tests; Ligands; Molecular docking; NMR; Nuclear magnetic resonance; Physical Sciences; Science & Technology; Single crystals; Viscosity measurement
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d3nj01327h

Three new N,N',N''-trisubstituted guanidine derivatives (L1, L2 and L3) were synthesized and characterized using NMR and mass spectral studies. The structures of these ligands have been confirmed using single-crystal XRD studies. The interactions between these ligands and calf-thymus DNA (CT-DNA) were investigated in vitro using different spectroscopic methods and molecular docking and simulation methods in a physiological buffer (pH 7.4). UV-Vis spectral titrations suggested the formation of an L2/CT-DNA complex. The addition of increasing amounts of CT-DNA enhanced the fluorescence of L2 with a binding constant on the order of 10(4) M-1, indicating fairly strong binding between them. Thermodynamic parameters ?G(0) < 0 and |?H-0| < T|?S-0| suggested that the complexation is spontaneous and entropy-driven where hydrophobic interaction plays a dominant role in stabilizing the complex. Molecular docking and metadynamics simulation studies indicated partial intercalation of one of the phenyl rings between the base pairs of DNA, which is strongly supported by circular dichroism, viscosity measurements and KI quenching studies.