TY - JOUR
T1 - Unraveling the Modulation of the Activity in Drugs Based on Methylated Phenanthroline When Intercalating between DNA Base Pairs
AU - Gil, Adrià
AU - Sanchez-Gonzalez, Angel
AU - Branchadell, Vicenç
PY - 2019/9/23
Y1 - 2019/9/23
N2 - © 2019 American Chemical Society. Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections. An analysis of the geometries, electronic structure, and energetics in the interaction was carried out for the studied systems. Our results were compared to experimental works to gain insight on the relation structure-interaction for the intercalated system with cytotoxicity. The trends are explained including not only intrinsic contributions to energy, ΔEPauli, ΔEdisp, ΔEorb, and ΔEelstat, but also the solvation energy, ΔESolv. A subtle balance between the number of stabilizing weak interactions (CH/π, CH/n, etc.) and steric hindrance seems to be related to the efficiency of such drugs.
AB - © 2019 American Chemical Society. Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections. An analysis of the geometries, electronic structure, and energetics in the interaction was carried out for the studied systems. Our results were compared to experimental works to gain insight on the relation structure-interaction for the intercalated system with cytotoxicity. The trends are explained including not only intrinsic contributions to energy, ΔEPauli, ΔEdisp, ΔEorb, and ΔEelstat, but also the solvation energy, ΔESolv. A subtle balance between the number of stabilizing weak interactions (CH/π, CH/n, etc.) and steric hindrance seems to be related to the efficiency of such drugs.
U2 - 10.1021/acs.jcim.9b00500
DO - 10.1021/acs.jcim.9b00500
M3 - Article
C2 - 31419117
VL - 59
SP - 3989
EP - 3995
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
SN - 1549-9596
ER -