Elucidating the intercalation of methylated 1,10-phenanthroline with DNA: the important weight of the CH/H interactions and the selectivity of CH/π and CH/n interactions

Abstract

Intercalation of ligands forming CH/π and CH/n interactions with DNA is ruled by key acceptor atoms of DNA. It suggests some key and lock mechanism where the interacting fragments fit like puzzle pieces to achieve the stabilization of the system.

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes

“…Refs. [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 46 , 47 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ] Thus, our main goal has been to understand, at a fundamental level, the interaction of phen derivatives with dDNA and how the substitution by means of different functional groups can modulate their interaction, efficiency as intercalators, and their cytotoxicity. Small molecules, including phen derivatives and dDNA, can interact in different modes [ 15 ] (see Figure 1 ): Cross-link interactions occur when the molecule reacts with DNA by forming covalent bonds between two nucleotides [ 111 , 112 ] and the small molecule is placed mainly in the major groove.…”

“…Refs. [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 46 , 67 , 113 ] In the case of phen derivatives, substitution by different functional groups may increase or decrease the strength of the intercalation between bps. X-H··Y, CH/π, CH/n, H···H bonds or other weak interactions, not only with the bps but also with the sugar and phosphate backbone, may stabilize intercalation of phen derivatives (as we recently demonstrated).…”

“…Refs. [ 39 , 40 , 41 , 42 , 46 ] Moreover, intercalation may be achieved in two different orientations, namely through the MG and via mg. (see Scheme 1 ).…”

“…Refs. [ 38 , 39 , 40 , 41 , 42 , 46 , 47 , 114 ] Moreover, the use of QTAIM and NCI analyses provides a very detailed view of the weak interactions between atoms that rule the cytotoxic effects of the small molecules when interacting with DNA.…”

“…Refs. [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 46 , 47 ] In addition, for =O and -CH 3 we also analyzed the intercalation when the substitution occurred in positions five and six; for -CH 3 , we also studied monosubstitution in positions four and five, and tetrasubstitution in positions three, four, seven, and eight. Later, for the study of the interaction of Mo phen complexes with dDNA, we took advantage of the SIESTA method and software [ 60 ] to go one step beyond the state-of-the-art.…”