Comparative Structural Study of Metal-Mediated Base Pairs Formed outside and inside DNA Molecules

Abstract

The formation of copper(II)-mediated base pairs involving pyridine-2,6-dicarboxylate derivatives and canonical nucleosides has proven to be a smart approach to introduce copper(II) ions at specific locations of DNA duplexes. However, the structural characteristics of these metalized base pairs have not yet been revealed, and their effect on DNA structures is difficult to assess. Herein, for the first time, we report on the different structural details of copper-mediated base pairs formed by themselves and in DNA duplexes. The individual base pairs [Cu(mcheldwere obtained from the reaction of the metal complex [Cu(mcheld)(H 2 O) 2 ] (1Cu) (mcheld = 4-methoxypyridine-2,6-dicarboxylic acid) with model nucleosides (Cyt = N1-methylcytosine, Ade = N9-ethyladenine, Gua = N9-propylguanine, 7C Ade = N9-propyl-7-deazaadenine). The crystal structure of the five complexes was determined by means of single-crystal X-ray diffraction. Furthermore, the formation of the 1Cu_Cyt and 1Cu_Gua base pairs in the middle of DNA duplexes, duplex DNA 15 (917 atoms) and DNA 10 (649 atoms), respectively, was studied using highly demanding ab initio computational calculations. These theoretical studies aimed to validate, from a structural point of view, whether base pairs of the kind 1Cu_nucleosides can be included in a DNA double helix and how this situation affects the double-helical structure. The results indicate that the 1Cu_Cyt and 1Cu_Gua base pairs can be formed in a DNA molecule without significant structural constraints. In addition, the double-helix DNA structure remains virtually unchanged when it contains these Cu(II)-mediated base pairs.

Single‐Stranded DNA as Supramolecular Template for One‐Dimensional Palladium(II) Arrays

“…It is worth mentioning that our first attempt to apply this strategy was carried out using the [Cu(mCheld)(H 2 O) 2 ]c omplex (mCheld = 4-methoxypyridine-2,6-dicarboxylic acid) and DNAh omopolymers,i na ne ffort to prepare Cu-DNA hybrids.H owever,t he Cu-mediated base pairs were not suitable for this task which may be attributed to its coordination plasticity. [31] To demonstrate our hypothesis,atitration experiment was initially performed by the addition of acontrolled amount of 1Pd_CH 3 CN to ss-DNAh omopolymers,n amely: dX 15 or dA 15 ,a nd followed by circular dichroism (CD). TheC D spectrum for free dX 15 shows an egative band in the range 270-300 nm, whilst dA 15 displays apositive band in the same region (Figure 2).…”

“…Our previous reported example at this level included only one Cu IImediated base pair and no water molecules. [31] Theg eometry-optimized structures show that 1Pd-dA 12 and 1Pd-dX 12 consist of right-handed helical molecules comprising consecutively stacked Pd II -mediated base pairs that mimic natural base pair organization in double-stranded DNA, that is,with the presence of Watson-Crick hydrogen bonds and stacking interactions (Figures 6, S14, and S15). TheP d II ions are located along the helical axis that runs through the center of the metallo-base pairs,i nc lose contact with each other at 3.447-3.765 and 3.109-3.819 , [40] for 1Pd-dA 12 and 1Pd-dX 12 , respectively,a nd leading to an uninterrupted 1D array.…”