Interaction of osmium(ii) redox probes with DNA: insights from theory

Abstract

In the course of developing ultrasensitive and quantitative electrochemical point-of-care analytical tools for genetic detection of infectious diseases, osmium(ii) metallointercalators were revealed to be suitable and efficient redox probes to monitor the in vitro DNA amplification [Defever etal, Anal. Chem., 2011, 83, 1815-1821]. In this work, we thus propose a complete computational protocol in order to evaluate the affinity between Os(ii) complexes with double-stranded DNA. This protocol is based on molecular dynamics, with the parametrization of the GAFF force field for the Os(ii) complexes presenting an octahedral environment with polypyridine ligands, and QM/QM' calculations to evaluate the binding energy. For three Os(ii) probes and different binding sites, molecular dynamics simulations and interaction energies calculated at the QM/QM' level are successively discussed and compared to experimental data in order to identify the most stable binding sites. The computational protocol we propose should then be used to design more efficient Os(ii) metallointercalators.

Detection of a few DNA copies by real-time electrochemical polymerase chain reaction

“…The computational protocol (see the Experimental section) is the same as the one we have recently used to evaluate the interaction energies between different osmium bipyridyl complexes and ds-DNA. 14 MD simulations (Fig. S8-S16, ESI †) show that for [Os(bpy) 2 dppz] 2+ and MB, the intercalation binding modes arising from π-π interactions are more stable than others, while for PhP minor groove binding can also lead to a stable adduct, thanks to the formation of H bonds between the probe and ds-DNA.…”

“…In order to express the parameter C T as a function of ε, C i DNA , K b , and C 0 I , C CT DNA has to be replaced by eqn (9) or (10), thus leading after rearrangement to eqn (13) or (14), respectively:…”