Iron(II) Supramolecular Helicates Condense Plasmid DNA and Inhibit Vital DNA‐Related Enzymatic Activities

Abstract

The dinuclear iron(II) supramolecular helicates [Fe2 L3 ]Cl4 (L=C25 H20 N4 ) bind to DNA through noncovalent (i.e., hydrogen-bonding, electrostatic) interactions and exhibit antimicrobial and anticancer effects. In this study, we show that the helicates condense plasmid DNA with a much higher potency than conventional DNA-condensing agents. Notably, molecules of DNA in the presence of the M enantiomer of [Fe2 L3 ]Cl4 do not form intermolecular aggregates typically formed by other condensing agents, such as spermidine or spermine. The helicates inhibit the activity of several DNA-processing enzymes, such as RNA polymerase, DNA topoisomerase I, deoxyribonuclease I, and site-specific restriction endonucleases. However, the results also indicate that the DNA condensation induced by the helicates does not play a crucial role in these inhibition reactions. The mechanisms for the inhibitory effects of [Fe2 L3 ]Cl4 helicates on DNA-related enzymatic activities have been proposed.

Self‐Assembly of Functional Discrete Three‐Dimensional Architectures in Water

“…[109,110] An umber of studies have highlighted that due to the polycationic charge of many metal-organic complexes,they are efficiently able to condense polyanionic DNAa nd inhibit natural enzymatic processes. [103,111] Them ode of action of these small metal-organic constructs is however not limited to DNAi nteractions,a nd biophysical measurements have shown that some flexicates do not interact significantly with DNA. These complexes may still show excellent anticancer properties.…”

Catalytic Metallodrugs: Substrate‐Selective Metal Catalysts as Therapeutics

“…[16] In addition, other iron and copperc omplexes with novel structures have also been designed to improve nuclease activity. [28] Such complexes can potentially be used as the catalytic domain of ac atalytic metallodrug. [10c] Examples include the use of the amino terminal copper-and nickel-binding (ATCUN) motif as the catalytic domain.…”

Mechanistic studies of the anticancer activity of an octahedral hexanuclear Pt(II) cage

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