Detecting Counterion Dynamics in DNA–Protein Association

Due to a high density of negative charges on its surface, DNA condenses cations as counterions, forming the so-called “ion atmosphere”. Although the release of counterions upon DNA–protein association has been postulated to have a major contribution to the binding thermodynamics, this release remains to be confirmed through a direct observation of the ions. Herein, we report the characterization of the ion atmosphere around DNA using NMR spectroscopy and directly detect the release of counterions upon DNA–protein association. NMR-based diffusion data reveal the highly dynamic nature of counterions within the ion atmosphere around DNA. Counterion release is observed as an increase in the apparent ionic diffusion coefficient, which directly provides the number of counterions released upon DNA–protein association.     

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

By using X‐ray crystallography, we show that the complexes Λ/Δ‐[Ru(TAP)₂(11‐CN‐dppz)]²⁺ (TAP=1,4,5,8‐tetraazaphenanthrene, dppz=dipyridophenazine) bind DNA G‐quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn‐guanosine is adjacent to the complex at the 5′ end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ‐[Ru(phen)₂(11‐CN‐dppz)]²⁺ bound to d(TCGGCGCCGA), a duplex‐forming sequence, and use both structural models to provide insight into the motif‐specific luminescence response of the isostructural phen analogue enantiomers.     

Mitochondrial-DNA-Targeted IrIII-Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells

The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear Ir^III-containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)₃ handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd–even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting Ir^III-containing metallohelices as PDT agents.