Rh(phen)2phi3+ as a shape-selective probe of triple helices

Area of Science:

• Coordination Chemistry
• Nucleic Acid Chemistry
• Chemical Biology

Background:

• RNA triple helices are crucial structural motifs in folded RNA molecules.
• Targeting specific RNA structures requires selective chemical probes.
• Metal complexes offer potential for site-specific nucleic acid modification.

Purpose of the Study:

• To investigate the structure-specific photoactivated cleavage of RNA triple helices by a rhodium complex.
• To differentiate between purine-purine-pyrimidine (pur*pur-pyr) and pyrimidine-purine-pyrimidine (pyr*pur-pyr) triple helix motifs.
• To evaluate the potential of Rh(phen)2phi3+ as a chemical probe for RNA structure.

Main Methods:

• Synthesis of RNA triple helices (28mer hairpin duplex with a 12mer Hoogsteen strand).
• Photoactivation of the metal complex Rh(phen)2phi3+ (phen = phenanthroline, phi = 9,10-phenanthrenequinone diimine).
• Analysis of cleavage patterns on Watson-Crick and Hoogsteen strands using different triple helix motifs.

Main Results:

• Rh(phen)2phi3+ exhibits structure-specific cleavage of RNA triple helices.
• Distinct cleavage patterns were observed for pyr*pur-pyr (cleavage on both Watson-Crick strands) and pur*pur-pyr (cleavage primarily on the purine Watson-Crick strand) motifs.
• Minimal cleavage occurred on the Hoogsteen strand, and no cleavage was detected on RNA duplexes lacking the third Hoogsteen strand.
• Cleavage patterns are consistent with an intercalated model of the metal complex within the triple helix.

Conclusions:

• Rh(phen)2phi3+ selectively targets and cleaves RNA triple helices, not duplex regions.
• The observed cleavage patterns provide insights into the metal complex's interaction model within triple helices.
• This rhodium complex serves as a valuable chemical probe for investigating triplex binding sites in folded RNA molecules.