Photophysical and calorimetric studies on the binding of 9-O-substituted analogs of the plant alkaloid berberine to double stranded poly(A)

• Higher binding of 9-substituted berberines to double stranded poly(A) is reported.
• 9-O-ω-amino alkyl ether analogs exhibited binding of the order 105 M−1.
• The analogs significantly perturbed the conformation of double stranded poly(A).
• The binding was entropy driven and dominated mainly by hydrophobic forces.

This interaction of four novel 9-O-substituted analogs of the plant alkaloid berberine with double stranded poly(A) was studied using a variety of biophysical techniques. Remarkably higher binding of two 9-O-ω-amino alkyl ether analogs compared to the two 9-O-N-aryl/arylalkyl amino carbonyl methyl berberine analogs was observed. Quantum efficiency values suggested that energy was transferred from the adenine base pairs to the analogs on binding. Ferrocyanide quenching and viscosity studies revealed the binding mode to be intercalative for these analogs. Circular dichroism studies showed that these analogs induced significant conformational changes in the secondary structure of ds poly(A). Energetics of the binding suggested that 9-O-N-aryl/arylalkyl amino carbonyl methyl berberines bound very weakly to ds poly(A). The binding of 9-O-ω-amino alkyl ether analogs was entropy dominated with a smaller but favorable enthalpic contribution to the Gibbs energy. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy–entropy compensation established the involvement of multiple weak noncovalent interactions in the binding process.

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