RhIII-catalyzed synthesis and investigation of the DNA-binding properties of 11- and 13-substituted berberine derivatives

The Rh-catalyzed annulation reaction of 2-(ethynylaryl)ethaneamines was used as key step to synthesize two berberine derivatives with hydroxy and phenyl substituents in 11-and 13-position. These compounds showed absorption and emission properties comparable to the parent alkaloid berberine. The fluorescence of the hydroxy-substituted berberine (p K a = 6.3) is efficiently quenched under acidic conditions, whereas a fluorescence light-up effect was observed with increasing pH values. The interactions of the berberine derivatives with duplex DNA and quadruplex DNA were investigated with absorption, circular dichroism (CD), and linear dichroism (LD) spectroscopy. The 13-phenyl-substituted berberine binds to duplex DNA with a binding constant of K b = 1.2  10 5 M −1 and to quadruplex DNA with K b = 1.9  10 5 M −1 . The CD-and LD-spectroscopic studies showed that the 11-hydroxy-13-phenyl-substituted berberine binds to duplex DNA by intercalation and to quadruplex DNA by terminal π stacking.