Developing Dual-State Emission Berberine Derivatives as Theranostic Agents by Reducing Nonradiative Transition Pathways

Berberine,
an antibacterial natural product, shows promise as a
theranostic agent. However, berberine exhibits moderate antibacterial
efficacy and limited water solubility, restricting its clinical application.
In this study, we discovered that a berberine derivative B-12 exhibits
dual-state emission (DSE) characteristics, and its photodynamic antibacterial
activity is significantly higher than that of berberine and methylene
blue. The mechanistic studies suggested that substitution with a single
methoxy group at the C-3 position reduces the intramolecular electron
transfer and increases the energy gap between singlet and triplet
excited states, which reduces nonradiative transition pathways and
improves the fluorescence quantum yield. The C-3 methoxy group also
contributes to higher ROS production due to the longer lifetime of
the excited state. Through bioimaging, B-12 was able to discriminate
between Gram-positive and Gram-negative bacteria. Notably, this study
offers valuable insights for designing photodynamic and DSE-active
berberine derivatives, highlighting the potential of these derivatives
as theranostic agents.