Antibacterial Properties of the Peptide Conjugated Naphthalene Diimide Radical Anion in the Aggregated State.

A peptide-linked naphthalene diimide (PNDI) forms a nanospherical architecture in water medium in its J-type self-assembled state. In this aggregated state, the system becomes highly redox-active and undergoes single-electron reduction under photoreactive conditions (λ_max = 365 nm). The resulting photoreduced red fluorescent radical anions have significant stability. The stability of the photoreduced radical anion formation is highly dependent upon its self-assemblies as it is found that in the monomeric state, the PNDI molecule fails to generate the photoinduced radial anion where the assembled state shows good stability. A computational study supports the stabilization of the extra electron in the stacking state. This stabilization of the extra electron causes an increase in the intermolecular binding energy of PNDI molecules in their aggregated state. Furthermore, the formation of the radical anion under the photoirradiated condition is highly concentration-dependent. At a higher concentration, the formation of radical dimer is evident; however, at a lower concentration, no such dimerization is found. Interestingly, this stable and noncytotoxic radical anion is capable of generating the reactive oxygen species (ROS) in the aqueous medium, and this results in its high antibacterial efficacy against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, with very low minimum inhibitory concentrations (MICs) of 16 and 30 μg/mL. Mechanistic studies revealed that the photoirradiated PNDI causes the rupture of the bacterial cell outer and inner membrane, as observed with the 8-anilino-1-naphthalenesulfonic acid dye test. The presence of reactive oxygen species (ROS) is also confirmed using the 2,7-dichlorofluorescein diacetate (DCFDA) test.