Photophysical Properties and Protein Binding Studies of Piperazine-Substituted Anthracene-BODIPY Dyads for Antimicrobial Photodynamic Therapy

TL;DR

This paper describes the design and testing of two new BODIPY-anthracene compounds for antimicrobial photodynamic therapy, focusing on their light absorption, protein binding, and effectiveness against bacteria.

Contribution

The novel BODIPY-anthracene dyad BDP-2 introduces alkyne-piperazine substituents, offering improved photophysical and biocompatible properties for photodynamic therapy.

Findings

BDP-2 shows a red-shifted absorption and a long-lived triplet state, indicating efficient energy transfer.

BDP-2 binds strongly to bovine serum albumin and is more hemocompatible than BDP-1.

Both compounds show potent antimicrobial activity under 370 nm irradiation, though BDP-2 is less effective against Staphylococcus aureus.

Abstract

This work presents the synthesis, characterisation, photophysical properties, time-resolved spectroscopic behaviour, and biological evaluation of two structurally distinct heavy-atom-free BODIPY-anthracene dyads (BDP-1) and the newly designed 2,6-bis[1-(tert-butyl) 4-(prop-2-yn-1-yl) piperazine-1,4-dicarboxylate] BODIPY-anthracene (BDP-2), incorporating 2,6-alkynyl-piperazine substituents for potential application in antimicrobial photodynamic therapy. BDP-1 exhibits absorption and emission maxima at 507 nm and 516 nm, respectively, with a Stokes shift of 344 cm−1 in dichloromethane (DCM), characteristic of unsubstituted BODIPYs. In contrast, BDP-2 undergoes a red-shift in the absorption maximum to 552 nm (Stokes shift of 633 cm−1), which is attributed to the extended conjugation from the introduction of the alkyne groups. Time-resolved infrared spectroscopy confirmed efficient spin-orbit charge transfer intersystem crossing, and nanosecond transient absorption studies confirmed the formation of a long-lived triplet state for BDP-2 (up to 138 µs in MeCN). A binding constant (Kb) of 9.6 × 104 M−1 was obtained for BDP-2 when titrated with bovine serum albumin (BSA), which is higher than comparable BODIPY derivatives. BDP-2 displayed improved hemocompatibility compared to BDP-1 (<5% haemolysis of human erythrocytes up to 200 μg·mL−1). Antimicrobial activity of BDP-1 and BDP-2 was most potent when irradiated at 370 nm compared to the other wavelengths employed. However, BDP-2 did not retain the potent (6 log) and rapid (within 15 min) eradication of Staphylococcus aureus achieved by BDP-1 under irradiation at 370 nm. These findings demonstrate the rational design of BDP-2 as a biocompatible, and heavy-atom-free BODIPY offering promise for targeted antimicrobial photodynamic therapeutic applications.

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