The Meta-Substituted Isomer of TMPyP Enables More Effective Photodynamic Bacterial Inactivation than Para-TMPyP In Vitro
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Updated: Sep 21, 2025
LED-Based In Vitro Screening for Assessing Photoactivable Molecules in Bacterial Photodynamic Inactivation
Published on: January 24, 2025
Sebastian Schulz1, Svitlana Ziganshyna1, Norman Lippmann2
1Department of Anesthesiology and Intensive Care, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Abstract:
Porphyrinoid-based photodynamic inactivation (PDI) provides a promising approach to treating multidrug-resistant infections. However, available agents for PDI still have optimization potential with regard to effectiveness, toxicology, chemical stability, and solubility. The currently available photosensitizer TMPyP is provided with a para substitution pattern (para-TMPyP) of the pyridinium groups and has been demonstrated to be effective for PDI of multidrug-resistant bacteria. To further improve its properties, we synthetized a structural variant of TMPyP with an isomeric substitution pattern in a meta configuration (meta-TMPyP), confirmed the correct structure by crystallographic analysis and performed a characterization with NMR-, UV/Vis-, and IR spectroscopy, photostability, and singlet oxygen generation assay. Meta-TMPyP had a hypochromic shift in absorbance (4 nm) with a 55% higher extinction coefficient and slightly improved photostability (+6.9%) compared to para-TMPyP. Despite these superior molecular properties, singlet oxygen generation was increased by only 5.4%. In contrast, PDI, based on meta-TMPyP, reduced the density of extended spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli by several orders of magnitude, whereby a sterilizing effect was observed after 48 min of illumination, while para-TMPyP was less effective (p < 0.01). These findings demonstrate that structural modification with meta substitution increases antibacterial properties of TMPyP in PDI.
Insights
A new meta-substituted porphyrinoid (meta-TMPyP) shows enhanced effectiveness for photodynamic inactivation (PDI) against multidrug-resistant bacteria compared to its para-isomer. This structural modification improves antibacterial properties for PDI treatments.
Area of Science:
- Photochemistry
- Antimicrobial Therapy
- Organic Chemistry
Background:
- Photodynamic inactivation (PDI) offers a potential strategy for combating multidrug-resistant infections.
- Existing porphyrinoid photosensitizers, like TMPyP, have limitations in efficacy, toxicity, stability, and solubility.
- The para-substituted TMPyP (para-TMPyP) is known for its effectiveness against resistant bacteria.
Purpose of the Study:
- To synthesize and characterize a novel meta-substituted TMPyP (meta-TMPyP) variant.
- To evaluate the photophysical and photochemical properties of meta-TMPyP.
- To assess the antibacterial efficacy of meta-TMPyP-based PDI against multidrug-resistant bacteria.
Main Methods:
- Synthesis of meta-TMPyP and characterization using crystallographic analysis, NMR, UV/Vis, and IR spectroscopy.
- Assessment of photostability and singlet oxygen generation.
- In vitro evaluation of PDI efficacy against fluoroquinolone-resistant Escherichia coli.
Main Results:
- Meta-TMPyP exhibited a hypsochromic shift, a 55% higher extinction coefficient, and marginally improved photostability compared to para-TMPyP.
- Singlet oxygen generation increased by only 5.4% despite improved molecular properties.
- Meta-TMPyP-based PDI demonstrated significantly greater bacterial reduction (several orders of magnitude) and a sterilizing effect compared to para-TMPyP.
Conclusions:
- Structural modification of TMPyP to a meta-substitution pattern enhances its antibacterial efficacy in PDI.
- Meta-TMPyP represents a promising photosensitizer for treating multidrug-resistant bacterial infections.
- Further research into meta-substituted porphyrinoids could lead to improved PDI therapies.
