John Killoran

Synthesis of BF2 chelates of tetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behaviour

The synthesis, spectroscopic characteristics and in vitro cellular uptake properties of a new class of therapeutic window photosensitiser, namely the BF2 chelates of 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-2-ylidene amines (tetra-arylazadipyrromethenes), are described with the aim of developing a novel class of photodynamic therapeutic agents.

A potent nonporphyrin class of photodynamic therapeutic agent: cellular localisation, cytotoxic potential and influence of hypoxia

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics.

A substituted BF2-chelated tetraarylazadipyrromethene as an intrinsic dual chemosensor in the 650–850 nm spectral range

The synthesis and spectral analysis of a new class of long wavelength intrinsic fluorosensor is reported. Chemosensor performance reveals large off/on fluorescence intensity responses to acid analyte with low response to microenvironment polarity. Application to ratiometric fluorescence/UV-visible analysis is outlined.

A study of the effects of subunit pre-orientation for diarylpyrrole esters; design of new aryl-heteroaryl fluorescent sensors

The synthesis, single crystal X-ray structures, spectroscopic properties and molecular mechanics calculations of three systematically substituted 3,5-diaryl-1H-pyrrole-2-carboxylic acid ethyl esters 1a–c are described. The goal is to develop design principles for the generation of new class of fluorescent switches constructed from an aryl-heteroaryl architecture containing a virtual (C0) spacer. The spectroscopic effects of the electron donor p-dimethylamino substituent of 1b and the combined steric and electron donor impact of the o-methyl-p-dimethylamino groups of compound 1c were investigated to determine the required structural motifs to achieve orthogonal pre-orientation of the sensor subunits.