Measurement of the rate of uptake and subcellular localization of porphyrins in cells using fluorescence digital imaging microscopy.

A fluorescence imaging system incorporating a cooled slow-scan charge-coupled device camera was used to study the rate of uptake and subcellular localization of prophyrins in living cells. Measurements were carried out on human dermal fibroblasts (D532) using two different prophyrins meso-tetra(4-N-methylpyridyl)porphine (TMPP) and meso-tetra(4-N-hexylpyridyl)porphine (THPP). It was observed that TMPP was rapidly taken up by cells and principally located in the nucleus. The THPP, on the other hand, internalized more slowly and exhibited a particulate distribution in the cytoplasm.

Iron and haem complexation studies of 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (IMPY, NSC 51143), a tumour cell ribonucleotide reductase inhibitor.

Spectrophotometric studies have been undertaken of the interaction of various iron-based systems with the anti-tumour agent, 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (IMPY, NSC (51143), a ribonucleotide reductase inhibitor. No evidence was obtained of direct complexation in aqueous media at 25 degrees C between IMPY and Fe2+ (aq) (pH 1.5-6.8) or Fe3+ (aq) (pH 1.0-3.5), nor with a mu-oxo-bridged iron dimer (Fe--O--Fe) system. There was definitive spectral evidence of complexation of IMPY with protoporphyrin IX iron (II) at pH 7.4 and 12.9 both in the absence and presence of carbon monoxide bound at the haem-iron site. Binding of IMPY to protoporphyrin IX iron (III), in contrast, was not detected. Binding between IMPY and various iron sites important in biochemistry is discussed briefly, especially in relation to the structural properties of IMPY (from X-ray data) and the Fe--O--Fe bridge system in ribonucleotide reductase and model systems. The difficulties of the use of free heterocyclic nitrogenous bases in medicinal chemistry are discussed.