Some preparations and properties of porphyrins.

Porphyrins and the related tetrapyrrolic aacrocyclic compounds, chlorins, bacteriochlorins and corrins are prosthetic groups of a large number of biological molecules which serve diversified roles in nature. These macrocycles, coordinated to a central metal ion, perform functions such as oxygen transport and storage (hemoglobin and myoglobin), electron and energy transfer (cytochromes and chlorophylls) and biocatalysis (coenzyme B12 cytochrome P-450). The metal-free ("free-base") porphyrins on the other hand are generally present in organisms as precursors of metalloporphyrins and are accumulated and/or excreted in certain physiological disorders such as porphyrias (1). The selective biodistribution of free-base porphyrins was reported by Policard (2) as early as 1924, based on the observed orange-red fluorescence from neoplastic tissue. The preferential localization of certain parenterally administered porphyrins in tumor cells, coupled with the property of intense fluorescence, have since been used for convenient detection of such tissue i n s i t u . In addition, the ability of porphyrins to act as photosensitizers, especially in the production of highly reactive singlet oxygen which in turn exerts cytotoxic action, has been used extensively in the novel treatment of malignant tissue, a technique referred to as photoradiation therapy (PRT). Attention has been focussed primarily on a porphyrin preparation known as hematoporphyrin derivative (HPD) whose tumor localizing properties were first described by Lipson et al. (3). HPD, prepared (4) by the acetylation of hematoporphyrin (HP) in 5% H2SO4 in CH3CO2H and aubsequent treatment with aqueous NaOH (0.1 M), is a mixture of porphyrins whose chemical composition, tumor localization and photosensitization properties have been the aubjects of intense investigation for the past decade (5-7 ) . In order to avoid ambiguity of results due to the poss ble variations of composition (8) in different preparations of HPD, most studies have been carried out using a commercial preparation known to as Photofrin I. HPD has been partially purified using gel-filtration chromatography (see under chromatography) and the more active "aggregated” fraction is also available commercially as Photofrin II. Although considerable progress