SYNTHESIS, PHOTOPHYSICAL PROPERTIES, IN-VIVO PHOTOSENSITIZING EFFICACY, AND HUMAN SERUM-ALBUMIN BINDING-PROPERTIES OF SOME NOVEL BACTERIOCHLORINS

The synthesis, photophysical characteristics, in viva photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phot otoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-alpha, have long-waveleng th absorptions in the range lambda(max) = 734-758 nm. Preferential mig ration of ethyl over methyl substituents among ketobacteriochlorins ob tained in the pinacol-pinacolone rearrangements of vic-dihydroxybacter iochlorins was confirmed by NOE studies. The bacteriochlorins show rel atively law fluorescence quantum yields. Among all the bacteriochlorin s the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quant um yields. In preliminary in viva studies (DBA/2 mice, transplanted wi th SMT/F tumors), ketobacteriochlorins were found to be more photodyna mically active than the related vic-dihydroxy analogues. Replacement o f the methyl ester functionalities with di-tert-butylaspartic acids en hanced the in vivo efficacy. Site specific human serum albumin (BSA) b inding studies indicated a direct correlation between the ability of t he compound to bind to the diazepam binding site (albumin site II) and the in viva photosensitizing efficacy.