Abstract: Ifosfamide is one of the most important clinical alkylating agent due to its frequent use in cancer chemotherapy. It does not exhibit any cytotoxic activities in vitro, and requires hepatic oxidative metabolism in vivo to generate an alkylating ifosfamide mustard, which is regarded as the ultimate intracellular alkylating metabolite. However, its clinical uses are restricted due to they can not distinguish tumor cells from normal cells. Porphyrins could selectively accumulate in tumor tissues than in normal tissues. Based on these facts, an efficient one-pot method for the synthesis of ifosfamide mustards porphyrin dimers was achieved by treating hydroxyl substituted porphyrin first with POCl3 then with primary amine. The selective synthesis of ifosfamide mustards porphyrin dimers were achieved simply by controlling the ratio of POCl3 vis hydroxyl porphyrin and the reaction condition during the phosphonation step. Five ifosfamide mustards porphyrin dimers were synthesized accordingly by this one-pot procedure and their structures were affirmed by MS, 1H NMR, 31P NMR and elemental analysis. The MTT tests and the uptake tests showed that ifosfamide mustards porphyrin dimers could selectively accumulate and kill cancer cell. The interaction between ifosfamide mustards porphyrin dimers and bovine serum albumin (BSA) was investigated by fluorescence spectrum. The results showed that the ifosfamide mustards porphyrin dimers own a powerful ability of quenching the fluorescence of BSA via static quenching occurring in the non-covalent porphyrin-BSA complex.

Key words: Porphyrin dimer, Ifosfamide mustard, Cellular uptake, Bovine serum albumin(BSA)