Synthesis of cobalt bis(dicarbollide) conjugates with natural chlorins by the Sonogashira reaction

Abstract

Boron neutron capture therapy (BNCT) is one of the new and promising methods for cancer treatment. 1—4 The further development of this method is inseparably associ� ated with the design of new boroncontaining drugs that can selectively accumulate in the tumor tissue. Amino ac� ids, peptides, nucleotides, and some other molecules trop� ic to tumors can be used as molecules performing the tar� geted boron transport to the tumor. The ability of porphy� rins to be accumulated in cancer cells is well known. This ability in combination with the photoinduced generation of reactive oxygen species makes it possible to use them as photosensitizers in anticancer photodynamic therapy (PDT). 5—7 Photosensitizers based on natural chlorophylls with the enhanced tropicity to tumors, low toxicity, and an intense absorption in the nearIR spectral region, provid� ing the laser radiation action on deeply localized layers of cancer tissues, are of special interest. Therefore, synthesis of conjugates of polyhedral boron compounds with natural porphyrins is a topical issue. 8—16 The porphyrin fragment in these compounds provides the transportation of the bo� roncontaining conjugate to cancer cells and a possibility of visualization of the tumor. The subsequent irradiation of the cells with thermal neutrons and their interaction with the 10 B isotope of boron compounds selectively accu� mulated in cancer cells should result in the selective de� struction of malignant neoplasms. In the present work, the Sonogashira reaction, which is actively employed in modern organic chemistry, 17,18 was used for the synthesis of boroncontaining conjugates of natural porphyrins.