BC-77 Glycoconjugated Phthalocyanines: A Synthetic Journey

Glycoconjugated phthalocyanines hold significant potential as photosensitizers in targeted light therapies, possibly overcoming the drawbacks of their counterparts. Unlike other photosensitizers such as porphyrins and chlorins, phthalocyanines allow for deep tissue penetration via light absorption between wavelengths 650 and 700 nanometers. Thus, making them a promising candidate for Photodynamic Therapy (PDT), a phototherapy with implications in antimicrobial and cancer treatments. Our research aims to explore this potential by building a library of glycoconjugated phthalocyanines, from synthesis to characterization, unveiling various methods to functionalize these phthalocyanines. Synthesis was performed using three methods, pre-functionalized, post-functionalized, and sub-phthalocyanine ring expansion. The pre-functionalized method was split between only adding the linking group and adding both the linking group and the carbohydrate. For both, the nitro group on a phthalonitrile undergoes a substitution reaction with an alkynylated alcohol. That alkynylated alcohol then undergoes a condensation reaction using a 3:1 mixture of tert-butyl substituted and the alkynylated phthalonitrile to form the phthalocyanine, which is then glycoconjugated via click-reaction. Alternatively, the alkynylated phthalonitrile can be glycoconjugated through the same process and then undergoes a similar condensation reaction. The post-functionalized method begins with a condensation reaction using a 3:1 ratio of tert-butyl substituted and brominated phthalonitriles. The resulting brominated phthalocyanine is alkynylated by a palladium catalyzed cross-coupling reaction which is then glycoconjugated by a click-reaction. Lastly, the sub-phthalocyanine reaction can be performed with brominated, alkynylated, or glycoconjugated phthalonitriles, with the product being a monosubstituted phthalocyanine. This work was supported by funding through SC INBRE/NIH (P20GM103499-20) and an NIH R15 award (1R15GM148916-01).