Synthesis of Lysozyme-Metallacarborane Conjugates and the Effect of Boron Cluster Modification on Protein Structure and Function

Two complementary methods, “in solution” and “in solid state”, for the synthesis of lysozyme modified with metallacarborane (cobalt bis(dicarbollide), Co(C2B9H11)22−) were developed. As metallacarborane donors, oxonium adducts of cobalt bis(dicarbollide) and 1,4‐dioxane or tetrahydropyran were used. The physicochemical and biochemical properties of the obtained lysozyme–metallacarborane conjugates were studied for changes in secondary and tertiary structure, aggregation behavior, and biological activity. Only minor changes in primary, secondary, and tertiary protein structure were observed, caused by the single substitution of metallacarborane on lysozyme. However, the modification produced significant changes in lysozyme enzymatic activity and a tendency toward time‐ and temperature‐dependent aggregation. An “in solid‐state”, high temperature, method for protein modification with metallacarborane (3‐cobalt bis(dicarbollide) has been developed. Oxonium adducts of cyclic ether and metallacarborane were used as metallacarborane donors.