Synthesis and Characterization of Amphiphilic Fe4S4-Core Dendrimers as Protein Models

Abstract

The ultimate goal of this research is to clarify the structural effects on the rate and driving force for electron transfer in amphiphilic iron-sulfur core dendrimers, which can eventually be used as protein models. These dendrimers were synthesized by ligand exchange reactions, including the synthesis of dendrons via a modular synthesis approach. Their structure-property relationships were then investigated using electrochemical methods. Three different routes were used to synthesize thiol dendrons with both cationic and anionic peripheral units. The first utilized the disulfide linkage as a focal and protecting group. However, due to difficulties associated with generating free thiol from the disulfide, only partially-substituted dendrimers were prepared in ligand exchange reaction. Similar problems were encountered with the next two methods, which used thiocarbamate and trityl protecting groups, respectively. First generation dendrimers were successfully prepared and characterized using the thiocarbamate group; however, low thiol concentration resulted in only partially substituted dendrimers for the second generation. All synthetic attempts using the trityl focal group resulted in only partial substitution. Because the concentration of free thiol was the factor limiting the synthesis of these amphiphilic iron-sulfur core dendrimers, a protocol was established to measure the thiol concentration using Ellman?s reagent test. However, this proved to be inaccurate due to oxygen dissolved in solution and then re-oxidized thiols during the course of the test. The electrochemical properties of these cationic and anionic dendrimers were measured and compared to G1-flexible dendrimer previously studied by the Gorman Group. G1-cationic dendrimer exhibited more effective attenuation of the electron transfer rate than G1-flexible dendrimer. This was attributed to the difference of molecular weight in both dendrimers. The redox potential in the cationic dendrimer was shifted more positively by about 100 mV due to polar microenvironment around the iron-sulfur core. Cyclic voltammogram of G1-anionic dendrimer exhibited an unexpected peak so other electrochemical properties could not be measured. Only an approximate redox potential was obtained and exhibited a positive shift by about 60 mV compared to G1-flexible dendrimer.