Transition Metal Mediated Transformations in Small Molecule and Enzymatic Systems

This dissertation describes efforts toward achieving transformations in organic molecules – in particular, C–H functionalization and hydrosilylation, mediated by transition metal catalysts in small molecule, enzymatic, and artificial metalloenzyme systems.In Chapter 1, a proposed dual catalytic cycle system using two transition metal catalysts for non-directed C–H functionalization was introduced. The system may have the potential to achieve C–H functionalization via one-pot substrate C–H activation by a first metal catalyst, followed by functionalization of the activated substrate catalyzed by a second metal catalyst. Transmetallation of a hydrocarbyl fragment between the two metal intermediates is the lesser-known process in this system and was studied in this chapter. Several novel pre-formed metal precursors of transmetallation were synthesized and tested. The best transmetallation yield of this project was obtained with the preformed metal complexes iPr(PNP)RhPh and (SPhos)Pt(p-Tol)(Cl). Efforts to complete the dual catalytic system were also described. In Chapter 2, C–H functionalization of N-succinylated leucine (NsL) by Fe(II) alpha-KG-dependent hydroxylase SadA was explored. This work was built upon literature precedent of non-native chlorination of NsL by mutant SadA D157G in the presence of NaCl by exploiting the mechanistic similarities between Fe(II) alpha-KG-dependent hydroxylases and halogenase. The binding between exogenous anions and Fe(II) in SadA D157G was studied in this chapter via anion activity assay, steady-state kinetics, and UV-vis titration assay of the mutant in the presence of different anions. These studies provide several lines of evidence of anion binding to Fe(II) in the enzyme. In Chapter 3, the development toward an artificial metalloenzyme (ArM) comprising of streptavidin (SAV) and a bioconjugated Ni(II) salicylaldiminato catalyst was described. This ArM has the potential to perform olefin hydrosilylation or polymerization in aqueous medium. A small molecule Ni(II) salicylaldimine catalyst for aqueous olefin hydrosilylation was identified. A biotinylated analogue was synthesized and shown to bioconjugate to SAV. The resulting ArM has yet to demonstrate olefin hydrosilylation activity. Control reactions point to detrimental interaction between residue(s) in binding pocket of SAV and Ni(II) as cause for inactivity. Efforts to circumvent this issue are ongoing