Education

Harvard University, A. B., 1998
Stanford University, Ph.D., 2004 
Massachusetts Institute of Technology, NIH Postdoctoral Fellow, 2004-2007 

Research

My research lies at the interface between traditional inorganic chemistry and biochemistry.  Two diverse goals are pursued:  (1) the development of novel methodology for difficult organic transformations and (2) the production of biosensors capable of detecting reactive oxygen species.

Halogenation: 

Many natural products known to have medicinal properties contain chlorine and bromine at key positions in the molecular architecture.  These halogen atoms are found on aliphatic, olefinic, and aromatic carbons and have demonstrated the ability to profoundly impact the biological activity of the compound.  The lack of reactions capable of installing halogens regio- and/or stereoselectively hinders the independent syntheses of these natural products, complicating both identification and large-scale production.

Nature has developed the means to activate even aliphatic carbons for halogenation using first-row transition metal ions (V, Fe), dioxygen as the terminal oxidant, and salt water as the halogen source.  Of particular interest is the non-heme iron enzyme SyrB2, which uses a mononuclear iron atom to perform the halogenation of L-threonine.  The ultimate objective of this project is to replicate this reactivity with redox-active coordination compounds acting as bio-inspired catalysts. 

Site-Directed Oxidation:

Most oxidation processes are indiscriminate with respect to the site and extent of oxidation.  Methane, for instance, is commonly oxidized to carbon dioxide, as opposed to the more useful methanol or formaldehyde.  The target product must subsequently be separated from a number of side-products, which consumes a researcher’s time, energy, and patience.

The goal of this project is to develop transition metal oxidants capable of recognizing particular hydrocarbon environments, such that only particular portions either within a substrate or within a group of potential substrates are activated.  The addition of steric bulk or substrate docking groups to the organic component of the oxidant have proven to be effective strategies towards achieving regioselectivity.

Biosensors:

Reactive oxygen species (ROSs) have been implicated in a number of health conditions, including numerous inflammatory, cardiovascular, and neurological pathologies (e.g. Huntington’s and Alzheimer’s diseases).  The ability to monitor aberrant oxidative activity within living subjects would be a tremendous boon for medicine, with the potential to improve diagnosis and treatment of the associated diseases.

Recently, a number of compounds have been developed to detect ROS activity.  Most of these rely on a change in the fluorescent properties of the probe to signal the presence of a ROS.  This limits their application to cell cultures and thin tissues.  This project aims to develop novel ROS sensors and expand their application to include living subjects.   

Selected Publications

Zhang, Q.; Gorden, J. D.; Beyers, R. J.; Goldsmith, C. R. "A Manganese(II)-Containing MRI Contrast Agent Employing a Neutral and Non-Macrocyclic Ligand." Q. Zhang; J. D. Gorden; R. J. Beyers; C. R. Goldsmith. Inorg. Chem., (2011) 50, 9365-9373.

Coates, C. M.; Hagan, K.; Mitchell, C. A.; Gorden, J. D.; Goldsmith, C. R. "Structural Characterization of Manganese and Iron Complexes with Methylated Derivatives of Bis(2-pyridylmethyl)-1,2-ethanediamine Reveals Unanticipated Conformational Flexibility," Dalton Trans., (2011) 40, 4048-4058.

Goldsmith, C. R.; Coates, C. M.; Hagan, K.; Mitchell, C. A. “Hydrocarbon Chlorination Promoted by Manganese and Iron Complexes with Methylated Derivatives of Bis(2-pyridylmethyl)-1,2-ethanediamine,” J. Mol. Catal. A, (2011) 335, 24-30.

He, Y.; Goldsmith, C. R. “The Halogenation of Aliphatic C-H Bonds with Peracids and Halide Salts.” SynLett, (2010) 21, 1377-1380.

Coates, C. M.; Fiedler, S. R.; McCullough, T. L.; Albrecht-Schmitt, T. E.; Shores, M. P.; Goldsmith, C. R. “Synthesis and Characterization of an Asymmetric, Linear, Trinuclear Manganese(II) Complex.” Inorg. Chem., (2010) 49, 1481-1486.

Goldsmith, C. R.; Stack, T. D. P. “Hydrogen Atom Abstraction by a Mononuclear Ferric Hydroxide Complex:  Insights into the Reactivity of Lipoxygenase.” Inorg. Chem., (2006) 45, 6048-6055.

Goldsmith, C. R.; Jaworski, J.; Sheng, M.; Lippard, S. J. “Selective Labeling of Extracellular Proteins Containing Polyhistidine Sequences by a Fluorescein-Nitrilotriacetic Acid Conjugate.” J. Am. Chem. Soc., (2006) 128, 418-419.

Goldsmith, C. R.; Cole, A. P.; Stack, T. D. P. “C-H Activation by a Mononuclear Manganese(III) Hydroxide Complex:  Synthesis and Characterization of a Manganese-Lipoxygenase Mimic?” J. Am. Chem. Soc., (2005) 127, 9904-9912.