Research Projects in the Chen Group:

Mass spectrometry is a fascinating analytical and biological technology. Our research focuses on the new mass-spec innovation based on newly discovered ion chemistry and novel instrumentation. The current projects are:

1. Bioanalytical applications using ambient mass spectrometry

Desorption electrospray ionization (DESI),^1,2 an ambient ionization method, is capable of recording mass spectra on ordinary samples in seconds, in their native environment, without sample preparation. Our effort is being devoted to the development of novel methodologies for selective biomolecule detection in complex matrices (e.g. the detection of anabolic steroids in urine shown below³) based on newly uncovered ion chemistry (e.g. heterogeneous ionic oximation reaction below). Currently, we have extended the powerful DESI-MS method to analysis of solution samples such as big proteins. In addition, other projects relying on ion chemistry such as chiral recognition, reaction mechanism elucidation and chemical modification of nano-materials/surfaces are also under the investigation.

2. Proteome research applications of ambient ion thermal dissociation

Tandem mass spectrometry is invaluable for chemical structure elucidation via examination of fragment ions after the activation and dissociation of gaseous precursor ions. The fragmentation of peptide/protein ions is a central topic in proteomics and there is strong interest in novel dissociation methods. Recently, an ambient ion thermal dissociation method⁴ has been established which allows the isolation and re-ionization of neutral fragments of peptide/protein ions at atmospheric pressure outside of the mass spectrometer. We are applying this method to proteome research.

3. Protein footprinting using fast photolytic oxidation of protein (FPOP)

        Chemical footprinting of proteins has long been proven to be an efficient method for probing protein-protein interactions. FPOP⁵ achieves protein oxidation on a microsecond timescale, making it a strong candidate for protein footprinting. The objective of this project is to develop new FPOP methods with novel laser-generated oxidative chemical probes.

4. Ionic liquid study

        The thermochemical properties of carbenes, including their proton affinities (PAs), are of fundamental interest since carbenes play key roles as reactive intermediates in many organic reactions. However, due to their transient nature, limited accessibility, and the special experimental techniques required for their detection, the measurement of the PAs of carbenes is extremely challenging. Taking advantage of Cooks’ kinetic method⁶ (by measuring the fragment ion abundance ratio [I]/[I_i], as shown below) and the fact that N-heterocyclic carbenes can be generated by the deprotonation of an imidazolium salt (typically an ionic liquid), we are investigating the gas-phase proton affinity of various N-heterocyclic carbenes.

References:

1. Z. Takats, J. M. Wiseman, B. Gologan, and R. G. Cooks, Science, 2004, 306, 471

2. R. G. Cooks, Z. Ouyang, Z. Takats, J. M. Wiseman, Science, 2006, 311, 1566

3. G. Huang, H. Chen, X. Zhang, R. G. Cooks and Z. Ouyang, Anal. Chem., 2007, 79, 8327.

4. H. Chen, L. S. Eberlin, R. G. Cooks,  J. Am. Chem. Soc., 2007, 129, 5880

5. D. M. Hambly, M. L. Gross, J. Am. Soc. Mass Spectrom. 2005, 16, 2057

6. H. Chen, D. R. Justes and R. G. Cooks, Org. Lett. 2005, 7, 3949