Research

We are a young research group that is applying “systems” and supramolecular ways of thinking to solve problems in catalysis as it relates to organic chemistry and the chemical origins of life. Interrelated areas of focus include:

1) Self-organized reaction networks to understand the origin of life

metabolism

How did life’s chemical pathways emerge before there were enzymes to act as catalysts? Why does biochemistry use the reactions and pathways that it does and not others? This ERC-funded project aims to understand  the prebiotic origins of biological metabolism. We suspect that the metabolism underlying all living things started before the onset of Darwinian evolution as a self-organized reaction network that was driven into existence by a far-from-equilibrium environment, enabled by naturally occurring catalysts such as minerals and metal ions. To figure out the conditions that would have been required to initiate self-organization, we are searching for non-enzymatic versions of ancient, core metabolic processes. So far we have found non-enzymatic chemistry that resembles the acetyl CoA pathway [1,2], the reverse Krebs cycle [3], the Krebs cycle and glyoxylate cycle [4], and thioester-based energy conservation [5]. Once we have a few more processes in hand (gluconeogenesis, fatty acid synthesis, nucleotide synthesis) we expect to be able to triangulate the non-equilibrium conditions required to enable self-organization. Our results already support the hypothesis that biological metabolism was an outgrowth of geochemistry. For a (now slightly out of date) overview, see below for Joseph’s short talk from the 2018 ACS meeting in Boston.

[1] Nature Ecol. Evol. 2018, 2, 1019-1024. [2] BioRxiv 2019.  [3] Nature Ecol. Evol. 2017, 1, 1716-1721. [4] Nature 2019, 569, 104-107. [5] ChemRxiv 2019.

2) Vibrational Strong Coupling for organic chemistry and catalysis

TOC graphic

This project aims to develop a completely new way to control the rate and selectivity of organic reactions: by selectively modifying relevant molecular vibrations by running the reaction between appropriately-spaced mirrors. Vibrational Strong Coupling (VSC) is an emerging field in the quantum optics community.  A collaboration between our group (organic chemistry) and the group of Prof. Thomas Ebbesen (a world leader in VSC), aims to exploit this phenomenon for use in organic synthesis and catalysis. Thus far, we have shown that VSC can be used to change the rates [1] and selectivities [2] of ground state organic reactions. Ongoing work aims to understand and predict how VSC influences chemistry and to exploit it to streamline the outcomes of useful chemical transformations.

[1] Angew. Chem. Int. Ed. 2016, 55, 11462. [2] Science 2019, 363, 615.

3) Development of Catalytic Synthetic Methodology 

We are broadly interested in the development of new catalytic methods for organic synthesis. Recent interests include specific solvent effects (particularly nitromethane and HFIP) on the direct the direct nucleophilic substitution of alcohols [1][2], alkyl fluorides [3] and the ring opening of cyclopropanes [4]. We are also interested in extending the scope of cross-coupling reactions to include a broader range of functional groups [5].

[1] (a) Angew. Chem. Int. Ed. 2017, 56, 3085. (b)  J. Am. Chem. Soc. 2015, 137, 9555. (c) Org. Biomol. Chem. 2014, 12, 5990. [2] For our review of catalytic dehydrative alcohol substitution, see Synthesis 2016, 48, 935. [3] (a) ACS Catalysis 2016, 6, 3670. (b)  J. Fluor. Chem. 2017, 193, 45. [4] (a) Org. Lett. 2018, 20, 574. (b) Chem. Sci. 20189, 6411. [5] Angew. Chem. Int. Ed. 2019, 58, in press.

4) Catalyst discovery using complex mixtures – a systems approach

toc-synpacts

We have developed a simple algorithmic approach for screening and deconvoluting complex mixtures of catalyst components with the goal of rapidly identifying new catalysts and cooperative effects.[1] We have used this strategy to uncover new organoboron [2] and nickel [2][3] catalysts, and have found that catalysts selected in this way tend to be useful in multicatalysis.[4] While we still think this approach has untapped potential to discover new  cooperative effects and multicatalytic processes, we are no longer actively working on it.

[1] For an account of our recent work in this area, see: Synlett 2016, 27, 2637. [2] Chem. Sci. 2015, 6, 2501. [3] J. Org. Chem. 2015, 80, 6922. [4] Chem. Eur. J. 2016, 22, 12274.

For more information on ongoing projects, please contact Dr. Moran directly.