We are a young research group that is applying “systems” and supramolecular ways of thinking to solve problems in catalysis and the chemical origins of life.

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

How did the self-organized chemistry that gave rise to life 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 life 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 metals. 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 or studied non-enzymatic chemistry that resembles the acetyl CoA pathway [1,2], parts of the reverse Krebs cycle [3,4], the Krebs cycle and the glyoxylate cycle [5], reductive amination and transamination to form amino acids from ketoacids [6,7], and pyrimidine nucleobase biosynthesis[8]. By developing non-enzymatic versions of other critical metabolic pathways (gluconeogenesis, nucleotide biosynthesis, and some missing parts of the reverse Krebs cycle) we expect to be able to triangulate the non-equilibrium conditions required to enable self-organization. We’ve recently reviewed the topic [9]. See below for recent recorded talks.

[1] Nat. Ecol. Evol. 2018, 2, 1019. [2] Nat. Ecol. Evol. 2020, 4, 534.  [3] Nat. Ecol. Evol. 2017, 1, 1716. [4] Angew. Chem. Int. Ed. 2022, 61, e202212932. [5] Nature 2019, 569, 104. [6] J. Am. Chem. Soc. 2021, 143, 19099. [7] Angew. Chem. Int. Ed. 2022, 61, e202212237. [8] Angew. Chem. Int. Ed. 2022, 61, e202117211. [9] Chem. Rev. 2020, 120, 7708.

May 5, 2021

November 8, 2022

2) 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 nucleophilic substitution of alcohols [1], alkyl fluorides [2]; the ring opening of cyclopropanes [3] and epoxides [1c, 4]; alkene hydrofunctionalization [5,6]; the difunctionalization of alkenes [7] . We are also interested in extending the scope of cross-coupling reactions to include a broader range of functional groups [8].

[1] (a) Angew. Chem. Int. Ed. 2017, 56, 3085. (b)  J. Am. Chem. Soc. 2015, 137, 9555. (c) Chem 2021, 7, 3425. [2] ACS Catalysis 2016, 6, 3670. [3] (a) Org. Lett. 2018, 20, 574. (b) Chem. Sci. 2018, 9, 6411. [4] ACS Catalysis 2022, 12, 3309. [5] ACS Catal. 2022, 12, 10995. [6] Chem. Sci. 2022, 13, 8436. [7] Angew. Chem. Int. Ed. 2023, 62, online. [8] (a) Angew. Chem. Int. Ed. 2019, 58, 14959. (b) Angew. Chem. Int. Ed. 2021, 60, 25307.

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

 

3) Vibrational Strong Coupling applied to organic chemistry and catalysis

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], chemoselectivity [2] and stereoselectivity [3] of ground state organic reactions. Ongoing work aims to understand and predict how VSC influences chemistry, to develop it as a tool for mechanistic insight, 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] Angew. Chem. Int. Ed. 2021, 60, 5712.

Previous projects:

4) Catalyst discovery using complex mixtures – a systems approach

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. 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] Our method has recently been implemented by Boehringer-Ingelhgeim in the evaluation of all Cu-catalyzed C-N couplings, one of the most widely used reactions in the pharmaceutical industry.[5]

[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. [5] J. Org. Chem. 2021, 86, 1528.