Current Research Directions:

  • The Hyster Group: We are currently pursuing the development of radical biocatalytic approaches toward carbon-carbon (C-C) bond formation, where photoexcitation of flavin-dependent ‘ene’- reductases enables an enantioselective C-C bond formation of alkene-tethered -chloroamides to the corresponding chiral lactams with high yields and enantioselectivities. In collaboration with the Scholes and Rand labs, we aim to understand the photophysical processes that underlie these transformations in an effort to develop new light-driven biocatalytic reactions.

BioLEC Research Goals


To employ light harvesting and advances in solar photochemistry to enable unprecedented photoinduced cross-coupling reactions that valorize abundant molecules.


The energy input required to transform stable and abundant molecules to valuable products is greatly reduced by the use of catalysts. A fundamental aim in catalysis is to devise new ways to convert plentiful and unreactive molecules for energy-relevant applications. The research proposed for the BioLEC Energy Frontier Research Center (EFRC) will expand our fundamental understanding of both solar photochemistry and photosynthetic systems to enable sophisticated molecular editing, known as cross-coupling chemistry, powered by light, Figure 1. The resulting breakthroughs will yield energy-relevant chemicals, fuels, and materials. Imagine being able to combine two alcohols produced from biomass processing and combine them into jet fuel. That is the kind of breakthrough aspired by BioLEC.

Figure 1. BioLEC’s interdisciplinary approach will enable nonequilibrium chemistry.

BioLEC aims to catalyze reactions that have prohibitive energy barriers for equilibrium chemistry—reactants are more stable than products. The reactions that we target are presently inconceivable using the leading edge of modern synthetic chemistry. Our approach is inspired by the way that nature combines the energy of multiple photons to ramp up redox capability beyond that achievable with the energy from a single photon. The fundamental advance of the BioLEC EFRC, therefore, will be to establish a platform for directing difficult chemical transformations that are enabled by combining the energies of multiple photons. Managing multiple photogenerated charges for function will require input from diverse fields, including synthetic chemistry and ultrafast science. To succeed, BioLEC unites scientific communities that rarely interact—organic synthesis, biophysics, and physical chemistry.

Recent breakthroughs in chemical catalysis have led researchers to understand how molecules can be made incredibly more reactive by activating them with light, as exemplified by photoredox catalysis. The BioLEC proposal identifies the ceiling for using a single photo-excitation to drive chemical change and we hypothesize how two (or more) photo-excitations could be used to propel more powerful chemical reactions. Thus, the BioLEC EFRC will conceive of and explore new ways to facilitate uphill, catalytic cycles that deploy out-of-equilibrium chemistry. In the past half-century, transition metal catalysis has arisen as a uniquely enabling platform for molecular construction. The development of cross-coupling technologies, the Suzuki, Negishi, Stille, and Kumada couplings, wherein aryl or alkyl substrates can be forged together, have proven to be particularly powerful for the rapid construction of complex molecular frameworks from modular building blocks. Simply put, these reactions enable the attachment of two molecular units A and B to form the new molecule A–B, facilitated by organometallic reagents (Figure 2). Although slowed by energetic barriers, these cycles typically proceed downhill to stable products. We will focus on the key steps of reductive elimination and oxidative addition. Our approach is to harness the energy of light and develop ways to control nonequilibrium chemistry at the level of electrons and thereby enable these difficult bond activations.

Figure 2. (a) A general catalytic cycle for forming a new molecule A–B. (b) Predicted potential energy landscape for Negishi alkyl-alkyl cross-coupling and the perspective of the BioLEC EFRC. (c) Specific strategy for leveraging the energies of two photons, leading to the idea of an “agile catalyst” that changes along with reaction steps.

BioLEC is inspired by photosynthetic systems, that oxidize water and reduce CO2 by generating one of the largest electrochemical potentials in biology. The oxidative power required to split water is the combined energy of four red photons. Similarly, BioLEC imagines accessing chemistry that, in essence, requires the energy of ultraviolet light—almost 350 times ambient thermal energy. Our scientific approach is timely—we will build a new field inspired by recent results revealing how the merger of photoredox catalysis and transition metal catalysis, termed metallophotocatalysis, can facilitate a range of novel C–C and C–X bond-forming reactions by providing alternate pathways for traditional elementary steps in organometallic catalysis.

Key deliverables from the BioLEC EFRC will be impactful and will converge to address the center’s mission. Cross-coupling reactions provide general solutions for selective and generalizable bond cleaving and forming, enabling us to edit a wide range of molecules. Cross-coupling involves a two-electron exchange between substrates and the catalyst. BioLEC will shift the field from passive catalysts to catalysis where two-electron chemistry is controlled. Our approach is to master actuation of redox states of organometallic photocatalysts using a variety of approaches that leverage the energies of multiple photons. This will enable us to activate bonds that are too stable to be addressed by the present state-of-the-art synthetic methods. Improving the function of catalysts by empowering them with multiple photoexcitations will be enabled using light harvesting.