Chemical reaction design goes virtual

Date:
March 14, 2022
Source:
Hokkaido University
Summary:
Researchers aim to streamline the time- and resource-intensive
process of screening ligands during catalyst design by using
virtual ligands.



FULL STORY ========================================================================== Researchers aim to streamline the time- and resource-intensive process
of screening ligands during catalyst design by using virtual ligands.


========================================================================== Researchers at the Institute for Chemical Reaction Design and Discovery
and Hokkaido University have developed a virtual ligand-assisted
(VLA) screening method, which could drastically reduce the amount of
trial and error required in the lab during transition metal catalyst development. The method, published in the journal ACS Catalysis, may
also lead to the discovery of unconventional catalyst designs outside
the scope of chemists' intuition.

Ligands are molecules that are bonded to the central metal atom
of a catalyst, and they affect the activity and selectivity of a
catalyst. Finding the optimal ligand to catalyze a specific target
reaction can be like finding a needle in a haystack. The VLA screening
method provides a way to efficiently search that haystack, surveying a
broad range of values for different properties to identify the features
of ligands that should be most promising. This narrows down the search
area for chemists in the lab and has the potential to greatly accelerate
the reaction design process.

This new work utilizes virtual ligands, which mimic the presence of
real ligands; however, instead of being described by many individual constituent atoms -- such as carbon or nitrogen -- virtual ligands
are described using only two metrics: their steric, or space-filling, properties and their electronic properties. Researchers developed approximations that describe each of these effects with a single
parameter. Using this simplified description of a ligand enabled
researchers to evaluate ligands in a computationally efficient way over a
large range of values for these two effects. The result is a "contour map"
that shows what combination of steric and electronic effects a ligand
should have in order to best catalyze a specific reaction. Chemists can
then focus on only testing real ligands that fit these criteria.

Researchers used monodentate phosphorus (III) virtual ligands as a test
group and verified their models for the electronic and steric properties
of the virtual ligands against values calculated for corresponding
real ligands.

The VLA screening method was then employed to design ligands for a test reaction in which a CHO group and a hydrogen atom can be added to a double
bond in two different possible configurations. The reaction pathway was evaluated for 20 virtual ligand cases (consisting of different assigned
values for the electronic and steric parameters) to create a contour map
that shows a visual trend for what types of ligands can be expected to
result in a highly selective reaction.

Computer models of real ligands were designed based on parameters
extracted from the contour map and then evaluated computationally. The selectivity values predicted via the VLA screening method matched well
with the values computed for the models of real ligands, showing the
viability of the VLA screening method to provide guidance that aids in
rational ligand design.

Beyond saving valuable time and resources, corresponding author Satoshi
Maeda anticipates the creation of powerful reaction prediction systems
by combining the VLA screening method with other computational techniques.

"Ligand screening is a pivotal process in the development of transition
metal catalysis. As the VLA screening can be conducted in silico, it would
save a lot of time and resources in the lab. We believe that this method
not only streamlines finding an optimal ligand from a given library
of ligands, but also stimulates researchers to explore the untapped
chemical space of ligands," commented corresponding author Satoshi
Maeda. "Furthermore, we also expect that by combining this method with
our reaction prediction technology using the Artificial Force Induced
Reaction method, a new computer-driven discovery scheme of transition
metal catalysis can be realized."

========================================================================== Story Source: Materials provided by Hokkaido_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Wataru Matsuoka, Yu Harabuchi, Satoshi Maeda. Virtual
Ligand-Assisted
Screening Strategy to Discover Enabling Ligands for Transition Metal
Catalysis. ACS Catalysis, 2022; 3752 DOI: 10.1021/acscatal.2c00267 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220314095724.htm

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