From The University of Illinois-Urbana–Champaign: “Artificial intelligence and molecule machine join forces to generalize automated chemistry”

From The University of Illinois-Urbana–Champaign

Liz Ahlberg Touchstone

Researchers in the Molecule Maker Lab.
Illinois researchers led an international team that combined powerful AI and a molecule-making machine to find the best conditions for automated complex chemistry. Pictured, from left: University of Illinois chemistry professor Martin D. Burke, materials science and engineering professor Charles M. Schroeder, graduate student Nicholas Angello and postdoctoral researcher Vandana Rathore. Pictured on the screen behind them are international collaborators, led by professors Bartosz A. Grzybowski and Alán Aspuru-Guzik. Photo by Fred Zwicky.

Artificial intelligence, “building-block” chemistry and a molecule-making machine teamed up to find the best general reaction conditions for synthesizing chemicals important to biomedical and materials research – a finding that could speed innovation and drug discovery as well as make complex chemistry automated and accessible.

With the machine-generated optimized conditions, researchers at the University of Illinois Urbana-Champaign and collaborators in Poland and Canada doubled the average yield of a special, hard-to-optimize type of reaction linking carbon atoms together in pharmaceutically important molecules. The researchers say their system provides a platform that also could be used to find general conditions for other classes of reactions and solutions for similarly complex problems. They reported their findings in the journal Science [below].

“Generality is critical for automation, and thus making molecular innovation accessible even to nonchemists,” said study co-leader Dr. Martin D. Burke, an Illinois professor of chemistry and of the Carle Illinois College of Medicine, as well as a medical doctor. “The challenge is the haystack of possible reaction conditions is astronomical, and the needle is hidden somewhere inside. By leveraging the power of artificial intelligence and building-block chemistry to create a feedback loop, we were able to shrink the haystack. And we found the needle.”

Automated synthesis machines for proteins and nucleic acids such as DNA have revolutionized research and chemical manufacturing in those fields, but many chemicals of importance for pharmaceutical, clinical, manufacturing and materials applications are small molecules with complex structures, the researchers say.

Burke’s group has pioneered the development of simple chemical building blocks for small molecules. His lab also developed an automated molecule-making machine that snaps together the buildings blocks to create a wide range of possible structures.

However, general reaction conditions to make the automated process broadly applicable have remained elusive.

“Traditionally, chemists customize the reaction conditions for each product they are trying to make,” Burke said. “The problem is that this is a slow and very specialist-dependent process, and very hard to automate because the machine would have to be optimized every time. What we really want are conditions that work almost every time, no matter what two things you’re trying to snap together.”

An automated approach with generalized conditions could help standardize how some products are made, addressing the problem of reproducibility, said Illinois postdoctoral researcher Vandana Rathore, a co-first author of the study.

Burke’s group teamed up with a group led by Bartosz A. Grzybowski at the Polish Academy of Sciences’ Institute for Organic Chemistry, as well as the group of Alán Aspuru-Guzik at the University of Toronto, both leaders in using artificial intelligence and machine learning to improve chemical synthesis. The team integrated AI with the molecule machine to provide real-time feedback to the machine-learning system.

“To distinguish good and bad you need to know something about the bad, but people only publish the successes,” Grzybowski said. Published studies reflect conditions that are popular or convenient, rather than the best, so a systematic approach that included diverse data and negative results was necessary, he said.

First, the team ran the entire matrix of possible combinations using the building-block chemistry through an algorithm to group together similar reactions. Then, the AI sent instructions, inputted to a machine in the Molecule Maker Lab located in the Beckman Institute for Advanced Science and Technology at Illinois, to produce representative reactions from each cluster. The information from those reactions fed back into the model; the AI learned from the data and ordered more experiments from the molecule machine.

“We were looking to see two things: an increase in yield and a decrease in uncertainty, for a broad spectrum of reactions,” said Grzybowski, who now is at Ulsan Institute of Science and Technology in South Korea. “This loop continued without us having to intervene until the problem was solved. Figuring out the generalized conditions for protein-synthesis machines took 30 years. This took us two months.”

The process identified conditions that doubled the average yield of a challenging class of reactions, called heteroaryl Suzuki-Miyaura coupling, crucial for many biological and materials-relevant compounds.

“There are all kinds of building block combinations that we didn’t even study in our AI training, but because the AI had explored such a diverse space, it found good results even in those initially unexplored areas,” said Illinois graduate student Nicholas H. Angello, a co-first author of the study.

The machine-learning process described in the paper also could be applied to other broad areas of chemistry to find the best reaction conditions for other types of small molecules or even larger organic polymers, the researchers say.

“There are so many different materials classes that we want to know, target and discover for different functional properties. The extension possibility of this approach to other similar reaction chemistry, other types of carbon-carbon links, is exciting,” said study co-author Charles M. Schroeder, an Illinois professor of materials science and engineering and chemical and biomolecular engineering, and a Beckman Institute affiliate.

The Defense Advanced Research Projects Agency and the National Science Foundation supported this work.

Science paper:

See the full article here .


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Stem Education Coalition

The University of Illinois-Urbana-Champaign community of students, scholars, and alumni is changing the world.

The University of Illinois at Urbana–Champaign is a public land-grant research university in Illinois in the twin cities of Champaign and Urbana. It is the flagship institution of the University of Illinois system and was founded in 1867.

The University of Illinois at Urbana–Champaign is a member of the Association of American Universities and is classified among “R1: Doctoral Universities – Very high research activity”, and has been listed as a “Public Ivy” in The Public Ivies: America’s Flagship Public Universities (2001) by Howard and Matthew Greene. In fiscal year 2019, research expenditures at Illinois totaled $652 million. The campus library system possesses the second-largest university library in the United States by holdings after Harvard University. The university also hosts the National Center for Supercomputing Applications (NCSA).

The university contains 16 schools and colleges and offers more than 150 undergraduate and over 100 graduate programs of study. The university holds 651 buildings on 6,370 acres (2,578 ha). The University of Illinois at Urbana–Champaign also operates a Research Park home to innovation centers for over 90 start-up companies and multinational corporations, including Abbott, AbbVie, Caterpillar, Capital One, Dow, State Farm, and Yahoo, among others.

As of August 2020, the alumni, faculty members, or researchers of the university include 30 Nobel laureates; 27 Pulitzer Prize winners; 2 Turing Award winners and 1 Fields medalist. Illinois athletic teams compete in Division I of the NCAA and are collectively known as the Fighting Illini. They are members of the Big Ten Conference and have won the second-most conference titles. Illinois Fighting Illini football won the Rose Bowl Game in 1947, 1952, 1964 and a total of five national championships. Illinois athletes have won 29 medals in Olympic events, ranking it among the top 40 American universities with Olympic medals.

Illinois Industrial University

The original University Hall, which stood until 1938, when it was replaced by Gregory Hall and the Illini Union. Pieces were used in the erection of Hallene Gateway dedicated in 1998.

The University of Illinois, originally named “Illinois Industrial University”, was one of the 37 universities created under the first Morrill Land-Grant Act, which provided public land for the creation of agricultural and industrial colleges and universities across the United States. Among several cities, Urbana was selected in 1867 as the site for the new school. From the beginning, President John Milton Gregory’s desire to establish an institution firmly grounded in the liberal arts tradition was at odds with many state residents and lawmakers who wanted the university to offer classes based solely around “industrial education”. The university opened for classes on March 2, 1868 and had two faculty members and 77 students.

The Library which opened with the school in 1868 started with 1,039 volumes. Subsequently President Edmund J. James in a speech to the board of trustees in 1912 proposed to create a research library. It is now one of the world’s largest public academic collections. In 1870 the Mumford House was constructed as a model farmhouse for the school’s experimental farm. The Mumford House remains the oldest structure on campus. The original University Hall (1871) was the fourth building built. It stood where the Illini Union stands today.

University of Illinois

In 1885, the Illinois Industrial University officially changed its name to the “University of Illinois”, reflecting its agricultural; mechanical; and liberal arts curriculum.

During his presidency Edmund J. James (1904–1920) is credited for building the foundation for the large Chinese international student population on campus. James established ties with China through the Chinese Minister to the United States Wu Ting-Fang. In addition, during James’s presidency class rivalries and Bob Zuppke’s winning football teams contributed to campus morale.
Like many universities the economic depression slowed construction and expansion on the campus. The university replaced the original university hall with Gregory Hall and the Illini Union. After World War II the university experienced rapid growth. The enrollment doubled and the academic standing improved. This period was also marked by large growth in the Graduate College and increased federal support of scientific and technological research. During the 1950s and 1960s the university experienced the turmoil common on many American campuses. Among these were the water fights of the fifties and sixties.

University of Illinois at Urbana–Champaign

By 1967 the University of Illinois system consisted of a main campus in Champaign-Urbana and two Chicago campuses- Chicago Circle (UICC) and Medical Center (UIMC). People began using “Urbana–Champaign” or the reverse to refer to the main campus specifically. The university name officially changed to the “University of Illinois at Urbana–Champaign” around 1982. While this was a reversal of the commonly used designation for the metropolitan area- “Champaign-Urbana” – most of the campus is located in Urbana. The name change established a separate identity for the main campus within the University of Illinois system which today includes campuses in Springfield (UIS) and Chicago (UIC) (formed by the merger of UICC and UIMC).

In 1998 the Hallene Gateway Plaza was dedicated. The Plaza features the original sandstone portal of University Hall which was originally the fourth building on campus. In recent years state support has declined from 4.5% of the state’s tax appropriations in 1980 to 2.28% in 2011- a nearly 50% decline. As a result the university’s budget has shifted away from relying on state support with nearly 84% of the budget now coming from other sources.

On March 12, 2015, the Board of Trustees approved the creation of a medical school, the first college created at Urbana–Champaign in 60 years. The Carle-Illinois College of Medicine began classes in 2018.


The University of Illinois at Urbana–Champaign is often regarded as a world-leading magnet for engineering and sciences (both applied and basic). Having been classified into the category comprehensive doctoral with medical/veterinary and very high research activity by The Carnegie Foundation for the Advancement of Teaching Illinois offers a wide range of disciplines in undergraduate and postgraduate programs.

According to the National Science Foundation the university spent $625 million on research and development in 2018 ranking it 37th in the nation. It is also listed as one of the Top 25 American Research Universities by The Center for Measuring University Performance. Beside annual influx of grants and sponsored projects the university manages an extensive modern research infrastructure. The university has been a leader in computer-based education and hosted the PLATO project which was a precursor to the internet and resulted in the development of the plasma display. Illinois was a 2nd-generation ARPAnet site in 1971 and was the first institution to license the UNIX operating system from Bell Labs.