Synthesis games for chemists to puzzle over

Synthesizing a Wordle for chemists

The first time Ryan Shenvi played Wordle, when the popular word-guessing game was just taking off, he remembers thinking, “Oh, we should do this for retrosynthesis.”

The La Jolla–based Scripps Research synthetic chemist spent a while thinking about how to offer multiple choices to solve a chemical synthesis puzzle; he wrote several exams in this style and toyed with a portmanteau between “Wordle” and the name of E. J. Corey, a cofounder of the field of retrosynthesis.

But the idea didn’t really take off until Jonah Luo reached out to the Shenvi laboratory. Luo, then a rising sophomore in high school, had enjoyed Advanced Placement Chemistry and wanted to learn some practical skills at the bench. When Luo went looking for local researchers, Shenvi’s focus on synthetic chemistry inspired him.

There was just one problem: Luo was too young to work legally at Scripps. “Initially, they told me to come back when I was 16,” he tells Newscripts. But he was worried about the summer in between, “where I’d be idle if I didn’t have anything to do.” Shenvi says that the synthesis game idea, which had lingered on the back burner, seemed like a perfect match for a motivated volunteer.

To account for Luo being new to chemistry—not yet schooled in the many named reactions that make up a trained synthetic chemist’s tool set—Shenvi suggested starting with a simpler goal. Could Luo build a version of Wordle inspired by cooking, with problems such as converting a wheat emoji into a bread emoji by applying water and heat in the right order? Over the summer, Luo built a prototype dubbed Chefdle. He and Kevin Zong, a graduate student in the Shenvi lab, then worked together to adapt it for problems in organic synthesis.

“I wanted to stay true to what people are already used to with Wordle,” Zong says. They replicated features such as the flipping animation and the feedback loop of getting more information with every round of the game. But instead of working with a constant keyboard of the 26 English-language letters, they needed to populate the multiple-choice space with potential reactants. In place of a secret word list, they compiled a list of four-step reactions from Shenvi’s past exams, the textbook The Logic of Chemical Synthesis, a web database, and recent literature in total synthesis.

The completed game—which you can play at shenvilab.github.io/Synthordle—shows a starting molecule and product, with three steps of transformation in between. It offers players a choice of reagents that they might use to turn one into the other and gives six chances to choose the right sequence of manipulations. As with Wordle, a correct guess in the correct position turns green; a right guess in the wrong position, yellow.

Zong and Shenvi say the game has been well received. Several professors have asked about making the problems simpler so their students can use the game as a study tool. And during an interview with Newscripts, Zong made sure to highlight that the team is soliciting new problems.

And Luo, who’s now nearly 16, looks forward to his 2025 summer break from school, when he will be old enough to work in the lab.

Many ways to play

Playful synthetic chemists have developed numerous ways to convert total synthesis questions from problem set to puzzle game. In an interview with Newscripts, Scripps Research chemist Ryan Shenvi mentioned several:

▸ Denksport, German for “mind game,” is a web-based list of problems for making various elaborate molecules, complete with citations, maintained by Dirk Trauner at the University of Pennsylvania.

▸ Chemistry by Design is a web-based set of flash cards for synthesis compiled by Jon T. Njardarson of the University of Arizona.

▸ Chemdle, by Pharmaron chemist Sam Ellis, gives the user six chances to draw the correct product of an organic reaction.

Please send comments and suggestions to newscripts@acs.org.