Where a Nobel Legacy Was Forged
"The best way of studying science is to be an assistant to the master who is an ideal in his field."
This article explores the formative Prague years of Vladimir Prelog, a young chemist from Bosnia who would later win the Nobel Prize. It was in the labs and lecture halls of Prague that his scientific character was shaped, laying the foundation for a career that would revolutionize our understanding of molecular architecture. His journey from a student in Prague to a revered figure in Zurich is a testament to the enduring power of mentorship and intellectual curiosity.
Vladimir Prelog arrived in Prague in 1924, leaving his home in Zagreb to study chemical engineering at the Czech Technical University 1 6 . He completed his diploma in 1928 and earned his Sc.D. in 1929 1 . His official doctoral advisor was Professor Emil VotoÄek, one of the prominent founders of chemical research in Czechoslovakia 1 6 .
However, the most profound influence on his early scientific development was Rudolf LukeÅ¡, then a lecturer and later VotoÄek's successor 1 6 .
Arrived in Prague to study chemical engineering
Completed his diploma
Earned his Sc.D. as highest-achieving student
Prelog himself acknowledged this, noting that to Lukeš he owed "the greatest part of my early scientific education," and the two remained close friends until Lukeš's premature death in 1960 6 . Under Lukeš's mentorship, Prelog was granted a rare opportunity for an undergraduate: to collaborate on research, investigating alkaloids such as cocaine, quinine, and morphine 8 . This early foray into the complex world of natural products would become a central theme of his lifelong work.
His doctoral thesis focused on elucidating the structure of a recently discovered form of glucose, rhamnoconvolvulin 8 . Completing this task in record time amid financial difficulties, he graduated in 1929 as the highest-achieving student in his generation 8 .
The close of his studies coincided with the Great Depression, and academic positions were scarce 1 6 . Grateful for a position in the newly established laboratory of G.J. DrÃza, Prelog was put in charge of producing rare chemicals that were not commercially available 1 . Here, he continued his research in his spare time, investigating alkaloids in cacao bark 1 .
Production of rare chemicals
An intriguing anecdote from this period involves his work with N-methyl-2,5-diphenylpyrrole. Prelog discovered this substance exhibited remarkable triboluminescence—the property of emitting light when crushed 8 . The specific structure he achieved at that time has, remarkably, never been replicated, making this phenomenon one of the small, unresolved mysteries of his early career 8 .
One of Prelog's most enduring legacies, which connects directly back to his rigorous early training, is the Cahn-Ingold-Prelog (CIP) system of stereochemical nomenclature 5 7 . Before this system, there was no simple, universal language to unambiguously describe the three-dimensional structure of chiral molecules—molecules that exist as non-superimposable mirror images, like a pair of hands 5 .
Left-handed
Right-handed
Chiral molecules exist as non-superimposable mirror images
In the 1950s, Prelog joined forces with Robert Sidney Cahn, editor of the Journal of the Chemical Society, and Christopher Kelk Ingold, a towering figure in physical organic chemistry, to address this problem 5 . Prelog's logical insights were instrumental in refining and generalizing the "sequence rules" for assigning atom priorities, leading to the now-universal R/S nomenclature for specifying absolute configuration 5 . This system provided chemists worldwide with a standard and international language for precisely specifying a compound's structure, an indispensable tool for modern chemistry 7 .
Journal editor who collaborated on the CIP system
Physical organic chemist and co-developer of CIP system
Nobel laureate who helped Prelog escape WWII
Prelog's "later contacts" were not merely professional; they were deeply formative. He referred to Robert Robinson, Christopher Ingold, and Leopold RužiÄka as his "imaginary teachers"—scientists he admired from afar long before he met them 6 . He was fortunate to later become well acquainted with all three 6 .
He shared a famous anecdote about a meeting with Sir Robert Robinson, who disliked the CIP nomenclature 5 :
Robinson: "You know, Prelog, your and Ingold's configurational notation is all wrong."
Prelog: "Sir Robert, it can't be wrong. It is just a convention. You either accept it or not."
Robinson: "Well then, if it is not wrong, it is absolutely unnecessary." 5
Similarly, his friendship with the brilliant American chemist Robert Burns Woodward was filled with mutual respect and gentle ribbing. Woodward once relayed to Prelog that Robinson had said, "Prelog is a lousy chemist, but he is a rather nice guy," a comment that Prelog found highly amusing 5 .
Prelog's work, from his days in Prague to his Nobel-winning research in Zurich, relied on a deep understanding and innovative use of various chemical tools and substances. The table below details some of the key reagents and materials that were central to his research.
| Reagent/Material | Function in Prelog's Research |
|---|---|
| Alkaloids (Quinine, Strychnine, Cocaine) | Natural products whose complex structures he elucidated; a primary focus of his research from Prague to Zurich 1 9 . |
| Adamantane | A hydrocarbon with an unusual diamond-like structure; Prelog developed its first synthesis in 1941 while in Zagreb 1 . |
| Tröger's Base | An organic compound with chiral nitrogen atoms; Prelog separated its enantiomers in 1944, proving nitrogen can be a chiral center 1 . |
| Dicarboxylic Acid Esters | Used as starting materials in acyloin condensation to synthesize medium-sized rings (8-12 members), elucidating their unusual "nonclassical" strain 1 . |
| Microbial Metabolites (Nonactin, Boromycin, Rifamycins) | Antibiotics and complex natural products whose structures he elucidated, linking his work to biologically active compounds 1 9 . |
| Enzymes | Studied the stereospecificity of enzymatic reactions to understand their mechanism and the structure of the enzyme's active site 1 . |
A crucial experiment that highlights Prelog's ingenuity was his 1944 chiral resolution of Tröger's base 1 . At the time, it was speculated that nitrogen atoms could be the source of chirality in molecules, but it had not been definitively proven.
Separation of enantiomers using chiral column chromatography
Vladimir Prelog's story is one of a brilliant mind shaped by exceptional mentors in Prague, tested by adversity, and ultimately elevated through collaboration on a global stage. The intellectual foundation built during his "132 semesters of chemistry studies" 9 , which began in Prague under Lukeš, allowed him to make contributions that continue to resonate in every chemistry classroom and laboratory today.
From the CIP system that gives a voice to molecular shapes to his deep insights into the complex world of natural products, Prelog's work reminds us that science is a human endeavor, built on the shoulders of masters and advanced through friendship, curiosity, and a relentless pursuit of clarity.
Awarded in 1975 for his research into the stereochemistry of organic molecules and reactions
Education
Research
Collaboration
Legacy