THE SUCCESS WE KNOW, THE STORY WE DON’T

?Chemists' bandwidth to create novel and useful compounds is critical to many companies and disciplines of scientific research. When we examine nature's potency to develop chemical concoctions with our own, we can see that we've been mired in the stone age for a long time. Enzymes, which are very specialized instruments for constructing the chemical complexes that lend life its forms, tints, and functions, have morphed as a result of evolution. When scientists first discovered these chemical marvels, all they could do was admire them. Because the nails and cutting tools in their molecular building toolboxes were dull and dubious, they frequently ended up with a lot of undesired byproducts while copying nature's goods.

?With years of work, chemists have optimized the accuracy of their molecular creations with the instruments they have incorporated into their arsenal. Chemistry has slowly but steadily advanced from stone deburring to something more akin to exquisite workmanship. This has benefited mankind greatly, and some of these instruments have received the Nobel Prize in Chemistry.

?The discovery that led to winning the Nobel Prize in Chemistry 2021 is a breakthrough, that has pushed molecular building to a whole new dimension. It has not only rendered chemistry to be environmentally friendly, but at the same time, it has also enabled producing asymmetric molecules with tremendous ease. This year noble was presented to Benjamin List and David MacMillan for their discovery of organocatalysis, a revolutionary and creative technique for molecular construction.

?Benjamin List’s life and his work

German chemist, Benjamin List is the great-grandson of pediatric cardiologist Franz Volhard and the second great-grandson of famous chemist Jacob Volhard. He was born in Frankfurt to an upper-middle-class family of scholars and painters. His mother, architect Heidi List, is the sister of Christiane Nüsslein-Volhard, the 1995 Nobel prize winner in medicine. In 1993, List received his Diploma in Chemistry from the Free University Berlin, and later in 1997, he received his Ph.D. from Goethe University Frankfurt, where Johann Mulzer supervised his Ph.D. dissertation. In 1999, List wedded Dr. Sabine List in La Jolla, and the couple had two boys, Theo and Paul.

?Benjamin List’s main research work was focused on catalytic antibodies. Antibodies are normally meant to connect to foreign viruses and bacteria in our systems, but List with his fellow Scripps researchers altered them to stimulate chemical processes instead. Later, he developed a fascination for enzymes while researching catalytic antibodies. Enzymes are often enormous molecules made up of dozens of amino acids. He was aware that an amino acid known as proline had been employed as a catalyst in research dating back to the early 1970s, where it failed miserably. Without seeking any actual expectations, he continued to work with the same and examined if this amino acid might catalyze an aldol synthesis, in which carbon atoms from two distinct compounds are linked together. It was a straightforward approach that, miraculously, succeeded right away.

?Unlike the earlier researchers who failed to tap the possibilities of proline molecule, Benjamin List saw its immense potential owing to its simplicity, low-cost, and ecologically beneficial properties. His studies revealed the ability of proline to serve as an effective catalyst, so much so that it can induce asymmetric catalysis thereby resulting in the formation of one probable enantiomer in considerable yields over the other.?Thus, making Proline a scientist's dream tool in contrast to metals and enzymes.

?List defined asymmetric catalysis with organic compounds as a new idea with numerous possibilities when he announced his finding in February 2000. He wasn't the only one who felt this way. David MacMillan was working toward the same aim.

?David MacMillan’s life and his work

David MacMillan was born and raised in the Scottish town of Bellshill in 1968. He studied chemistry at an undergraduate level at the University of Glasgow, where he collaborated with Ernie Colvin. Thereafter, in 1990, he emigrated to initiate his doctoral studies in inorganic chemistry at the University of California, Irvine. In 1996, after completing his Ph.D., he focused on enantioselective catalysis, wherein he targeted designing and production of bisoxazoline complexes generated from Sn (II), as part of his postdoctoral research at Harvard University.

?David MacMillan concentrated on enhancing metal-based asymmetric catalysis. During that time scientists were paying close consideration to this field, and it was David MacMillan who pointed out that the catalysts that were produced were rarely employed in the industry. The reasons were, metals were just too complicated, expensive to work with, and toxic to the environment. Also, under laboratory conditions, establishing the oxygen- as well as moisture-free necessary conditions for some metal catalysts is simple, but large-scale commercial production in these circumstances is difficult. Thus, he felt the need to reconsider the chemical instruments that he was building if they were to be effective. As a result, he abandoned the metals behind when he went to Berkeley.

?Thereafter, David MacMillan began designing basic organic compounds that, like metals, could give or assimilate electrons briefly. He chose various organic compounds with the necessary characteristics and evaluated their propensity to steer the Diels–Alder process, which is used by chemists to construct carbon atom rings. It worked perfectly, just as he had anticipated and expected. Asymmetric catalysis was also a strength of several of the organic compounds, Cheaper, smaller and safer catalysts that used organic molecules had the same rich chemistry as metal compounds were chosen to catalyze reactions.

?When David MacMillan was poised to announce his findings, he realized the catalysis idea he'd found required a name. Researchers had earlier accomplished in catalyzing molecular reactions with tiny organic molecules, but these were isolated cases, and no one had grasped that the approach might be applied more widely. David MacMillan sought to coin a name to characterize the process so that other scientists would realize there were more organic catalysts to be discovered. Organo catalysis was his pick.

?Future of organocatalysts

Pharmaceutical research, which usually needs asymmetric catalysis, has benefited greatly from organocatalysis. Many pharma companies encapsulated both mirror reflections of a chemical compound until chemists discovered asymmetric catalysis; one was active, while the other could occasionally cause side effects. The thalidomide controversy of the 1960s, in which one mirror copy of the thalidomide medicine caused significant abnormalities in hundreds of developing human fetuses, was a tragic example of this.

?Benjamin List and David MacMillan had individually found a completely new notion for catalysis. Since 2000, there has been something akin to a gold rush in this field, with List and MacMillan leading the way. They've created a slew of low-cost, long-lasting Organo catalysts that can power a wide range of chemical processes.

?Organocatalysts are generally made up of simple molecules, and in certain circumstances, like enzymes, in essence, they can function on a conveyor system. Previously, each intermediary product had to be isolated and purified in chemical manufacturing processes, or the number of byproducts would be too high. As a result, part of the material was lost at each step of the chemical process. Organocatalysts are significantly more forgiving since multiple phases in a manufacturing process may typically be done in a continuous sequence. This is known as a cascade reaction, and it may help minimize waste in chemical manufacture significantly.

This article is written by Dr. Abha Kathuria and Mr. Dushyant Gupta