Discover
Living, Breathing Tools
Published December 26, 2022
Rustic homesteads and towering citadels speckle the fields behind, an elder ambles into a sea of weeping willows. The arching branches, the slender leaves: a web of wilting green.
He chooses the one aged brown, and its drooping arms swallow him. Kneeling, running fingers over its deep furrows. He draws a knife from his knapsack. As though a blade piercing the scales of a winged beast, his bronze edge going chip chip chip, the wood from his prying hands making a sudden, aching snap.
Inside the soft skin of the willow, inside its thick, yellow sap, resides a substance some proclaim as magic. They do not know what it is, nor how it works.
He wraps the scraps of bark in cloth. Tucks it carefully in his bag.
In a town of farmers, merchants, artisans and elites, in a room many come and go, a commoner languishes in a wool bed. On the countertop opposite her sit seven or eight plants, none of them she recognizes. Eyes flitter, whisk, then dart to a nearby mug. The woman turns over, and the world goes vile.
Affliction. Misery.
A shadow marches across the room. Disappearing then reappearing, gone again and a door swings open. There’s the healer with a rigid composure, a gentle grasp on the cloth from his knapsack. The shaving of the bark. The vibrant clang of a watered pot.
Three strokes from a flint. Sparks turn to embers, then embers to crackling light. Two breaths onto the brush. A leaf twists and coils; a bright orange pervades. The man glances toward the bed to a heightened face, fatigue or dismay, it’s hard to say.
With the lid on the pot, the frothing of bubbles softens. Off and away from trivet and flame, he pours the brew through a linen sieve. The essence of the willow bark drips into a tall, handled vessel.
In her palms the vessel glows a divine citrine. Dregs swirl in disarray. He watches her drink until there’s no more.
Moments pass. The swell of her back fades; heat relents like a vanquished evil. But within her an erratic mess of figures vibrates, distorts, and spins—the workings from the same living, breathing tool that’s gone as far as to craft the entirety of yourself.
The Catalyst
A catalyst is a substance that acts to lower the activation energy of a chemical reaction, allowing for the reaction to require less energy to initiate, and as a result, complete faster. Catalysts are typically added in small amounts to a reaction because their structures do not change after interacting with reactants. Even a single catalyst can interact with multiple substrates one by one until the conversion of reactants to products is complete. Their greatest property: they are selective; they are tools.
A saw wouldn’t be used to nail a board in place, nor a spoon to chop lettuce. A catalyst, whether manufactured or found in nature, is designed to select the molecule their crafter had foreseen, and serves no purpose otherwise. To make a catalyst discriminate to their liking, the artist chooses from a palette of elements.
For decades, a catalyst—with few exceptions—was classified as a metal or enzyme.
Metals are exceptional at catalysis due to their ability to receive and donate electrons between molecules. These metals speed up chemical reactions by inducing the breaking and forming of bonds on molecules. But metals have one major downside: they react readily with oxygen and water, making them difficult to manage in large-scale manufacturing facilities.
Enzymes are nature’s tools for construction. They vary by the thousands, responsible for driving chemical processes in all living things. They are selective—suitable participants for asymmetric catalysis.
The world has had more than four billion years to perfect its craft, and the enzyme has been elegantly shaped to build its portfolio. Enzymes, however, are incredibly large compared to the substrates they interact with, and because of their complex configurations they are expensive to synthesize. An enzyme is made up of hundreds of amino acids responsible for its catalytic activity. It was at this point the scientist Benjamin List wondered how far you can simplify an enzyme while preserving its functionality. Stripping away its tangled threads, that jumbled muck of finesse, what remains is a single amino acid—an organic catalyst.
The Organic Catalyst
Organocatalysis is the addition of organic compounds to expedite a chemical reaction. The process has contributed to the more efficient production of pharmaceuticals and has made tremendous strides with integrating the principles of green chemistry into several industries worldwide.
Many organic catalysts are in the form of biomolecules, synthetic compounds derived from biomolecules (amino acids), hydrogen-bonding catalysts, and triazolium salts.
Synthetic catalysts are notably the most responsible for the rapid expansion of organocatalysis and its recognition as a new class of catalysis. The ability to synthesize catalysts from life’s fundamental elements—carbon, hydrogen, nitrogen, oxygen, sulfur, phosphorus—had every chemist and biochemist turning their heads. No more worrying about the dwindling stockpile of precious metals, the headaches from using bioreactors and animal cell culture.
An organic catalyst typically comprises a secondary amine: a nitrogen atom bonded to two carbon atoms. This functional group underlies an organic compound’s ability to catalyze because it can participate in numerous reactions, such as alkylation, acylation, condensation, substitution, reduction, and oxidation.
One of the most common synthetic organic catalysts is proline. Granted its natural presence in the proteins of all organisms, it is extensively synthesized for drug development. An example of catalytic proline in an aldol reaction is shown below:
The formation of more complex organic compounds requires multiple steps, as the product of one reaction will be used as a reactant of another reaction. This sequence of separate reactions continues until the target compound is produced.
Industrially, the formation of complex organic compounds through a sequence of separate reactions produces unwanted by-products and results in low yields of the target compound. Alternatively, the addition of an organic catalyst can induce a series of interconnected reactions, otherwise known as cascade reactions. Target compounds form from simple starting materials in one step with much higher yields.
Cascade reactions would prove useless if not for an organic catalyst’s remarkable selectivity, specifically its ability to perform asymmetric catalysis—a type of catalysis in which an asymmetric catalyst guides the formation of an asymmetric compound.
The production of asymmetric compounds has for many decades been unsatisfactory. A great percentage of products in synthetic organic reactions happen to be mirror images of the target compound. When dealing with symmetric compounds, the target compound and its mirror image are conveniently identical. However, the mirror image of an asymmetric compound exhibits rather undesirable properties, and, in most cases, can be hazardous.
Organic catalysts performing asymmetric catalysis can drive reactions to favor producing an asymmetric compound with significantly lower yields of its mirror image, leading to a more efficient production process and a safer end product for consumers.
Applications
Organic catalysts have simplified processes in pharmaceutical drug development that were once complicated and inefficient. Some of these are the Knoevenagel condensation, esterification, Baylis-Hillman reaction, Stetter reaction, aldol reaction, asymmetric Diels-Alder reaction, asymmetric Michael reaction, Shi epoxidation, transfer hydrogenation, and Friedel-Crafts alkylation. The widespread approval of these simplified processes has conferred greater permissibility to green chemistry.
Green chemistry emerged as a movement after the Pollution Prevention Act of 1990, and in the following years evolved into a philosophy with principles concerning several environmental pursuits, such as waste prevention, energy efficiency, atom economy, the design of safer chemicals, and catalysis.
In particular, organic catalysts have made astounding progress in upholding the principle atom economy—a measure of the conversion efficiency of all atoms in a chemical reaction. Expressed as a percentage, it represents the amount of atoms that have successfully been converted from the makeup of a reactant to that of a product. As chemists maximize the atom economy of any reaction, they simultaneously reduce the amount of generated waste.
Atom economy is especially important to follow in the pharmaceutical industry because a lack of resources in drug development will lead to higher costs, and, more consequentially, increasing rates of morbidity and mortality in lower-class citizens. Pollution, climate change, overuse, and a rise in demand due to a growing global population are all possibilities for limited raw materials or intermediates needed for the many chemical processes in drug development.
A Simple Idea
The mere idea of an organic catalyst would not have come to fruition without applying the fundamentals of biomimicry. For millennia, nature inspires so many to mimic its ways as though they are blueprints for invention. Examining the wings of a bird, to crafting a box to lift us above. Watch the fins of a humpback whale sway through the sea, then hoist turbine blades amid an open field.
The enzyme: a curiosity to humanity. Life’s chisel and hammer. It picks and hugs, shoves and twirls about. Untangle its meshed spaghetti, pull along its drapes, unveil the one behind the curtain—the amino acids—one, sometimes two. Use it to make anything carbon, anything hydrogen.
For many, the organic catalyst is too simple an idea, though its discovery stalled for decades.
Assumptions are often costly in the realm of science. Often we subject ourselves to believing the world always holds true to preconceived fundamentals, rejecting any afterthought to anomalies. We choke on our understanding of the universe as we write off avenues yet to be explored due to their similarity to those with lackluster results.
Similar, but not the same.
Despite our mistakes, organocatalysis is now another tool for shaping the world as we please. It brings us closer to visualizing a future where nature and humanity coexist in productive harmony.