Synergy in Chemistry

1 + 1 > 2. True? Yes, in the world of Synergy advertisements. Synergy is one of those corporate-speak buzzwords that has invaded academia. (Are there any that haven’t invaded?) Earlier this week I read a paper from the Journal of Theoretical Biology on the role of synergy in biological evolution – and whether such synergy can be modeled mathematically. That got me thinking about where one might find synergy in chemistry. After all, chemistry is all about energy. Stick a syn in front, and maybe you can describe all of chemistry by uniting energy.

The sticky point is that synergy implies that the unity, or the whole, is greater than the sum of its parts – at least in buzzword usage. One formulation of the first law of thermodynamics says that energy cannot be created or destroyed, but it can be converted from one form to another. Energy is a shape-shifter but when you add up all its parts, the total energy cannot change. The law forbids it. Assuming you’re operating in a closed system, of course.

A similar law forms the bedrock of writing chemical equations. They must be balanced, i.e., the number and types of atoms are identical from start to finish. Assuming a closed system, of course. This is the law of conservation of matter. (We’ve ignored nuclear reactions for now where mass-energy conservation still operates.) The atoms can exchange partners in their dance, taking on new molecular shapes; but when the accountant comes a-calling, all atoms declare themselves present.

If there was an area within chemistry that might spark an inkling of synergy, it would be Catalysis. Formally, a catalyst is a substance that speeds up a chemical reaction but does not change the identity of the reactants and products. This is a textbook definition. The catalyst does its magic by lowering the activation barrier for the chemical reaction to take place. Another textbook definition. If molecules A and B normally react to form molecules C and D, then A and B first have to climb an energy hill (the activation barrier) before rolling down into their new identities C and D. Adding the catalyst does not change the outcome, but it lowers the height of the hill. Crucially, the net energy difference between A + B and C + D does not change. Since a picture is worth at least 157 words, here is an unadorned version I could find from a quick web search.

When teaching general chemistry, we make a song and dance about separating thermodynamics and kinetics. Thermodynamics tells us which direction the equilibrium state lies. Kinetics tells us how fast we will get there. Assuming a closed system, of course. And if all that existed was our isolated simple reaction of the involving our compatriots A, B, C, and D, the dance gets boring after a while.

But outside of the carefully isolated test-tube reaction, chemistry gets a lot more interesting. If there were competing chemical reactions, the dance may take you in unexpected directions depending on whether catalysts are present. Maybe A and B would form E and F instead of C and D, if an appropriate catalyst was present. A catalyst can be present in just tiny amounts to do its work. For example if you started with a thousand molecules of A and B, just ten molecules of catalyst might be enough to shunt those thousand molecules down a different path. A single Detour sign can shunt the traffic of thousands of cars. The catalyst seems to be punching way above its weight. Is this synergy?

In a non-linear web of chemical reactions, small differences in energy hills can lead to very different final product distributions. Hence, adding catalysts may change the reaction outcome – not the textbook definition. Things get more interesting if one of the intermediate molecules (or even a product) can itself catalyze an earlier step in a cascade. Such autocatalytic reactions are possibly the heart of the riddle of the chemistry of the origin of life. The big question is not how the molecules used in extant biochemistry could be formed. The big question is why life uses so few of the myriad possibilities. Any undirected chemical soup experiment produces an embarrassment of riches. What’s embarrassing: the molecules that life uses form a tiny fraction of those riches – and they don’t seem to be very different from their chemical cousins who were not “chosen” for such an honor.

Somehow, somewhere, sometime, a single-cell organism, a multi-celled organism, and a pondering creature calling himself Homo Sapiens showed up. From a chemical point of view, all three exhibit a complex web of molecules involved in an intricate dance. We don’t know where the dance is going, at least as a collective. Single organisms live and then die; we can predict their food-for-worms thermodynamic end. But a chemical world governed by kinetics defies easy prediction. Catalysts rule that world. You won’t get to your predicted thermodynamic end if you can’t get over the hill. Unless you’re in a closed system, of course, and you’re willing to wait a very, very, very long time. The future paths of evolution governed by kinetics are not known.

To “catalyze” or “act as a catalyst” are buzzwords in corporate tech-speak. Maybe this infection started from academic chemists, instead of the other way round. There are probably glossy brochures, websites and PowerPoint presentations extolling how synergy can be catalyzed – if you used product X or the services of company Y or changed Z. Can that synergy be measured? Can it be modeled mathematically? Does it mean anything if it cannot?

P.S. For the college students and professors out there, here’s something from one of my colleagues that made me laugh out loud. (Hint: It’s relevant to college-age students particularly in the U.S.)