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Why Think Up New Molecules?

Adding to the world of known chemical structures is a wonderful mental experiment

Roald Hoffmann

Design and Saltation

Compounds and molecules are often useful, ergo the vast transformative chemical industries (and the reasonably populated chemistry and chemical engineering departments of the world). Properties make for function. Be they materials for electronics, polymers with specific properties or pharmaceutical activity, adhesives working under extreme conditions—molecules perform tasks. But never as adequately and cheaply as we desire, of course. So there is a need for further design of molecules with specific properties.

Design is often a matter of tuning. Say one has a pharmaceutical lead, a compound with antitumor activity. The chances are that even as it works, the compound is toxic at some level, and that its biological efficacy can be improved. One wants to change a methyl group here for a fluorine, add two hydrogens there. This quantized perturbation of an underlying molecular skeleton is our métier, the craftsmanship as explicit in dye as drug design. But tuning is not random change. One needs a way to think about a property—the thinking need not be computational, it may be qualitative—before one sets to the work of synthesis. Here is a great place for theory.

Although modifying molecular bits here and there works, one lesson of chemistry has been that really new properties or functions come from big jumps, in structure and electronic properties. I'm thinking as much of liquid crystals and nylon as I am of fullerenes and metal-metal bonds. Here there is a still more significant role for theory. For small extrapolations are easy—you can calibrate your calculation; predicting the properties of a really different, unusual molecule is risky.

There are pitfalls, psychological ones, in the service of design. The designer's role is at times exaggerated in the process of seeking patronage, a forgivable sin. It is also what journalists think their audience wants to hear—fables of superminds whose predictions are always right. And people—scientists for sure—fall too easily into an excessive valuation of their own mastery of design, to burnish an impression of their rationality. An age-old problem for science, or rather for scientists….

Everything has antecedents and lush interconnections. Still, there is a real opportunity for theoretical chemistry in the creation of new classes of molecules. Instead of being servants to reductionism, we can signal emergence.

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