Small Molecules Have More Information per Atom Than Biologics

Is there an unstated connection to computational complexity here? The article focuses on the number of possibilities and basically argues that N is impractically large, but I think that means there's an implicit claim behind that that we don't have an efficient search algorithm so the large N is fatal rather than a hardware problem. Does that make sense to anyone else?

> Most approaches to simplifying small-molecule synthesis do so by vastly reducing the addressable space, enabling simple “Lego brick”–style routes to be employed. While there are sure to be improvements in synthetic technology over the decades to come, I think that making arbitrary small molecules will continue to be a difficult and complex task for fundamental and unescapable reasons.

I wonder if the author is aware of Fourier Transform Ion Cyclotron Resonance Spectroscopy / Synthesis?

Different molecules have different weights. Strip an electron from them and now they have a charge-to-mass ratio: given a magnetic field and a kinetic energy from linear motion orthogonal to this field, the molecules in vacuum will follow circular paths (or helical if there were a parallel velocity term).

imagine the magnetic field orthogonal to your square monitor, now imagine placing sensing electrodes on top and bottom of your screen and actuating electrodes on the left and right. Now you can sweep over frequency (or use white noise) on the actuating antenna electrodes, while receiving on the sense antenna electrodes. Next there's ion-ion chemical reactions that are possible:

A+B -> C+D

for example, which might need a certain activation energy (if the collisions CoM energy was not high enough they just bounce of each other), but if you give ion species A and ion species B half of the required activation energy, then they can react with each other resulting in ion species C and D.

woops! apperently A+E -> F+G with activation energy less than half the above activation energy for A+B -> C+D ?

Decrease power sent to species A, while increasing power sent to species B until the undesired A+E no longer happens.

In other words, FT-ICR spectroscopy can be both eyes and hands!

If this piques your interest, certainly read this very accessible primer (assumes basic physics and knowledge about Fourier transforms):

https://warwick.ac.uk/fac/sci/chemistry/research/oconnor/oco...

The technique originates with Melvin B. Comisarow with first publication around 1974 (2*26=52 years ago), not sure why people would argue difficulty of synthesizing small molecules in 2026. If one believed healthcare to be ethical, one would first use FT-ICR for generating small quantities easily, sufficient for experimentation, and upon hitting a suitable one investigate efficient manufacture at scale (i.e. not in vacuum, or perhaps in vacuum, but then in space to scale up, and keep the magnets cool with solar reflector / shades ).

good read