Chemical space: limits, evolution and modelling of an object bigger than our universal library

Abstract

Chemical space entails substances endowed with a notion of nearness that comes in two flavours: similarity and synthetic reachability. What is the maximum size for the chemical space? Is there an upper bound for its classes of similar substances? How many substances and reactions can it house? Can we store these features of the chemical space? Here I address these questions and show that the physical universe does not suffice to store the chemical one embodied in the chemical space. By analysing the historical evolution of the space as recorded by chemists over the centuries, I show that it has been mainly expanded by synthesis of organic compounds and unfolds at an exponential rate doubling its substances each 16 years. At the turn of the 20th century it left behind an expansion period driven by reactions and entered the current era ruled by substance discovery, which often relies on some few starting materials and reaction classes. Extrapolating from these historical trends, synthesising a large set of affordable chemicals in the foreseeable future would require trebling the historical stable speed rate of discovery of new chemicals. Likewise, creating a database of failed reactions accounting for 25% of the known chemical space to assist the artificial intelligence expansion of the space could be afforded if the synthetic efforts of the coming five years are entirely dedicated to this task. Finally, I discuss hypergraph reaction models to estimate the future shape of the network underlying the chemical space.