Computational history of chemistry: the case of the chemical space, its expansion and interplay with socio-political effects

Computational history of chemistry is an emerging field leveraging the rather stable ontology of chemistry represented by its substances and reactions, which constitute the chemical space. Over more than two centuries, chemists have annotated and curated information on the chemical space in a systematic manner, which is today available at our fingertips thanks to digitisation efforts. Here we show results of our explorations of the chemical space between 1800 and the present day. We found that chemists have expanded the space at an stable exponential rate, where every 16 years the number of new chemicals is doubled. The stability of this expansion has not even been affected in the long term by social setbacks such as world wars. By using time series analysis methods, we found that the expansion of the space has occurred through the sequence of three statistical regimes. Each regime is characterised by a stable variability in the number of new reported chemicals. Taken in chronological order, regime after regime the variability drops, indicating a regularisation of the discovery process in chemistry. The three statistical regimes are clearly demarcated by two drastic transitions, one about 1860 and the other in 1980. The first transition was strongly related to the development and adoption of molecular structural theory and the second one is presumably related to a technological shift allowing for the synthesis of by far more complex compounds. We also found chemists have followed a simple rule of combination of chemicals to expand the chemical space, which we dubbed the fixed-substrate approach. It is characterised by the combination of no more than three starting materials in chemical reactions such that one of the substances is a well-known chemical, while the rest of the combined substances are rather new substances in the chemical space. By focusing on the recent unfolding of the chemical space, we analysed the role of different countries and traced back the surge of China in the early 2000s as the hegemon of the chemical space. We also explored the details of the unfolding of the rare-earth subspace, which is strongly associated to the widespread current electronic technologies. Our results indicate that China is today not only the largest producer of rare earths, but also the country producing more knowledge on these chemicals and on the chemical space, in general.