Understanding how matter complexifies, ultimately towards life, is a longstanding challenge embraced by the Matter-to-Life program. Since life as we know it is primarily chemistry, the challenge amounts to understanding how complexity and function can emerge and grow in a complicated chemical network. This grant supports Leroy Cronin, Professor of Chemistry at the University of Glasgow, to deploy a systems chemistry approach to addressing this question. Cronin will leverage state-of-the-art robotics to enable long-term chemical evolution experiments that exploit a new parameter that quantifies molecular complexity that is both experimentally accessible and embedded within a larger theoretical framework. Cronin plans to use that framework to nudge a chemical system towards ever-increasing complexity. Selection as a concept is most commonly deployed within Darwinian evolution, where natural selection refers to the preferential survival of individuals with certain genetic traits by means of natural controlling factors. Here Professor Cronin proposes to observe selection within a chemical system, and in this context, selection refers to the preferential survival of molecules with certain traits by means of natural controlling factors (the local environment). Cronin is primarily interested in one trait: complexity. Professor Cronin will use a measure of molecular complexity called the “assembly index.” The assembly index of a molecule is, in essence, equal to the number of ‘steps’ (chemical bonds) needed to construct the molecule using system-dependent basic building blocks (atoms or molecules).  Cronin has demonstrated that assembly index is well-correlated to three relatively-easy-to-perform types of measurements: mass spectrometry, IR spectroscopy, and NMR spectroscopy. The research team will run recursive chemistry experiments that rely on automated measurements to determine which molecules are present and adjust conditions to nudge a system towards a ‘selection regime’ where new forms of complexity are generated. The adjustable conditions include things like temperature (heating & cooling), evaporation and rehydration, how long a mixture is stirred, the duration of an experimental cycle, solution pH, whether various minerals are added, and whether or not an electrical discharge is applied. Cronin expects that a single experiment (a series of cycles) will run continuously for several hundred cycles, corresponding to several weeks or months. Over that time, there are four types of complex molecules / structures that the researchers will seek to detect: self-reproducing molecules and autocatalytic sets; production of high assembly index molecules; formation of primitive sequence polymers; and emergence of microscopic containers.