‘Ring Breaker’: Assessing Synthetic Accessibility of the Ring System Chemical Space

<p>Ring systems in pharmaceuticals, agrochemicals and dyes are ubiquitous chemical motifs. Whilst the synthesis of common ring systems is well described, and novel ring systems can be readily computationally enumerated, the synthetic accessibility of unprecedented ring systems remains a challenge. ‘Ring Breaker’ enables the prediction of ring-forming reactions, for which we have demonstrated its utility on frequently found and unprecedented ring systems, in agreement with literature syntheses. We demonstrate its performance on a range of ring fragments from the ZINC database and highlight its potential for incorporation into computer aided synthesis planning tools. Additionally, we generate a multi-label dataset using bipartite reaction graphs on which we train ‘Ring Breaker’ to model the relationship between one ring fragment and the multiple reactions recorded for its synthesis in the dataset; we thereby overcome the single-label approaches previously used. These approaches to ring formation and retrosynthetic disconnection offer opportunities for chemists to explore and select more efficient syntheses/synthetic routes. </p>

‘Ring Breaker’: Assessing Synthetic Accessibility of the Ring System Chemical Space

<p>Ring systems in pharmaceuticals, agrochemicals and dyes are ubiquitous chemical motifs. Whilst the synthesis of common ring systems is well described, and novel ring systems can be readily computationally enumerated, the synthetic accessibility of unprecedented ring systems remains a challenge. ‘Ring Breaker’ enables the prediction of ring-forming reactions, for which we have demonstrated its utility on frequently found and unprecedented ring systems, in agreement with literature syntheses. We demonstrate its performance on a range of ring fragments from the ZINC database and highlight its potential for incorporation into computer aided synthesis planning tools. Additionally, we generate a multi-label dataset using bipartite reaction graphs on which we train ‘Ring Breaker’ to model the relationship between one ring fragment and the multiple reactions recorded for its synthesis in the dataset; we thereby overcome the single-label approaches previously used. These approaches to ring formation and retrosynthetic disconnection offer opportunities for chemists to explore and select more efficient syntheses/synthetic routes. </p>

COMPUTING ALL SPARSE KINETIC STRUCTURES FOR A LORENZ SYSTEM USING OPTIMIZATION

In this paper, all possible sparse chemical reaction network structures of a classical three-dimensional Lorenz system are computed assuming a given chemical complex set. The original nonkinetic equations are transformed into kinetic form using two different approaches: firstly, using a state-dependent time-rescaling and secondly, by applying the theory of X-factorable systems. Using the notions of core reactions and core complexes, an effective optimization-based computation approach is proposed for the calculation of all structurally different sparse reaction graphs. The resulting structures are briefly analyzed and compared from a structural point of view.