Correlated first-principles methods for applications in exploration-supported synthesis planning

点击翻译按钮获取中文摘要

In this proposal, first-principles quantum chemical calculations shall be exploited to probe the viability of proposed chemical reaction cascades. Specifically when new chemical compounds are synthesized, there is usually an evaluation of multiple paths leading to the compound.The paths are often generated starting from the final target, then breaking into smaller so-called synthons, this process is called retrosynthesis.These retrosynthetic suggestions will be evaluated computationally before experimental efforts to synthesize the compund are started.The key requirement for a flexible algorithm that allows for such a validation is an automated benchmarking system that allows the created program to validate its calculations internally.For a generally unknown reaction path it is imperative to have a robust electronic structure method that allows for the accurate calculation of any system encountered during the exploration of the reaction space.Here, we propose to develop a computationally feasible multi-configuration approach for accurate internal benchmarking.We plan to combine the description of short-range electron-electron interactions by density functional theory (DFT), and the description of long-range electron-electron interactions by a complete-active-space wave function optimized by the density matrix renormalization group (DMRG) algorithm.In particular, we propose a spin-contamination-free approach for open-shell electronic structures, which are known to be plagued by spin contamination if treated by unrestricted Kohn-Sham theory. The resulting implementation will be integrated into software that allows for the automated exploration of reaction space in order to validate retrosynthetic suggestions.To this end, the existing exploration software will be extended to drive its exploration along a predetermined path and evaluate possible side reactions.Finally the implementation will be tested on the syntheses of known pharmaceutical compounds, in order to be applied to the syntheses of unkown compunds in the future.