Towards EMIC rational design: setting the molecular simulation toolbox for enantiopure molecularly imprinted catalysts

Abstract

A critical appraisal of the current strategies for the synthesis of enantiopure drugs is presented, along with a systematic background for the computational design of stereoselective porous polymers. These materials aim to achieve the enantiomeric excess of any chiral drug, avoiding the racemic separation. Particular emphasis is given to link statistical mechanics methods to the description of each one of the experimental stages within the catalyst’s synthesis, setting a framework for the fundamental study of the emerging field of molecularly imprinted catalysts.Graphical abstractThe envisaged modelling tools in the EMIC toolbox: quantum mechanics (QM), molecular dynamics and Monte Carlo (in the NPT and NVT ensembles), grand canonical Monte Carlo (GCMC) and kinetic Monte Carlo (kMC), for the synthesis of an enantiopure drug via our proposed EMIC catalyst.

Recent Advances in Electrosynthesized Molecularly Imprinted Polymer Sensing Platforms for Bioanalyte Detection

“…Drawbacks that need to be considered include the time required for development and optimization, which can be overcome using high-through screening or computational methods, and adapting the polymers to work in aqueous environments since water interferes with non-covalent interactions between monomer and template [ 6 ]. MIPs have been developed for small ions (known as ion imprinted polymers) ranging to large macromolecules, and this versatility means they can be employed for numerous applications, including solid-phase separation [ 16 ], purification [ 17 ], catalysis [ 18 ], sensors [ 3 ], drug delivery [ 19 ], and therapeutic applications [ 20 ]. The main commercial application lies in the removal or extraction of low-level contaminants since MIPs are powerful tools for the selective extraction of compounds in complex matrices [ 21 ] (e.g., whole blood, plasma, urine, food samples, environmental samples, etc.).…”

Microcystins Detection Methods: A Focus on Recent Advances Using Molecularly Imprinted Polymers

“…The MCs recognition potential of MIPs can be further improved by taking advantage of the diversity of molecular modeling tools and rational design strategies currently available. , In past years, a series of computational strategies have been successfully used to assist monomer selection and optimization of prepolymerization mixtures for specific templates recognition. ,− Virtual monomer screening is customarily applied to guide the selection of monomers exhibiting the highest affinities toward a target template. ,,,− These methods automatically evaluate the affinity of template–monomer interactions using empirical binding score functions and searching algorithms to rank a series of binding poses for each functional monomer within a library of monomer candidates . Quantum mechanics (QM) calculations at semiempirical, HF, and DFT levels have been applied to estimate the strength of template-monomer affinities and examine the atomistic details of the template–monomer interactions responsible for MIPs recognition. ,,,, The computational cost associated with these high-accuracy methods limits their applicability to a few molecules (usually a template-monomer pair) without explicit consideration of solvent molecules or cross-linkers.…”

An Update on Molecularly Imprinted Polymer Design through a Computational Approach to Produce Molecular Recognition Material with Enhanced Analytical Performance

“…The computational approach to design MIPs generally employs molecular modeling (quantum mechanics), molecular mechanics or molecular dynamics [25]. Quantum mechanics includes ab initio approaches and semiempirical and functional density strategies.…”