# Unravelling Rational Design of Molecularly Imprinted Polymer for Selective Mitragynine Isolation from Kratom: Quantum Mechanical, Molecular Dynamics, and Experimental Insights

## TL;DR

This paper explores using computational and experimental methods to design a polymer that can selectively isolate mitragynine, a psychoactive compound in kratom.

## Contribution

The study introduces a rational design approach for molecularly imprinted polymers using quantum mechanics and molecular dynamics.

## Key findings

- Methacrylic acid was identified as the optimal monomer for mitragynine imprinting in methanol.
- A 1:3 mitragynine-to-monomer ratio was confirmed as optimal through experiments and simulations.
- Computational methods effectively guided the design of selective molecularly imprinted polymers.

## Abstract

Mitragyna speciosa, commonly referred to as kratom, is known for its active compound, mitragynine, which is classified as a new psychoactive substance. The availability of mitragynine standards remains a challenge, highlighting the need for effective and efficient methods for isolating this compound from kratom. This study aimed to computationally design a molecularly imprinted polymer (MIP) for the selective isolation of mitragynine. Computational studies were conducted using the B3LYP def2TZVP method with DFT-D4 dispersion, and the results were verified by a laboratory experiment and a molecular dynamics study. The study revealed that methacrylic acid was the optimal monomer for MIP interactions in methanol. Laboratory experiments, employing the association constant and Job plot methods, confirmed that methanol was the ideal solvent for the pre-polymerization complex, with an equilibrium template-to-monomer ratio of 1:3. Radial distribution function analysis from molecular dynamics simulations further supported that the 1:3 template-to-monomer ratio was optimal, aligning with experimental findings. This study’s findings suggest that computational analysis may be employed for the rational design of improved MIPs and for further laboratory investigation into the selective isolation of mitragynine from plants.