A Molecular Investigation of the Solvent Influence on Inter- and Intra-Molecular Hydrogen Bond Interaction of Linamarin

Lucas Paul,Geradius Deogratias,Andrew S Paluch,Kelvin M Mtei,Celestin N Mudogo,Revocatus L Machunda,Daniel M Shadrack,Fidele Ntie-Kang

doi:10.3390/pr10020352

Abstract

Linamarin has been reported to have anticancer activities; however, its extraction and isolation using different solvents yield a low amount. Therefore, understanding the physical properties, such as solvents’ solubility, membrane permeability and lipophilicity and how they are associated with different solvents, is a paramount topic for discussion, especially for its potential as a drug. Linamarin has a sugar moiety with many polar groups responsible for its physical properties. Following current trends, a molecular dynamics simulation is performed to investigate its physical properties and how different solvents, such as water, methanol (MeOH), dimethyl sulfoxide (DMSO) and dichloromethane (DCM), affect such properties. In this work, we have investigated the influence of intermolecular and intramolecular hydrogen bonding and the influence of polar and non-polar solvents on the physical properties of linamarin. Furthermore, solvation free-energy and electronic structure analysis are performed. The structural analysis results show that the polar groups of linamarin have strong interactions with all solvents except the etheric oxygen groups. A detailed analysis shows intermolecular hydrogen bonding between polar solvents (water, MeOH and DMSO) and the hydroxyl oxygens of linamarin. Water exhibits the strongest interaction with linamarin’s functional groups among the investigated solvents. The findings show that within the first solvation shell, the number of water molecules is greatest, while MeOH has the fewest. Centrally to the structural analysis, solvation free energy confirms DMSO to be the best solvent since it prefers to interact with linamarin over itself, while water prefers to interact with itself. While the solute–solvent interactions are strongest between linamarin and water, the solvent–solvent interactions are strongest in water. As a result, the solvation free-energy calculations reveal that linamarin solvation is most favourable in DMSO.

Highlights

Linamarin and its methylated analogue lotaustralin, are cyanogenic glycosides found in the roots and leaves of cassava (Manihot esculenta), flax (Linum usitatissimum), lima beans (Phaseolus lunatus) and white clover (Trifolium repens) [1]
The hydrogen bonding of a drug occurs conditionally; when the donor and receptor are at certain a proximity in the same compound, it leads to the existence of an equilibrium between the closed conformation and an open conformation, where the polar groups interact with the surrounding solvents
We performed molecular dynamics simulations to understand the solvation of linamarin, covering a range of polar protic, aprotic and non-polar solvents

Summary

Introduction

Linamarin and its methylated analogue lotaustralin, are cyanogenic glycosides found in the roots and leaves of cassava (Manihot esculenta), flax (Linum usitatissimum), lima beans (Phaseolus lunatus) and white clover (Trifolium repens) [1]. Small organic compounds (drugs) are characterized by the presence of functional groups that can participate in hydrogen bond formation. These properties determine their solubilities and their interaction capabilities with their target receptors. The hydrogen bonding of a drug occurs conditionally; when the donor and receptor are at certain a proximity in the same compound, it leads to the existence of an equilibrium between the closed conformation (intramolecular hydrogen bonding) and an open conformation, where the polar groups interact with the surrounding solvents.

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Results

Conclusion