Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water

Geradius Deogratias; Daniel M Shadrack; Joan J E Munissi; Grace A Kinunda; Fortunatus R Jacob; Regina P Mtei; Rose J Masalu; Issakwisa Mwakyula; Lucy W Kiruri; Stephen S Nyandoro

doi:10.1016/j.jmgm.2022.108243

Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water

J Mol Graph Model. 2022 Nov:116:108243. doi: 10.1016/j.jmgm.2022.108243. Epub 2022 Jun 23.

Affiliations

¹ Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania. Electronic address: dgeradius@udsm.ac.tz.
² Department of Chemistry, Faculty of Natural and Applied Sciences, St. John's University of Tanzania, P.O. Box 47, Dodoma, Tanzania.
³ Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania.
⁴ Department of Molecular Biology and Biotechnology, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 25179, Dar es Salaam, Tanzania.
⁵ Mbeya College of Health and Allied Sciences, University of Dar es Salaam, P.O. Box 608, Mbeya, Tanzania.
⁶ Department of Chemistry, Kenyatta University, P.O.Box, 43844-00100, Nairobi, Kenya.

PMID: 35777224
DOI: 10.1016/j.jmgm.2022.108243

Abstract

Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility. This study aimed at investigating the hydrophobic interaction and hydration of luteolin towards the improvement of its solubility when used as a drug. We report the aggregation properties of luteolin in water by varying the number of monomers using atomistic molecular dynamics simulation. Results show that the equilibrium structure of luteolin occurs in an aggregated state with different structural arrangements. As the monomers size increase, the antiparallel flipped conformation dominates over T-shaped antiparallel, T-shaped parallel, and antiparallel conformations. The formation of intramolecular hydrogen bonding of 0.19 nm between the keto-enol groups results in hydrophobic characteristics. A larger cluster exhibits slow hydrogen bond dynamics for luteolin-luteolin than luteolin-water interaction. Water structure at large cluster size exhibited slow dynamics and low self-diffusion of luteolin. The existence of hydrophobic π-π and hydrogen bonds between luteolin molecules drives strong self-aggregation resulting in poor water solubility. Breakage of these established interactions would result in increased solubility of luteolin in water.

Keywords: Hydrogen bonding; Hydrophobic; Luteolin; Solubility; π-π Interactions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Luteolin*
Molecular Dynamics Simulation
Water* / chemistry

Substances

Water
Luteolin