Properties and behaviour of tetracyclic allopsoralen derivatives inside a DPPC lipid bilayer model

Abstract

Allopsoralens are angular psoralen derivatives presenting advantages over the parent compound because of monofunctional DNA-photobinding and consequent lower toxicity. Allopsoralen molecules with three different substituents and different protonation states were studied using the molecular dynamics technique. The location of these molecules when inside the lipid bilayer is of major importance because their photochemical properties can change with the environment. Also, the ability of psoralens to form photoadducts with unsaturated phospholipids depends on the preference of the molecules to locate themselves closer to the bilayer middle were the double bond functionality can be found. Herein we show that the allopsoralens tend to accumulate inside the lipid bilayer closer to the water interface when protonated or closer to the interface middle otherwise. Allopsoralens containing one amine terminated carbon chain tend to have different rotational and orientational behaviour and an orientation preference close to the ones shown by the lipids. The size and chemical nature of the substituent also affect the molecular mobility and capacity to interact with water molecules and the nitrogen or phosphorus atoms of the lipids.

Tunable transmembrane chloride transport by bis-indolylureas

“…For this purpose, it is also essential to understand, at the molecular level, the first stages of these transporters insertion into the bilayers and what factors control this insertion. Molecular dynamics (MD) simulations are a very useful and powerful tool in achieving this as illustrated by several recent MD studies on drug delivery, 24 diffusion of small biological molecules across lipid bilayers 25 and protein ion channels. 26 In this context, the general all-atom AMBER force field (GAFF), 27 designed to model organic molecules, has recently proved to be also suitable for the simulation of the structural and dynamic properties of DOPC, 28 POPC, 29 and DMPC 30 bilayers.…”

Tris–thiourea tripodal-based molecules as chloride transmembrane transporters: insights from molecular dynamics simulations

“…13,26 On the other hand, molecular dynamics (MD) simulations are a powerful tool to investigate, at the atomistic level, the energetics and mechanisms of anion transport, as well as the impact caused by the synthetic molecules on the structural and dynamic properties of the phospholipid bilayers, from the rst interactions with the membrane until their internalization. Nevertheless, the permeation events through the membranes, addressed with MD studies, are typically focused on drug delivery, 27 protein ion channels 28 and diffusion of small biological molecules across phospholipid bilayers, 29 leaving anion transport operated by synthetic molecules almost unexplored. Indeed, to the best of our knowledge, our recent reports on transmembrane chloride transport mediated by bis-indolylureas and bis-ureas are the rst studies reporting MD simulations in this eld.…”

A Theoretical Rationale why Furan‐side Monoadduct is More Favorable Toward Diadduct Formation in 8‐Methoxypsoralen and Thymine Complexes

“…The relevant reaction mechanisms remain still unclear up to now. As part of the ongoing studies , the photoreaction of undoubtedly physical models between 8‐MOP and thymine bases on the lowest lying triplet state is herein explored to illuminate what dynamic processes occur for mono‐ and diadducts formation and to answer unambiguously why the furan‐side monoadduct is more possible to form the final diadduct than the pyrone‐side one. The present work aims to contribute toward further knowledge on the photobinding mechanism of psoralens, and stimulate to further experimental studies.…”