A Simulation Model for the Non-Electrogenic Uniport Carrier-Assisted Transport of Ions across Lipid Membranes.

Mariano Andrea Scorciapino,Claudia Caltagirone,Giacomo Picci,Vito Lippolis,Roberto Quesada

doi:10.3390/membranes12030292

Mariano Andrea Scorciapino, Claudia Caltagirone + Show 3 more

Open Access

https://doi.org/10.3390/membranes12030292

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Journal: Membranes	Publication Date: Mar 3, 2022
Citations: 2	License type: CC BY 4.0

Affiliation: University of Cagliari, University of Burgos

Abstract

Impressive work has been completed in recent decades on the transmembrane anion transport capability of small synthetic transporters from many different structural classes. However, very few predicting models have been proposed for the fast screening of compound libraries before spending time and resources on the laboratory bench for their synthesis. In this work, a new approach is presented which aims at describing the transport process by taking all the steps into explicit consideration, and includes all possible experiment-derived parameters. The algorithm is able to simulate the macroscopic experiments performed with lipid vesicles to assess the ion-transport ability of the synthetic transporters following a non-electrogenic uniport mechanism. While keeping calculation time affordable, the final goal is the curve-fitting of real experimental data—so, to obtain both an analysis and a predictive tool. The role and the relative weight of the different parameters is discussed and the agreement with the literature is shown by using the simulations of a virtual benchmark case. The fitting of real experimental curves is also shown for two transporters of different structural type.

Highlights

Received: 6 February 2022Since the pioneering work on chelating Lewis acids [1] and ammonium-based cryptand halide receptors [2] in the late 1960s, the anion receptor chemistry has become one of the most popular topics in the realm of supramolecular chemistry [3–8]
Impressive work has been completed, covering different aspects such as anion recognition, sensing, extraction, crystal engineering, self-assembling, catalysis, and transmembrane anion transport. The latter has lately attracted considerable attention, as transmembrane anion transport is crucial to several biological processes [9–15]
Failure in maintaining chloride homeostasis in cells is related to various diseases [16] such as cystic fibrosis, in which a malfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes defective chloride transport [17]

Summary

Introduction

Received: 6 February 2022Since the pioneering work on chelating Lewis acids [1] and ammonium-based cryptand halide receptors [2] in the late 1960s, the anion receptor chemistry has become one of the most popular topics in the realm of supramolecular chemistry [3–8]. Impressive work has been completed, covering different aspects such as anion recognition, sensing, extraction, crystal engineering, self-assembling, catalysis, and transmembrane anion transport. When designing an artificial chloride transporter, with the aim of eventually testing it in vivo and using it as a drug for patience treatment, the optimization of ADME (absorption, diffusion, metabolism and excretion) properties is clearly crucial [19]. This can be achieved by using small molecules (low molecular mass) properly functionalized to obtain suitable logP values (i.e., the log of the octanol–water partitioning coefficient).

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Conclusion