Interaction and Reactivity of Cisplatin Physisorbed on Graphene Oxide Nano-Prototypes.

Ma Del Refugio Cuevas-Flores,Marco Antonio García-Revilla,Cecilia Coletti,Massimiliano Bartolomei

doi:10.3390/nano10061074

Abstract

The physical adsorption of cisplatin (CP) on graphene oxide (GO) and reduced graphene oxide (rGO) is investigated at the DFT level of theory by exploiting suitable molecular prototypes representing the most probable adsorbing regions of GO and rGO nano-structures. The results show that the CP binding energy is enhanced with respect to that for the interaction with pristine graphene. This is due to the preferential adsorption of the drug in correspondence of the epoxy and hydroxy groups located on GO basal plane: an energy decomposition analysis of the corresponding binding energy reveals that the most attractive contribution comes from the electrostatic attraction between the -NH ends of CP and the oxygen groups on (r)GO, which can be associated with hydrogen bonding effects. Moreover, it is found that the reactivity of the physically adsorbed CP is practically unaltered being the free energy variation of the first hydrolysis reaction almost matching that of its free (unadsorbed drug) counterpart. The reported results suggest that the CP physical adsorption on GO and rGO carriers is overall feasible being an exergonic process in aqueous solution. The CP adsorption could facilitate its solubility and transport in water solutions, exploiting the high hydrophilicity of the peripheral carboxylic groups located on the edge of the GO and rGO nano-structures. Moreover, the the higher affinity of CP with respect to the oxidized sites suggests a possible dependence of drug loading and release on pH conditions, which would highly facilitate its specific delivery.

Highlights

Specific delivery is one of the main issues to be addressed to obtain the ideal pharmaceutical effect of drugs, that is to ensure that the desired biological target is preferentially reached, minimizing in this way possible collateral damages and undesired side effects
We have found [19] that ovalene is a very suitable polycyclic aromatic hydrocarbon (PAH) in terms of binding energy convergence and related computational cost in order to study the noncovalent interactions between CP and a graphic plane and that the PBE-D3 (BJ) level of theory is capable of providing reliable estimations of the related binding energies
From the comparison with the MP2C/complete basis set (CBS) results, which can be considered here as the reference ones, it can be seen that for all cases the PBE-D3 (BJ) and M062X approaches globally provide an underestimation of the interaction energy, while the opposite is observed for the B3LYP-D3 (BJ) predictions, which lead to larger discrepancies of about 150 meV

Summary

Introduction

Specific delivery is one of the main issues to be addressed to obtain the ideal pharmaceutical effect of drugs, that is to ensure that the desired biological target is preferentially reached, minimizing in this way possible collateral damages and undesired side effects. Suitably chosen nanocarriers, depending on their lipo- or hydro-philicity, can allow solubilization in different media and facilitate the drug administration Since their introduction, graphene-based biomaterials have shown excellent physico-chemical properties and have been widely tested as promising nanocarriers [6,7,8,9]. Graphene-based biomaterials have shown excellent physico-chemical properties and have been widely tested as promising nanocarriers [6,7,8,9] Their dominant two-dimensional character offers a large surface area-to-volume ratio, ideal for drug loading. Graphene Oxide (GO) in particular can present hydrophilic (epoxy, hydroxy, carboxylic, etc.) groups allowing an efficient dispersion in water and making it a very good candidate for drug transportation

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