Impact of Doxorubicin on Self-Organization of Congo Red: Quantum Chemical Calculations and Molecular Dynamics Simulations

Klaudia Kwiecińska,Jacek Korchowiec,Anna Stachowicz-Kuśnierz,Anna Jagusiak,Irena Roterman

doi:10.1021/acsomega.0c01095

Abstract

Quantum-chemical calculations and molecular dynamics simulation were applied to a model self-organization process of Congo red (CR) molecules in aqueous solution and the impact of doxorubicin (DOX) molecules on such a process. It was demonstrated that both pure CR/CR and mixed CR/DOX dimers were stable. Van der Waals interactions between aromatic units were responsible for a stacked dimer formation. An important source of stabilization in the CR/CR dimer was the polarization energy. In the CR/DOX mixed dimer long range, electrostatic interactions were the main driving force leading to complexation. An implicit solvent model showed that the formation of the CR/CR dimer was favored over the CR/DOX one. Molecular dynamics simulations demonstrated rapid complexation. In the pure CR system, short sequences of ribbon-like structures were formed. Such structures might be glued by hydrogen bonds to form bigger complexes. It was shown that the aromatic part of the DOX molecule enters CR ribbons with the sugar part covering the CR ribbons. These findings demonstrated that CR may find applications as a carrier in delivering DOX molecules; however, further more extensive investigations are required.

Highlights

Development of supramolecular chemistry opens up new horizons for many fields of science
We focus on the microscopic description of Congo red (CR) and CR/DOX clusters, including interactions responsible for dimer stabilization, the influence of solvent, and the mechanism of the clustering process in aqueous solution
The highest destabilization contribution to the INT energy in the CR/CR system is the ES term. This behavior was not surprising because the CR is negatively charged. This energy term in a mixed CR/DOX system is negative; the ES term should enhance the self-organization of molecules or at least promote the incorporation of DOX molecules into ribbon-like supramolecular structures of CR

Summary

■ INTRODUCTION

Development of supramolecular chemistry opens up new horizons for many fields of science. The self-assembled ribbon-like structures that form elongated Congo red systems owing to their unique properties are used in targeted drug delivery to cancer tissue.[10] Such systems are an example of a new type of ligand for proteins to which they bind using a nonclassical mode of interaction.[4] An example is binding to antigen−antibody complexes while not binding to free antibodies.[11] This interaction is the basis for the use of such systems in immunotargeting.[12] At the same time, CR systems effectively bind to various molecules, including drugs, to form co-micelles with them.[13] Research to date has demonstrated the possibility of using CR systems in vivo as potential drug carriers These systems bound to the immune complexes formed in the body and were gradually removed. Five independent trajectories were computed for each molecular system, and their average is reported as the final result

■ RESULTS

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES