Adsorption of Chiral [5]-Aza[5]helicenes on DNA Can Modify Its Hydrophilicity and Affect Its Chiral Architecture: A Molecular Dynamics Study

Giuseppina Raffaini,Tullio Caronna,Andrea Mele

doi:10.3390/ma13215031

Abstract

Helicenes are interesting chiral molecules without asymmetric carbon atoms but with intrinsic chirality. Functionalized 5-Aza[5]helicenes can form non-covalent complexes with anticancer drugs and therefore be potential carriers. The paper highlights the different structural selectivity for DNA binding for two enantiopure compounds and the influence of concentration on their adsorption and self-aggregation process. In this theoretical study based on atomistic molecular dynamics simulations the interaction between (M)- and (P)-5-Aza[5]helicenes with double helix B-DNA is investigated. At first the interaction of single pure enantiomer with DNA is studied, in order to find the preferred site of interaction at the major or minor groove. Afterwards, the interaction of the enantiomers at different concentrations was investigated considering both competitive adsorption on DNA and possible helicenes self-aggregation. Therefore, racemic mixtures were studied. The helicenes studied are able to bind DNA modulating or locally modifying its hydrophilic surface into hydrophobic after adsorption of the first helicene layer partially covering the negative charge of DNA at high concentration. The (P)-enantiomer shows a preferential binding affinity of DNA helical structure even during competitive adsorption in the racemic mixtures. These DNA/helicenes non-covalent complexes exhibit a more hydrophobic exposed surface and after self-aggregation a partially hidden DNA chiral architecture to the biological environment.

Highlights

The DNA can be considered as a chiral helical polymer in a double-stranded arrangement that generally adopts right-handed helices under physiological conditions, B-DNA, one of three biologically active double-helical structures with right-handed double-helical structure, and it may change to left-handed, Z-DNA, one of three biologically active double-helical structures with left-handed double-helical structure first discovered by Robert Wells and colleagues [1], depending on the sequence and medium conditions (B–Z transition)
The molecular mechanics (MM) and molecular dynamics (MD) simulations are useful tool to study the adsorption process on the DNA surface of chiral helicenes to better understand the possible influence of intrinsic chirality and structural selectivity
Following the kinetics of the adsorption process during the MD runs, at first a helicene layer adsorbed on DNA surface was obtained, nanoaggregates were formed by adsorbing on the first layer

Summary

Introduction

The DNA can be considered as a chiral helical polymer in a double-stranded arrangement that generally adopts right-handed helices under physiological conditions, B-DNA, one of three biologically active double-helical structures with right-handed double-helical structure, and it may change to left-handed, Z-DNA, one of three biologically active double-helical structures with left-handed double-helical structure first discovered by Robert Wells and colleagues [1], depending on the sequence and medium conditions (B–Z transition). Helicenes are chiral hydrophobic polycyclic compounds formed by a variable number of ortho-fused benzene or other aromatic rings with a helical backbone, without asymmetric carbon atoms but with intrinsic chirality [6,7,8,9,10]. These chiral molecules interacting with π–π interactions are useful as building blocks of materials important in optoelectronic applications, for their chelating properties [7]

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Conclusion