Adsorption and Self-Aggregation of Chiral [5]-Aza[6]helicenes on DNA Architecture: A Molecular Dynamics Study

Helicenes are an extremely interesting class of conjugated molecules without asymmetric carbon atoms but with intrinsic chirality. These molecules can interact with double-stranded chiral B-DNA architecture, modifying after their adsorption the hydrophilicity exposed by DNA to the biological environment. They also form ordered structures due to self-aggregation processes with possible different light emissions. Following initial studies based on molecular mechanics (MM) and molecular dynamics (MD) simulations regarding the adsorption and self-aggregation process of 5-aza[5]helicenes on double-stranded B-DNA, this theoretical work investigates the interaction between (M)- and (P)-5-aza[6]helicenes with double-helix DNA. Initially, the interaction of the pure single enantiomer with DNA is studied. Possible preferential absorption in minor or major grooves can occur. Afterward, the interaction of enantiopure compounds (M)- and (P)-5-aza[6]helicenes, potentially occurring in a racemic mixture at different concentrations, was investigated, taking into consideration both competitive adsorption on DNA and the possible helicenes’ self-aggregation process. The structural selectivity of DNA binding and the role of helicene concentration in adsorption and the self-aggregation process are interesting. In addition, the ability to form ordered structures on DNA that follow its chiral architecture, thanks to favorable van der Waals intermolecular interactions, is curious.


Figure S1
. Initial two different non-optimized geometries considered for the 20 and 120 (M)-5aza [6]helicene molecules on the left (panel a) and on the right (panel b), respectively, without DNA in the simulation box.The same geometries not reported here are also considered for the (P)-5-aza[6]helicene enantiomer.S3 The MD runs obtained starting from the four different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.S3   The carbon atoms are in grey, the nitrogen atoms are in blue and the hydrogen atoms are in white.S3 The MD runs obtained starting from the four different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.The carbon atoms are in grey, the nitrogen atoms are in blue, and the hydrogen atoms are in white.S4 The MD runs obtained starting from the two different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.
MIX_only 20\MD run_only20m_10e10_azaMeP_20ns.aviMIX_only_120\MD run_onlyMIX60e60_aza6_20ns.aviThe carbon atoms are in grey, the nitrogen atoms are in blue, the oxygen atoms are in red, the phosphorus atoms are in pink, and the hydrogen atoms are in white.S5 The MD runs obtained starting from the four different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.The carbon atoms are in grey, the nitrogen atoms are in blue, the oxygen atoms are in red, the phosphorus atoms are in pink and the hydrogen atoms are in white.S6 The MD runs obtained starting from the four different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.The carbon atoms are in grey, the nitrogen atoms are in blue, the oxygen atoms are in red, the phosphorus in pink and the hydrogen atoms are in white.S7 The MD runs obtained starting from the two different initial optimized geometries considered are reported in file.avigenerated by using Materials Studio program, visualizing every 10 frames of the 1000 frames saved during MD runs lasting 20 ns.

Concentration profile
The Concentration profile is calculated for 3D periodic structures by computing the profile of atom density within evenly spaced slices parallel to the bc, ca, and ab planes.In practice, this is equivalent to taking the a, b, and c components of the fractional coordinates of each atom and independently generating a plot for each component.For 2D periodic structures, the u and v components of the fractional coordinates are used, resulting in two plots.
As an alternative to generating profiles along each axis, it is also possible to specify a particular direction in the form of an (h k l) vector.In this case, Forcite will produce a single plot of the concentration profile parallel to the plane defined by that vector.
Each direction is divided equally into a number of bins (potentially, a different number for each axis).For each atom in the unit cell, a contribution is added into the relevant cell in the binning vector corresponding to each axis.The contribution is a constant value determined so that the average value along each axis becomes 1.0 (i.e., a homogeneous structure would have values close to 1.0).
The relative concentration of a set of atoms in a slab is: where [set]slab = (no.atoms in slab)/(volume of slab) [set]bulk = (total no.atoms in system)/(volume of system) The relative concentration is a dimensionless quantity, a value of 2 means that there are twice the number of atoms in the slab that if all atoms were distributed homogeneously across the system.The total number of atoms across all slabs is equal to the number of atoms in the entire system.So the sum of the relative concentrations of all slabs is equal to the number of slabs.
For plotting, the bin values are converted from fractional positions to Cartesian values.To allow for the possibility of the unit cell changing, the values used for the unit cell dimensions are the average over all the frames under consideration.
As with other structural analyses, the concentration profile can be calculated for a subset of the atoms in the input structure by specifying a set in the input document or simply by manually selecting the atoms you wish to include in the calculation.

Figure S6 .Figure S1 .
Figure S6.Side view and top view of the only helicenes adsorbed on the chiral DNA structure in the final optimized geometries considering 120 (M)-6H and (P)-6H enantiomers on the left (panel a) and on the right (panel b), respectively, without DNA for clarity.The (M)-6H enantiomers are colored in red, and the (P)-6H enantiomers are colored in blue.All θ dihedral angles values calculated for all molecules of the first layer closer to the DNA chiral structure are shown in light blue.S8 Figure S2.Initial two different non-optimized geometries considering racemic mixtures of 20 and 120 (M)-5-aza[6]helicene and (P)-5-aza[6]helicene enantiomers on the left (panel a) and on the right (panel b), respectively, without DNA in the simulation box.

Figure S3 .
Figure S3.Initial two different non-optimized geometries considered for the (M)-5-aza[6]helicene molecules on the left near the DNA minor groove (panel a) and on the right near DNA major groove (panel b).The same geometries not reported here are also considered for the (P)-5-aza[6]helicene enantiomer.

Figure S4 .
Figure S4.Initial two different non-optimized geometries considering 20 and 120 (M)-5-aza[6]helicene molecules on the left (see panel a) and on the right (see panel b), respectively, with DNA in the simulation box.The same geometries not reported here are also considered for the (P)-5-aza[6]helicene enantiomer.

Figure S6 .
Figure S6.Side view and top view of the only helicenes adsorbed on the chiral DNA structure in the final optimized geometries considering 120 (M)-6H and (P)-6H enantiomers on the left (panel a) and on the right (panel b), respectively, without DNA for clarity.The (M)-6H enantiomers are colored in red, and the (P)-6H enantiomers are colored in blue.All θ dihedral angles values calculated for all molecules of the first layer closer to the DNA chiral structure are shown in light blue.S8