43
priate components of the electrostatic energy rather than in terms of total electrostatic energy [107, 122, 123]. The same conclusion was drawn above with respect
to the van der Waals energy.
2.4.3.4 Polyelectrolyte Energy, ΔG pe
The polyelectrolyte contribution contains both an enthalpic term, originating from
coulombic interaction of solute molecule with counterions present in solution, and
an entropic term, coming from disordering of ion atmosphere upon ligand intercalation. Within the framework of the approach being reviewed in this chapter, the
ΔG pe component is separated from the total electrostatic energy because it can be
measured experimentally and the experimental values for some drugs are available
in the literature (for review see [124]). It is also assumed that the main contribution
to the polyelectrolyte energy comes from the ligand insertion stage.
Analysis of literature suggests that the magnitudes of ΔG pe for aromatic intercalators show very similar values even though the ligands may have very different
structures. By that reason it is reasonable to take the average value, ΔG pe ≈ − 1.1 kcal/
mol, for the set of aromatic molecules studied [107]. In general, the polyelectrolyte
contribution favours formation of complexes. The effect is predominantly entropic
in origin and is due to entropically favourable ion release upon ligand insertion into
DNA.
2.4.3.5 Hydrogen Bonding Energy, ΔG HB
Hydrogen bonding in the complexation of ligands with DNA comes from [107, 115]:
1. formation of intermolecular H-bonds between the ligand and DNA within the
intercalation cavity, characterized by the number of intermolecular H-bonds, N
im
,
and
2. the loss of hydrogen bonds to water due to dehydration of the ligand upon insertion into the intercalation site, characterized by change in hydration index, ΔN
solv
.
As noted in section 2.4.2, within the framework of the methodology used for energy analysis the magnitude of ΔG HB does not bear the meaning of real energy of
H-bonding, and an analysis of the number of hydrogen bonds, N
im
and ΔN
solv
, is
considered to be more appropriate.
It is seen from Table 2.3 that the sign of ∆N conf
solv
value is positive indicating the
predominant solvation of the intercalation cavity on DNA unwinding, whereas the
∆N ins
solv
value is negative pointing out on the net removal of water molecules on ligand insertion. The resulting effect of the whole complexation process is negative,
∆N
solv
< 0, indicating that there is a dehydration of the ligand and DNA molecules
during the intercalation.
The dehydration on insertion (∆N ins
solv
) is not overbalanced by the sum of hydration on unwinding ( ∆N conf
solv
) and formation of intermolecular H-bonds ( N ins
im
), resulting in net positive contribution of H-bonding to the total energy of the intercalation
2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions
priate components of the electrostatic energy rather than in terms of total electrostatic energy [107, 122, 123]. The same conclusion was drawn above with respect
to the van der Waals energy.
2.4.3.4 Polyelectrolyte Energy, ΔG pe
The polyelectrolyte contribution contains both an enthalpic term, originating from
coulombic interaction of solute molecule with counterions present in solution, and
an entropic term, coming from disordering of ion atmosphere upon ligand intercalation. Within the framework of the approach being reviewed in this chapter, the
ΔG pe component is separated from the total electrostatic energy because it can be
measured experimentally and the experimental values for some drugs are available
in the literature (for review see [124]). It is also assumed that the main contribution
to the polyelectrolyte energy comes from the ligand insertion stage.
Analysis of literature suggests that the magnitudes of ΔG pe for aromatic intercalators show very similar values even though the ligands may have very different
structures. By that reason it is reasonable to take the average value, ΔG pe ≈ − 1.1 kcal/
mol, for the set of aromatic molecules studied [107]. In general, the polyelectrolyte
contribution favours formation of complexes. The effect is predominantly entropic
in origin and is due to entropically favourable ion release upon ligand insertion into
DNA.
2.4.3.5 Hydrogen Bonding Energy, ΔG HB
Hydrogen bonding in the complexation of ligands with DNA comes from [107, 115]:
1. formation of intermolecular H-bonds between the ligand and DNA within the
intercalation cavity, characterized by the number of intermolecular H-bonds, N
im
,
and
2. the loss of hydrogen bonds to water due to dehydration of the ligand upon insertion into the intercalation site, characterized by change in hydration index, ΔN
solv
.
As noted in section 2.4.2, within the framework of the methodology used for energy analysis the magnitude of ΔG HB does not bear the meaning of real energy of
H-bonding, and an analysis of the number of hydrogen bonds, N
im
and ΔN
solv
, is
considered to be more appropriate.
It is seen from Table 2.3 that the sign of ∆N conf
solv
value is positive indicating the
predominant solvation of the intercalation cavity on DNA unwinding, whereas the
∆N ins
solv
value is negative pointing out on the net removal of water molecules on ligand insertion. The resulting effect of the whole complexation process is negative,
∆N
solv
< 0, indicating that there is a dehydration of the ligand and DNA molecules
during the intercalation.
The dehydration on insertion (∆N ins
solv
) is not overbalanced by the sum of hydration on unwinding ( ∆N conf
solv
) and formation of intermolecular H-bonds ( N ins
im
), resulting in net positive contribution of H-bonding to the total energy of the intercalation
2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions