25
it is possible to observe the atomic groups, which represent hydration centers, to
estimate the order and the degree of their filling with water molecules, to determine
distinctive features of the formation of DNA secondary structure in the complexes
with ligands and the structure of the hydration environment. This procedure enables
to control the state of water and the state of individual structural groups of the
biopolymer and the ligand as a function of film moistening. Such an approach also
gives an opportunity to estimate thermodynamic parameters of hydration and to
construct a model of hydration shell of the complexes [55].
In order to reveal the energy contribution of water to stabilization of nucleic acid
structures and their complexes, it is necessary to know the thermodynamic parameters characterizing hydration of DNA, the ligands and the DNA-ligand complexes.
Various physico-chemical methods may be used to solve this problem experimentally. In particular, a sufficiently sensitive piezomicrobalance or piezogravimetric
method based on the use of quartz resonator, allows to obtain hydration isotherms
or dependencies of sorption on relative humidity (in moles of water per mole of
sorbent) [51, 52]. The isotherms measured for biopolymers or their complexes with
ligands give insight into heterogeneity in the energies of interaction between the
hydration sites and the sorbed water molecules.
2.2.4 Calorimetry
Structural studies are crucial for identifying the specific molecular interactions between the host DNA and the ligand, such that the overall three-dimensional shape of
the complex and exact position or binding mode can be determined. But structural
analysis alone can provide little knowledge on the nature of molecular forces that
drive the complex formation in solution, and on the relative energetic contributions
of specific molecular interactions. It is therefore essential to complement structural
studies with detailed and rigorous thermodynamic analysis to fully characterize bimolecular complex formation. Differential scanning calorimetry (DSC) is one of
the most convenient and informative methods for determining the energy parameters of interaction of the ligands with DNA. Direct measurement of heat effects
caused by melting of DNA and its complexes enables to determine the full set of
thermodynamic binding parameters and the energetic parameters of structural transitions: enthalpy, entropy and free energy changes, melting temperature and melting
interval [56–61]. In order to quantify the energetic parameters of the interaction
from DSC heat capacity curves, specific theoretical models must be used. The most
well-elaborated approaches for the analysis of heat capacity curves have so far been
developed only for protein interactions with ligands, because protein unfolding can
often be described by simple two-state model [62, 63]. When the DNA-ligand system is being analysed, certain specificities of the complexation and melting of linear
polymeric molecules should be taken into consideration. Recently a novel analytical
approach for detailed analysis of the DNA-ligand interactions from DSC data was
proposed [64]. The DNA macromolecule in this study is represented as an assembly
2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions
it is possible to observe the atomic groups, which represent hydration centers, to
estimate the order and the degree of their filling with water molecules, to determine
distinctive features of the formation of DNA secondary structure in the complexes
with ligands and the structure of the hydration environment. This procedure enables
to control the state of water and the state of individual structural groups of the
biopolymer and the ligand as a function of film moistening. Such an approach also
gives an opportunity to estimate thermodynamic parameters of hydration and to
construct a model of hydration shell of the complexes [55].
In order to reveal the energy contribution of water to stabilization of nucleic acid
structures and their complexes, it is necessary to know the thermodynamic parameters characterizing hydration of DNA, the ligands and the DNA-ligand complexes.
Various physico-chemical methods may be used to solve this problem experimentally. In particular, a sufficiently sensitive piezomicrobalance or piezogravimetric
method based on the use of quartz resonator, allows to obtain hydration isotherms
or dependencies of sorption on relative humidity (in moles of water per mole of
sorbent) [51, 52]. The isotherms measured for biopolymers or their complexes with
ligands give insight into heterogeneity in the energies of interaction between the
hydration sites and the sorbed water molecules.
2.2.4 Calorimetry
Structural studies are crucial for identifying the specific molecular interactions between the host DNA and the ligand, such that the overall three-dimensional shape of
the complex and exact position or binding mode can be determined. But structural
analysis alone can provide little knowledge on the nature of molecular forces that
drive the complex formation in solution, and on the relative energetic contributions
of specific molecular interactions. It is therefore essential to complement structural
studies with detailed and rigorous thermodynamic analysis to fully characterize bimolecular complex formation. Differential scanning calorimetry (DSC) is one of
the most convenient and informative methods for determining the energy parameters of interaction of the ligands with DNA. Direct measurement of heat effects
caused by melting of DNA and its complexes enables to determine the full set of
thermodynamic binding parameters and the energetic parameters of structural transitions: enthalpy, entropy and free energy changes, melting temperature and melting
interval [56–61]. In order to quantify the energetic parameters of the interaction
from DSC heat capacity curves, specific theoretical models must be used. The most
well-elaborated approaches for the analysis of heat capacity curves have so far been
developed only for protein interactions with ligands, because protein unfolding can
often be described by simple two-state model [62, 63]. When the DNA-ligand system is being analysed, certain specificities of the complexation and melting of linear
polymeric molecules should be taken into consideration. Recently a novel analytical
approach for detailed analysis of the DNA-ligand interactions from DSC data was
proposed [64]. The DNA macromolecule in this study is represented as an assembly
2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions