Mechanism of DNA Chemical Denaturation.

We developed a method to evaluate the degree of influence of attraction and electrostatic repulsion forces in DNA during its chemical denaturation. Our approach shows that when a solution can split apart a target molecule, the forces inside the molecule can be deduced by analyzing the properties of the surrounding solution. Our method is suitable for selecting DNA (or other systems with controllable denaturation) targeted for specific applications or to optimize the denaturants for any given DNA. Our theory has been developed for the chemical denaturation of DNA for low- and medium-denaturation degrees, including the denaturation of 50% as a reversible first-order reaction. Specifically, we show the degrees of influence of hydrogen bonding, dispersion, polar forces, proton donor/acceptor ratio, dipole induction, orientation parameter, and electrostatic interaction on the denaturation process of DNA. The absolute enthalpy values for DNA chemical denaturation are significantly lower than those in the thermal denaturation process (where values are positive). We show that the mechanism for reaching 50% DNA denaturation differs thermally and chemically. The thermal denaturation process mainly involves breaking hydrogen bonds via heating, while the chemical denaturation process involves replacing DNA's hydrogen bonds with denaturants. We show that hydrogen bonding is the dominant enthalpic contributor to the chemical denaturation of T4 bacteriophage DNA, and the proton-donor effect is the dominant mechanism for disrupting hydrogen bonds during DNA denaturation. The influence of this effect is two times greater than that of the proton-acceptor effect. We also show that the orientation component is another essential factor for DNA denaturation, which is part of the polar cohesion parameter. We show that the total cohesion parameter measured at 50% of DNA chemical denaturation represents the electrostatic (repulsion) forces that maintain the DNA helix. The conclusions above were achieved using the cohesive energy density approach and corresponding equations based on the thermodynamics of the denaturation process. Independent experimental data, which we analyzed using our theory, support these conclusions.