Mechanism of DNA Chemical Denaturation

We developed a method to evaluate the degree of influence of electrostatic repulsion and different attraction forces on DNA during its chemical denaturation. Our method can be suitable for selecting DNA (or other systems with controllable denaturation) targeted for specific applications and/or to optimize the denaturants for any given DNA. Our theory has been developed for DNA chemical denaturation for low and medium denaturation degrees, including but not limited to 50\% denaturation 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 (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 DNA, while the chemical denaturation process involves replacing the hydrogen bonding of DNA with denaturants. We also show that hydrogen bonding is the most significant part of the enthalpy of chemical denaturation for the T4 bacteriophage DNA, and the proton-donor effect is the dominant mechanism in disrupting hydrogen bonds in DNA denaturation. The influence of this effect is two times greater than that of the proton-acceptor effect. We also show that another essential factor for DNA denaturation is the orientation component, 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, supported these conclusions.