Mechanism of DNA Chemical Denaturation

We develop the theory of chemical denaturation of DNA for low and medium denaturation degrees, including but not limited to 50% denaturation as a reversible first-order reaction. We show the degree 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 in the thermal denaturation process (positive). We show that the mechanism of reaching 50% DNA denaturation thermally and chemically differs. The thermal denaturation process mainly involves breaking hydrogen bonds via heating DNA, while the chemical denaturation process involves replacing DNA hydrogen bonding with denaturants. We also show that hydrogen bonding is the most significant part of the enthalpy of chemical denaturation for 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 larger than the influence of the proton-acceptor effect. Another essential factor for DNA denaturation is the orientational component, part of the polar cohesion parameter. We suggested that the total cohesion parameter measured at 50% of DNA chemical denaturation represents the electrostatic (repulsion) forces maintaining the DNA helix. We demonstrate that theoretical and prior experimental results show that the Hildebrand, Hansen, Karger, Snyder, and Eon equations are applicable and instrumental in studying DNA chemical denaturation. We developed a novel method to reveal and estimate the degree of influence of electrostatic repulsion and different attraction forces in DNA during its chemical denaturation. Our method can be suitable for selecting DNA (or other systems with controllable denaturation) targeted for specific applications.