# Mechanism of DNA Chemical Denaturation

## TL;DR

The paper explains how chemical denaturation of DNA works by analyzing forces like hydrogen bonds and electrostatic repulsion.

## Contribution

A novel method to deduce DNA denaturation forces by analyzing surrounding solution properties is introduced.

## Key findings

- Hydrogen bonding is the main enthalpic contributor to DNA chemical denaturation.
- Proton-donor effect disrupts hydrogen bonds twice as much as proton-acceptor effect.
- Electrostatic repulsion forces maintain DNA helix at 50% chemical denaturation.

## Abstract

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.