3.3 Structure and Energetics:
The structure of a molecule contains the features responsible for its
physical, chemical and biological properties. The variations in similar
kinds of structures can be correlated with changes in reactivity
descriptors that reflect their molecular properties. The computational
analysis of the molecular geometry of a chemical molecule plays a
crucial role in determining the structure-activity relationship.
Molecular geometries can be determined to a high accuracy by the quantum
mechanical behaviour of the electrons computed by ab-initio quantum
chemical methods. Depending on the arrangement of atoms in 3D geometry,
one can calculate various properties like reactivity, polarity, phase of
matter, colour, magnetism and biological activity of that particular
molecule using the various quantum chemical and molecular dynamics
techniques. Hence, to study the structural and electronic properties of
the proposed molecules, all the molecules further underwent a full
geometry optimization to obtain their energy minimized structures at the
DFT level. Analysing the eigenvalues from the Hessian calculations of
the optimized structures, we have observed the presence of positive
eigenvalues only, which indicates the structures to be true minima on
the potential energy surface (PES). The eigenvalues for all the
modifications for the optimized structures are included in the
Supplementary Table
S2. We have also calculated the density of states (DOS) and the IR
spectra and are given in Supplementary Figure S3. Different vibrational
modes present in the individual modifications would be influencing
various bonds like N-H and O-H that are important for the base pairing.
As the modifications proposed are novel, this data may prove to be of
immense help to the experimentalist. The parameters like electronic
energy, dipole moment, polarizability, thermal energy, and heat capacity
for all modifications have been listed in Table 3.
The electronic energy trend observed for the standard modifications is
DC>RC>LCC>CME. It was also
observed that the addition of phosphorothioate to any modified
nucleotide lowered the electronic energy. In the proposed modifications
the electronic energy trend is
A1>A2>A3>A4>A5. Some
of the proposed modifications were also showing lower energy values than
the standard modifications. A dipole moment is a measurement of the
separation of two opposite electrical charges. Even though the total
charge on a molecule is zero, the nature of chemical bonds is such that
the positive and negative charges do not completely overlap in most
molecules. Such molecules are said to be polar because they possess a
permanent dipole moment. The magnitude of the dipole moment induced is a
measure of the polarizability of the molecules. The highest dipole
moment can be seen in CMS modification compared to all others.
Polarizability allows us to better understand the interactions between
nonpolar atoms and molecules and other electrically charged species,
such as ions or polar molecules with dipole moments. Neutral nonpolar
species have spherically symmetric arrangements of electrons in their
electron clouds. When in the presence of an electric field, their
electron clouds can be distorted. The ease of this distortion is defined
as the polarizability of the atom or molecule. The created distortion of
the electron cloud causes the originally nonpolar molecule or atom to
acquire a dipole moment. It has been suggested that polarizability is
related to reactivity64. The polarizability is a
measure for the change in the charge distribution within a molecule
induced by an electric field. Thus, a system with low polarizability is
supposed to be more stable, i.e. less
reactive44. According to our calculations, DC, RC,
LCC, and A1 were the molecules with the smallest values for the
polarizability, with values 173, 174, 181 and 178 a.u., respectively.
The addition of phosphorothioate slightly increased the polarizability
of the molecules. Thermal energy is also known as random or internal
kinetic energy, due to the random motion of molecules in a system.
Kinetic energy is seen in three forms namely vibrational, rotational and
translational. Thermal energy is directly proportional to the
temperature within a given system. The heat capacity is the measurable
physical quantity that characterizes the amount of heat required to
change a molecule’s temperature by a unit amount. Thermal energy is
decreased and heat capacity is slightly increased with the addition of
phosphorothioate for the modified molecules.