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.