3.4 Global reactivity descriptors:
The frontier orbitals, HOMO and LUMO are the most important in a
molecule. These orbitals determine the way how the molecule interacts
with other species and gives information about reactivity or stability
of specific regions of the molecule. The energy of HOMO characterizes
electron donating ability of a molecule while LUMO energy determines the
ability to accept an electron. Therefore, higher values of
EHOMO indicate a better tendency towards the donation of
an electron. As can be seen in Table 4 and Table 5, the molecules CME,
CMS, RCS & A2 have high LUMO energies, hence they can accept electrons
while molecules DC, DCS, LCC & A3 have the highest HOMO energies that
allow them to be the best electron donors. Frontier molecular orbitals
(FMOs), HOMO and LUMO plot for all the modifications were shown in
Figure 5. The values of the calculated quantum chemical parameters such
as the energy of highest occupied molecular orbital
(EHOMO), the energy of the lowest unoccupied molecular
orbital (ELUMO), energy gap (ΔEGap),
ionization potential (I), electron affinity (A), global hardness (η),
global softness (S), chemical potential (μ), and electrophilicity index
(ω) were presented in Table 4 and Table 5.
The highest occupied molecular orbital (HOMO) and lowest unoccupied
molecular orbital (LUMO) are very popular quantum chemical parameters.
The similar kind of quantum calculations and reactivity descriptor
derivation approach has been used by several groups for different kinds
of molecules like nucleobases, small chemical compounds and their
derivatives65-68. We have used this strategy for
studying antisense modifications at the monomer level. The FMOs are
important in determining molecular reactivity and the ability of a
molecule to absorb light. The vicinal orbitals of HOMO and LUMO play the
same role as electron donor and electron acceptor respectively. The
energies of HOMO and LUMO and their neighboring orbitals were all
negative, which indicates that the corresponding molecule is stable. The
HOMO-LUMO energy gap (ΔEGap) is an important stability
index. The HOMO-LUMO energy gap of any molecule reflects the chemical
stability of the molecule. Through Koopman’s theorem, the HOMO and LUMO
energy values are related to the ionization potential ((I=
-EHOMO) and electron affinities (A=
-ELUMO). (I) and (A) is calculated as the negative of
energy Eigenvalues of HOMO and LUMO respectively.
The energies of the HOMO and LUMO as well as the energy gap separating
those are useful descriptors for the reactivity of nucleotide bases and
base pairs. Due to the delocalization of the mobile electrons, these
energies provide information on the stabilization of the molecules. The
HOMO-LUMO energy gap is very important in determining the chemical
reactivity of the molecule. The high value of the energy gap indicates
that the molecule shows high chemical stability, while a small HOMO-LUMO
gap means small excitation energies and hence easily reactive. Higher
values of the HOMO-LUMO gap were observed in RCS, RC, CMS, and A2
modifications. Ionization potential (I), which is defined as the amount
of energy needed to remove an electron from a molecule. High ionization
energy indicates high stability and chemical inertness and small
ionization energy indicates high reactivity of the atoms and molecules.
Modifications DC, DCS, LCC, and A3 were showing lower ionization
potential values, which indicate better electron donors. The electronic
affinity (A) is defined as the energy released when an electron is added
to a neutral molecule. A molecule with high electron affinity (A) values
tends to take electrons easily. From Table 4 and Table 5, RCS, CME, CMS
and A2 have been the reactive modifications.
This kind of information may be contained within the orbital energies of
the HOMO and LUMO but, instead, it may be more useful to study the
global reactivity descriptors. The global chemical reactivity
descriptors, chemical potential (μ), absolute electronegativity (χ) and
chemical hardness (η), global softness (S) and electrophilicity (ω)
which were calculated from HOMO and LUMO energies obtained at the level
of theory B3LYP/6-31G(d,p) for gas phase as given in Table 4 and
B3LYP/6-311G(d,p) for solvent phase as given in Table 5. According to
these parameters, the chemical reactivity varies with the structural
configuration of molecules. The chemical potential μ (eV) measures the
escaping tendency of an electron and it can be associated with the
molecular electronegativity then, as μ becomes more negative, it is more
difficult to lose an electron but easier to gain one. As shown in Figure
6, Tables 4 and 5, modifications DC, DCS, LCC, LCS, and A3 have the
least stability and more reactivity among all the modifications.
Electronegativity (χ), representing the ability of molecules to attract
electrons and is the negative of the chemical potential (μ) in Mulliken
sense. The (χ) values displayed in Tables 4 and 5 show that
modifications RCS and A2 have higher electronegativity values compared
to other modifications. The global hardness (η) and softness (S) are
useful concepts for understanding the behaviour of the chemical system.
Softness (S) is a property of molecules that measures the extent of
chemical reactivity; it is the reciprocal of hardness. A hard molecule
has a large energy gap and a soft molecule has a small energy gap.
Therefore, soft molecules will be more polarizable than hard molecules.
Theoretical calculations established that the modifications RCS and A5
have the highest hardness values, which indicates the hardest molecules.
The modifications LCS and A3 have the highest softness values or can be
stated as chemically more reactive molecules. Parr defined the
electrophilicity index (ω), as a numerical value which is related to the
stabilization of energy when the system acquires an electronic charge
and serves as an indicator of the reactivity of a system towards
nucleophiles. Electrophilicity gives an idea of the stabilization energy
when the system gets saturated by electrons, which come from the
external environment. This reactivity information shows if a molecule is
capable of donating electrons. The lower values of (ω) indicate the
presence of the nucleophilic character, while higher values indicate the
presence of a good electrophilic character. Our results indicate that
modifications DC, DCS, LCC, and A5 have lower values of (ω) so that
these are good nucleophiles. However, the modifications RCS, CMS, and A2
are good electrophiles.