DFT studies of drug molecuels

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3. Computational Methods Of Theoretical Chemistry
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Simulation chemical structures
Calculation vibrational wavenumbers, intensities
and normal DIAGRAM
modes of vibrations
Simulation of vibrational spectra by applying
quantum chemical calculations
Yields useful information on molecular potential
energy surfaces and force constants

4. THEORETICAL METHODS
MOLECULAR MECHANICS QUANTUM MECHANICS
Ab initio quantum
chemical method
Ab initio followed by
empirical scaling
of force constants
DENSITY
FUNCTIONAL
THOERY
MOLLER
PLESSET
Semiempirical
Quantum Chemical
HARTREE
FOCK
Method
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5. Classical approach
Does not use molecular Hamiltonian
operator and wave function
It views the molecule as atoms held by
bonds
Expresses energy in terms of internal
degrees of freedom
Using NCA, appropriate frequency
assignment can be performed
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6. With the increase of complexity, molecular mechanics no
longer suitable for large molecules
Larger deviation between theoretical and experimental
frequencies
Unable to predict intensities
Impossible to simulate IR and Raman spectra
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7. Quantum Chemical Methods
Uses the laws of quantum mechanics rather than
classical physics
Energy and related properties of the molecule
obtained by solving Schrodinger equation
There are different QCMs, characterized by their
mathematical approximation to its solution.
1.Semi empirical methods
2. Ab- inito method
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H y =Ey

8. SEMI EMPIRICAL METHODS
It uses simpler Hamiltonian rather than the correct
one
Use parameters whose values are adjusted to fit with
experimental data.
Provides fairly good theoretical results
Demerits with the Vibration prediction using
empirical forces:
sufficient accuracy is not obtained
depends on the choice of force constants
leads to wrong vibrational assignments
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9. AB INITIO METHODS
Derived directly from theoretical principles
Does not use experimental data other than the values
of the fundamental physical constants
Uses exact Hamiltonian
Merits
Ab initio methods includes treatment of electron
correlation
Lead to calculations of molecular geometries
Spectroscopic properties are very close to experimental
data.
Efficient to predict the properties of molecule
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10. AB INITIO METHODS
Hartree Fock self
consistant field
•Simulation of the
infrared and
Raman intensities
•Simulation of
vibrational spectra
•Large deviation
between the
calculated and
observed frequency
at the HF-SCF level
•This is due to
neglect of electron
correlation and
anharmonicity
Moller–Plesset
Perturbation theory
•Which treats electron
correlation as a
perturbation of the
Fock operator.
Disadvantages
•It does not use
variational method.
•The estimate of the
correlation energy can
be too large.
Density Functional
Theory
•Calculates molecular
energy from electron
density
•Deliver force field of
high accuracy
•Its lower
computational
requirements allow it
to tackle larger poly
atomic molecules
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11. DFT allows all properties to be determined
by electron density ,n(r), as a function of
three variables r = (x,y,z)
DFT offers an elegant formulation of N-particles
quantum mechanics, conceptual
simplicity and computational efficiency
Extends limitations of accuracy from
approximation to unknown energy terms
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12. Finite number of atomic orbitals centered
at each atomic nucleus within the molecule
Initially, these atomic orbitals were Slater
Type Orbital (STO), which corresponded to
a set of functions which decayed
exponentially with distance from the nuclei
STOs could in turn be approximated as
linear combinations of Gaussian
orbitals(G)
Types are
Minimal basis sets
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13. Polarized basis sets
* - Addition of polarized function ‘d ̕
**- Addition of polarized function ‘p ̕
6-31G(d) or 6-31G*
6-31G(d, p) or 6-31G**
Diffuse functions
+ - Diffuse functions added to heavy atoms
++ - Diffuse functions added to light atoms
Exchange and correlation functional
B3LYP - Becke’s three parameter exchange
functional + Correlation functional of Lee, Yang and
Parr.
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14. Drawbacks of Ab Initio Methods
The calculated frequencies are higher than their
experimental counterpart
Over estimation of force constant is due to,
Basis set incompleteness
Incomplete implementation of electronic
correlation
Neglect of anharmonicity effect in theoretical
treatment
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15. Scaled Quantum chemical Calculations
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Introduces empirical adjustment at two levels
molecular geometry, force constant
The procedure empirical correction of Ab initio method–
Scaling
Scale factors depends on the usage of both method and
basis set (6-31G, 6-31G*, 6-311+G**)
Types of Scaling applied for correcting the Ab initio force
field
Uniform Scaling
Selective scaling
Using the number of scale factors, the observed
frequencies are reproduced reasonably well
Employs different scale factors for different coordinates

16. FLOW CHART OF COMLETE SQM
PROCEDURE
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