Describes introduction to theoretical methods in chemistry, the tools of computational quantum chemistry

1. Computational Chemistry
Dr. Anjali Devi J S
Guest Faculty
School of Chemical Sciences
MG University
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2. Computational Chemistry
• Also known as Molecular modelling.
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Computational Chemistry is a set of techniques for investigating
chemical problems on a computer.

3. Questions Commonly Investigated Computationally
• Molecular geometry:
The shape of the molecules- bond lengths, angles, and dihedrals.
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4. • Energies of molecules and Transition states:
This tells us which isomer is favoured at equilibrium and how fast a
reaction should go.
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Questions Commonly Investigated Computationally

5. Questions Commonly Investigated Computationally
• Chemical reactivity
For example, Identifying electrophilic sites and nucleophilic sites and predict
where various kinds of reagents will attack a molecule.
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6. • IR, UV, and NMR spectra
Questions Commonly Investigated Computationally
These can be calculated, if
the molecule is unknown,
someone trying to make it
knows what to look for.
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7. • The interaction of substrate with enzyme
Questions Commonly Investigated Computationally
Seeing how molecules fit into active sites of a enzyme
(one approach to design better drugs.
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8. • The physical properties of substances
Questions Commonly Investigated Computationally
These depends on the properties of individual molecules and the molecule
interact in the bulk material.
Example: The strength and m.p of polymer depends on how well the
monomers fit together and how strong the force between them. 8

9. Tools of Computational Chemistry
Molecular
Mechanics
(MM)
Ab initio
calculations
Semiempirical
calculations
(SE)
Density
functional
calculations
Molecular
dynamics
calculations
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10. (1) Molecular Mechanics
• Based on the model of a molecule as collection of balls (atoms) held
together by springs (bonds)
Geometry optimisation: Identifying the geometry of molecule (having
lowest energy) by changing the geometry until the lowest energy is
calculated. 10

11. • Molecular mechanics is fast:
A large molecule (eg: steroid like cholesterol C27H46O ) can be optimised
in seconds on a powerful desktop computer (a work station).
(1) Molecular Mechanics (Contd.)
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Cholesterol

12. • Ab initio is from the Latin: “from first principles”
• Based on Schrödinger equation.
(2) Ab initio Calculations
The ab initio method solve Schrödinger equation for a
molecule and give energy and wavefunction.
Schrödinger
Equation of
molecule
Energy and
wave function
Electron
distribution
How Polar the molecule?
Where is Reaction centre of molecule?
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13. • Ab initio Calculations are slow.
Geometry and spectra of simple molecule (propane ) can be calculated
in minutes on a premium type machine.
(2) Ab initio Calculations (Contd.)
Propane
But steroids take weeks!! 13

14. (3) Semiempirical calculations
• Based on Schrödinger equation (like ab initio) but parametrized with
experimental values (empirical=experimental).
• Mixing of theory and experimental (It makes method is “semiempirical”)
• Parameterization: The plugging of experimental values into a
mathematical procedure to get the best calculated value.
Here, more approximations are made in solving Schrödinger equation, and
the very complicated integrals (that must be calculated in ab initio methods
are not actually evaluated in Semi empirical calculations.
Instead, the program daws a library of integrals that was compiled by finding
the best fit of some calculated entity (eg: energy) to experimental value 14

15. • Semi empirical calculations are slower than molecular mechanics but
much faster than ab initio calculations.
(3) Semiempirical calculations (Contd.)
Ab initio
Calculations
Molecular
Mechanics
Semiempirical
calculations
fast
Cholesterol-
Geometry
optimisation
slow
Several Weeks
On Pentium type
machine
A minute on
premium type
machine
In seconds on
a desktop
computer
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16. • often called density functional theory (DFT) calculations.
• Based on Schrödinger equation (like ab initio and semiempirical
methods).
(4) Density functional Calculations
DFT does not calculate wavefunction but rather
derives the electron distribution (electron density
function) directly.
A Functional is a mathematical entity related to a function.
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17. • DFT calculations are faster than ab initio but slower than
semiempirical calculations
Ab initio
Calculations
Molecular
Mechanics
Semiempirical
calculations
fast
slow
DFT
calculations
(4) Density functional Calculations (Contd.)
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18. • DFT is relatively new: DFT computational chemistry goes back to
1980s. Computational chemistry with SE and ab initio were done in
1960s.
Ab initio
Calculations
Semiempirical
calculations
Time (years)
1980s
DFT
calculations
1960s
(4) Density functional Calculations (Contd.)
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19. • Apply the laws of motion to molecules.
• Thus, one can simulate the motion of an enzyme as it changes shape
on binding to a substrate, or the motion of a swarm of water
molecules around a molecule of solute.
(5) Molecular Dynamics
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20. (5) Molecular Dynamics (Contd.)
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21. Uses of Computational chemistry
• Pharmaceutical industry –to explore drug-biomolecule interactions.
• Material science-properties of solids (material science).
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22. Advantages of Computational Chemistry
• Cheap
• Fast
• Environmentally safe
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23. Thank You
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