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An Introduction to

An Introduction to
Molecular Orbital
Molecular Orbital
Levels of Calculation
Classical (Molecular) Mechanics (previous 2 lectures)
quick, simple; accuracy depends on parameterization;
no consideration of orbital interaction; not MO theory)
Molecular Orbital Theory (Quantum Mechanics)
Ab initio molecular orbital methods...much more
demanding computationally, generally more accurate.
Semi-empirical molecular orbital methods ...
computationally less demanding than ab initio, possible
on a pc for moderate sized molecules, but generally less
accurate than ab initio, especially for energies.
Relative Computation Cost
Molecular mechanics...cpu time scales as square
of the number of atoms...
Calculations can be performed on a compound of
~MW 300 in a minute on a Pentium computer, or in
a few seconds on a high performance computer.
This means that larger molecules (even peptides)
can be modeled readily by MM methods.
Relative Computation Cost
Semi-empirical and ab initio molecular orbital
methods...cpu time scales as the cube (or fourth
power) of the number of orbitals (called basis
functions) in the basis set.
Semi-empirical calculations on ~MW 300
compound take a few minutes on a Pentium pc, or
several seconds on a high performance computer.
Ab initio calculations (to be discussed later) of
such molecules can take hours.
Molecular Orbital Theory
Uses simplifications of the Schrdinger equation
E + = H + to estimate the energy of a system
(molecule) as a function of the geometry and
electron distribution.
The simplifications require empirically derived
(not theoretical) parameters (fudge factors) to
bring calculated values in agreement with
observed values, hence the term semi-empirical.
Properties Calculated by
Properties Calculated by
Molecular Orbital Theory
Molecular Orbital Theory
Geometry (bond lengths, angles, dihedrals)
Energy (enthalpy of formation, free energy)
Vibrational frequencies, UV-Vis spectra
NMR chemical shifts
IP, Electron affinity (Koopmans theorem)
Atomic charge distribution (...but charge is
poorly defined)
Electrostatic potential (interaction w/ point +)
Dipole moment.
History of Semi-Empirical
History of Semi-Empirical
Molecular Orbital Theory
Molecular Orbital Theory
1930s Hckel treated t systems only
1952 Dewar PMO; first semi-
quantitative application
1960s Hoffmann Extended Huckel;
included o bonds
1965 Pople CNDO; first useful MO
1967 Pople INDO
1975 Dewar MINDO/3; was widely used
1977 Dewar MNDO
1985 Dewar AM1; added vdW
attraction & H-bonding
1989 Stewart PM3; larger training set
1970s Zerner ZINDO; includes transition
metals, parameterized for
calculating UV-Vis spectra
Basis of Molecular Orbital Theory
Basis of Molecular Orbital Theory
Schrdinger equation:
E = H
(can be solved exactly ONLY for the Hydrogen atom,
but nothing larger!!)
P.A.M. Dirac, 1929: The underlying physical laws
necessary for the mathematical theory of a large
part of physics and the whole of chemistry are thus
completely known.
Basis of M.O. Theory...
Basis of M.O. Theory...
Three Simplifying assumptions are employed to
solve the Schrdinger equation approximately:
Born-Oppenheimer approximation allows separate
treatment of nuclei and electrons
Hartree-Fock independent electron approximation
allows each electron to be considered as being
affected by the sum (field) of all other electrons.
LCAO Approximation
Variational Principle
Born-Oppenheimer Approx.
States that electron motion is independent of
nuclear motion, thus the energies of the two are
uncoupled and can be calculated separately.
Derives from the large difference in the mass of
nuclei and electrons, and the assumption that the
motion of nuclei can be ignored because they
move very slowly compared to electrons
o (T
) + T
+ V
+ V
+ V
Kinetic energy Potential
is omitted; this ignores relativistic effects,
yielding the electronic Schrdinger equation.)
Hartree-Fock Approximation
Hartree-Fock Approximation
Assumes that each electron experiences all the
others only as a whole (field of charge) rather
than individual electron-electron interactions.
Introduces a Fock operator F:
F + = c +
which is the sum of the kinetic energy of an
electron, a potential that one electron would
experience for a fixed nucleus, and an average of
the effects of the other electrons.
LCAO Approximation
Electron positions in molecular orbitals can be
approximated by a Linear Combination of Atomic
This reduces the problem of finding the best
functional form for the molecular orbitals to the
much simpler one of optimizing a set of coefficients
) in a linear equation:
= c
+ c
+ c
+ c
where is the molecular orbital wavefunction
and |
represent atomic orbital wavefunctions.
Variational Principle
The energy calculated from any approximation of
the wavefunction will be higher than the true
The better the wavefunction, the lower the energy
(the more closely it approximates reality).
Changes are made systematically to minimize the
calculated energy.
At the energy minimum (which approximates the
true energy of the system), oE
~ 0.
Basis sets
A basis set is a set of mathematical equations
used to represent the shapes of spaces (orbitals)
occupied by the electrons and their energies.
Basis sets in common use have a simple
mathematical form for representing the radial
distribution of electron density.
Most commonly used are Gaussian type basis
sets, which approximate the better, but more
complicated Slater-Type orbitals (STO).
Slater-type orbitals (STO)
Slater-type orbitals
describe the electron
distribution quite well,
but they are not simple
enough to manipulate
Several Gaussian-type
orbitals can be added
together to approximate
the STO. Here 4 GTOs
mimic 1 STO fairly well.
Basis Sets
STO-3G (Slater-type orbitals approximated by 3
Gaussian functions) a minimal basis set,
commonly used in Semi-Empirical MO
(L-click here)
Hartree-Fock Self-Consistent
Hartree-Fock Self-Consistent
Field (SCF) Method...
Field (SCF) Method...
Computational methodology:
guess the wavefunction (LCAO orbital coefficients)
of all occupied orbitals
compute the potential (repulsion) each electron
would experience from all other electrons (taken
as a group in the H-F approximation)
solve for Fock operators to generate a new,
improved wavefunction (orbital coefficients)
repeat above two steps until the new wavefunction
is not much improved; at this point the field is
called self-consistent. (SCF theory)
Semi-empirical MO Calculations:
Semi-empirical MO Calculations:
Further Simplifications
Further Simplifications
Neglect core (1s) electrons; replace integral for
by an empirical or calculated parameter
Neglect various other interactions between
electrons on adjacent atoms: CNDO, INDO,
MINDO/3, MNDO, etc.
Add parameters so as to make the simplified
calculation give results in agreement with
observables (spectra or molecular properties).
Steps in Performing a Semi-
Steps in Performing a Semi-
empirical MO Calculation
empirical MO Calculation
Construct a model or input structure from MM
calculation, X-ray file, or other source (database)
optimize structure using MM method to obtain a
good starting geometry
select MO method (usually AM1 or PM3)
specify charge and spin multiplicity (s = n + 1), where
n = # unpaired electrons, usually 0, so s usually is 1.
select single point or geometry optimization
set termination condition (time, cycles, gradient)
select keywords (from list of >100) if desired.
Comparison of Results
Comparison of Results
Mean errors relative to experimental measurements
, kcal/mol 11.7 6.6 5.9 --
IP, eV -- 0.69 0.52 0.58
, Debyes -- 0.33 0.24 0.28
r, Angstroms -- 0.054 0.050 0.036
o, degrees -- 4.3 3.3 3.9
More results...
More results...
Enthalpy of Formation, kcal/mol
MM3 PM3 Expt
ethane -19.66 -18.14 --
propane -25.32 -23.62 -24.8
cyclopropane 12.95 16.27 12.7
cyclopentane -18.87 -23.89 -18.4
cyclohexane-29.95 -31.03 -29.5
Some Applications...
Calculation of reaction pathways (mechanisms)
Determination of reaction intermediates and
transition structures
Visualization of orbital interactions (formation of new
bonds, breaking bonds as a reaction proceeds)
Shapes of molecules including their charge
distribution (electron density)
more Applications
QSAR (Quantitative Structure-Activity Relationships)
CoMFA (Comparative Molecular Field Analysis)
Remote interactions (those beyond normal covalent
bonding distance)
Docking (interaction of molecules, such as
pharmaceuticals with biomolecules)
NMR chemical shift prediction.
As we will see, ab initio and DFT calculations generally give
better results than Semi-empirical MO calculations