Introduction to

Computational Chemistry
Shubin Liu, Ph.D.
Research Computing Center
University of North Carolina at Chapel Hill

Outline
Introduction
Methods in Computational Chemistry
Ab Initio
Semi-Empirical
Density Functional Theory
New Developments (QM/MM)
Hands-on Exercises
The PPT format of this presentation is available here:

http://its2.unc.edu/divisions/rc/training/scientific/
/afs/isis/depts/its/public_html/divisions/rc/training/scientific/short_courses/
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About Us
ITS Information Technology Services

its.unc.edu

http://its.unc.edu
http://help.unc.edu
Physical locations:
401 West Franklin St.
211 Manning Drive
10 Divisions/Departments
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3

Research Computing
Where and who are we and what do we do?

ITS Manning: 211 Manning Drive

Website
http://its.unc.edu/research-computing.html

Groups

Infrastructure -- Hardware
User Support -- Software
Engagement -- Collaboration

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About Myself
Ph.D. from Chemistry, UNC-CH
Currently Senior Computational Scientist @ Research Computing Center, UNC-CH
Responsibilities:
Support Computational Chemistry/Physics/Material Science software
Support Programming (FORTRAN/C/C++) tools, code porting, parallel computing, etc.
Offer short courses on scientific computing and computational chemistry
Conduct research and engagement projects in Computational Chemistry
Development of DFT theory and concept tools
Applications in biological and material science systems

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About You
Name, department, research interest?
Any experience before with high
performance computing?

Any experience before with

computational chemistry research?

Do you have any real problem to solve

with computational chemistry
approaches?

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Think BIG!!!
What is not chemistry?
From microscopic world, to nanotechnology, to daily life, to

environmental problems
From life science, to human disease, to drug design
Only our mind limits its boundary

What cannot computational chemistry deal with?

From small molecules, to DNA/proteins, 3D crystals and surfaces
From species in vacuum, to those in solvent at room temperature,

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and to those under extreme conditions (high T/p)

From structure, to properties, to spectra (UV, IR/Raman, NMR,
VCD), to dynamics, to reactivity
All experiments done in labs can be done in silico
Limited only by (super)computers not big/fast enough!

Central Theme of
Computational Chemistry

STRUCTURE

DYNAMICS

REACTIVITY

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CENTRAL DOGMA OF MOLECULAR BIOLOGY

SEQUENCE

STRUCTURE

DYNAMICS

FUNCTION

EVALUTION

Multiscale Hierarchy of
Modeling

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What is Computational
Chemistry?
Application of computational methods and
algorithms in chemistry

Quantum Mechanical
i.e., via Schrdinger Equation
also called Quantum Chemistry

Molecular Mechanical
i.e., via Newtons law F=ma
also Molecular Dynamics

Empirical/Statistical

ii

H
H

tt
Focus
FocusToday
Today

e.g., QSAR, etc., widely used in clinical and medicinal chemistry

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10

How Big Systems Can We

Deal with?
Assuming typical computing setup (number of CPUs,
memory, disk space, etc.)

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Ab initio method: ~100 atoms

DFT method: ~1000 atoms
Semi-empirical method: ~10,000 atoms
MM/MD: ~100,000 atoms

11

Starting Point: Time-Independent

Schrodinger Equation

ii

H
H

tt

H E

N
Z
h2
2
H i -

2m
i 1
1 ri
n

j i

i 1

1
rij

1
H h i
i 1
ji i 1 rij

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Equation to Solve in
ab initio Theory

H E
Known exactly:
3N spatial variables
(N # of electrons)

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To be approximated:
1. variationally
2. perturbationally

13

Hamiltonian for a Molecule

electrons
electrons 22

nuclei
electrons
nuclei 22
electronsnuclei
nuclei e 22Z
2
2
e ZAA
2
2

H
i
A
H
i
A
2
m
2
m
riA
e
A
2
m
2
m
riA
ii
AA
ii
AA
e
A
electrons
nuclei
electronse 22
nucleie 22Z Z
e ZAA ZBB
e

i i j j

rijr A B RRAB
ij
AB
A B

kinetic energy of the electrons

kinetic energy of the nuclei
electrostatic interaction between the electrons and
the nuclei
electrostatic interaction between the electrons
electrostatic interaction between the nuclei

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14

AbInitio Methods
Accurate treatment of the electronic distribution using the

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full Schrdinger equation

Can be systematically improved to obtain chemical accuracy
Does not need to be parameterized or calibrated with respect
to experiment
Can describe structure, properties, energetics and reactivity
What does ab intio mean?
Start from beginning, with first principle
Who invented the word of the ab initio method?
Bob Parr of UNC-CH in 1950s; See Int. J. Quantum Chem.
37(4), 327(1990) for details.

15

Three Approximations

Born-Oppenheimer approximation

Electrons act separately of nuclei, electron and nuclear

coordinates are independent of each other, and thus

simplifying the Schrdinger equation
Independent particle approximation
Electrons experience the field of all other electrons as
a group, not individually
Give birth to the concept of orbital, e.g., AO, MO, etc.
LCAO-MO approximation
Molecular orbitals (MO) can be constructed as linear
combinations of atom orbitals, to form Slater
determinants

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16

Born-Oppenheimer
Approximation
the nuclei are much heavier than the electrons and move more slowly than the electrons
freeze the nuclear positions (nuclear kinetic energy is zero in the electronic
Hamiltonian)

electrons
22 22 electrons
i

22mme i
ii

electrons
electrons

H
Helel

ii

2
2
electronse 2 nuclei
nucleie 2Z Z
ee22ZZA electrons
e
e ZAA ZBB
A

ij A
rriA
rrAB
AA
i i j j rr
ABB
iA
ij
AB

nuclei
nuclei

calculate the electronic wave function and energy

**

el
elelH
eleldd

el
E , E
H
Helel elel Eelel , E
**

el el dd

el the
el nuclear-electron attraction and nuclear E depends on the nuclear positions through

nuclear repulsion terms

E = 0 corresponds to all particles at infinite separation

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17

Approximate Wavefunctions
Construction of one-electron functions (molecular orbitals,
MOs) as linear combinations of one-electron atomic basis
functions (AOs) MO-LCAO approach.

NN

l qqi
uukl k rri ii ;;
l
i
kl k
i

1
k

k 1

--up)
(spin
(spin
up)
ii
(spin
(spin--down)
down)

Construction of N-electron wavefunction as linear

combination of anti-symmetrized products of MOs (these

anti-symmetrized products are denoted as Slaterdeterminants).

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The Slater Determinant

a 1 b 2 c 3 z n

a 1 b 2 c 3 z n
1n1!
b 2 2c 3 3
z n n a 2 2b 11c 3 3
z n n

a 1

a
b
c
z
a
b
c
z
n!

a 11
a
b 11
b
1n1! c 11
c
n!

z 11
z

a 2 2
a
b 2 2
b
c 2 2
c

z 2 2
z

a 3 3
a
b 3 3
b
c 3 3
c

z 3 3
z

a n n
a
b n n
b
c n n
c

z n n
z

a 11b 2 2c 3 3
z n n abc
z

a
b
c
z
a b c
z

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The Two Extreme Cases

One determinant: The HartreeFock method.

1 2 3 N

HF
HF 11 122 2 33 3 NN N
There are N MOs and each MO is a linear combination of N AOs.
Thus, there are nN coefficients ukl, which are determined by
making stationary the functional:
N

HF H HF
EE
ij
HF

HF HF H HF
ij
i , j 1
i , j 1

uu SS uu ij

ij
k ,l 1

k ,l 1
N
N

*
*
ki kl lj
ki kl lj

The ij are Lagrangian multipliers.

All possible determinants: The full CI method.
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The Full CI Method

The full configuration interaction (full CI) method expands

the wavefunction in terms of all possible Slater determinants:

2N
2 N
n n

CICI
cc; ;

1
1

There are

EE
CICI CICI HH CICI

2N
2 N
n n

cc SS cc

, 1
, 1

2N

possible ways to choose n molecular orbitals

from a set of 2N AO basis functions.
The number of determinants gets easily much too large. For
example:
40

9
Davidsons method can be used to find one
9
40 10
10
10
or a few eigenvalues of a matrix of rank 109.
10
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21

The HartreeFock Method

1 2 3 N

HF
HF 11 122 2 33 3 NN N

*

*S u

EE

u
HFHF HFHF H HFHF i
ijij
ukiki Sklkl uljlj ijij

, j 1
k ,l 1

i , j 1 k ,l 1
N
N

NN

NN

N
N

NN

E P h 11 P mk nl ; P u **u
HFHF HH
HFHF Enucnuc Pmnmn hmnmn 22 Pklkl mk nl ; Pklkl ukikiulili
mm, n, n11
k k,l,l 11
i i 11

E HF 0
uuki E HF 0
ki

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HartreeFock equations

22

The HartreeFock Method

c F c S

Overlap integral

F H P

S |

| 1 |
2

occ

Density Matrix
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P 2 ci ci
i

23

Self-Consistent-Field (SCF)
c F c S

1. Choose start coefficients for MOs

2. Construct Fock Matrix with coefficients
3. Solve Hartree-Fock-Roothaan equations
4. Repeat 2 and 3 until ingoing and outgoing
coefficients are the same

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24

Ab Initio Methods
Semi-empirical
Semi-empiricalmethods
methods
(MNDO,
(MNDO,AM1,
AM1,PM3,
PM3,etc.)
etc.)

excitation
excitationhierarchy
hierarchy
(CIS,CISD,CISDT,...)
(CIS,CISD,CISDT,...)
(CCS,
(CCS,CCSD,
CCSD,CCSDT,...)
CCSDT,...)

Hartree-Fock
Hartree-Fock
(HF-SCF)
(HF-SCF)
perturbational
perturbationalhierarchy
hierarchy
(MP2,
MP3,
MP4,
(MP2, MP3, MP4,)
)

excitation
excitationhierarchy
hierarchy
(MR-CISD)
(MR-CISD)

perturbational
perturbationalhierarchy
hierarchy
(CASPT2,
CASPT3)
(CASPT2, CASPT3)

Multiconfigurational
MulticonfigurationalHF
HF
(MCSCF,
(MCSCF,CASSCF)
CASSCF)

Full
FullCI
CI
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Whos Who

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26

Size vs Accuracy
Full CI

Accuracy (kcal/mol)

0.1
Coupled-cluster,
Multireference
Nonlocal density functional,
Perturbation theory

Local density functional,

Hartree-Fock
Semiempirical Methods

10
1

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10

100
Number of atoms

1000

27

AN EXAMPLE
Equilibrium structure of (H2O)2
W.K., J.G.C.M. van Duijneveldt-van de Rijdt, and
F.B. van Duijneveldt, Phys. Chem. Chem. Phys. 2, 2227 (2000).

95.7 pm

symmetry:
RCOO,e
= 291.2
s
96.4 pm

95.8 pm

pm

Experimental [J.A. Odutola and T.R. Dyke, J. Chem. Phys 72,5062(1980)]:

ROO2 = 297.6 0.4 pm
SAPT-5s potential [E.M. Mas et al., J. Chem. Phys. 113,6687(2000)]:
ROO2 ROO,e= 6.3 pm ROO,e(exptl.) = 291.3 pm

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28

Experimental and Computed

Enthalpy Changes He in kJ/mol
Exptl.
Exptl. CCSD(T)
CCSD(T)

SCF
SCF

G2
G2

DFT
DFT

CH
CH44
CH22++H
H22
CH

544(2)
544(2)

542
542

492
492

534
534

543
543

CC22H
H44
H22++H
H22
CC22H

203(2)
203(2)

204
204

214
214

202
202

208
208

H
H22CO
CO
CO++H
H22
CO

21(1)
21(1)

22
22

3
3

17
17

34
34

22NH
NH33
N22++33H
H22
N

164(1)
164(1)

162
162

149
149

147
147

166
166

22H
H22O
O
H22O
O22++H
H22
H

365(2)
365(2)

365
365

391
391

360
360

346
346

22HF
HF
FF22++H
H22

563(1)
563(1)

562
562

619
619

564
564

540
540

Gaussian2(G2)methodofPopleandcoworkersisacombinationofMP2andQCISD(T)

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LCAO Basis Functions

cc

s, which are atomic orbitals, are called basis

functions

usually centered on atoms

larger number of well chosen basis functions yields

more accurate approximations to the molecular orbitals

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can be more general and more flexible than atomic

orbital functions

30

Basis Functions

Slaters (STO)

Gaussians (GTO)

Angular part * exp(

exp(r)r)
Better behaved than Gaussians
2-electron integrals hard

22
xxllyymmzznn **exp

r
exp r

2-electron integrals simpler

Wrong behavior at nucleus
Decrease too fast with r

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Contracted Gaussian Basis Set

Minimal
STO-nG

Split Valence: 321G,4-31G, 631G

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Each
Eachatom
atomoptimized
optimizedSTO
STOisisfit
fitwith
withnn
GTOs
GTOs
Minimum
Minimumnumber
numberof
ofAOs
AOsneeded
needed

Contracted
ContractedGTOs
GTOsoptimized
optimizedper
peratom
atom

Doubling
Doublingof
ofthe
thenumber
numberof
ofvalence
valenceAOs
AOs

32

Polarization /
Diffuse Functions
Polarization: Add AO with higher angular
momentum (L) to give more flexibility

Example: 3-21G*, 6-31G*, 6-31G**, etc.

Diffusion: Add AO with very small exponents for

systems with very diffuse electron densities such

as anions or excited states
Example: 6-31+G*, 6-311++G**

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Correlation-Consistent
Basis Functions

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a family of basis sets of increasing size

cc-pVQZ, cc-pV5Z, cc-pV6Z

can be used to extrapolate to the basis set limit

cc-pVDZ DZ with ds on heavy atoms, ps on H
cc-pVTZ triple split valence, with 2 sets of ds and
one set of fs on heavy atoms, 2 sets of ps and 1 set
of ds on hydrogen
can also be augmented with diffuse functions (augcc-pVXZ)

34

Pseudopotentials,
Effective Core Potentials

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core orbitals do not change much during chemical

interactions

valence orbitals feel the electrostatic potential of the

nuclei and of the core electrons

can construct a pseudopotential to replace the

electrostatic potential of the nuclei and of the core
electrons

reduces the size of the basis set needed to represent the

atom (but introduces additional approximations)

for heavy elements, pseudopotentials can also include of

relativistic effects that otherwise would be costly to treat

35

Correlation Energy
HF does not include correlations anti-parallel electrons
Eexact EHF = Ecorrelation
Post HF Methods:

Configuration Interaction (CI, MCSCF, CCSD)

Mller-Plesset Perturbation series (MP2, MP4)
Density Functional Theory (DFT)

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36

Configuration-Interaction (CI)
In Hartree-Fock theory, the n-electron wavefunction is approximated by one single
Slater-determinant, denoted as:

HF

This determinant is built from n orthonormal spin-orbitals. The spin-orbitals that

form HF are said to be occupied. The other orthonormal spin-orbitals that

follow from the Hartree-Fock calculation in a given one-electron basis set of
atomic orbitals (AOs) are known as virtual orbitals. For simplicity, we assume that
all spin-orbitals are real.

In electron-correlation or post-Hartree-Fock methods, the wavefunction is

expanded in a many-electron basis set that consists of many determinants.

Sometimes, we only use a few determinants, and sometimes, we use millions of
them:
In this notation,
is a Slater
determinant that is obtained by

CI HF c

replacing a certain number of

occupied orbitals by virtual ones.

Three questions: 1. Which determinants should we include?

2. How do we determine the expansion coefficients?

3. How do we evaluate the energy (or other properties)?

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Truncated configuration interaction:

CIS, CISD, CISDT, etc.
We start with a reference wavefunction, for example the HartreeFock determinant.

HF i 11j 2 2k 3 3
NN NN
HF
i
j
k

We then select determinants for the wavefunction expansion by

substituting orbitals of the reference determinant by orbitals that

are not occupied in the reference state (virtual orbitals).

Singles (S) indicate that 1 orbital is replaced, doubles (D) indicate

2 replacements, triples (T) indicate 3 replacements, etc., leading
to CIS, CISD, CISDT, etc.
ia aa 11j 2 2k 3 3
NN NN , ,
i
a
j
k

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ijababa 11b 2 2k 3 3
NN NN , ,
ij
a
b
k

etc.
etc.

38

Truncated
Configuration Interaction
Number of linear variational parameters
in truncated CI for n = 10 and 2N = 40.
Levelof
excitation

Numberof
parameters

Example

CIS

n(2Nn)

300

CISD

+[n(2Nn)]2

78,600

CISDT

+[n(2Nn)]3

18106

FullCI

2N
n

109

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39

Multi-Configuration
Self-Consistent Field (MCSCF)
The MCSCF wavefunctions consists of a few selected determinants or CSFs. In the
MCSCF method, not only the linear weights of the determinants are variationally
optimized, but also the orbital coefficients.

One important selection is governed by the full CI space spanned by a number of

prescribed active orbitals (complete active space, CAS). This is the CASSCF method.
The CASSCF wavefunction contains all determinants that can be constructed from a
given set of orbitals with the constraint that some specified pairs of - and -spinorbitals must occur in all determinants (these are the inactive doubly occupied
spatial orbitals).

Multireference CI wavefunctions are obtained by applying the excitation operators to

the individual CSFs or determinants of the MCSCF (or CASSCF) reference wave
function.

Internally-contracted MRCI:
MR - CISD (ck C1k C 2 k ) k
k

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IC - MRCI (ck C1k ) k C 2 d k k

k

40

Coupled-Cluster Theory
System of equations is solved iteratively (the convergence is

accelerated by utilizing Pulays method, direct inversion in

the iterative subspace, DIIS).

CCSDT model is very expensive in terms of computer

resources. Approximations are introduced for the triples:

CCSD(T), CCSD[T], CCSD-T.

Brueckner coupled-cluster (e.g., BCCD) methods use Brueckner

orbitals that are optimized such that singles dont contribute.

By omitting some of the CCSD terms, the quadratic CI method

(e.g., QCISD) is obtained.

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41

Mller-Plesset Perturbation
Theory
The Hartree-Fock function is an eigenfunction of the
n-electron operator

F.

We apply perturbation theory as usual after decomposing the

Hamiltonian into two parts:
HHHH 0 0 HH11
HH 0 0 FF
HH11 HHFF

MP2, MP3, MP4, etc.

number denotes order to which
energy is computed (2n+1 rule)

More complicated with more than one reference determinant

(e.g., MR-PT, CASPT2, CASPT3, )

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Semi-Empirical Methods
These methods are derived from the HarteeFock model, that is, they

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are MO-LCAO methods.

They only consider the valence electrons.
A minimal basis set is used for the valence shell.
Integrals are restricted to one- and two-center integrals and
subsequently parametrized by adjusting the computed results to
experimental data.
Very efficient computational tools, which can yield fast quantitative
estimates for a number of properties. Can be used for establishing
trends in classes of related molecules, and for scanning a
computational poblem before proceeding with high-level treatments.
A not of elements, especially transition metals, have not be
parametrized

43

Semi-Empirical Methods
Number 2-electron integrals () is n4/8, n = number of basis functions
Treat only valence electrons explicit
Neglect large number of 2-electron integrals
Replace others by empirical parameters
Models:
Complete Neglect of Differential Overlap (CNDO)
Intermediate Neglect of Differential Overlap (INDO/MINDO)
Neglect of Diatomic Differential Overlap (NDDO/MNDO, AM1, PM3)

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Approximations of 1-e
integrals
H
U
H
VVABAB
U

Ufrom atomic spectra

Vvalue per atom pair

BBAA

H
H 00

on the same atom

H
ABSS
H
AB

11 A B
AB

AB
B
22 A
One parameter per element

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45

Popular DFT
Noble prize in Chemistry, 1998
In 1999, 3 of top 5 most cited journal
articles in chemistry (1st, 2nd, & 4th)

In 2000-2003, top 3 most cited journal

articles in chemistry

In 2004-2005, 4 of top 5 most cited

journal articles in chemistry:

1st, Beckes hybrid exchange

functional (1993)

2nd, LYP correlation functional (1988)

3rd, Beckes exchange functional
(1988)

4th, PBE correlation functional (1996)

Citations of DFT on JCP, JACS and PRL
http://www.cas.org/spotlight/bchem.html
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Brief History of DFT

First speculated 1920
Thomas-Fermi (kinetic energy) and Dirac
(exchange energy) formulas

Officially born in 1964 with HohenbergKohns original proof

GEA/GGA formulas available later 1980

Becoming popular later 1990
Pinnacled in 1998 with a chemistry Nobel
prize

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47

What could expect from DFT?

LDA, ~20 kcal/mol error in energy

GGA, ~3-5 kcal/mol error in energy
G2/G3 level, some systems, ~1kcal/mol
Good at structure, spectra, & other
properties predictions

Poor in H-containing systems, TS, spin,

excited states, etc.

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48

Density Functional Theory

Two Hohenberg-Kohn theorems:
Given the external potential, we know the

ground-state energy of the molecule when we

know the electron density .
Energy

Energy E
The energy density functional is variational.
E E 0 if 0
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49

But what is E[]?

E[] = TS[] + Vne[] + J[] + Vnn[] +
Exc[]

How do we compute the energy if the density is known?

The Coulombic interactions are easy to compute:

E nn [ ]

nuclei

A B

Z AZ B
, E ne [ ] r Vext r dr, J [ ]
rAB

1
2

r r
r r drdr ,

But what about the kinetic energy TS[] and exchange-correlation energy
Exc[]?

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50

Kohn-Sham Scheme
H nk nk nk ,

Suppose, we know the

exact density.

Then, we can formulate a

Slater determinant that

generates
this
exact
density
(=
Slater
determinant of system of
N
non-interacting
electrons
with
same
density ).

We know how to compute

the kinetic energy Ts

exactly from a Slater
determinant.

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Then, the only thing

unknown is to calculate

where
H K Vne (r ) Vee ( r ) Vxc (r )
and
K

1 2
,
2

The Only
, Unknown

Za
a | r Ra |
(r ) 3
Vee (r )
d r,
| r r |
E xc
Vxc ( r )
,

Vne (r )

( r ) f nk | nk (r ) |2 ,
nk

51

All about Exchange-Correlation

Energy Density Functional
Q f r, r , r , dr
2

XC

LDA f(r) is a function of (r)

only

GGA f(r) is a function of (r)

and |(r)|

Mega-GGA f(r) is also a

function of ts(r), kinetic
energy density

Hybrid f(r) is GGA functional

with extra contribution from

Hartree-Fock exchange energy

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Jacob's ladder for the five generation of DFT functionals,

according to the vision of John Perdew with indication of
some of the most common DFT functionals within each rung.

52

LDA Functionals
Thomas-Fermi formula (Kinetic) 1
parameter

TTF C F

5/3

3
r dr, CF 3 2
10

2/3

Slater form (exchange) 1 parameter

E CX
S
X

4/3

3 1/ 3 2 / 3 1/ 3
r dr , C X 3 4
8

Wigner correlation 2 parameters

r
W
EC a
dr
1 / 3
1 b r
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Popular Functional: BLYP/B3LYP

Two most well-known functionals are the Becke exchange functional
Ex[] with 2 extra parameters &
2

2
B
LDA
4/3
EX EX
,

1 2
4/3

The Lee-Yang-Parr correlation functional Ec[] with 4 parameters a-d

EcLYP a

1
1 2
1
2 / 3
5/3

2
t

W
W
F
1 d 1/ 3
9
18

c
e

1 / 3

dr

Together, they constitute the BLYP functional:

E xcBLYP E xB EcLYP r exB , dr r ecLYP , dr

The B3LYP functional is augmented with 20% of Hartree-Fock
exchange:
E
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B3LYP
xc

aE E
B
x

LYP
c

m , n 1

k ,l 1

b Pmn Pkl km nl
54

VWN5
BLYP
HCTH
BP86

TPSS
M06-L
B3LYP
B97/2
MPW1K
MPWB1K
M06
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Increasing quality and computational cost

Density Functionals
LDA
local density
GGA
gradient corrected
Meta-GGA
kinetic energy density
included
Hybrid
exact HF exchange
component
Hybrid-meta-GGA

Better scaling with

system size
Allow density fitting for
even
better scaling

Meta-GGA is bleeding
edge and therefore
largely untested (but
better in theory)
Hybrid makes bigger
difference in cost and
accuracy
Look at literature if
somebody
has compared
functionals for
systems similar to
yours!

55

Density Functionals

Percentage of occurrences of the names of the several functionals indicated in Table 2, in

journal titles and abstracts, analyzed from the ISI Web of Science (2007).
its.unc.edu

S.F. Sousa, P.A. Fernandes and M.J. Ramos, J. Phys. Chem. A 10.1021/jp0734474 S1089-5639(07)03447-0 56

Problems with DFT

ground-state theory only
universal functional still unknown
even hydrogen atom a problem: self-interaction
correction

no systematic way to improve approximations like LDA,

GGA, etc.

extension to excited states, spin multiplets, etc., though

proven exact in theory, is not trivial in implementation
and still far from being generally accessible thus far

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57

DFT Developments
Theoretical
Extensions to excited states, etc.
Better functionals (mega-GGA), etc
Understanding functional properties, etc.

Conceptual
More concepts proposed, like electrophilicity, philicity, spin

philicity, surfaced-integrated Fukui fnc

Dynamic behaviors, profiles, etc.

Computational
Linear scaling methods
QM/MM related issues
Applications
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58

Examples DFT vs. HF

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59

Chemical Reactivity Theory

Chemical reactivity theory quantifies the reactive propensity of
isolated species through the introduction of a set of reactivity indices
or descriptors. Its roots go deep into the history of chemistry, as far
back as the introduction of such fundamental concepts as acid, base,
Lewis acid, Lewis base, etc. It pervades almost all of chemistry.
-- Morrel H. Cohen, and Adam Wasserman, J. Phys. Chem. A 2007, 111,2229

Molecular Orbital Theory

Fukuis Frontier Orbital (HOMO/LUMO) model

Woodward-Hoffman rules
Well developed: Nobel prize in Chemistry, 1981
Problem: conceptual simplicity disappears as computational
accuracy increases because its based on the molecular orbital
description
Density Functional Theory (DFT)
Conceptual DFT, also called Chemical DFT, DF Reactivity Theory
Proposed by Robert G. Parr of UNC-CH, 1980s
Still in development
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60

DFT Reactivity Theory

General Consideration
E E [N, (r)] E []
Taylor Expansion: Perturbation resulted from an

external attacking agent leading to changes in N and

(r), N and (r),
E E N N , r r E N , r
E
N
N

2!

r dr
N

N 2
N 2
N

2E

N r dr

2E

2 r

r r ' drdr '

Assumptions: existence and well-behavior of all above partial/functional derivatives

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61

Conceptual DFT
Basic assumptions
E E [N, (r)] E []
Chemical processes, responses, and changes
expressible via Taylor expansion

Existence, continuous, and well-behavedness

of the partial derivatives

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62

DFT Reactivity Indices

Electronegativity (chemical potential)

Hardness / Softness

HOMO LUMO

1 2E
LUMO HOMO

, S 1 /
Maximum Hardness
(MHP)
2Principle

2 N
2
HSAB (hard and Soft Acid and Base) Principle

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63

DFT Reactivity Indices

Fukui

function

f r

Nucleophilic attack

f r N 1 r N r
Electrophilic attack

r N r N 1 r

Free radical activity

f r f r
f r
2

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64

Electrophilicity Index
2

2
Physical meaning: suppose an electrophile is immersed in an
electron sea

1
E N N 2
2
The maximal electron flow and accompanying energy decrease
are

N max
E min

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Parr, Szentpaly, Liu, J. Am. Chem. Soc. 121, 1922(1999).

65

Experiment vs. Theory

log (k) = s(E+N)

Prez, P. J. Org. Chem. 2003, 68, 5886. Prez, P.; Aizman, A.; Contreras, R. J. Phys. Chem. A 2002, 106, 3964.
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66

Minimum Electrophilicity Principle

Analogous to the maximum hardness principle (MHP)
Separately proposed by Noorizadeh and Chattaraj
Concluded that the natural direction of a chemical reaction is
toward a state of minimum electrophilicity.

Noorizadeh, S. Chin. J. Chem. 2007, 25, 1439.

Noorizadeh, S. J. Phys. Org. Chem. 2007, 20, 514.
Chattaraj, P.K. Ind. J. Phys. Proc. Ind. Natl. Sci. Acad. Part A 2007, 81, 871.
non-

-0.093

-0.093

LA
Aa

-0.091

0.085

Bb

-0.089

-0.172

-0.088

-0.089

-0.171

0.246

-0.083

-0.090

-0.087

-0.0842

0.087
-0.230

-0.220

0.247
Bb

-0.087

0.088

0.084
Aa

0.0892
-0.226

-0.2518

0.218
-0.247

-0.233

0.221

0.2161

-0.226

-0.2506

0.2157

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67
Yue
Xia, Dulin Yin, Chunying Rong, Qiong Xu, Donghong Yin , and Shubin Liu, J. Phys. Chem. A, 2008, 112, 9970.

Nucleophilicity
Much harder to quantify, because it related to local
hardness, which is ambiguous in definition.

A nucleophile can be a good donor for one electrophile

but bad for another, leading to the difficulty to define a

universal scale of nucleophilicity for an nucleophile.
1 B
A
2 A B

= -N - S()2
Minimizing in Eq. (14) with respect to ,
one has
=-N and = - N2.
Making use of the following relation

A B
A B

Jaramillo, P.; Perez, P.; Contreras, R.; Tiznado, W.; Fuentealba, P. J. Phys. Chem. A 2006, 110, 8181.
its.unc.edu

68

Philicity and Fugality

Philicity: defined as f(r)

Chattaraj, Maiti, & Sarkar, J. Phys. Chem. A 107, 4973(2003)

Still a very controversial concept, see JPCA 108, 4934(2004);
Chattaraj, et al. JPCA, in press.

Spin-Philicity: defined same as but in spin resolution

Perez, Andres, Safont, Tapia, & Contreras. J. Phys. Chem. A 106,

5353(2002)

Nuclofugality & Electrofugality

( )2
E n A
2

( )2
Ee I
2

Ayers, P.W.; Anderson, J.S.M.; Rodriguez, J.I.; Jawed, Z. Phys. Chem. Chem. Phys. 2005, 7,
1918.
Ayers, P.W.; Anderson, J S.M.; Bartolotti, L.J. Int. J. Quantum Chem. 2005, 101, 520.
its.unc.edu

69

Dual Descriptors
3rd-order cross-term derivatives

2
f r

2 N r

f 2 r dr 0

f 2 r f

2 E
r 2 N

r f r

f r

f 2 r LUMO r HOMO r

Recovering Woodward-Hoffman rules!

its.unc.edu

Ayers, P.W.; Morell, C., De Proft, D.; Geerlings, P. Chem. Eur. J., 2007, 13, 8240
70
Geerling, P. De Proft F. Phys. Chem. Chem. Phys., 2008, 10, 3028

Steric Effect
one of the most widely used concepts
in chemistry

originates from the space occupied by

atom in a molecule

previous work attributed to the

electron exchange correlation

Weisskopf thought of as kinetic

energy pressure

Weisskopf, V.F., Science 187, 605-612(1975).

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71

Steric effect: a DFT description

Assume
since

E[] Es[] + Ee[] + Eq[]

E[] = Ts[] + Vne[] + J[] + Vnn[] + Exc[]

Ee[] = Vne[] + J[] + Vnn[]
Eq[] = Exc[] + EPauli[] = Exc[] + Ts[] - Tw[]
Es[] E[] - Ee[] - Eq[] = Tw[]

we have

1
TW
8

dr

S.B. Liu, J. Chem. Phys. 2007, 126, 244103.

S.B. Liu and N. Govind, J. Phys. Chem. A 2008, 112, 6690.
S.B. Liu, N. Govind, and L.G. Pedersen, J. Chem. Phys. 2008, 129, 094104.
M. Torrent-Sucarrat, S.B. Liu and F. De Proft, J. Phys. Chem. A 2009, 113, 3698.
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72

Experiment vs. Theory

In 1956, Taft constructed a scale for the steric effect of different substituents, based
on rate constants for the acid-catalyzed hydrolysis of esters in aqueous acetone. It
was shown that log(k / k0) was insensitive to polar effects and thus, in the absence
of resonance interactions, this value can be considered as being proportional to
steric effects. Hydrogen is taken to have a reference value of EsTaft= 0

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73

QM/MM Example:
Triosephosphate Isomerase (TIM)

DHAP
H2O

GAP
494 Residues, 4033 Atoms, PDB ID: 7TIM
Function: DHAP (dihydroxyacetone phosphate) GAP (glyceraldehyde 3-phosphate)
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74

TIM 2-step 2-residue Mechanism

DHAP

GAP

Glu 165 (the catalytic base), His 95 (the proton shuttle)

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75

QM/MM: 1st Step of TIM

Mechanism

QM/MM size: 6051 atoms

QM Size: 37 atoms
QM: Gaussian98
Method: HF/3-21G
MM: Tinker
Force field: AMBER all-atom
Number of Water: 591 Model for Water: TIP3P
MD details: 20x20x20 3 box, optimize until the RMS energy
gradient less than 1.0 kcal/mol/. 20 psec MD. Time step 2fs.
SHAKE, 300 K, short range cutoff 8 , long range cutoff 15 .

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76

QM/MM: Transition State

=====================
Energy Barrier (kcal/mol)
-----------------------------------QM/MM
21.9
Experiment
14.0
=====================

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77

Whats New: Linear Scaling

O(N) Method
Numerical Bottlenecks:

diagonalization ~N3
orthonormalization ~N3
matrix element evaluation ~N2-N4

100

90

80

Computational Complexity: N log N

Theoretical Basis: near-sightedness of density
70

matrix or orbitals

Strategy:

CPUsecondsper CGstep

60

Diagonalization

50

40

sparsity of localized orbital or density

30

matrix

direct minimization with conjugate

gradient

OLMO
NOLMO

20

10

Models: divide-and-conquer and variational

0

methods

100

200

300

400

500

600

700

800

900

Atoms

Applicability: ~10,000 atoms, dynamics

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78

What Else ?
Solvent effect

Implicit model vs. explicit model

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Relativity effect
Transition state
Excited states
Temperature and pressure
Solid states (periodic boundary condition)
Dynamics (time-dependent)

79

Limitations and Strengths

of ab initio quantum
chemistry

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80

Popular QM codes
Gaussian (Ab Initio, Semi-empirical, DFT)
Gamess-US/UK
Spartan

(Ab Initio, DFT)

(Ab Initio, Semi-empirical, DFT)

NWChem (Ab Initio, DFT, MD, QM/MM)

MOPAC/2000

(Semi-Empirical)

DMol3/CASTEP

(DFT)

Molpro

(Ab initio)

ADF (DFT)
ORCA
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(DFT)
81

Reference Books

Computational Chemistry (Oxford Chemistry Primer) G. H.

Grant and W. G. Richards (Oxford University Press)

Molecular Modeling Principles and Applications, A. R. Leach

(Addison Wesley Longman)

Introduction to Computational Chemistry, F. Jensen (Wiley)

Essentials of Computational Chemistry Theories and Models,
C. J. Cramer (Wiley)

Exploring Chemistry with Electronic Structure Methods, J. B.

Foresman and A. Frisch (Gaussian Inc.)

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82

Questions & Comments

Please
Pleasedirect
directcomments/questions
comments/questionsabout
aboutresearch
researchcomputing
computingtoto
E-mail:
E-mail:research@unc.edu
research@unc.edu
Please
Pleasedirect
directcomments/questions
comments/questionspertaining
pertainingtotothis
thispresentation
presentationtoto
E-Mail:
E-Mail:shubin@email.unc.edu
shubin@email.unc.edu

The PPT format of this presentation is available here:

http://its2.unc.edu/divisions/rc/training/scientific/
/afs/isis/depts/its/public_html/divisions/rc/training/scientific/short_courses/

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83

Hands-on: Part I
Purpose: to get to know the available ab
initio and semi-empirical methods in the
Gaussian 03 / GaussView package

ab initio methods
Hartree-Fock
MP2
CCSD

Semiempirical methods
AM1
The WORD .doc format of this hands-on exercises is available here:

http://its2.unc.edu/divisions/rc/training/scientific/
/afs/isis/depts/its/public_html/divisions/rc/training/scientific/short_courses/labDirections_compchem_2009.doc
its.unc.edu

84

Hands-on: Part II
Purpose: To use LDA and GGA DFT methods to
calculate IR/Raman spectra in vacuum and in
solvent. To build QM/MM models and then use
DFT methods to calculate IR/Raman spectra

DFT
LDA (SVWN)
GGA (B3LYP)

QM/MM

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85