molecular modeling activities

Chemistry
y 202 (Spring ‘14)
P
Page 1
Re-Introd
duction to Mo
olecular Mod
deling with Spartan’14
S
Some of the
t laboratory
y experiments
s in Chemistry
y 202 generatte data that can be interpre
eted using mo
olecular
models. This
T
handout introduces
i
(re
eminds) you how
h
to make models using
g Spartan’14 ((Sp14).1
First, a sm
mall word of warning:
w
this experiment
e
as
sks you to wo
ork with quanttities (relative energies, ge
eometrical
parameters) that can be
b measured experimental
e
ly. The nume rical values o
obtained from models rarelly agree
e measured in
n the lab, and
d for a simple reason: the vvalues obtaine
ed from mode
els are based
d on
with those
approxima
ations that sa
acrifice realism
m for practical (fast) compu
utation.
vides a wide assortment
a
of modeling tools of varying
g reliability and practicality.. The specificc
Sp14 prov
modeling tools used in this activity are
a useful for predicting the
e relative ene
ergy of conforrmers, but the
ey are not
suitable fo
or many otherr common tas
sks, such as computing
c
rea
action energie
es. Chem 333
3 (Quantum
Mechanic
cs) and Chem 324 (Adv. Ph
hysical Organ
nic Chem.) pro
ovide more in
nformation ab
bout methods for
generating
g molecular models
m
and predicting mole
ecular properrties.
This hand
dout shows yo
ou how to use
e models to analyze the co
onformational preferences of three mole
ecules.
Specifically, you will:
1. Build gauche and
a anti confo
ormers of 1-bromopropan
ne using intern
rnal rotation, o
optimize their
ge
eometries, ob
btain bond angles and dista
ances, and co
ompare their energies.
2. Build conforme
ers of trans-1-ethyl-3-metthylcyclohex
xane, optimize
e their geome
etries, and compare
th
heir energies.
3. Build conforme
ers of trans-2
2-ethyl-6-metthylcyclohex
xanone, optim
mize their geo
ometries, and compare
th
heir energies.
All three activities
a
shou
uld be comple
eted before yo
ou do the mod
deling require
ed for NaBH4 reduction exp
periment.
Sp14 actiivity #1 - Build a model of
o anti 1-brom
mopropane, C
CH3CH2CH2B
Br
Reminderrs:
 Unless
U
told oth
herwise, click with the left mouse
m
button
n.

Start Sp14 by double-clickin
ng on its desk
ktop icon
M
the program
p
wind
dow by clicking on the Max
ximize button
in the up
pper right corn
ner (you
 Maximize
must
m
do this to
o make the en
ntire window visible
v
and to see message
es that appea
ar at the botto
om of the
window)
w

Perform tasks by clicking on
n icons or by making menu
u selections, e
e.g., you can start a new “build” by
cllicking
or by selecting File:
F
New Bu
uild.
Br
1
C
C
1-brromopropane
C
a
anti conformer
H are not shown
n
These insttructions rely on model “building” instead of “sketc
ching.” Building tturns out to be m
more convenient ffor generating sp
pecific
conformations and stereoiso
omers, but many of these models can be sketched
d (at least the firsst version can be
e). If you have tim
me, try
mind yourself how
w this technique works.
sketching a couple of these molecules to rem
Chemistry
y 202 (Spring ‘14)

Start a new “bu
uild” using
P
Page 2
or File: New
w Build. Thiss opens a “bu
uild” window (atom palette is on the
ght). It also highlights the Edit
E Build ico
on
rig

.
s
the sp3 hybridized C atom in the p
palette
If necessary, select
, then click somewhere in the
a
in the wi ndow. Notice
e that C has fo
our yellow bonds
grreen window. This places one carbon atom
stticking out of it. We will calll these “free valences”
v
beccause it is po
ossible to add more atoms to these
siites. Free vale
ences automa
atically chang
ge into hydrog
gens wheneve
er you do a calculation or leave the
“b
build” window
w. This means it is almost never
n
necessa
ary to add hyd
drogens to yo
our model.
 Add
A a second carbon by clic
cking on the tip
t of a free va
alence. Repe
eat this action to add a third
d carbon.
You
Y should have a three-ca
arbon model at
a this point.
A bromine to
o your model by clicking on
n the Br atom
m in the palette
hen click on th
he tip of
, th
 Add
th
he anti free va
alence of an end
e carbon. Your
Y
model sh
hould have an
n anti conform
mation (see drrawing)
W
you finis
sh building, click on the Vie
ew icon
 When
tto return to th
he “view” wind
dow.
 Correcting
C
miistakes.
o
o
o
o
orr Edit: Undo. This will only
y undo the mo
ost recent operation.
or
o Build: Dele
ete. After you
u select this o ption, click on
n the atom tha
at offends you
u.
Edit: Clear
C
makes the entire mo
odel vanish.
or Build: Edit Build allow you
y to add mo
ore atoms.
M
your model.
m
Try th
hese operations:
 Moving
o
Rotate
e. Press left mouse
m
button and move m ouse.
o
Shift. Press right mouse
m
button and move mo
ouse.
o
Grow//Shrink. Pres
ss Shift key and right mousse button sim
multaneously, and move the
e cursor
up and
d down on the
e screen
nd bond angles
Measure some bond distances an
Whenever you build a model, Sp14 uses a table of standard b
bond distance
es and bond a
angles to possition the
atoms. Th
his “initial” geo
ometry is a re
easonable firs
st guess as to
o what your m
molecule lookss like, but it is not
trustworth
hy because most
m
molecules do not have
e “standard” g
geometries.
o
this yourself:
y
You can observe

or Geometry:
G
Measure
M
Distance. Notice the Distance
e(,) label that appears in th
he lower
Select
ght corner.
rig
 Click
C
on a pairr of neighborin
ng C atoms. The
T atoms turrn gold to sho
ow that they h
have been sellected.
When
W
you sele
ect two atoms
s, the interatomic distance (in Å) appearrs in the lowe
er right cornerr.
Chemistry
y 202 (Spring ‘14)
P
Page 3
o
Hint: You
Y can also get
g a bond distance by cliccking directly on a bond. T
The bond turnss gold to
show that
t
it is selec
cted.
o
Y can UNse
elect any item
m by clicking o
on it a second
d time.
Hint: You
 C1
C is defined as
a the carbon
n bonded to brromine. Reco
ord the C1-C2
2 and C2-C3 b
bond distance
es in the
fo
ollowing table under “Initial geometry.”

Select
orner.
co

Select (in this order):
o
C3, C2
2, and C1. Th
he atoms turn
n gold and the
e CCC bond a
angle (in o) ap
ppears in
th
he lower right corner. Reco
ord the CCC bond
b
angle un
nder “Initial ge
eometry.”
G
Measure
M
Angle. Notice the
e Angle(,,) lab
bel that appears in the low
wer right
or Geometry:
 Use
U the same technique to obtain the BrrCC bond ang
gle. Record th
his under “Initial geometry.”
 Which
W
of the geometrical pa
arameters listted under “inittial geometry”” might sugge
est that the m
model is
ba
ased on “stan
ndard” distanc
ces and angle
es?
Inittial geometry
Optim
mized anti geo
ometry
O
Optimized gau
uche
geometry
C1-C2 bond
b
distance
e
C2-C3 bond
b
distance
e
CCC bond angle
BrCC bond angle
calculated
d MMFF enerrgy
Optimize your model’’s geometry and energy using a mole
ecular mechanics calcula
ation (Minim
mize)
“Optimiza
ation” (also called “geometrry optimization”, “minimiza tion”, and “en
nergy minimizzation”) is a prrocedure
for calcula
ating the mos
st likely geome
etry of a mole
ecule. The pri nciple that gu
uides optimiza
ation is this: the most
likely geometry is the one
o that make
es the molecu
ule’s internal p
potential enerrgy as low as possible.2 In practice,
optimization must proc
ceed by trial-a
and-error: the computer ca lculates a mo
olecule’s enerrgy, shifts the atoms to
new positions, calculattes the energy
y again, and then
t
shifts the
e atoms again
n. The processs stops only when the
geometry of lowest pos
ssible energy (aka the equ
uilibrium geom
metry, minimu
um-energy geometry, or op
ptimized
geometry) has been identified.3
Naturally, the outcome
e of a geometrry optimizatio
on calculation is no better tthan the meth
hod used to ca
alculate
the molec
cular energy. This
T
activity uses
u
a method of energy ccalculation callled “MMFF m
molecular mecchanics”
to calculate energies th
hat relies on a large numbe
er of approxim
mations. As a result, this p
produces resu
ults
O upside to MMFF molec
cular mechanics calculatio ns is that the energies can
n be used to g
generate
quickly. One
optimized geometries and
a to compa
are the energies of differen
nt conformers.

2
or Build: Minim
mize. This perrforms an MM
MFF molecular mechanics g
geometry opttimization
Select
an
nd the model’s bond distan
nces and ang
gles are autom
matically adjusted on the sscreen to show
w the
The same principle explains why water natu
urally flows to the
e bottom of a cup
p or glass. This iis the position tha
at makes the wa
ater’s
al potential) energ
gy as low as pos
ssible.
(gravitationa
It is often possible
p
to identiffy more than one
e geometry of “lo
owest” energy forr a given molecu le. For example, optimization of b
butane can
produce eith
her a gauche or anti
a geometry. We
W know that the anti geometry is the geometry off “lowest” energyy, but the optimizzation
procedure doesn’t look at thiings this way bec
cause it considerrs only small atom
m movements. S
Small changes in
n the geometry off gauche
e its energy.
butane raise
3
Chemistry
y 202 (Spring ‘14)
P
Page 4
op
ptimized geom
metry. The ca
alculated enerrgy of this mo
odel (in kJ/mo
ol) is shown in
n the window’’s lower
rig
ght corner.
 Record
R
the callculated energ
gy in the table
e shown abovve in the “Opttimized anti geometry” colu
umn. If
yo
ou have follow
wed all of the directions co
orrectly, your m
model’s MMF
FF energy will be –8.96 kJ//mol.4
 Measure
M
the bond distances and bond angles in yourr optimized model and ente
er your data in
n the
“O
Optimized antti geometry” column
c
of the table. The diistances and angles should
d have chang
ged
sllightly. Notice
e that optimiza
ation makes the CC bond d
distances diffferent from ea
ach other and
d it makes
th
he bond angle
es different fro
om each othe
er. These diffe
erences occur because ato
oms always a
adjust
th
heir positions to reflect the unique intera
actions peculi ar to a given molecule. Op
ptimization is
s an
es
ssential step
p in construc
cting useful molecular
m
m odels.
Sp14 actiivity #2 – Convert anti 1-b
bromopropa
ane into its g
gauche confo
ormer and re-optimize
onformation
Use interrnal rotation to change co

or Build: Edit Build. Click
C
on the C1-C2
C
bond to
o make it “actiive” (a small-rred arrow enccircles an
active” bond).
“a
M
the curso
or into the dark strip on the
e left side of tthe screen (
 Move

appears a
at the top of th
his strip).
Perform an inte
ernal rotation by pressing the
t left mous e button and moving the ccursor up and down
hat they are rroughly gauch
in
nside the strip
p. Adjust the positions
p
of Brr and C3 so th
he. (Hint: it m
may help
to
o rotate the en
ntire model firrst into an orie
entation that a
allows you to
o distinguish a
anti and gauch
he
ea
asily.)
Optimize your model’’s geometry

or Build: Minimize. Re
ecord your mo
odel’s energyy in the “Optim
mized gauche
e geometry” ccolumn of
th
he data table in Activity #1.. If you followed all of the d
directions corrrectly, your m
model’s MMFF
F energy
will
w be –7.35 kJ/mol.
Use relattive energies to calculate
e equilibrium concentrati ons
Your calculations shou
uld show that the anti confo
ormer is more
e stable than tthe gauche by 1.61 kJ/mol. This
number may
m not seem terribly mean
ningful so let’s
s see how to translate thiss energy differrence into a m
more
useful qua
antity: the rela
ative concentrations of the anti and gau
uche conforme
ers. Assuming these confo
ormers
are at equ
uilibrium (this seems reaso
onable given the
t very high speed of inte
ernal rotation)), their concen
ntrations
can be de
erived from the equilibrium constant for the anti-gaucche equilibrium
m, Keq. This cconstant is related to
the relativ
ve free energies of the two conformers:
–G/2.3RT
–
[antii]eq / [gauche]eq
e = Keq = 10
nd
an
G = G(a
anti) – G(gau
uche)
Unfortuna
ately, the enerrgy difference
e that we calc
culated, -1.61 kJ/mol, is an estimate of 
H and not G
G. (Key
point: H is negative because the equilibrium con
nstant defined
d above treatts the anti con
nformer as the
e product
auche conforrmer as the re
eactant and H = H(producct) – H(reacta
ant).) H and G are differe
ent
and the ga
because the
t entropies of the anti an
nd gauche conformers are not identical (S  0). Reccall,

G
 =H – TS
S
4
‘MMFF ene
ergy’ simply mea
ans the energy prroduced by an MMFF
M
molecular mechanics calcu
ulation.
Chemistry
y 202 (Spring ‘14)
P
Page 5
ollow the sepa
arate effects of
o enthalpy an
nd entropy a bit more easiily if we do a llittle algebra, first
We can fo
replace G with H – TS,
T
and then
n separating enthalpy
e
and entropy:
Keq = 10
– (H – TS)/2.3R
RT
= ( 10
–H/2
2.3RT
)( 10
TS//2.3RT
) = ( 10
0
–H/2.3RT
)( 1
10
S/2.3R
)
ormula on the
e right shows us that we ne
eed two kindss of informatio
on in order to calculate an
The last fo
equilibrium
m constant (o
or equilibrium concentration
ns): we need H (= -1.61 kkJ/mol) and w
we need the e
entropy
change (
S). We also need to define a temperature (T) and w
we need to ob
btain a value ffor the gas co
onstant
(R) in suittable units. Plugging H = -1.61 kJ/mol, R = 8.31 J/m
mol K, and T = 298 K into the first term,
–H/2.3R
RT
10
, we get 1.9
90 so the form
mula simplifies
s to:
Keq = 1.90 (10
S/2
2.3R
)
S
S/2.3R
The secon
nd term, 10
, is roughly equal to th
he ratio (# an
nti)/(# gauche), where # an
nti and # gaucche are
the numbe
er of independent, equivalent forms of each
e
conform
mer. To determ
mine these va
alues, we nee
ed to
figure out how many eq
quivalent way
ys we can dra
aw/build each conformer. T
There is only o
one conforme
er that we
call anti so
o #anti = 1, but there are tw
wo mirror-ima
age gauche cconformers. T
This makes (#
# anti)/(# gaucche) =
1/2.5 Inserting this into our formula for
f Keq gives:
Keqq = ( 1.90 )( 1//2 )
[anti]eqq / [gauche]eq = 0.95
This is a very
v
interestin
ng outcome. Even
E
though the
t anti confo
ormer is more
e stable, we a
actually predicct that the
concentra
ation of gauch
he will be grea
ater. The take
e-home lesso n is that we ccannot establiish conformattional
preferences just by loo
oking at H.
Measure some bond distances an
nd bond angles
 Measure
M
the appropriate bo
ond distances
s and bond an
ngles in gauch
he conformerr, and record tthem in
th
he “Optimized
d gauche geom
metry” column of the table
e in Activity #1
1
Compare the distances
s and angles for the two op
ptimized confformers. Base
ed on these o
observations, can you
formulate a hypothesis
s that explains
s why the gau
uche geometrry is higher en
nergy? (Hint: compare bon
nd
angles.)

ct
To finish, selec
or File
e: Close.
Sp14 actiivity #3 – Conformationa
al analysis off trans-1-ethy
yl-3-methylcy
yclohexane
Geometry
y and energy are always closely connec
cted, but the cconnections ccan be hard to
o fathom. Con
nsider the
two chair conformers of
o trans-1-ethy
yl-3-methylcyclohexane (n ext page). Ne
either conform
mer can get both
substituen
nts into the prreferred equa
atorial position
ns so predictin
ng the preferrred geometryy from variouss rules-ofthumb is virtually
v
impos
ssible. We ne
eed to ask the
e computer to
o predict the e
energies for us. The followiing
activity sh
hows you how
w this might be
e done.
5
If you also
o allow for interna
al rotation of the methyl group, there are actually tthree equivalent anti forms (# an
nti = 3), and six equivalent
gauche form
ms (# gauche = 6). This still leads to (# anti)/(# gau
uche) = 1/2 so th
he methyl group’ s rotation can be
e ignored.
Chemistry
y 202 (Spring ‘14)
P
Page 6
H
H
C
H3C
H
H
H
H
CH3
C
CH3
H
CH3
H
d optimize “e
equatorial ethyl” trans-1--ethyl-3-meth
hylcyclohexa
ane
Build and


or File: Ne
ew Build.
enu, and click somewhere in the green w
window.
Select Cyclohexane from the Rings me
 Add
A C atoms to create an axial
a
methyl grroup and an e
equatorial eth
hyl group (abo
ove, left struccture).

ecord the ene
ergy here: ___
_______
or Build: Minimize. Re
The ethyl group can ro
otate about the
e ring-ethyl bo
ond. This gen
nerates three different equ
uatorial ethyl
conformers. To find the
e preferred on
ne, you will ne
eed to rotate the ethyl grou
up into each sstaggered position and
calculate the molecule’’s MMFF energy.
H
H
H
H
C
H3C
H

CH
C 3
H
H3C
H3
CH
H
C
C
H
H3C
H
H
H
H3
CH
H
Select the ring-ethyl CC bon
nd. Use intern
nal rotation to
o move the ethyl group into
o another stag
ggered
osition. Use
or Build:: Minimize to optimize the geometry an
nd obtain the M
MMFF energyy. Record
po
it here: ______
____
 Repeat
R
the pre
evious step to
o obtain the MMFF
M
energy for the third sstaggered possition of the e
ethyl
grroup. Record the energy here:
h
_______
___
 Compare
C
the MMFF
M
energie
es of the three “equatorial ethyl” conforrmers, and reccord the lowe
est energy
in
n the appropriate spot in the left-hand co
olumn:
F energy (kJ/m
mol)
MMFF
trans-1-ethyll-3-methylcyc
clohexane
M
MMFF energyy (kJ/mol)
trans-2-ethyl-6-methyylcyclohexano
one
equatoria
al ethyl
axial ethyl
e
[eq Et]/[ax
x Et] @
298
8K
Build and
d optimize “a
axial ethyl” trrans-1-ethyl--3-methylcyc
clohexane
 Use
U the same strategy to crreate and optimize three “a
axial ethyl” co
onformers. Re
ecord the low
west
MMFF
M
energy in the table.
Chemistry
y 202 (Spring ‘14)

P
Page 7
Based on the energies
e
in th
he table, which
h conformer iis more stable
e, equatorial e
ethyl or axial ethyl?
Why
W do you su
uppose this is
s?
atio of the
 Use
U the energy
y difference between
b
the most
m
stable co
onformers to calculate the equilibrium ra
eq
quatorial ethy
yl and axial etthyl conforme
ers.6 Record th
his ratio in the
e table.
Chemists (and chemisttry students )
 like to belie
eve that the p
properties of ccomplicated m
molecules can
n be
n when they a
agree that the
e rules-of-thum
mb might not lead to
predicted from a few siimple rules off thumb. Even
clear pred
dictions, they like to believe
e that the properties of a ccomplicated m
molecule can b
be extrapolated from
the properties of a similar, but simpller, molecule.. In fact, this kkind of predicction is possib
ble for things llike bond
esist change. It takes a lot of energy to stretch or squ
ueeze a bond
d more
distances because these strongly re
than a few
w percent of itts length. Bon
nd angles are
e easier to cha
ange and therefore harderr to predict. So
o where
does this leave us with
h conformation
nal preferences? These prreferences de
epend on torssion (dihedral)) angles
and it take
es very little energy
e
to change these angles. Does th
his mean that rules-of-thum
mb and structu
ural
analogies
s are useless?
?
We will look into this by
y asking whetther the confo
ormational pre
eferences of a “simple molecule,” transs-2-ethyl6-methylc
cyclohexane, can predict th
he conformational preferen
nces of a “com
mplicated molecule,” trans-2-ethyl6-methylc
cyclohexanone.
H
H3C
O
H
CH2CH3
versus
H 3C
CH2CH3
First, notic
ce that the sta
andard drawings look quite
e similar. Seccond, take ano
other look at the cyclohexa
ane
models yo
ou have built on the compu
uter and imag
gine, if you ca
an, C=O in pla
ace of CH2. W
What would yo
ou
predict? The
T same pre
eferred conforrmation and a similar conce
entration ratio
o in both mole
ecules? The ssame
preferred conformation
n, but a largerr concentratio
on ratio? (Whi ch molecule m
might show th
he larger ratio
o?) A
change in
n preferred co
onformation? Circle
C
your prredictions belo
ow:


k
same
e as/opposite from cycloalkkane
Preferred confformation for ketone:
Concentration
C
ratio (degree
e of preference) in ketone: smaller than//about the sam
me as/larger than the
co
oncentration ratio
r
in the cy
ycloalkane
Build and
d optimize “e
equatorial ethyl” trans-2--ethyl-6-meth
hylcyclohexa
anone

or File: Save As
s to make a copy
c
of “equa
atorial ethyl” 1-ethyl-3-meth
hylcyclohexan
ne (or
Select
uild it again frrom scratch)
bu

Select
or Build: Edit Build
B
to make
e changes in yyour model
C
on the sp
p2 C hybridize
ed atom in the
e palette
, and then double-clickk on the C2 ccarbon
 Click
attom. This replaces the two
o single bond free valencess with one do
ouble bond fre
ee valence (se
ee first
sttep below):
6
You can ignore entropy for this calculation because
b
there arre identical numb
bers of equatoria
al and axial confo
ormers. In other words,
assume S = 0.
Chemistry
y 202 (Spring ‘14)
P
Page 8
O
H3C
CH2CH3
H3C
CH
H2CH3
H3C
CH2C
CH3
 Click
C
on the do
ouble bond O atom in the palette
p
and single--click on the ttip of the doub
ble-bond
free valence. This
T
creates a CO double bond
b
(second
d step above).
 Now
N
use the procedure prev
viously descrribed for the ccyclohexane tto position the
e ethyl group, optimize
th
he model geometry, record
d the MMFF energy,
e
and de
etermine the lowest energ
gy equatorial e
ethyl
co
onformer. Record the MMF
FF energy of the lowest en
nergy conform
mer in the table (two pagess up).
d optimize “a
axial ethyl” trrans-2-ethyl--6-methylcyc
clohexanone
e
Build and
 Repeat
R
the pre
evious proced
dure starting with
w “axial eth
hyl” trans-1-etthyl-3-methylccyclohexane tto build
th
he correspond
ding cyclohex
xanone. The repeat
r
the opttimization/inte
ernal rotation steps to iden
ntify the
lo
owest energy “axial ethyl” conformer
c
and
d record its M
MMFF energy in the table ((two pages up
p).

Based on the energies
e
in th
he table, which
h ketone confformer is morre stable, equ
uatorial ethyl o
or axial
etthyl? Why do you suppose
e this is? (Loo
ok closely at yyour models fo
for clues.)
 Use
U the differe
ence in conforrmer strain en
nergies to calcculate the equilibrium ratio
o of the equattorial ethyl
an
nd axial ethyl conformers.7 Record this ratio in the ta
able.
The follow
wing are just rhetorical
r
que
estions, but they are worth thinking abou
ut:
 Are
A simple rule
es like “equatorial is preferrred” always u
useful?
 Are
A simple molecules neces
ssarily a good
d guide to the
e geometries a
and energies of complicate
ed
molecules?
m
 What
W
aspects of a molecula
ar formula oug
ght to encoura
age you to make a model((s)?
Parting in
nstructions
Hold on to
o this handout. You will need to determiine the conforrmational pre
eferences of yyour two cyclo
ohexanol
products for
f your lab re
eport. The pro
ocedure used
d here to studyy cyclohexan
nes can be ap
pplied directly to your
cyclohexa
anols: the OH group will ne
eed to be positioned in thre
ee different orrientations jusst like the ethyl group,
and the MMFF
M
energie
es can be use
ed to determin
ne conformati onal preferen
nces.
7
You can ignore entropy cha
anges again.

Download Report