(sor), université de...
TRANSCRIPT
11
Maq
sood
Ah
med
CR
M2 ,
UM
R 7
036,
UL
, In
stit
ute
Jea
n B
arri
ol,
Nan
cy, F
ran
ce
May 3
0th
, 2
01
2
Ult
ra h
igh
res
olu
tion
cry
stal
logr
aph
y
of s
mal
l m
olec
ule
s an
d p
rote
ins
112
Thio
phene
Ove
rvie
w
Subst
itute
d h
om
olo
gues
of
thio
phenes
find e
xtensi
ve
applic
atio
ns
in t
he p
roduct
ion o
f:
1.
Org
anic
sem
iconduct
ing m
ate
rials
2.
Ele
ctric
field
effect
tra
nsi
stors
3.
Dye
-sensi
tized s
ola
r ce
lls (
DS
SC
s)*
Ad
van
tag
es o
ver
Si b
ased
sem
ico
nd
ucto
rs:
1.
Their e
lect
ronic
pro
pert
ies
are
easi
ly t
unable
by
chem
ical m
od
ifica
tions.
2.
A c
hem
ical s
ubst
itutio
n r
eact
ion is
very
easy
to c
arr
y out.
A s
ubst
itute
d th
iophene c
om
pound
* G
rätz
el,
M. (2
001),
Natu
re. 414, 338.
In c
oll
abora
tion
wit
h
SR
SM
C, gro
up
Syn
thè
se O
rga
no
mé
talli
que e
t R
éa
ctiv
ité (
SO
R),
Un
ive
rsité
de
Lo
rra
ine
.
Saji
da N
ou
reen
, M
arc
Bele
y, P
hil
ipp
e C
. G
ros
3
Cor
rect
kn
owle
dge
ab
out
stru
ctu
re is
cru
cial
for
a r
atio
nal
su
bst
itu
tion
.
•Pos
itio
n o
f th
e su
bst
itu
ents
,
•Ste
reoc
hem
istr
y
•Ele
ctro
nic
pro
per
ties
Inte
rmol
ecu
lar
inte
ract
ion
s in
T
hio
ph
enes
N
N
N N
N
NR
u
2+
SN
S
S
NS
S
NS
SN
S
SN
S
S
NS
R
R
R
R
R
R
2P
F6
-X
-ray
s cr
ysta
llog
rap
hy
give
s th
e m
ost
accu
rate
str
uct
ure
as
com
par
ed
to o
ther
tec
hn
iqu
es (
lik
e N
MR
).
A t
ypic
al R
uth
eniu
m c
omp
lex
app
lica
ble
in D
SS
Cs.
*
No
ure
en
et
al.
, (2
01
2).
Da
lto
n T
ran
sa
cti
on
s, 4
1, 4
83
3.
4
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
enes
2.C
har
ge
den
sity
an
aly
sis
of
a T
hio
ph
ene
com
po
un
d
3.L
on
e p
airs
ele
ctro
n d
ensi
ty a
nd
H b
on
ds
4.T
ran
sfer
abil
ity
of
elec
tro
n d
ensi
ty p
aram
eter
s
a
-S
mal
l m
ole
cule
b
-P
rote
in
5.C
on
clu
sio
ns
& P
ersp
ecti
ves
OU
TL
INE
5
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
enes
2.C
har
ge
den
sity
an
aly
sis
of
a T
hio
ph
ene
com
po
un
d
3.L
on
e p
airs
ele
ctro
n d
ensi
ty a
nd
H b
on
ds
4.T
ran
sfer
abil
ity
of
elec
tro
n d
ensi
ty p
aram
eter
s
a
-S
mal
l m
ole
cule
b
-P
rote
in
5.C
on
clu
sio
ns
& P
ersp
ecti
ves
OU
TL
INE
6
1,4
-bis
(2-t
hie
nyl)
bu
tan
e-1
,4-d
ion
e
Data
reso
luti
on
:
0.7
7 Å
R
(F)
initi
al
=
7.4
%
wR
2(F
)in
itial
= 7
.5
%
=
0
.71
07
3 Å
Mo
no
clin
ic
P2
1/n
a =
5.5
516(5
) Å
=92.2
40(6
)°
b =
6.1
567(4
) Å
V
= 5
53.3
(2)
ų
c=
16.1
989(1
6)
Å Z
= 2
Tem
pera
ture
= 1
00K
Dis
ord
er
in
+-
Fourier
resi
dual
M1
7
R(F
) %
=
7.4
to
5.6
wR
2(F
) %
= 7
.5 to
4.9
Wit
h m
od
ell
ing
of
dis
ord
er,
th
e r
esid
ual
ele
ctr
on
den
sit
y s
ho
ws
sig
nif
ican
t im
pro
vem
en
t alo
ng
wit
h r
efi
nem
en
t sta
tisti
cs.
Pa=
88(3
)%
Pb=
12(3
)%
Pa
+P
b=
1
Po
sit
ive
Ne
ga
tiveM
1
8R
atio
of
dis
ord
er a
re d
iffe
ren
t, e
ven
fo
r th
iop
hen
e ri
ng
s w
ith
in a
sam
e m
ole
cule
a=
5.5
822(2
) Å
=64.4
87(4
)°
b=
14.2
465(5
) Å
= 9
2.2
396(6
)°
c=
14.3
776(7
) Å
= 8
0.6
37(3
)
Z=
2 V
=1018.0
5(7
)ų
Tem
pera
ture
= 1
00K
R(F
2)
= 17.4
%
5
.7%
49.7
(2)
/ 50.3
(2)
%59.7
(3)
/ 40.3
(3)
%
Tri
clin
ic P
-1
M2
1-(
p-H
exyl
ph
enyl
)-2
,5-d
i(2
-th
ien
yl)
pyr
role
Dis
ord
er i
n
9
( i
) =
x+
1, y
, z
C-
inte
ract
ion
s Dis
tan
ce b
etw
een
H14
A a
tom
&
the
pla
ne
of t
he
rin
g (S
1,C
2A,C
3A)
=
2
.6Å
C2
AC3
A
10
Wit
h S
3 62.5
(5)
/ 37.5
(5)
a=
12.3
15(5
) Å
= 9
6.5
67(5
)°
b=
12.5
92(5
) Å
= 9
9.0
16(6
)°
c=
16.3
86(5
) Å
= 9
6.9
46 (
5)
°
Z=
4 Z
’ = 2
* V
=1234.0
(16)
ų
Tem
pera
ture
= 1
00K
Tri
clin
ic P
-1
M 3
2-cy
ano-
3-[1
-(4-
hex
ylp
hen
yl)-
2,5-
di(
thio
ph
en-2
-yl)
-1H
-pyr
rol-
3-yl
]acr
ylic
aci
dD
isor
der
in
*Th
ere
are
tw
o m
ole
cu
les in
th
e a
sym
metr
ic u
nit
.
On
ly o
ne is s
ho
wn
fo
r th
e r
easo
n o
f cla
rity
.
R(F
2)
= 14.2
%
6
.9%
11
( i
) =
-x
+3
, -y
, -z
+1
O-
12
12
Th
iop
hen
e ri
ng
show
s st
ruct
ura
l dis
ord
er i
n
the
abse
nce
of
a st
eric
hin
dra
nce
.
Con
clu
sion
13
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
enes
2.C
har
ge d
ensi
ty a
nal
ysis
of
a T
hio
ph
ene
com
pou
nd
3.L
on
e p
airs
ele
ctro
n d
ensi
ty a
nd
H b
on
ds
4.T
ran
sfer
abil
ity
of
elec
tro
n d
ensi
ty p
aram
eter
s
a
-S
mal
l m
ole
cule
b
-P
rote
in
5.C
on
clu
sio
ns
& P
ersp
ecti
ves
OU
TL
INE
14
X-r
ays
char
ge d
ensi
ty a
nal
ysis
Inte
rnal s
ymm
etr
y co
de:
(i)
= -
x,
-y,
-z
1,4
-bis
(5
-hex
yl-
2-t
hie
nyl)
bu
tan
e-1
,4-d
ion
Tetr
aeth
yl
(4,4
’-d
iph
osp
ho
na
te-2
,2’-
bip
yri
din
e)
15
1,4
-bis
(5
-he
xy
l-2
-th
ien
yl)
bu
tan
e-1
,4-d
ion
*
Tri
clin
ic P
-1
a=
5.0
47(1
) Å
= 9
8.7
9(5
)°
b=
6.9
79(4
) Å
= 1
12.8
45(4
)°
c=
16.3
33(6
) Å
= 9
5.3
9(5
)°
Z=
1 V
= 564.3
(7)
ų
Tem
pera
ture
= 1
00K
Da
ta r
es
olu
tio
n =
0.4
8 Å
Exp
eri
men
tal an
d t
heo
reti
cal ch
arg
e d
en
sit
y a
naly
sis
*Ah
med
et
al.
(A
cta
Cry
st.
A…
.In
pre
p.)
Ap
plic
ati
on
of
a V
irtu
al A
tom
Mo
de
l
Rin
t
# R
efl
ecti
on
s T
ota
l
&
Un
iqu
e
Ab
so
rpti
on
Co
rrecti
on
Tm
in,T
max
0.0
53
70 0
42
10 2
27
An
aly
tical
0.9
3, 0
.98
Data
co
llecti
on
sta
tisti
cs:
16
Ex
pe
rim
en
tal d
efo
rma
tio
n d
en
sit
y
aft
er
sp
he
ric
al a
tom
mo
de
l re
fin
em
en
t
Th
e d
iffr
acti
on
data
are
very
go
od
as:
1.
Bo
nd
ing
den
sit
y i
s v
ery
well
defi
ned
.
2.
Lo
ne p
air
s o
n O
1 a
nd
S1 a
tom
s c
learl
y v
isib
le.
Fourier
resi
dual m
ap
).
2ex
p(
).ex
p(
][
1)
(1
exp
rHi
iF
FK
Vr
IAM
IAM
Ho
usi
ng
Sh
elxl
& M
oPro
R(F
) =
5.3
%
17
17
Ha
nse
n &
Co
pp
en
s m
ult
ipo
lar
ato
m m
od
el
dip
ole
q
uad
rup
ole
o
ctu
po
le
Acta
Cry
st.
A34,
909.
(1978)
con
trib
uti
on
s
18
1S
cale
+ S
ph
eric
al A
tom
Mod
el
N [
3(x
yz)
+6
Uij
]
9 p
aram
eter
s p
er a
tom
+
Mu
ltip
olar
Ato
m M
odel
Nn
on-H
[1P
v+
1K+
1K’
+ 3
(Dip
)+
5(Q
uad
)+
7(O
ct)
+9
(Hex
) ]
+
NH
[1
K’
+1
(Dip
)]
20-3
0 p
aram
eter
s in
ad
dit
ion
Nu
mb
er o
f re
fin
able
par
amet
ers
Mu
ltip
olar
ato
m m
odel
has
mu
ch m
ore
par
amet
ers
to
refi
ne,
We
may
nee
d t
o u
se c
onst
rain
s an
d r
estr
ain
ts.
How
str
ong
shou
ld t
he
rest
rain
ts b
e?
19
R-
fre
e r
efi
ne
me
nts
*
* Brü
nge
r (1
99
2).
Na
ture
,3
55
, 4
72
-47
5
*Pa
ul e
t a
l.,
(20
11).
Acta
Cry
st.
B6
7, 3
65
-37
8.
*Za
rych
ta e
t a
l.,(
20
11).
Acta
Cry
st.
B6
7. 2
50
-26
0.
The d
iffra
ctio
n d
ata
were
div
ided in
to
2
0 s
ets
with
5%
of
free r
efle
ctio
ns.
30 d
iffere
nt
rest
rain
ts w
eig
hts
were
test
ed
for
the c
hem
ical e
quiv
ale
nce
(kappas, vale
nce a
nd m
ultip
ola
r p
ara
mete
rs )
The v
alu
es
of
R-f
ree f
act
ors
were
ave
raged.
The b
est
rest
rain
was
found t
o b
e
Wre
str
ain
=50
(re
stra
in=0.0
2)
weig
ht
20
Mo
Pro
refi
nem
en
t an
d r
esid
ual ele
ctr
on
den
sit
y
R(F
) %
fin
al =
4.3
w
R2(F
) %
fin
al =
4.9
No
t m
uch
ele
ctr
on
den
sit
y i
s l
eft
to
refi
ne. T
he m
od
el is
co
mp
lete
.
C2
-C5, C
7 &
C10 a
nd
C8 &
C9 w
ere
co
nstr
ain
ed
(P
val,
K,K
’&
Plm
) to
geth
er
du
rin
g r
efi
nem
en
t.
usin
g R
free
refi
nem
en
t
).
2ex
p(
)ex
p(
][
1)
(1
rHi
iF
FK
Vr
Mult
Mult
H
ore
s
21
(b)
(a)
Exp
erim
enta
ldata
Sta
tic
de
form
ati
on
ele
ctr
on
de
ns
ity
Th
eo
reti
cal
Str
uctu
re f
acto
rs
CR
YS
TA
L09
DF
T B
3LY
P
6-3
1G
**
po
sit
ive
/n
eg
ati
ve
/ z
ero
Th
eore
tica
l wor
k w
as p
erfo
rmed
in
col
lab
orat
ion
wit
h D
r. A
you
b N
asso
ur
at C
RM
2
)(
)(
)(
rr
rsp
hst
at
22
Dif
fere
nc
e in
lo
ne
pa
ir e
lec
tro
ns
on
Su
lph
ur
sp
2&
sp
3
Pla
ne o
f th
e lo
ne p
airs
*G
uil
lot,
R., e
t a
l. (
20
01
). A
cta
Cry
st.B
57, 5
67
-57
8.
sp
2
23
Hyd
rog
en
bo
nd
ing
wit
h lo
ne
pa
irs
on
S a
tom
is
dir
ecti
on
al
H3B
= x
+1,
y-1
, z
; H
12A
= x
-1,
y, z
Pla
ne o
f th
e lo
ne p
airs
24
Co
nto
urs
@ 0
.00
5 e
/ Å
3
Exp
erim
enta
l
Theo
reti
cal
Str
uct
ure
fac
tors
Th
e el
ectr
osta
tic
pot
enti
al
3D
ele
ctro
n d
ensi
ty s
urf
ace
colo
ure
d a
cco
rdin
g t
o t
he
Ele
ctro
stat
ic P
ote
nti
al
Com
pute
d b
y V
MoP
ro &
MoP
roV
iew
er*
*Gu
illo
t, B
. (2
011
). A
cta
Cry
st.
A6
7,
C5
11-C
51
2.
25
Han
sen
& C
opp
ens
mu
ltip
olar
ato
m m
odel
Str
ateg
y fo
r vi
rtu
al a
tom
mod
el r
efin
emen
t
1
-T
he
vir
tual
ato
ms
wer
e in
itia
lly p
lace
d i
n t
he
mid
dle
of
two
ato
ms.
2
-T
he
init
ial
char
ges
Pvir
wer
e eq
ual
to
zer
o.
3
-T
he
Uij
par
amet
ers
for
the
H &
vir
tual
ato
ms
wer
e co
nst
rain
ed.
4
-
Ref
inem
ent
of
Pvir,
and
p
osi
tio
n o
n b
on
d
A s
imp
lifi
ca
tio
n o
f H
an
se
n &
Co
pp
en
s m
od
el
*Dad
da
et a
l. (
2012
). A
cta
Cry
st. A
Han
sen
& C
opp
ens
mu
ltip
olar
ato
m m
odel
26
Sta
tic
def
orm
atio
n e
lect
ron
den
sity
Co
nto
urs
@ 0
.05
e /
Å3
Exp
erim
enta
l M
ult
ipol
arE
xper
imen
tal V
irtu
al
Th
eore
tica
l Vir
tual
Th
eore
tica
l Mu
ltip
olar
R(F
) =
4.3
%R
(F)
=
4.4
%
R(F
) =
0.3
3%
R(F
) =
0.5
1 %
27
Mu
ltip
ola
rm
od
el
Vir
tua
la
tom
mo
de
l
Res
idu
al e
lect
ron
den
siti
es w
ith
exp
erim
enta
l dat
a
Sin
/=
0.7
Å-1
Co
nto
urs
@ 0
.05
e /
Å3
Th
e tw
o m
od
els
beh
ave
sim
ilar
ly f
or
exp
erim
enta
l d
ata
R(F
) =
4.3
%
R(F
) =
4.4
%
28
Res
idu
al e
lect
ron
den
siti
es w
ith
th
eore
tica
l dat
a
Th
eo
reti
ca
lM
ult
ipo
lar
Th
eo
reti
ca
lV
irtu
al
sin
/=
1.2
Å-1
Co
nto
urs
@ +
/-0
.05
e /
Å3
Th
e v
irtu
al a
tom
mo
del
beh
aves
wel
l ex
cep
t fo
r lo
ne
pai
rs i
n c
ase
of
theo
reti
cal
dat
a
R(F
) =
0.3
3%
R(F
) =
0.5
1 %
29
Ele
ctro
stat
ic P
oten
tial
Exp
erim
enta
l dat
a
Vir
tual
Co
nto
urs
@ 0
.00
5 e
/ Å
3
Mult
ipola
r
30
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
enes
2.C
har
ge
den
sity
an
aly
sis
of
a T
hio
ph
ene
com
po
un
d
3.L
one
pai
rs e
lect
ron
den
sity
an
d H
bon
ds
4.T
ran
sfer
abil
ity
of
elec
tro
n d
ensi
ty p
aram
eter
s
a
-S
mal
l m
ole
cule
b
-P
rote
in
5.C
on
clu
sio
ns
& P
ersp
ecti
ves
OU
TL
INE
31
Lon
e p
airs
ele
ctro
n d
ensi
ty o
f O
xyge
n a
tom
D
FT
32
32
Som
e
oxy
gen
acc
epto
rs
O HX
X
X
X
XH
....
....
C
XX
XO
H
H
........
1)
Ph
en
ols
2)
Alc
oh
ols
3)
Ca
rbo
nyl
O
C
C
X
X
XX
X
XH
....
....
O
C
C
O
X
X
X
X
H..
....
..
4)
Es
ters
5)
Eth
ers
CO
X1 X
2
....
.... H
33
Nu
mb
er
of
str
uctu
res r
etr
ieved
Don
or
Acc
epto
r
-O-H
-N-H
Car
bon
yl18
645
12 3
32
Ph
enol
s1
287
401
Alc
ohol
s8
840
1 48
4
Est
ers
176
88
Eth
ers
1 73
962
8
Cam
bridge
Cry
stallo
gra
ph
ic
Data
C
entr
e
34
0510152025
05
1015
2025
3035
4045
5055
6065
7075
8085
90
All
d<
1.6
d 1.
6 -
2
d 2
-2.7
An
gle
Be
ta°
% o
cc
urr
en
ce
s
va
ryin
g d
ista
nc
es
O…
Hd
Ste
reoc
hem
istr
y of
H b
ond
s
wit
h C
arb
onyl
acc
epto
rs
02468
10
12
14
16
18
05
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
Dis
t al
l
Dis
t <
1.6
Dis
t 1.
6-2
Dis
t 2-
2.7
an
gle
alp
ha
°
% O
ccu
rre
nce
s v
ary
ing
dis
tan
ce
s O
…H
d
°
35
An
gle
(°)
Ste
reoc
hem
istr
y of
H b
ond
s w
ith
Alc
ohol
s &
Ph
enol
s a
ccep
tors
In a
lco
ho
ls,
ther
e is
a t
end
ency
fo
r an
gle
to
be
larg
er t
han
in
ph
eno
ls
Alc
ohol
Ph
enol
36
OU
TL
INE
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
ene
2.E
xp
erim
enta
l ch
arg
e d
ensi
ty a
nal
ysi
s
3.L
on
e p
airs
ele
ctro
n d
ensi
ty a
nd
H b
on
ds
4.T
ran
sfer
abil
ity
of e
lect
ron
den
sity
par
amet
ers
a
-S
mal
l m
olec
ule
b
-P
rote
in
5.C
on
clu
sio
ns
& P
ersp
ecti
ves
37
Th
e E
LMA
M2
Lib
rary
Sm
all
un
it c
ell
sp
recis
e c
harg
e
den
sit
y s
tud
ies
Ato
m t
yp
es d
efi
nit
ion
:
Base
d o
n c
hem
ical s
peci
es,
hyb
ridiz
atio
n
state
, fir
st a
nd s
eco
nd n
eig
hbor
ato
ms.
Ave
rag
ing
of
ato
m t
yp
es p
ara
mete
rs.
Only
sig
nif
ican
t m
ult
ipo
les
are
kept.
Usi
ng
local S
ym
metr
yof
defo
rmatio
n
ele
ctro
n d
ensi
ty
E
LMA
M2
Tra
nsfe
r E
LM
AM
2to
-larg
e s
yste
ms
-sm
all
mole
cule
s-low
er
reso
lutio
n d
ata
Used
as :
-
Sta
rtin
g s
et
of para
mete
rs-
Pro
pert
ies
com
puta
tion
Exp
eri
men
tal L
ibra
ry o
f M
ult
ipo
lar
Ato
m M
od
el
Do
mag
ala
et
al.
(2011
) A
cta
.Cry
st.
A38
2, 2
’-(E
tha
ne
-1, 2
-diy
l) b
is [
2-b
rom
oth
iop
he
n-5
-yl)
-1, 3
-Dio
xo
lan
e*
Mo
no
cli
nic
C2/c
a=
19.2
55
(1)
Å
=
112.8
5(4
)°
b=
5.7
800(4
) Å
V=
1736.6
(2)
ų
c=
16.9
33(6
) Å
Z=
4
C16 H
16 B
r2 O
4 S
2
EL
MA
M2
d
ata
ba
se
tra
ns
fer
Da
ta r
es
olu
tio
n =
0.8
3 Å
T
=1
00
K
Co
nto
ur:
0
.05
e/A
3
Exp
eri
men
tal
Defo
rmati
on
Den
sit
y
*Ah
me
d e
t a
l. (
20
11).
Ac
ta C
rys
t. C
67
, o
32
9-o
33
3.
Fo
uri
er
map
aft
er
IAM
refi
nem
en
t (s
ph
eri
cal a
tom
s)
39
EL
MA
M2
da
tab
as
e t
ran
sfe
r
Re
sid
ua
l e
lec
tro
n d
en
sit
y m
ap
aft
er
EL
MA
M2
tra
ns
ferr
ed
No
t m
uch
ele
ctro
n d
ensi
ty i
s le
ft t
o r
efin
e, h
ence
th
e m
od
el i
s co
mp
lete
.
ato
m(r
) =
cor(
r)+
Pva
l 3
(r)
+
’3R
(’r
)P
lm±
ylm
±
The p
ara
mete
rs o
f P
va
l,&
’and
Plm
±
were
tra
nsf
err
ed f
rom
ELM
AM
2.
Br
atom
typ
e p
rovi
ded
by
S. D
ahao
ui o
f C
RM
2.
In the s
ubse
quent
refin
em
ent,
only
S
cale
,X
YZ
and
Uij
para
mete
rs w
ere
refin
ed
.
IAM
Mu
ltip
ola
r A
tom
Mo
del
R(F
) %
2.7
2.2
wR
2(F
) %
4.1
3.1
Refin
em
ent
statis
tics
40
Ele
ctr
osta
tic p
ote
nti
al o
f asym
metr
ic u
nit
*
Ele
ctro
n d
ensi
ty
Com
pu
ted
usi
ng
EL
MA
M2
dat
abas
e tr
ansf
er
*Com
pute
d b
y V
MoP
ro &
MoP
roV
iew
er
41
Ap
pli
cati
ons
of
ult
ra h
igh
res
olu
tion
met
hod
s
to P
rote
ins
42
Pro
tein
Ch
oles
tero
l Oxi
das
e at
0.7
2 Å
Th
e st
ruct
ure
was
ref
ined
wit
h P
hen
ix*
* A
fonin
e e
t al., A
cta C
ryst
D, 2012
F
AD
co
fact
or
Org
anis
m
Mo
lecu
lar
wei
gh
t
Met
ho
d
Sp
ace
gro
up
Cel
l d
imen
sio
ns
# M
easu
red
ref
lect
ion
s
# U
niq
ue
ref
lect
ions
R(F
) %
Rfr
ee (
F)
%
wR
2(F
) %
# of
Res
idu
es
# R
esid
ues
in
-h
elic
es
# R
esid
ues
in
-s
hee
ts
Bre
vib
acte
rium
ster
oli
cum
55
kD
a
X-r
ays
dif
frac
tion
P 2
1
a=
51
.273
A°
b=
72
.964
A°
c =
63
.036
A°
=1
05
.18°
46
5 3
85
44
4 5
11
11
.5
14
.0
13
.5
499
12
5
53
Fla
vin
ad
enin
e d
inu
cleo
tid
e
In c
ollo
bor
atio
n w
ith
Pro
f. A
lice
Vri
elin
k, P
erth
, Au
stra
lia
43
Th
e el
ectr
osta
tic
pot
enti
al o
f th
e ac
tive
sit
e ca
vity
*
Com
pu
ted
usi
ng
EL
MA
M2
dat
abas
e tr
ansf
er
*Com
pute
d b
y V
MoP
ro &
MoP
roV
iew
er
Imag
es a
re m
ade
wit
h P
yM
ol
and
Mo
Pro
Vie
wer
.44
Top
olog
y of
Pro
tein
-Lig
and
inte
ract
ion
s
Sh
orte
st in
tera
ctio
ns
usi
ng
EL
MA
M2
dat
abas
e tr
ansf
er
45
d=
1.7
9Å
(rcp
) =
0.2
6 e/
Å3
d=
1.7
8Å
(rcp
) =
0.2
7 e/
Å3
Intr
a-m
olec
ula
r in
tera
ctio
ns
in F
AD
Th
ese
intr
a-m
olec
ula
r in
tera
ctio
ns
are
sup
pos
edly
res
pon
sib
le
for
the
spec
ific
geo
met
ry o
f th
e F
AD
mol
ecu
le.
46
1.S
tru
ctu
ral
dis
ord
er i
n T
hio
ph
enes
2.C
har
ge
den
sity
an
aly
sis
of
a T
hio
ph
ene
com
po
un
d
3.L
on
e p
airs
ele
ctro
n d
ensi
ty a
nd
H b
on
ds
4.T
ran
sfer
abil
ity
of
elec
tro
n d
ensi
ty p
aram
eter
s
a
-S
mal
l m
ole
cule
b
-P
rote
in
5. C
oncl
usi
ons
& P
ersp
ecti
ves
OU
TL
INE
47
Con
clu
sion
s
47
1.
Chal
lengin
g X
-ray
s st
ruct
ure
s of
thio
phen
es w
ere
solv
ed w
hic
h
hel
ped
to u
nder
stan
d t
he
phen
om
enon o
f dis
ord
er.
2.
Usi
ng u
ltra
-hig
h r
esolu
tion c
ryst
allo
gra
phic
met
hods,
exp
erim
enta
l
and t
heo
reti
cal
char
ge
den
sity
anal
ysi
s of
mole
cule
s w
hic
h h
ave
signif
ican
ce f
or
org
anic
sola
r ce
lls
was
car
ried
out.
3.
An e
xte
nsi
ve
use
of
cryst
allo
gra
phic
dat
abas
e (C
CD
C)
was
mad
e to
find h
ow
lone
pai
rs e
lect
ron d
ensi
ty a
ffec
ts H
bondin
g.
4.
In t
he
abse
nce
of
a hig
h r
esolu
tion d
ata,
the
‘tra
nsf
erab
ilit
y
pri
nci
ple
’ w
as s
ucc
essf
ull
y a
pp
lied
to a
sm
all
mole
cule
and a
lar
ge
pro
tein
to c
alcu
late
ele
ctro
n d
eriv
ed p
rop
erti
es.
48
Per
spec
tive
sP
ersp
ecti
ves
1.
Str
uct
ure
s up
to l
igan
d h
ave
bee
n c
orr
ectl
y d
eter
min
ed.
S
truct
ure
s of
com
ple
xes
wil
l b
e st
udie
d n
ext.
N
N
N N
N
NR
u
2+
SN
S
S
NS
S
NS
SN
S
SN
S
S
NS
R
R
R
R
R
R
2P
F6
-
Lig
and
49
Per
spec
tive
s
2. I
ntr
odu
ctio
n o
f m
oder
n c
ryst
allo
grap
hy
in P
akis
tan
.
C
urr
ent
acti
vit
y i
s li
mit
ed t
o s
tru
ctu
re r
epo
rts
on
ly.
Pakis
tan
is a
majo
r p
art
ner
in t
he
SE
SA
ME
syn
ch
rotr
on
bein
g c
on
str
ucte
d in
Jo
rdan
.
htt
p:/
/ww
w.s
esa
me
.org
.jo/s
esa
me/
50
Ack
now
led
gem
ents
Su
per
viso
rs:
Pro
f. C
lau
de
Lec
omte
,
Dr.
Ch
rist
ian
Jel
sch
&
Dr.
Ben
oit
Gu
illo
t
All
col
leag
ues
at
CR
M2
My
fam
ily
in P
akis
tan
Col
lab
orat
ors:
Saj
ida
Nou
reen
, P
rof.
M. B
eley
& D
r. P
. Gro
s,
(SR
SM
C, S
OR
gro
up
, N
an
cy)
Pro
f. A
lice
Vri
elin
k, (
Per
th, A
ust
rali
a)
Th
e H
igh
er E
du
cati
on C
omm
issi
on o
f P
akis
tan
(H
EC
)
for
fin
anci
ng
this
Ph
D t
hes
is.
(ww
w.h
ec.g
ov.p
k)
51
Th
ank
you
!
52
5 2
Re
solu
tio
n i
n C
ryst
all
og
rap
hy
No
d
etai
ls
(en
velo
p)
0.8
Å~
1 Å
8Å
4Å
Sec
on
dar
y
stru
ctu
re
(Pro
tein
s)
~2.
5Å
Mai
n C
hai
n
(Pro
tein
s)
~0.
5Å
Ato
mic
P
osi
tio
ns
2X
ZM
3.9
Å
3D
O3
2.5
Å
H a
tom
po
siti
on
s F
ine
dif
fere
nce
s in
elec
tro
nic
clo
ud
n=
2d
sin
d =
n /
2si
n(Å
)
Bra
gg
’s L
aw
Lo
wM
ed
ium
Hig
hU
ltra
Hig
hV
ery
Lo
w
H
Yo
un
ath
et
al,
19
98
Rib
oso
mes(
70
S),
10
Å
53
54
VII
Ch
arg
e d
en
sit
y a
na
lys
is
55
(1)-
Sim
ple
Mu
ltip
ole
s r
efi
nem
en
t
(2)
-3rd
ord
er
Gra
m C
harl
ier
an
harm
on
ic
(3)
–4th
ord
er
Gra
m C
harl
ier
an
harm
on
ic
56
57
58
Ele
ctr
on
Den
sit
y o
f V
irtu
al A
tom
s
59
Pre
vio
us
Re
sult
s o
f S
OR
G
rou
p
Na
zee
rud
din
et
al.
J.
Am
. C
he
m.
So
c.
19
93
, 1
15
, 6
38
2.
Gra
bu
losa
, A
.; M
art
ine
au
, D
.; B
ele
y, M
.; G
ros,
P.C
.; C
azz
an
ti,
S.;
Ca
ram
ori
, S
.; B
ign
ozz
i, C
.A.
Da
lto
n T
ran
s.
20
09
, 6
3.
__
S
OR
2
__
__
S
OR
1
N3 (
Sta
ndard
dye
)
Th
iop
hen
e r
esu
lt !!
!!!!