(sor), université de...

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 !!

!!!!