Hiệu ứng dung môi trong phản ứng cộng aldol

SQ GlAo Dl,IC vA eAo T~O

TRUONG e~1 HOC eA L~T

LU~N VAN TH~C Sy
Nganh : HoA HOC

HI~U I1NG DUNG MO~
TRONGPHAN I1NG CONG ~~LDOI.!

Can b~ huang dan: TS.
HQc vien:

Oa lat : 2002

Bui ThQ Thanh

HUYNH OINH DONG


LClICAMON
f)~

hoan thanh lu~n VAn nar. xm tran tr~mg bar to s1l biet

on sau sAc den TS. 8ili ThQ Thanh. Chit nhiem {{hoa
Hoa hoc, Tmong dQ.i hoc {{hoa hoc, T11 nhtcn, f)Q.i hoc
cung cap tu h¢u va co nhuilg dmh htiong

Ml)C Ll)C

M<1DAU
PHAN 1.
1.1

TONG QUAN

HIEU UNG DUNG MOl

1.2. CAC PHUONG PHAP HOA HOC BAN KINH NGHIEM BE TIEN BOAN VA
GIAI THfcH HI~UUNG DUNG MOl LEN TOC BO "PHAN UNG VA cAN
BANGHOA HQC
1.2.1 Thang Yx Grunwald-Winstein hoac Bentley-Schleyer
1.2.2 Thang ET(30 ) Dimrot h-Reichardt
1.2.3 Thang AN -ON Gutmann
1.2.4 Thang Abraham-Kamlet-Taft
1.2.5 H~ so phan bo octanol-mroc Hansch-Leo
1.3. CACH TIEP cAN NHI~TBONG HQC
104. BAI CVONG VE CAC PHVONG PHAP LV THUYET NGHIEN CUU
HI~U UNG DUNG MOl
104.1 M6 hinh hoa Iy thuyet cua dung m6i bang cac tinh toan sieu phan til'
1.4.2 M6 hlnh hoa Iy thuyet ciia dung m6i bang cac tinh toan dung m6i lien
tuc

1.4.3 M6 hinh hoa Iy thuye] cac nrong tac n¢i phan til' va ngoai phan tu
1.4.4 SI! lira chon dOi vdi viec m6 hinh hoa Iy thuyet cac M thong sol vat hoa
1.5. cAC MO HINH CO HQC LU<;jNG TV VE cAC H~ TRaNG DUNG DlCH

1.5.1 M6 hinh roi rae
1.5.2 Cac m6 hinh solvat hoa lien tuc
1.5.3 Cac phuong phap t6 hop QMIMM
1.6. PHAN UNG CONG ALDOL
1.6.1 So d6 chung cua phan ling cong aldol
1.6.2 Oanh phap
1.6.3 M¢t so d~c di6m
1.6 .3 Mot so d~c di6m
1.6.5 £)¢ chon IQc I~p th6
1.6.5 £)¢ chon loc I~p th6
1.6.6 Co che' phdn ling cong aldol
1.6.7 Hoa hoc enolate
1.6.8 M6 t so nhan xet
Phdn 2. '
. DOl TU(1NG vA PHU<1NG PHAP NGHIEN CUU
2.1 BOI TV<;jNG NGHIEN CUU
2.2 PHUONG PHAP NGHIEN CUU
2.2.1 Cac phuong phap dinh tinh dl! doan hirdng phan ling trong phan ling
cong aldol

Trang
I

3
3

5

6
7

8
8
I
O
II
12
13
13
14
14
16
17
17
20
23
24
24
24
25
25
25
27
28
36
38
38
40

40

2.2.2
2.2.3
2.2.4
2.2.5

Cac rna hlnh solvat hoa lien tuc
Cac birdc solvat hoa trong hoa hoc tinh toan
Cac mire dO tinh toan
Tie'n hanh tinh toan

PHAN 3.
3.1.
3.2

KET QUA vA THAo LU!N KET QUA.

NGHIEN CUU DJNH TfNH HUONG eVA PHAN UNG CONG ALDOL

cAe NGHIEN CUU DJNH LU<}NG VE HI~U UNG DUNG MOl TRONG

42
44
45
49
52
52
55

PHAN UNG CONG ALDOL 1

3.2. I Khao sat phan ling trong pha khi
3.2.2 Khao sa t phan ling (1) bang cac rna htnh sol vat h6a
3.3
cAe NGHIEN CUU VE HI~U UNG DUNG MOl TRONG PHAN UNG CONG

55
56
61

ALDOL 2

KETLU!N
TAILItUTHAMKHAO
PHl) Ll)C

64
65


LUAN VAN CAO HOC
?

~

MODA D
Anh huang cua dung moi le n phan rmg hoa h9C lfin dfru tien diroc Berthel ot, Pe an de
Saint-Gills nhan thily vao narn 1862 khi ngh ie n ClYU su hinh than h es te : "sir es te hoa bi cham
la i va bi phan huy khi su dung nhirng dun g moi kh6ng thich hop vo i phan irng ". Nam1890,

Menschutkin dil nghie n cuu tI ml phan irng cu a trialkyla min vdi alkylhalogenua, v~ sau phan
irng duoc mang ten ong, va dil di de'n ke't lua n rhng "khong th~ xem xet phan rmg tach bie t vd i
moi tnron g trong do phan irng xay ra ". Menschutkin cling nhan thily din g, trang pha n urig giua
cac chilt lo ng , mo t trang cac chat long co th~ la moi tnrong khon g thuan IQi d6 i vd i phan
trng. Men schutkin dil giai thich a nh huang ciia dung mo i d6i voi pha n irng tnroc he't Iii do tinh
ehilt hoa hoc chu khon g pha i Iii do tinh chat v~t Iy cua dung mo i. Anh huan g ciia du ng moi le
n trang thai ca n ba ng ciia cac pha n ting hoa ho c dil duo c phat hien na rn 1896 d6 ng thai vdi
hien nro ng ta uto me hoa xeto -e nol. Wisli eenu s dil ngh ien ciru di n ban g xeto-e nol tra ng ta
m dung moi va dil di de'n ke't lua n ra ng, tra ng cac nro u chiern uu the' la da ng xeton, can trong
cloraform va benzen dang enol la chf yeu . Khi do , d€ co th~ do duoc a nh huang na y, ong dil
neu ra khai niern dO dien mo i [1].

Tra ng qua trinh va n don g va pha t tri~n cua hoa hoc, anh huang cua dung moi tra ng
phan irng hoa h9 C ngay ca ng thu hu t su' chii y cua cac nha nghien cUU. Ngiroi ta dil nha n
thily rhng, dung moi co th~ ga y anh huang nhieu ma t len phan ung hoa h9C, cha ng dung moi
anh huang len : ha ng s6 s6 din ban g va to e dO phan irng, cac bien d6i v~ cau trang va tautome
hoa , co che' phan ung, hoar tinh cua cac tac chat, sir chuyen pha va hmh thanh tinh th~ qua ca c
giai doa n kha c nha u tu rna rn tinh th~ de'n slf phat tri~n cac morphology va hinh thanh cac cilu
true poly morphic [2] ...
Phan ung cOng a ldolla mOt trang nhun g phuong pha p hu u hi~u nhilt d€ tqO lien ke't
carbon-carbon md i tra ng khi dn ba o v~ nhung vi tri phan ung cho ca e chuy~n hoa hoa h9C
khac . Phan ung eOng aldo l la 10qi phan ung rilt d~c thil v~ m~t hoa I~p th~. M~c dil phan ung
cOng aldo l dil ducjc c6ng b61frn dfr u tie n vao nam 1838, nhung trudc nam 1970 chi co nhung
nghien cuu ta n mqn lien qua n de'n hoa I~p th~ eua no . Trang nhung nam 1970 cac nghien cu u
v~ hoa I~p th~ eua phan ung quan trQng nay mdi tMt slf tra thanh ehinh qui , tuy nhien hi~u ung
dung m6i tra ng phan ung cOng aldol viln chua dUQc d~ c~p Mn nhu mOt d6i tucjng nghie n
cuu chin h thl1c [3 ] .
Trudc day , vi~e ngh ien cuu hi~u ung dung m6 i trang phan ung hoa h9C chu ye'u dlfa
vao cae phuong phap ban kinh nghi~m. Cac phuong phap nay doi ho i cac M du li~u thlfC nghi~m
rilt lOn, vi v~y milt nhi~u thai gian va c6ng suc nghien cUu. Trang khoang muai nam tra Iqi day ,

nhi~u Iy thuye't va m6 hinh dung m6i mdi dil dUcjc phM tri~n, cac c6ng CI,I tinh toa n (phfrn
cung, ph<1n m~m) co nhi~u tie'n bO vUQt b~c, dil va

Dgi h\JC DALA T

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2

LUJN VAN CAD HOC

da ng ta o ra cac hudn g tiep can mdi d§y hieu qua d~ nghie n ciru hie u irng dung moi tron g hoa
hoc, Hien nay, co hai xu hirdn g chinh, mot Iii: xil' If thu dn tuy c6 di€n ; ha i Iii: khao sa t cac rna
hlnh hoa II1<,1ng til' du a tren su phan bo Iie n tuc die n mo i cua dung mo i [41. Cac rna hlnh
nay co n dl1<,1C goi la cac rna hin h sie u phan til'diroc tl1€ hie ri dirdi dan g cac cluster chua
mOt phan til' chilt tan va mot so' khong gid i ha n cac pha n til' dung mo i xac dinh, phan b6 tron
g mo t moi tnro ng die n mo i lien tuc dI1<,1c dij. c trung bd i han g so' di~n moi vi mo ciia dung
moi . Su nghien cuu cac rna hmh noi tre n co th~ tri€ n kha i the o hirdn g th6n g ke chu ye u du a
tren cac rna hinh Monte Carl o va dong luc hoc phan til'; hoac thea hirong hoa hoc II1<,1ng til'
du a tren co sa Iy thuyet tnro ng pha n irng Ons age r va ca c rna hlnh phat tri~n ttt Iy thuye t nay.

VI tth~ cua pha n iing nay rna trong do dung moi do ng g6p phan a nh hudn g rilt quan trong [3,4,5],

do d6 trong luan va n na y, chu ng ta i da sil' dun g cac rno hinh so lvat ho a tren cd si'i Iy thuyet
truong phan ung (m o hinh Onsager, mo hlnh Tomasi P C M, DPC M, IPCM, SC I-PCM ...) ke"t
hop vO'i cac phuong phap ti nh to an ab initio Hatree-Fock, ly thuye"t ham mat de} (DF T) va
thuyet orbital bien (F MO ) M dtf doan huong phan u ng, khao sat hi~u ung dung m oi t r o ng
pha n ung ce} ng aldol va xem xet tinh cho n IQc I~p thi cua phan ung nay duO'i tac d{l ng cua

ye"u t6 dung mo l.

D(li hoc DALAT

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3

LUJ-N VAN CAO HO C

A?

PHA N 1.

TONG QUAN.

1.1. HI E U UNG DUNG MOl :

Ca c phan irng hoa ho c thirong xay ra trong pha lon g, tron g do cac d iu til' pha n irng
duoc hoa tan trong mo t m6 i tnro ng lon g. Thuc nghiem dil chiing to : dung m6 i kh6n g phai lil
moi tnro ng tro d6 i vo i ion hoa c pha n til' bi hoa tan ; thi du : dung mo i co th~ an h huang len :
•

•

G in bdng hod hoc:
- Acid -ba se.
- Tautomer hoa keto-enol.
- Cllu tran g ,

Toe d{) phdn ling :
Phan irng Men shutkin (1890):
1,l,l -Trichloroetha ne

Ch lo ro benze ne
Acet on e

18

Bcnz onitrilc
Nitrobenzene

43

52

Brom hoa alkene :
Nu;

t+l

B I"" B -

cs:
Dung mo i

r

-

N

Sd n pham

k

Carbon tetrac hloride
1A-Dioxane
Acetic acid
Methanol
Wate r

1

51
4860
1.6x10S
1.1x10

10

Phan irng Diels -A lde r:

~o -[c»::o]~
Ot.le u

Dun"rno;

0\1. J

Krel

n-Hexa-n-e- - - - '-"1
Aceton itri le
9

Water

Dgi hoc DALAT

13000

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4

LUJ,N VA N CA D HQ C

• Co cht phdn ring va hod ho c ldp the':
Sir ca nh tranh gifra SN1 va SN2 :

X- = N3- . SCt't. Br', 1Dung rnai khOng proto n

+X
_- sO·

Dung rna i prot on

~,

hornoallyl

san phlfm
~
x

VI v~y m9t 19 thuyet v~ cac hieu ling dung moi ph a i giai thich duo c cac du kien
neu tren,

.

Trang ca c ph an ling ph a long, cac hieu ling dung moi dliQc th~ hi~ n rilt da dang [71:
•

Dung rnoi c6 th~ b8n hoa hoac lam bilt 6 n dinh cac tac nhan phan ling , trang thai
chuyen tie'p va cac sa n pham .
• Dung moi c6 th~ ga y a nh hirdng len trang thai can ba ng va t6 c d9 phan ling, tron g
m9t s6 tnrong hop c6 th~ lam thay d6i co che' pha n ling .
• \ C6 th~ nhan bie't anh hirdng cu a cac hieu ling dung moi len phan ling hoa ho c
khi so sanh voi cling phan ling trong pha khi .
• Dung moi c6 th~ ga y a nh hirong len trang thai can ba ng va t6 c d9 phan ling , trong
m9t s6 tnrong hop c6 th~ lam tha y d6i co che' phan ling .

Da i ho c DALAT

Thdng 0 112002


5

•

LU!.N VAN CAO HQC

Co th€ nhan bie't anh huang cua cac hieu ling dung moi le n pha n ling hoa hoc
khi so sa nh voi cung phan ling trong pha khi,
Trang thai chuyln tiip

,
,

E

,

~Ct (T8),,,1

,,

,
,

~~

Dung mo i 1

,
\

,

,,
,,,

Dung mo i 2

\
I

1

••

I

,"

1

I•

Tdc ch5t

,
\

,

ll G1 (P)
San philm

L...

...__

Toa dQ pha n ':1!1g
•

Hie u ling dung moi co th€ la h~ qua cua sir thay a6i phan b6 ai~n tich tron g cac
tac cha], tra ng tha i chuye n ti ep va san pharn (qui tilc Hughes -Ingol d), vi du:
- Tran g thai chuyen tiep hoac ho p cha t trung gian bi solvat hoa nhieu hem ta c
chllt:
CQng
nucleophile
K

R

R+X -

)LR

R

R

· X·

- Tra ng thai chuyen tiep hoac hop chllt trung gian bi solvat hoa it han ta c chdt :
Tdi kit hop

cation-anion

H

,,-

R

+ ,\

}!:-R

x +y_
+

[

1.....Y....:-:1: 0
]

1.2. CAC PHUONG PHAP HOA HOC BAN KINH NGHIEM DE TIE N DOAN
vA GIA I THICH HIEU UNG DUNG MOl LEN TOC DO PH AN UNG vA
CAN BANG HOA HOC :
D€ nghien cuu hie u ling dung moi, trong hoa hoc thirong sa dung cac phirong pha p
ban kinh nghiern [7]:
• Grunwa ld-Wi nstei n (duoc b6 sung bai Be ntle y-Schle ye r)
• Kosower, Re ichardt-Dimroth
• Gutmann
D(li hoc DALAT

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6

LUj,.N VAN CAD HQ C

• Abraham-Kamlet-Taft
• H~ s6 phan b6 octano l-mro c Han sch-L e o ...
1.2.1 Thang Y){ Grun wald- Winst ein had c Bentley-Schl e yer:
Khi khao sa t hie u ling dung m6i cac tac gia nay aa dua tren phan ling phfin Iy solvat
hoa cua (CH3hC -CI tro ng M dung m6 i 80% etanol -mroc va alta ra c6ng thuc kinh nghie rn:
Trong 06 :
k ... h5ng s6 t6c do phan ¥ng cua R+ trong
pha nud e,
'
ko ... hang s6 t6c do phan ling ciia R+ trong pha
htru cotetanol) .

( k ) =y IOQl . k o I -BuGI

D6i vdi cac dan xuat RX khac :

m, c oo. cac M so ban kinh nghiern .

IOg(~) = mY +c
ko. RX

D6i vdi cac hop cha t Yang, thi du cac dan xuat cua 1- va 2-adamantyl:

Thang Yx va tie u chuan co hoc :

Y(IL
-2.4
-2..2
-0.84 -0.81
0.00
0 .00

--':-:--::-'--~"--.-Y !!=~}

10% EtOH
Nu'dc

2.62

2.46

4.17
4.44

3.95
4.24

Nh ir vay :
• Kha nang ion hoa ta ng tu : EtO H -+ mroc .
• Do nha y d6i vdi dung m6i ta ng thea clay: Ots < I < Br < Cl.

Da i ho c DALAT

Thang 0112002


7

LU;'N VAN CAD HO C

M6i lien h~ na y khon g th~ hien etuQc eti~u gi v~ cac tinh chat vi rna rna chi dua ra cac
ke't luan gidi han c'J mire eto tnrc qu an , cha ng han :
- Ca c tac chat bi ca n trc'J I~p th~ tham gia phan irng SNI ~ m e 1
- Cac chat tham gia phan irng vd i su hiS tro ciia ca c dun g mo i c6 tinh nucle ophile ~ m c l
•

m=1
m = 0 .63

1.2 .2 Thang En30J Dim roth -Reich ardt :
Tr en co s0 nghien ciiu phdn ung Sol vatoch rom hoa ciia phamrnau zwitte rionic bet ain
e (I~n et~u tien duoc dua ra bc'Ji Kosow er , dird i ten go i la tha ng Z):
!

R, = R2 =H. ;)110".)'1
X - Q. S

R, = R2 = H; X = 0

Cac tac gia tre n eta dua ra khai niern thang E T(30);
D ung m oi

Ama l( (11 m )

Meth a no l

515

Mii u
re d

EttKlnol

550

viol e t

Isoamyl alcohol
Acej one
Etf(yi llcet ale

608
677
769

blue
g reen

yellow-qreen

ET(301

kc allmol

55.4
51.9
4!).O

42.2
38.1

va xay du ng c&g thirc ban kinh nghiern :

28591

T ir et6 di ete'n ke't lua n: hieu irng solva tochro m hoa bi ga y ra bdi su solva t hoa khac nhau
cua trang tha i co ba n va trang tha i kich thich.

Dq.i ho c DA LA T

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8

L UAN VAN CAO HQC

1.2.3 Thang AN-DN Gut mann :
Trang m6i tnrong phan iing, dung m6i co th€ bi€ u hie n cac kha nang:
• Chilt cho di~n tU' (tinh base Lewis)
:

Chi so cho:
•

o + SbC1S

"

ION =

( k ca l/mol )

- 6.H I

.. D..·SbC1S

Chilt nhan di~n tU' (tinh acid Lewis)

Et3P=O + A

4;

,.

Et3P=O···A

Chi so nhan :

AN = o(A) - 8(hexane) . 100 8(EtPO SbCls ) - o(hexane)
Theo qui irdc : AN = 100 doi vdi Et3PO...sbCIs
Dung md i
'l,2-D ic l-. lo l-oe tl-.a ne
Aceto n it r i le

Elhyl a cel ... Lee

DN

AN

(0 ,0)

'lG .7

14 .1
1 7. 1

1U .9
g _:.~

Diet hyl e t her

19.2

:3 _ ~J

DM F
DMSO

26 .6

'1 6 . 0

2~J,8

PyrieJin o
VValor

::J:">; .1

n -Hox<:1r1 0

'1 ~J. 3

14 . 2
54 .a
( 0 . 0)

Thang AN-ON co th€ giai thich duoc ca c viln d~ sa u:
•
Kha nan g phan urig anion tan g tron g cac dung m6i co chi so ON cao va AN thap
• Khii nan g pha n irng cation tang tro ng cac dun g m6i co chi so AN cao va ON thilp.
Cac phan irng ionic (vi du SNI) xiiy ra tot trong ca c dung m6i vdi chi so AN cao va ON
cao VI diroc gia tan g kha nan g solva t hoa do i vd i cation va anion.
• Phan irng SN2 tien hanh thuan IQi trong cac dung m6i co chi so AN thilp VI tra ng tha i
chuye n tiep (T S) solva t hoa it han ca c tac chill.
Thi du : moi lie n M giCi'a chi so AN va h~ng so to c d(i phan irng cua phan ung:
•

CH31 + 1*- ~ CH31* + 1dl1Qc bi€u di8n bang d6 thi 1.
1.2.4 Than g A b raham -Kam let-Tait:
Koppe l va Palm lin diu tien dil dua ra moi lien M cua hieu irng du ng moi vdi nhie u
tham so kha c nhau . H~ dCi'li~u cho moi ~en h~ do va n lien tuc dl1Qc b6 sung bd i
cac nghi en ciru pha t trien v~ sa u (tha ng Abra ha rn-Ka mle t-Taft) . Than g Abra ham Karn let- Taft dl1Qc xay dung tren co sa phiron g trm h ba n kinh nghie rn :

lJgi hoc lJALAT

Thd ng 0112002


9

LU!.N VAN CAO HOC

I A=Ao+S(1l *+dO)+aCl:+bI3]
Phuong trinh nay bi~u thi m6i lien h~ nang hrcng solvat hoa tuyen tinh (LSER).

~lt I.k

D6 thi 1: M6i lien M gitra chi so' AN va toe d(\ phan ling .

ver.
•

Alogarithm cua hang s6t6e dO hoac hang so' can b~ing.
An logarithm cua hang so' t6e dO hoac hang so' can bang trong dung m6 i so sanh
(eyelohexane) .

•

Jr *

•

Chi so' phan eve (thuong ty l~ vdi moment luang eve) .

• () M so' hieu chinh dO phan eve.
•
•

akha nang eho hydro (tinh acid BH) .

f3 kha nang nhan hydro (tinh base BH) .

/
Da i hoc DALAT

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10

Du ng m6i

Cyclohexane

Chloroform
Pyridine
Diethyl ethe r
Acetone

DMSO
Acetonitrile
DMF
Ethanol

Water

-0.08
0.00
0.58
0.87
0.27
0.71
1.00
0.75
0.88
0.54
1.09

0.00
0.00
0.4
0.00
0.00
0.08
0.00
0.19
0.00
0.83
1.17

0.00
0.00
0.00
0.64

0.47
0.48
0.76
0.31
0.69
0.8
0.2

M6i nrong quan giita cac thang kha o sat:
Thang ET( 30) :
Vrn rl X

•

ex.

1t*

n-Hexane

•

LUf.,N VAN CAO HOC

=10 .60

1
+ 5 .12(n:* - 0. 230 ) + 5 .78 (1 (10 3 crn- )

Tha ng AN:

I AN =1.04 + 15.4(11:* - 0.088) + 32.6(;; I
Tit do co th~ nhan thay:
• Thang ET(30) va thang AN thirc te' phu thuoc vao ha i tinh chat (rt* va ex).

•

Y nghia cua cac dai hrong n:*, ex, ~ ... phu thuoc ma nh vao cac qua trinh dUQC chon

cho viec phan tich thong ke .
• Co nhieu kha nang la kho ng co mo t hie n uro ng quan sat don nhllt nao co th~ rna til
tllt cii cac nrong tac chat tan - dung moi dan g xay ra .
1.2.5 He sfI phfin bo octano l -mMc Hansch-Leo:
H~ so' phan b6 gitra mroc va octanol:
\

K

=P
o/w

Dai h9C DALAT

0 .1 11'

= cj (1 - octancilil

cj (wa te r) ~

Thdng 0112002

II

LUf,.N VAN CAO HQ C
log t:

Dung m8i

1.97

0.77
0.64
-0 .24
-0 .32
-0.34
-1 .0 Ei
-2 .03

Acetoni trile
N-Methylacetami de
DMSO

LogP la mo t da i IU<;1ng ritt hfru hieu M danh gia tinh ky nud e (ail uc d6 i vdi dftu).
1.3. CA C H TIEP CAN NHIET DONG HOC [10] :
Pha n ling cua ta c ehitt R trong dung moi A va B:

lien h~ vdi nhau bang mo t ehu trinh nhie t do ng hoc :

TS:;t:(A)

lLG'~"
Trong do :
• TS *- (A)
• TS *- (B)

Dgi hoc DALAT

trang thai chuyen tiep trong dung moi A.
trang thai chuyen tiep trong dung mo i B.

Thdng 0112002

\


12

•

LUf,.N VAN CAO H Q C

•

!lG,A->B(TS ) ... bien thien nang lirong ur do ciia TS khi chuye n ttt dung mo i A sang
dung moi B, day Iii dai hrcng din phai xac dinh khi ngh ien cu u hieu ling dun g moi bang
each tiep c~n nhiet oQng h9C.
!lG/->B( R) ... dtt<;1C xac dinh tir ca c phep do he; s6 hoat oQ.

•

!10 : , !10 : ...diroc xa c dinh

ttt cac do dac don g hoc, cluin g phu thuoc vao R

va TS .
Th i du: Cach tiep c~n nhiet oQng h9Cd6i vd i phan ling Men schutkin:

Dung mo i /i:\GT
Hexane 6.34
.~c"tojne
0.97
D'\,fF

0

DMSO

-0.59

Elha nol

2,63
', Go,tTS ' ~ 3.77 - 1'. 11, ,, ' - 0.51"

Ttr bang tren co th~ nhan thily:
• Hieu ling dung moi len tac chilt yeu han len trang thai chuye n tie p .
•
•

*

M G phu thuoc va o dQ phan eire dung moi, khong phu thuo c va o tinh acid HB ; !
lGo! (TS) phu thuo c vao tinh acid HE.
EtO H th~ hien hieu ling klm ham : no lam ben hoa R va lam milt 6n dinh TS.

Cac h tiep c~n nhiet dQng hoc d~ nghien ciru hieu ling dun g moi la mot phtron g pha p
rilt hieu qua , nhirng viec ap dun g no milt nhieu tha i gia n va ob i ho i dit Iieu tir nhieu ngu on
khac nhau .

1.4. DAI CUONG
U UNG DUNG MOl :

VE CAC PHUONG PHAP LY THUYlh NGHIEN CUU HIE

Da c di~m chun g cu a cac phuong phap na y la sii' dun g cac rno hlnh Iy thuyet o~ nghi
e n ciru cac tuo ng ta c chdt tan - dung moi, Hau he't ca c phirong pha p d~u dQ'a tren su so sa nh
giO'a pha n ling tran g pha khi va dun g dich [2,9,10 , II ]. Chu ng co mOt
sa u:
•

Muu va nhuoc di~m

Cae u'U di~m:

I. Kho ng di n cac thong s6 ban kinh nghi e rn, cac dO' kien thuc ngh iern tie u chu a n,
cling nh u phan tich thon g ke .
2. Giai thich, danh gia hie u ling dung mo i thong qua ca c da i hron g v~t ly (pha n b6 oi(:n
tich, cac moment da eire, hinh dan g orbia l pha n tii' (MO) ...).
3. Cac phirong phap co h9C thong ke co th~ tinh duoc cac dai luong nhiet dong h9Cdin thie

t cho vie c mo hlnh hoa cac hieu ling dun g mo i.
•

Ca e nhtfde di~m:

Dai hoc DALAT

Thdng 0112002


13

LU/tN VAN CAO HQC

I. Tro ng nhieu tnrong hop co th~ pha i d n de'n cac co ng cu tinh toan d~t ti€n cling
nhir pha i xil' 19 mot khd i IU2. MOt so' phiron g phap bi han che' trong viec xil' 19 cac phan til' e61~p.
104.1 MfJ hlnh hOG lV thuytt CUG dun g mfJi biing cac tinh toan sieu ohiin til:
Chat tan M
,

J

sa

Cac tinh toan sieu phan til' co xu huang ap dung eho cac h~ thong IOn va dua tren co
cac phirong phap dOng life hoc phan til', Monte - Carlo ... MOt trong nhG'ng nhiern vu cua no la
xac dinh mOt each ehinh xac dn bao nhieu phan til' dung moi eho mot phan til' ehilt tan nhat dinh,
VI v~y cac mo hinh nay con du

rae .
1.4.2 MfJ hlnh hoa lV thuytt CUG dung mfJi biing cac tin h toan dung mfJi lien tuc :

Chilt tan dUlien tuc vdi hang so' dien moi E nhilt dinh .

Dai h9C DALAT

Thang 0112002


L u AN VAN CAO HO C

14

898
IwrlmQtr M~1,
~

..

.1

~If ~ttmt ltodt:U.1t't M~rj

!(tI'oSCl'CM

Trang phirong phap giln dung don gian nhat (rna hinh Onsager), tnrong ph an ling
dttQc dinh nghia bdi cong thtrc:

~

2(1:: - 1)

3-

R = 2£ + 1 8 0 ~l
Han che' cua rna hmh Onsager Ia khong xii' Iy du<;lc cac ch al tan kh on g co moment
luang cue , cac nrong tac di.ic biet nhu tao lien ke't hyd ra kh6ng dUQC rna hinh hoa mOL each
day du oYe'u to' dong vai tro quyet dinh trong cac rna hinh solvat ho a lien tuc la hlnh dang cu a
10 trong (cavity) .
104.3 Mo hinh hod LV thuyet cdc t/long tdc noi phdn til va ngoai phdn til:
• Cac rna hinh kinh nghiem (rna hlnh co hQC phan nr) :
Cac phirong phap kinh nghiern dua tren mot t~p hop ca c h5.ng:s6 hrc duoc dinh
nghIa tnrdc d6i voi lien ket, cac bien dang goc lien ke't ... M irdc liron g va danh giav~ hieu ling
dun g maio Trong do , cac phirong phap co hoc c6 di~n duo c sii' dung M ird c IUQng nhanh,
nhirng la i bi gidi han d mire d(i VI rna, vi v~y clui ng chi a p dung cho cac
h~ th6ng IOn.

Cac rna hinh co hoc luang tii' :
I . Cac rna hinh ban kinh ngh iem :
Noi chu ng cac rna hmh na y kh ong th~ hien mot ea ch dily du cac tiron g tac ye u .
2 . Phuong phap Ab initi o va Iy thuye't ham mat <16 :
T hai gia n va khdi IUQng tinh toan kha ldn , nhirng ch o ke't q ua chi n h xac va cu ng cap
•

nhi eu thon g tin d n thiet han . Cac phucng phap na y ch u ye'u ap dung cho cac M th6ng
nho .

• Ca c rna hinh mat d t ph an ling :

1. Cau truc tInh : xac dinh mot ea ch chinh xac cac cau true va nang IUQng tre n b~
ma t the' nang .
2 . Cac phuong phap co ho c th6ng ke : ch u ye u d ua tren cac phuong pha p Monte
Ca rlo, dOng hrc ho c pha n tii'.
10404 S/l l/la cho n do'i veJi vie c mo hinh hod LV thuy et cdc he tht/ng sol vat hod :

D9i ho c DALAT

Thdng 0112002

/


15

LUf,N VAN CAD HQC

.----------. /
:Md hln.h Dung

mdil '-.
~

r--------.. /'
Ptnrong p bap
Iy tlluy et

I

IR~i~c I

I

Lie'ntl!c

1'-----11

"""--------''"I

E>qng 11(C

I

Trang thuc te' nghie n ciru, cac rna hi nh hoa Iy thuyet cua cac M so lvat hoa hilu he't la
nhftng t6 hop phirong phap:
• Ke't ho p co ho c hrong tli' vd i cac rna hin h dung moi roi rae, rna hlnh dung rnoi
lien tuc, cac ca u true tinh ...
• Ke't ho p cac phirong phap kinh nghi em, b~ ma t the' na ng vdi rna hinh dung moi roi
rae , do ng hrc ho c phan tli'.
• Hoac la nhftng phucng phap t6 hop (QM /M M ) ke't hop gifta co hoc luong tli' (QM)
vdi co hoc phan tli' (MM) .
• Phuong phap mdi nhat, con da ng dUhrc ho c hrong tli' ke't ho p vdi phirong phap DFT Car - Parrinello .
C6 th~ nhan , thay cac phirong phap rna hinh hoa cho ca c h~ so lva t hoa la rilt da
dang, tuy kha c nhau v~ eac h tiep c~n nhung tilt cii d~u tho ng nhilt ~di nhau d nhftng di~m
sa u:
I. Ca c dung moi vdi cac tinh chat khac nhau (thuo ng rilt kh6 dinh nghia ) c6 th~ lam thay
d6i kha nang ben hoa cua ta c chilt va kha nang phan irng .
2. Nhirng thay d6i d6 la do tuong ta c chat tan dung mo i lam 6n dinh hoac bilt 6 n
dinh cac cau tli' phan ung .
.

J
3. Ca c hieu irng dung moi th~ hien dudi nhieu g6c dO:
TII~ sa n pham ,
Co che' phan ung .
Tie'n trtnh hoa I~p th~ ...
4. Khong c6 mo t each tiep c~n "va n nang" d~ xli' Iy cac hie u irng dung mo i.
5 . Tuy thuoc vao rmic dO ap dung, cac phirong phap kin h nghiern c6 th~ cho nhftng du
doan t6t v~ nhftng qu an h~ neu tren .
6. Ne'u c6 dily dll cac dft kien d n thiet, hoan toan c6 th6 tinh toan duoc ca c thong so' nhiet
dOng hoc cua mOt h~ solvat hoa.

Thang 0112002


LUJN VAN CAD HQC

16

7. Hien nay cac co ng cu rna hinh ho a 19 thu yet cu ng nhu cac cong cu tinh toan dang pha t
tri~n manh me va don g vai tro nga y ca ng quan trong trang linh vue nghien cu u 19
thuyet v~ hi eu irng dun g ma i o

1.5. CAC MO HINH cO HOC LUONG TlJ VE CAC HE TRONG DUNG DICH:
Hoa hoc IUQng tii' khao sat ca c he;: trang ph a khi dua tren su tuo ng tac gifi'a cac die;:n
tii' va ha t nhan , M Ot trang nhfi'ng nhiern VI} ella n6 la giai phirong trt nh:

I H(r ,R)tp(r ,R)=E(R)tp(r ,R) I

.>
DOng na ng + nrong tac hut die;:n tii' d ie;: n tii' + nrong tac My die n tii' die;: n tii' + nron g tac dii'y hat nha n hat nh an .

<,

3n toa dO ell a tat ca n die;:n tii' (r)
+ cac toa dO at nha n (R)
(giin dung Born - Oppenheimer)

Trang hiiu he t cac tnro ng hQP, kho ng th~ gia i phuong trlnh tren mot each chinh xac rna
chi e6 th~ gia i gii n dun g bhn g eac h tha y the ham 3n toa dO ella n 'd ie;: n ttl' bhng n ham (cac or
bital phan tii' - cac MO ) ella 3 toa dO. Nhu vay cac dien 'ttl' OLfmot tnrong tru ng binh cua cac dien ttl' kha c . Phuong phap giin dung Hartree-Foek (H F) dua tren

co sCJ :
Bat d6i xiing Fermion => Ham s6ng don -din h thirc.
T6i iru hoa cac MO=> Cue ti~u hoa nang IUD~ tinh toan tren rmrc dO HF d n ph d i tinh den tac d,)ng nrong ho nrc thai dien ttl' - dien tii'.

•
•

D6i vdi cac he;: trang du ng dich, su kha o sat phan tii' dua tren cac mo hi nh eo l<} p la khong
phil hop , Cac rna hinh phan ttl' trang pha lo ng ph a i bao ham anh hudng ella
ttl' CJ
moi tnrong phan irng (tnrong die;:n tll' ngoa i va
dung moi) va khai niern he;: phan
day phai th~ hien OLfQe stf t u ong hie giUa cac di~n tii"va hat nhan + rnd i truong phan ung. VI vay
cac tinh toan hoa IUQng ttl' tluro ng dua tren mot toan ttl' m~i:

Trang do :
- Truong ngoai Vex, bao g6m tnrong die;:n va nr "e 6 di€ 'n " .

- Truong dung moi VII bieu thi cac nrong tac phan ttl' chat tan - dung maio

Dai hoc DALAT

Thdng 0112002

/


LUJ,N VAN CA O HO C

17

D~ rna hinh hoa nrong tac phan til' eh§t tan - dung moi , ca c each tiep e~n e6 kha nan g

la :
1. Mo hrnh roi rae: rna ta cu th~ cac phan til' dun g moi tron g khon g gian so lva t hoa . 2.
Mo hinh lien tuc: xil' Iy dung moi nhir mot moi tnron g lien tuc vdi hang s6 dien
moi nhdt dinh .
3. Ca c rna hmh t6 hQP giffa ro i rae va lien tuc :
- Dfru tien xil' Iy kh6i d u sol vat hoa mot each ro i rae , sa u do xil' ly cac du ng mo i
baa xun g quanh bang mot rna hinh lien tuc .
.
- Cac rna hinh nay thuon g xil' Iy phan ben trong ella lop vo so lva t hoa ba ng eel hoc
IUQng til', phan be n ngoai ella ldp vo solvat hoa bang eo ho c phan til'.
1.5.1 Ma hlnh riJi rae :
Viec xa y dung rna hinh ro i ra e eh o mot h~ so lva t hoa thiron g xuft phat ba ng viec gia
dinh tnro c mot s6 nhat dinh ca c phan til' dung moi eho mot ph a n til' ch§t tan , thi du, tron g
phan irng thuy phan diin xuat hal og en :
\

C-C I

,"/

HO- C.

1

+

\'"

mo t rna hinh QM (rna hinh eo hoc IUQng til') ella cac ph an til' nude roi rae duoc sil' du ng ph 6
bi en e6 th~ bi~u di~n nhtr sa u:

Birdc tiep theo, til rna hinh gia dinh ne u tren xay du ng cac rna

hm h tnro ng life

ella cac phan til' nude roi ra e, e6 ba Ioai rna hinh di;ie tnrn g:
•

Ma hin h cirng vdi cac Wong ta c duo c rna ta bd i the' Co ulomb va Lennard - Jones .

•
•

Ca c rna hinh mern .

Ca c rna hinh phan cue.

Thi du : Ca c rna hin h cirng ella ca c phan til' nude : TIP3 P, TIP4P , TIP5P .

1.5. 2 Cdc rna hlnh salvat had lie n tue :

D{li ho c DA LAT

Th d ng 0112002

\


18

LUJN VAN CAD HQC

Cac mo hlnh lien tuc xe m dun g moi nhu mQt moi tnro ng pha n cue d6ng nhat vdi han g
s6 dien moi E c6 dinh, trang do phan til' chat tan M diro c d~H tran g mot 16 trong c6 hinh dang
thich hop . Khi do , nang hron g so lva t hoa diroc tinh the o bitiu thirc:
t1.G,o/v = t1.Gc/ec + t1.Gcav + t1.Gdi + t1.Gwh + t1.GiIh + t1.Golher
W>

tron g do :
t1.Gc/e<

\l\'Hr-v~~.N 8~\'H9C

• sc.;
t1.G

l'O

•••

Tiron g ta c Lo ndo n va Van de r waals.:~

\

C' A :'- ~T ,':7!'1 'N

.: L ~JC l.!.: J C;- - J
t1.Gwh •• • Nan g hron g dao dQng do bi kich thich .
P.
---t1.G'ihNang IUQng chuyen ttt da o dQng quay va tinh tie n thanh da o dQng tu do
t1.Golher
Ba o g6 m bien thien e nta lpi cua dun g rnoi , bien thien e ntrapi cau true,

d

•

--~

Tirong ta c tinh dien chat tan - dum g mo i .
Na ng hron g ta o thanh lo tr on g.

1;:'

CC

').1-::-:::- __

dai IUQng PV ...
Truong phan irng tra ng cac rno hinh lien tuc diroc phan biet theo narn tieu chi :
.:. Kich thua c va hlnh dan g ctia liJ tr/ing chdt tan .
•:. Phuong phdp tinh liJ trdng va cac ph /in bO°khu ech tan .
•:. SI! ph/in bodi en tich cua chat tan M .

•:. Tuy thuoc chdt tan M dua c rna ta ban g co ho c cd ditn hodc ca hoc l uang til.
•:. Tuy thuoc moi truon g dien moi duac rna ta nhu the' nao .
Trang mo hlnh lien tu c, phan d~m gifra chat tan va dung mo i dUQc goi la 16 tro ng ("cavi

a

ty"): chat tan dtroc duo c d~t ben trang 16 tron g, tai do ha ng s6 dien moi nron g d6i la E = I
(gia tri han g s6 di~n moi cua cha n khon g), tran g khi do ph an ben ngo a i cua 16 tro ng ha ng

a

s6 dien moi ciia dun g moi c6 giti tri nron g d5i IOn (VI du E cua nude
298 K la 78.39 ). Hlnh dan g va kich third c ciia 16 tron g la nhtrn g thon g s6 qu an tro ng cua
cac mo hi nh lien tuc . Ph6 bien nha t la cac mo hi nh : kh6 i d u i(Bo rn ), e llipsoid (Ons age r),
Van der Waals (Kir kwood).

K h81 du
(Born)

Ellipsoid
(Onsager)

van de r Waal S \

(Kirkwood)

D6i vdi phan IOn cac mo hlnh lie n tuc, cac nron g tac chil t ta n - du ng mo i diro c tinh toan
thon g qua mot nhi e u lo an diroc them vao toa n til' Ha mi lto n:
A

0A

H =H +V u

(I )

A0

Trang d6 : H

... Hamiltonian d6i vdi chat tan co I~p.

D(li ht;J c DALAT

Tha ng 0112002


LUf.,.N VAN CAO HO C

19
A

V" ... bi~u thi tnrong ph an irng cu a du ng moi , ng uC1i ta aft clui ng min h ding toan
bO tnron g ph an iing co th~ duo c mo ta dudi dang m~t dQ di<$ n tiel; (J xuilt hien tre n

b~ mij.tcavity . D~ thuan tien tinh to an co thli gia thiet

(J

la khon g ddi , vi v~y V" co thli bieu th j

dudi dan g td ng cac dien tich ai~m (" a i<$ n tic h solvat hoa ", [q. ]) aij. t tre n b~ mat cavity.

(2)

Tron g cac mo hinh so lva t hoa lien tuc co ban (PC M, D-P CM ), die n tic h so lvat ho a
phu thu o c vao cac hQP ph an thon g thiron g cua dien tnro ng tren b~ mat cavity, can tron g cac
mo hlnh ciii tien (I-PC M , SCI-PCM, C -P AM , IEF-PCM ...) thi phu thuoc vao the' tinh dien tre
n b~ mat cavity . Tron g bilt cu tnrong hQP na o , dien tfc~ so lvat hoa cling
dircc xac dinh bd i:

M~t dO dien ta va hat nhan cu a ph an ta ch ilt tan (V" la mot nh ieu lo an phi tu ye n, ph u

•

thu oc va o ham so ng) .

Vi vay , d~ tim dien tich so lva t hoa d n phai giai h<$ N puo ng trinh tuy en tinh lie n
hop , vdi N la s6 b~ mat yeu t6 (tesse ra e) hinh thanh cavi ty .
Truo ng phan rrng tron g thuc te' co th~ diroc tinh vdi ca c a lgorith m' PCM kha c nhau tuy
th uoc vao viln d~ ngh ien ciiu cu th~, nhung no i chu ng trong m6 i vo ng Iij.p SC F dien tic h so
lvat ho a thuon g diro c xac dinh bling ea ch gid i h<$ phiron g trinh tuye n tinh:
(3)
D q = -bso\
•

Trong 06 , vector q ch ua die n tich , vec tor b ch ua the' tinh dien va rna tr~n D phu thuoc vao
hling s6 dien mo i cua d ung moi va cac tho ng s6 hl nh hoc qu i dinh hm h dang cua ca vity . Voi sir co
ma t ciia cac die n tich so lvat hoa , roan ta Foc k diroc biliu thi bd i
cac ph irong trinh :
A
A

0

A

A

0

0

=

F =F +V = F
F=F + V
A

A

0

A

0

{

+"~.

L. lr-r,1

= F + L~.= F + L._
A

0

.

A

Z
11 _

d day

:

III1e1e!

~1ll1C
=

L

II

h-

va

v/ = -

+"..

D~'

7 Ir {

)

_ Y_ ( E'lllc_ EeI

F

A

(I
tp

I

;1

J

tJ _. ( v ·me _ V

D-'

0

tJ

Jr - r, I
Sol ute

0

Ir - I;I

Ir- II )
rJ tp

J

eI

J

\

)

)

J

}

(4)

la cac phan b6 ha t nhan

rjl
pha n b6 die n ta d6i voi the' tinh ai<$n chilt tan trong b~ mij. t ye'u t6 thu j ; va E]''',£;' la cac di
<$n truong tho ng th uo ng cua cac hlj, t nhiln va cac di<$n ta d6i voi b~ mij.t cavity .

D g i hQCDALAT

Thdng 0112002

va


L Uf, N VAN CAO HOC

20

Bi~u thuc (4) cho phep ta bi~u thi toan tu Fock nhi eu loa n tre n co so mQt

ngu yen tu

{lxl' )'\Xv)}:
; 1' "

=;0-~Ir~~JI(Xl' I,.-Ijl-Ilx,.)

(5)

hoa c bi~u thiic tuon g diron g vdi toan tu di~n tnron g .
VI roan tu tnron g ph an irng phu thuo c vao ha m s6 ng cua pha n tu chilt ta n (nghi a
A 0

la n6 la mQt nh ieu loan ph i tuyen d6i vd i H ), nen kh i eire ti~u bien se suy ra diro c nan g luon
g nr do tron g dung dich:
G =/ \fl
\

iJo+~V
2

o

2

\fl)+~IqV "IIC = / \fl iJo\fl)+~')q(V"IIC+ Vel)
I

"

2 '7"

\

I

,

= / \fl iJo+~I .si: \fl)+~Iq,V,"IIC
\

2 ,

I,. - 'iI

(6)

2 ,

M s6 Yz xua't hien la do mot mra nang luong nrong tac chdt ta n -

dun g mo i dil duoc su

dun g i
Cac phtron g trinh (4) , (5), (6) c6 th~ kha c nhau d6 i vd i cac nhi eu loan be n ngoa i
(dien tnron g , tu tnrong) va d6 i vdi cac toa dQ hat nhan . Chung cho phep tinh toa n giai tich cac
gradient na ng hrcn g nr do va cac vi phan bac ha i: ca c da i IUQng nay duo c du ng

i tilt ca cac mo hinh PCM , cac phucng trlnh tren la algorithm ra't hieu q ua d6i vd i cac tho ng s6 hin h hoc , N6 dftn de'n viec them vao
gradient cu a cac phan tu co I? p s6 hang sa u day:

2
Trang d6 :

[~IInq,v,]X='"I q,v,x+

v,xla vi ph a n rieng phan cua

21Z'C

I ~,(x)
I

(7 )
I

C-

I 'ErOJ

V, d6i vdi tho ng s6 x.

S6 hang V, (x) lien qu a n de'n cac thon g s6 hmh ho c c ua cavity, tuy nh ie n trang
cac tinh toa n thuc te' ngiro i ta thirong bo qu a dai hron g na y va thu diroc cac ke't qu a giln
dung kha t6 t d6i vdi cha't tan phan cue tro ng dun g moi phan c ue.
1.5 .3 Cdc phu(Jflg pM p [6 help OM/M M :
Cac phirong phap co hoc phan tu (MM) c6 th~ mo hln h hoa cac h~ thon g ph a n tu IOn
rilt de dang va nhanh ch6 ng . Cac phirong phap co hoc luo ng tu :c6 kha na ng Hnh toan nh i8 u
Hnh cha't va mo hln h hoa cac pha n ung hoa hQc, Vi~c ke't hejp hai phuong ph a p na y lil giai
phap c6 tri~n vQng hlnh hoa biing MM , co n philn di)c bi~t eua pha n tu dUQc xu ly biing QM . Thl dl,! : d6i vdi

vi~c mo hlnh hoa co che' cua mQt enzyme, phuo ng phap MM kho ng cho ke't qu a t6t , va ne'u su
dl,! ng phuon g pha p QM m(H cach dQc I?p thi qu a dilt

Dq.i hQc DALAT

Thdng 0112002

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