715

Tp ch Ha hc, T. 45 (6), Tr. 715 - 721, 2007

TNG HP, CU TRC VA HOAT TNH SINH HC CA MT VAI
PHC CHT cis-ICLORO(SAFROLE)(AMIN)PLATIN(II)
n Ta son 9-2-2007
Nguyn Th Thanh Chi, Trn Th
Trng i hc S phm H& Ni
Summary
Three complexes of platinum(II) including cis-[Pt(Saf)(piperridine)Cl
2
] (P4), cis-[Pt(Saf)
(aniline)Cl
2
] (P5), cis-[Pt(Saf)(o-toluidine)Cl
2
] (P6) have been synthesized. The structure of the
complexes have been determinded by elemental analysis, molar conductivity, API MS, IR, Raman,
electronic and
1
H NMR spectra studies. The biological test shown that complexes P4 exhibit
antimicrobial activity on C.albicans, P5 on E. coli bacterium and F. oxysporum. P4 exhibit
inhibitor activity on Hep-G2 cancel cell, P6 on Hep-G2 and RD cancel cell at concentration 1.7 -
3.2 g/ml.

I - M u
Phc cht ca platin c ng dng lm xc
tc cho nhiu qu trnh tng hp hu c trong
cng nghip nh oxi ha olefin, refoming trong
ha du...[1]. Phc cht platin(II) - olefin
thng l cht trung gian quan trng trong
nhiu qu trnh . V vy, phc cht ca
platin(II) cha olefin ngy cng dnh c s
quan tm nhiu phng th nghim trn th gii
[2, 3]. Tuy nhin, phc cht ca platin(II) vi
safrole (olefin c tch t tinh du x x) hu nh
cha c nghin cu.
Trong bi bo trc [4], chng ti I thng
bo iu kin tng hp v xc nh cu trc ca
mt s phc cht trans-[Pt(safrole)(amin
thm)Cl
2
]. Tip theo, trong bi bo ny chng
ti trnh by kt qu: tng hp, cu trc v hot
tnh sinh hc ca mt vi phc cht cis-icloro
(safrole)(amin)platin(II). Safrole c cng thc
CH
2
=CHCH
2
C
6
H
3
OOCH
2
c vit tt l Saf.
II - Thc nghim
1. Tng hp cc phc
- Tng hp P1, P2, P3: Phc cht P1, P2 v
P3 ln lt c tng hp theo phng php m
t trong ti liu [5 - 7] tng ng.
- Tng hp P4, P5, P6: Cho t t khong 1,5
mmol dung dch safrole vo dung dch bIo ho
ca 1 mmol P1, P2 v P3 tng ng. Khuy
dung dch phn ng 30 40
o
C (i vi phc
cht P4, P5) v 15 20
o
C (i vi phc cht P6)
trong khong 6 gi. Lc, thu kt ta v ra ln
lt bng dung dch nc v ru lnh nhiu ln.
Sn phm c kt tinh li trong hn hp ru-
nc.
2. Phng tin v phng php nghin cu
- Hm lng Pt c xc nh bng phng
php trng lng. dn in phn t o trn
my HI 88119 N ca M ti Khoa Ha hc,
Trng H S phm H Ni. Hm lng C, H,
N c xc nh bng phng php phn tch t
ng trn my NCHS system.mth. Phn t khi
ca cc phc cht c xc nh t khi ph o
trn my 1100 Series LC - MSD - Trap - SL ca
hIng Agilent theo phng php API-MS
(Atmosphere Presure Ionization Mass
716
Spectrocopy). Ph Raman ghi trn my Micro
Raman LABRAM trong vng t 4000 - 100
cm
-1
. Ph IR c ghi trn my IMPAC-410-
NICOLET trong vng 4000 - 400 cm
-1
. Ph UV
c ghi trn my GBC Instrument - 2855. Ph
1
H NMR ca cc phc cht c o trn my
Brucker ADVANCE (500 MHz) ti Vin Ha
hc, Vin Khoa hc v Cng ngh Vit Nam.
- Hot tnh sinh hc ca cc phc cht c
th ti Phng th nghim hot tnh sinh hc,
Vin Ha hc Cc hp cht thin nhin, Vin
Khoa hc v Cng ngh Vit Nam.

III - Kt qu v tho lun
Vic tng hp, xc nh cu trc cc phc
cht u K[Pt(piperiin)Cl
3
] (k hiu l P1),
K[Pt(anilin)Cl
3
].H
2
O (k hiu l P2), K[Pt(o-
toluiin)Cl
3
].H
2
O (k hiu l P3) I c phn
tch k trong cc ti liu [5 - 7] tng ng.
Theo qui lut nh hng trans, khi thay th 1
nguyn t clo trong phc cht K[Pt(amin)Cl
3
] bi
1 phn t Saf s to ra sn phm trong Saf v
tr cis so vi amin. Phn ng xy ra nh sau:

(P1, P2, P3 ) (P4, P5, P6)
amin: C
5
H
10
NH (P1, P4), C
6
H
5
NH
2
(P2, P5), o-CH
3
C
6
H
4
NH
2
(P3, P6)

Sau khi kt tinh li, phc cht P4 c dng
hnh kim mu ghi, phc cht P5, P6 c dng
tinh th nh mu nu vng v vng trng tng
ng. Khi lng phn t c xc nh bng
phng php ph khi, trn thit b LC-MSD-
Trap-SL vi ngun bn ph API. c im ca
cc phn t phc cht nghin cu l c cha 1
nguyn t Pt v 2 nguyn t Cl. C 2 nguyn t
ny u c ng v hm lng ln:
35
Cl 75,77%,
37
Cl 24,23%,
194
Pt 32,9%,
195
Pt 33,8%,
196
Pt 25,3%,
198
Pt 7,2%. T cm pic phn t s bao gm rt
nhiu pic v do vy vic nhn ra pic ion phn t l
phc tp. Theo quy c, khi lng phn t c
tnh theo khi lng ca cc ng v c hm
lng ln nht. Nh vy khi lng phn t ca
cc hp cht nghin cu s c tnh vi cc
ng v
12
C,
1
H,
14
N,
195
Pt,
35
Cl v
16
O. Do , nu
tnh theo s khi quy trn ca cc ng v th, th d
khi lng phn t ca P4 s l M= 516. T nhng
gi tr l thuyt ny (M
l thuyt
), chng ti I quan st
v tm ra ph MS thc nghim ca cc phc cht
P4, P5, P6 cc pic c gi tr tng ng (M
thc nghim
).
Hm lng Pt, C, H, N ca cc phc cht ph
hp vi cng thc d kin (bng 1). dn in
phn t ca dung dch cc phc cht o ngay
sau khi pha c gi tr 12 15
-1
.cm
2
.mol
-1
cho
thy cc phc cht thu c l phc trung ho
khng in li (bng 1).
Cc vn hp th chnh trn ph IR v
Raman ca cc phc c qui kt da theo ti
liu [8, 4] v c lit k bng 2.
Bng 2 cho thy, hu ht cc vn hp th
xut hin trn ph IR th cng xut hin trn
ph Raman v u c trng cho cc nhm
nguyn t trong phn t ca cc phc cht (do
pht hunh quang mnh nn khng ghi c ph
Raman ca P5, cn trn ph Raman ca P6
khng quan st thy vn yu vng trn 3100
cm
-1
).
S xut hin vn hp th c trng cho dao
ng ha tr
Pt-N
vng 666 430 cm
-1
trn ph
dao ng ca tt c cc phc cht P4 P6 v
vn hp th c trng cho dao ng ha tr
NH

vng 3256 3174 cm

-1
(1 vn i vi ca phc
cht cha amin bc 1 l P4 v 2 vn i vi i
vi phc cht cha amin bc 2 l P5, P6), gim
so vi cc amin t do (3450 3300 cm
-1
) I
chng t c s to phc ca cc amin vi Pt(II)
qua nguyn t nit ca amin.
Vn hp th
C=C
allyl Saf t do th hin
khong 1640 cm
-1
[8]. Trn ph dao ng ca cc
phc P4 P6, vn ny th hin vng 1628
Pt
Cl
Cl Cl
amin
K
+
+ KCl
safrole
Pt
Cl
Cl safrole
amin
717
1480 cm
-1
. Tn s c trng cho dao ng ha tr

C=C
allyl cc phc cht chuyn dch v vng
tn s thp nh vy cng vi s xut hin vn c
trng cho dao ng ha tr

Pt-C=C
trn ph Raman
ca phc cht P4, P6 cho php ta khng nh
trong phc cht P4 P6, Saf phi tr vi Pt(II)
qua lin kt i C=C nhnh allyl [1, 8].
Cc vn hp th trn ph electron ca cc
phc cht tng hp c ch ra bng 3.
Bng 1: Phn t khi, hm lng nguyn t, n in phn t () ca cc phc cht
Phn t khi, hmlng nguyn t,
(% l thuyt/% thc nghim) K
hiu
Cng thc phn t
M
l thuyt

M
thc nghim

Pt hoc
Pt+K
2
SO
4
C H N
(
-1
cm
2
mol
-1
)
P4 [Pt(Saf)(C
5
H
10
NH)Cl
2
]
516
516
38,77
38,45
- - - 15
P5 [Pt(Saf)(C
6
H
5
NH
2
)Cl
2
]
524
524
37,43
37,80
36,85
39,08
3,65
3,20
2,69
2,69
12
P6 [Pt(Saf)(o-CH
3
C
6
H
4
NH
2
)Cl
2
]
538
538
36,45
36,24
38,13
36,37
3,55
4,04
2,62
2,79
14
Bng 2: Cc vn hp th chnh trn ph IR v Raman ca cc phc cht
IR (cm
-1
) / Raman (RAM) (cm
-1
)
Phc
cht

NH

CH (thm, anken)

CH (bo)

NH
,
C=C

Pt-N

Pt-C=C

Pt-Cl

PtCl2
IR 3174 3056 2942, 2864 1610, 1489 430 - - -
P4
RAM 3179 3070 2952, 2868 1628, 1502 666 372 324 190
P5 IR 3256, 3213 3090 2898 1599, 1494 449 - - -
IR 3254, 3182 2981 2895 1582, 1480 479 - - -
P6
RAM - 3067 2984 1590,1500 544 484 338 179
Bng 3: Cc vn hp th trn ph electron ca cc phc cht v safrol t do
Hp cht K hiu

max
(nm)/lg
Saf t do - 265 / 3,98 304 / 4,19
[Pt(Saf)(C
5
H
10
NH)Cl
2
] P4 202 / 4,52 - 288 / 3,24
[Pt(Saf)(C
6
H
5
NH
2
)Cl
2
] P5 202 / 4,63 233 / 4,12 285 / 3,85
[Pt(Saf)(o-CH
3
C
6
H
4
NH
2
)Cl
2
] P6 205 / 3,97 259 / 3,68 288 / 3,48
Bng 3 cho thy, khc vi ph eletron ca
Saf v amin t do [8], trn ph electron ca cc
phc cht P4 P6 u xut hin vn hp th
khong 203 nm vi cng mnh (lg = 3,97
4,63), y l vn do chuyn mc km chuyn
in tch t Cl
-
n Pt(II) [9]. vng 233 304
nm, trn ph electron ca cc phc cht xut
hin 1 hoc 2 vn hp th vi cng kh
mnh, lg = 3,24 4,12 ( Saf v amin thm t
do tng ng cng th hin 2 vn nhng khc
bit v gi tr
max
v lg), y l do s t hp
ca cc vn c trng cho chuyn mc -
*

phi t vi cc vn do chuyn mc km chuyn

in tch t Saf n Pt(II) v ngc li [9].
718
quy kt c chun xc tn hiu ca cc
proton Saf trn ph
1
H NMR ca cc phc cht
tng hp c, chng ti da vo dch
chuyn ha hc (), cng , s tch vn ph
do tng tc spin - spin, gi tr hng s tch J
i vi mi vn ph v ti liu [8]. thun tin
cho vic phn tch ph, s ch v tr phi t
safrole c ghi nh trong hnh 1. Kt qu phn
tch c trnh by bng 4.
Bng 4 cho thy, c rt nhiu s khc bit
gia tn hiu cng hng ca cc proton ca Saf
trong cc phc cht nghin cu so vi tn hiu
tng ng ca chng Saf t do, l: S tn
hiu cng hng ca proton trong cc phc cht
nhiu hn 1 so vi Saf t do, nguyn nhn l
do 2H8 Saf t do tng ng v chng th
hin bi 1 tn hiu, cn cc phc cht chng
tr nn khng tng ng v th hin bi 2 tn
hiu (chng ti k hiu l H8a v H8b).
chuyn dch ha hc ca tt c cc proton (tr
H8a, H9 v 2H10) u tng. Hnh dng ( bi)
ca tt c cc proton tr H3, H7 trong cc phc
cht v H5, H6 trong phc cht P4, P6 u thay
i. iu ny khng nh Saf I phi tr vi
Pt(II) qua C=C nhnh allyl.

C C
Htrans
Hcis
CH
2
O
CH
2
H
10 9
8
1
2
3
4
5
O
6
7
Hnh 1: S ch v tr cacbon phi t Saf
Vic phn bit H10cis, H10trans v gii
thch s khng tng ng ca 2 proton H8
safrole khi phi tr vi Pt(II) I c phn tch
k trong [4, 10].
S gim mnh chuyn dch ha hc ca
cc proton H9, H10 (nhng proton ngay trung
tm to phc) so vi safrol t do I khng
nh s phi tr ca Saf vi Pt(II) qua lin kt
C=C ca nhnh allyl theo kiu lin kt ba tm
[4, 10]. Kiu lin kt ba tm ny cn th hin r
phc cht P4 qua tn hiu v tinh (mi tn
hnh 2a) do tng tc spin - spin ca
195
Pt vi
H9, H10cis v H10trans. Khong cch gia 2 tn
hiu v tinh ny chnh l gi tr hng s tch
2
J
PtH
v xc nh c l 68 Hz. Gi tr ny
ph hp vi cc cng trnh trc y I cng b
v phc ca Pt(II) vi olefin [4, 10, 11].
Bng 4: Tn hiu proton ca Saf trong cc phc cht v Saf t do (ppm); J(Hz)
Phc
cht
H3 H5 H6 H7 H8a H8b H9 H10trans H10cis
Saf
t do
6,65; d
4
J 1,5
6,60; dd
3
J 7,5;
4
J 1,5
6,70; d
3
J 7,5
5,8
5 s
3,26; d
3
J 6,5 5,90; m 5,04; m 5,02; m
P4 7,00; s
6,90; d
3
J
7,5
6,79; d
3
J 8,0
5,96
s
3,07, ov
3,52; dd
2
J 14,5;
3
J 6,0
4,75; m
J
PtH
70
4,46; d
3
J 13,5; J
PtH
65
4,20; d
3
J 7,5
J
PtH
68
P5 6, 83; s 6,76, un
6,76,
un
5,94
s
2,90; dd
2
J 15;
3
J 6,5
3
J
PtH
50
3,40; dd
2
J 15;
3
J 7,0
4,74; br 4,44; br 3,97; br
P6 6,86; s
6,75, dd
3
J 9,0;
4
J 1,0
6,76, dd
3
J 9,0;
5
J 0,5
5,9
8s
2,86; dd
2
J
15;
3
J 6,5
3
J
PtH
50
3,45; dd
2
J 15;
3
J 6,5
4,37; br 4,29; br 3,46; br
s: singlet (vn n); d: doublet (vn i); dd: doublet of doublets (vn i - i); m: multiplet (vn bi),
br: broadened (vn rng), ov: overlapped (b xen lp), un: unresolved (khng phn gii).
phc cht P4, tn hiu cng hng ca cc
proton thm (H3, H5, H6) v proton anken (H9,
H10cis v H10trans) c chuyn dch ha
hc, hnh dng v gi tr J ph hp vi l thuyt
(hnh 2a) v ging vi tn hiu tng ng ca n
trong phc cht K[Pt(Saf)Cl
3
] [10] v trong mt
s phc cht trans-[Pt(Saf)(amin thm)Cl
2
] [4].
Nhng trn ph ca phc cht P5, P6, tn hiu
719
cng hng ca H5 v H6 khng phn gii r
rng, cn tn hiu ca H9, H10cis v H10trans
th th hin dng vn t (hnh 2b). Chng ti
cho rng s chn xa ca dng in vng ca
amin thm v tr cis vi safrole I nh hng
ti cc proton thm v proton anken ca safrole.
piperiin khng c dng in vng nn mc
d n v tr cis so vi Saf cng khng lm nh
hng n tn hiu ca cc proton ny.
Tng t nh trn, da vo chuyn dch
ha hc, cng vn ph v c bit l s tch
vn ph do tng tc spin - spin ca cc proton
v theo ti liu [8, 12] chng ti I quy kt c
tn hiu ca cc proton trong cc amin phi tr
vi Pt(II) nh trong bng 5.
So snh vi cc amin t do [8] th chuyn
dch ha hc ca tt c cc proton tng ng
amin trong cc phc cht nghin cu u ln
hn, c bit l proton nhm amino. Ring
phc cht P4, s proton khng tng ng
piperiin phi tr tng ln nhiu so vi
piperiin t do [8] v tn hiu ca chng khng
phn gii r rng nh phc cht
K[Pt(piperiin)Cl
3
] [12] do nh hng bi s
chn xa ca nhn thm safrol. iu chng
t cc amin ny I phi tr vi Pt(II) qua N v
tr cis so vi safrol.
T cc kt qu phn tch v qui kt trn
cho thy cu trc ca cc phc tng hp c
ph hp vi cng thc ngh hnh 3.

Hnh 2: Tn hiu cng hng ca H3, H5, H6, H9, H10trans v H10cis phc cht
a) cis-[Pt(Saf)(piperiin)Cl
2
] (P4), b) cis-[Pt(Saf)(anilin)Cl
2
] (P5)
Bng 5: Tn hiu proton ca cc amin trong cc phc cht nghin cu, (ppm); J(Hz)
Cht Am H12 H13 H14 H15 H16 H 17 NH
P4
a
a
a a
a
e
e
e
e
e
12
13
14
15
16
HN
e: 3,13;

d
2
J
ea
12
a: 3,37; m
e: 1,64; m
a: 1,58; m
e: 1,62; m
a: 1,46; m
e: 1,64; m
a: 1,58; m
e: 3,01; d
2
J
ea
12
a: 3,27; m
_
4,15
br
P5
16 12
13
14
15
NH
2
7,34;
m
7,28; m
7,25;
m
7,28;
m
7,34;
m
_ 5,91 br
P6
16
13
14
15
CH
3
11
NH
2
17

_
7,29; d
3
J 7,5
7,18; t
3
J 7,0
7,22; td

3
J 7,0;
4
J 1,5
7,29; d

3
J 7,0
2,46; s 6,65 br
t: triplet (vn ba); td: triplet of doublet (vn ba i), cc k hiu khc ging bng 4.

a) b)
H9
H10trans
H10cis
H9
H10trans
H3
H5 H6
H3
H5
H6
NH
H10cis
720
Pt
Cl
Cl N H
CH
2
CH
2
CH
CH
2
O
O
Pt
Cl
Cl
CH
2
CH
2
CH
CH
2
O
O
NH
2
Pt
Cl
Cl
CH
2
CH
2
CH
CH
2
O
O
CH
3
NH
2
Hnh 3: Cu trc ca cc phc cht tng hp c
Kt qu th hot tnh sinh hc ca cc phc
cht tng hp c trn 2 i tng l vi sinh
vt kim nh v t bo ung th ngi, bao
gm t bo ung th gan (Hep-G2), t bo ung
th mng tim (RD) v t bo ung th phi (LU)
cho thy, phc cht P4 khng nm men
C. albicans v c ch s pht trin t bo ung
th gan vi hot tnh rt mnh (IC
50
= 1,7
g/ml), P5 khng vi khun E. coli (vi khun gy
bnh ng rut) v nm mc F. oxysporum.
P6 c ch c 2 dng t bo ung th Hep-G2 v
RD vi hot tnh kh mnh (bng 6).

Bng 6: Kt qu th hot khng vi sinh vt kim nh v c ch pht trin t bo ung th ngi
Nng c ch ti thiu (MIC: g/ml)
Vi khun Gr (-) Vi khun Gr (+) Nm mc Nm men
Phc
cht
E. coli P. aeruginosaB. subtillis S. aureus Asp. niger F. oxysporum S. cerevisiae C. albicans
P4 > 50 > 50 > 50 > 50 > 50 > 50 > 50 50
P5 25 > 50 > 50 > 50 > 50 50 > 50 > 50
Nng c ch 50% i tng th IC
50
(m/ml)
Hep-G2 RD LU
P4 1,7 > 5 -
P5 >5 >5 -
P6 2,39 3,19 >5
Ch : MIC < 50, IC
50
< 5

l c hot tnh, cn MIC > 50, IC
50
> 5 l khng c hot tnh

IV - Kt lun
I tng hp c 3 phc cht cis-
icloro(safrole)(amin)platin(II) cha c m t
trong cc ti liu l: cis-iclorosafrolepiperiin-
platin(II), cis-iclorosafroleanilinplatin(II) v cis-
iclorosafrole octhotoluiinplatin(II). Cu trc
ca cc phc cht I c xc nh da vo kt
qu phn tch hm lng Pt, C, H, N, phn t
khi, o dn in phn t, phn tch ph IR,
Raman, ph hp th electron, ph API MS v
ph
1
H NMR.
Kt qu th hot tnh sinh hc ca 3 phc
cht P4, P5 v P6 cho thy, phc cht P4 khng
nm men C. albicans v c ch s pht trin t
bo ung th gan vi hot tnh rt mnh, P5
khng vi khun E. coli v nm mc F.
oxysporum, P6 c ch c 2 dng t bo ung th
gan v mng tim vi hot tnh kh mnh
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(1974).
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10855 (2000).
(P4) (P5) (P6)
721
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