TAP CHi HOA HOC T.50(6) 721-726 THANG 12 NAM 2012
PHU'C Fe(lll) V a i BAZa SCHIFF ISATIN-8-AMINOQUINOLIN:
T 6 N G H O P , C A U TRUC VA HOAT T I N H SINH HOC
Phan Tir Quy', Duwng Tuan Quang^*, Tran Dl^ffng^ Nguyen Thi Quynh O a n h \ Nguyen Hiru Hien^
Khoa Hoa hgc, Dgi hgc Tdy Nguyen
^Khga Hoa hgc. Dgi hgc Suphgm-Dgi hgc Hue Din Toa sogn 30-5-2012
Abstract
Fe(III) complex of Schiffbase from isatin and 8-aminoquincline has been synthesized and characterized by MS and NMR spectra. The data showed that there were two complexes found in the product with the formulae [FeLClj] and [FeL(HS04)3] (L = isatin-8-aminoquinoline). Both had the octahedral geometry and their fragmental schemes under bombardment in the mass specUomeler were established. Their antibacterial, antiflingal activities were also tested
Keywords: Fe(IIl) complex, Isatin, 8-aminoquincline.
l.DATVANDE
Isatin dugc biet den nhu la mot thudc thir mau cho aminoaxit prolin, tgo thanh mgt dan xuat mau xanh [1]. Tinh chat dd da dugc khai thac de xac dinh lugng aminoaxit nay trong phan hoa va cac thanh phan thyc vgt khac bang each sir dyng sac ky giay [2, 3]. No ciing da dugc sir dung trong xet nghiem sang lgc theo phuang phap so mau de thir chung tang proline trong huyet thanh ciia ngudi. Isatin con dugc sir dyng trong vi?c xac dinh do boat dgn^
enzyme cua men khu ketopantoyl-lacton va mgt sd men khir khac. Khi tac dyng vdi amin se tao thanh baza Schiff isatin cd hogt tinh sinh hgc dang quan tam nhu hogt tinh khang nam [4-7], khang khuan [8- 10], kha nang Ore chi sy phat trien t6 bao ung thu, cung nhu kha nang chdng lgi vi khuan HIV [11,12].
Cac nha khoa hgc ciing nhgn thay rang bazo Schiff isatin co kha nang tgo phiic rat tot vdi ion kim logi chuyin tiep. Dieu dang luu y la, sau khi tgo phuc hogt tinh sinh hgc dugc tang len dang ke so vdi isatin va baza Schiff isatin [13-16].
Trong bai bao nay chung tdi trinh bay sy tong hgp, die trung va tham dd hoat tinh sinh hgc cua phijrc chat tgo thanh giiJa Fe(lII) va bazo Schiff isatin-$-aminoqulnolin.
2.THUCNGHI$M 2.1. May mdc vk tbi^t b}
- Ph6 hong ngoai dugc do tr6n may quang pho
ke hong ngogi FTIR IMPACT 4010 (CHLB Dire), Vi?n Hoa hgc, Vien Khoa hgc va Cong ngh^ Viet Nam.
- Pho khoi lugng dugc do tren may LD-MSD- Trap-SL (Nhgt Ban) ciia Vi^n Hoa hgc, Vi?n Khoa hgc va Cong ngh? Vi^t Nam.
- Pho cgng hudng tir proton dugc do tren may cgng hudng tir hgt nhan phan giai cao 500 MHz (Brucker, Due) d phong cgng hudng tir hat nhan, Vi?n Hoa hgc, Vi?n Khoa hgc va Cong nghe Viet Nam.
- Vi?c thir boat tinh khang vi sinh vat kilm dinh dugc tien hanh theo 2 budc. Budc 1: Thu djnh tinh theo phuang phap khuech tan tren thgch, sir dung khoanh giiy lgc tam chat thir theo nong dp tieu chuan. Budc 2; Cac mau cho hogt tlnh (+) d budc I se dugc tien hanh thu tilp d budc 2 de tinh ra nong dg ire chi toi thieu (MIC) theo phuong phap ciia Vander Bergher va Vlietlinck (1991), MCKane, L.,
& Kandel (1996) tien hanh tren cac phien vi lugng 96 gieng. Cac chiing vi sinh vat kiem djnh bao gom:
vi khuan Gr(-), vi khuan Gr(+), nim m6c, nkm men.
2.2. Tong hqrp phiirc chat
Hoa tan 0,1825 gam isatin trong 30 ml C2H5OH
(dung djch A); 0,1790 gam 8-aminoquinolin trong
15 ml C2H5OH (dung dich B); 0,6304 gam
Fe2(S04)3-6H20 trong 40 ml H^O (dung djch C). Rot
tir tir dung dich A vao dung djch B, khuay deu dugc
dung djch mau vang da cam cd pH ~ 6-7 (dung dich
X). Dun hoi luu va khuiy 30 phut d nhi^t dO SCC
T C H H , T. 50(6), 2 0 1 2
roi chinh d i n p H = 3-4 b a n g axit H C l loang, sau d 6 dun hoi luu va k h u a y d u n g djch X them 3 0 phiit. R6t tir tir d u n g dich C v a o d u n g djch X , khi d o d u n g djch chuyen tir mau v a n g da c a m s a n g v a n g lye ( d u n g djch Y). T i l p tyc d u n hoi luu va khuay d u n g djch Y them 1 gid nua, hon h g p cd mau den tim roi d u n hoi luu trong v o n g 4 gid d nhi?t dg S C C . Hdn h g p sau phan img de yen cho ket tinh, sau k h o a n g 4 8 gid xuat hipn nhii'ng tinh the mau xdm. Lgc rira tinh
Duong Tudn Quang vd cgng sif the b a n g n u d c cat, rira n h a n h b a n g etanol loBng. Ket tinh lgi t r o n g h d n h g p c t a n o l - n u d c . L a m kho nhthig tinh the t r o n g binh hiit a m chu'a silicagel.
3 . K E T Q U A V A T H A O L U ^ N
Hinh 1 trinh bay p h o khoi l u g n g c u a phu-c. MSu d u g c ban p h a b a n g d d n g electron cd nang lirgng 70 e V .
Average (rf 7.968 lo 8 661 mm 0ANH-MAU1
Hinh T. Pho kh6i l u g n g ciia phiirc Tren pho nay xuat hi^n cym pic m / z = 4 3 4 , m/z
= 432, m/z = 4 3 5 , m/z = 436 phii h g p vdi so khoi ciia phan tir phirc [FeLCl3]. T r o n g phd con xuat hi^n cym pic m/z = 3 9 9 , m/z = 3 9 7 , iing vdi manh C n H i | N 3 0 F e C l 2 ^ d o sy mat di mgt nguyen tir Cl lir ion phan tu. S y xuat hi^n cym pic m/z = 3 6 4 , m/z - 3 6 2 , m/z = 3 6 5 , m/z = 366 va cym pic m/z = 3 2 9 , m/z = 327, m/z - 3 3 0 , m/z = 331 u n g vdi manh C n H i i N j O F e C r , C n H n N j O F e ' d o sy mat t i l p nhirng nguyen t u Cl con lgi.
Sy xuat hien pic m/z = 273 irng vdi vdi manh phoi tir C n H n N j O * . N g o a i ra con co cac pic m / z = 145, m/z = 128 t u o n g irng vdi c a c manh chi chira thanh phan hiru c o : C6H,C2NHON*, CeH^CjHjN^ d o ion C I T H U N S O ^ tiep tyc bj ban pha.
Beti cgnh d o , trong phd khoi l u g n g ciia m a u nay cdn xuat hi?n cum pic m/z = 6 1 8 , m/z = 6 2 0 , m / z =
6 2 1 , m / z = 6 2 2 phii h g p v d i sd khoi cua phiirc [FeL(HS04)3]. N h u vgy, t r o n g san pham t6ng hgp ciia c h u n g tdi ton tgi d d n g thdi hai phuc chai [ F e L C l 3 ] v a [ F e L ( H S 0 4 ) 3 ] .
M g t s6 k i t q u a tinh toan ti 1? giifa cac pic dirtjic trinh bay d b a n g 1. C a c so lieu cho thay co syph"
h g p c a o gitta ly t h u y i t va t h y c nghi?m, chiimgtosii qui ket c u a chiing toi la d a n g tin cay.
S o d o p h a n m a n h c u a phirc [FeLClj] khi bj ban pha trong p h d khdi l u g n g d u g c trinh bay tr£n hinh2.
S o d o p h a n m a n h ciia p h u c [FeL(HS04)3] cung t u o n g t y .
Di p h a n tich p h o c g n g h u d n g tii proton cua iAi»
tong h g p , t r u d c tien chiing tdi m d phong pho n' N M R ciia phoi tii b a z a Schiff isatin 8-aminoquinoliD sir d y n g p h a n m e m C h e m D r a w Ultra 9.0 (hinh 3).
rCHH, T. 50(6), 2012 PhOc Fe(LII) vdi baza Schiff...
Bdng 1: Ti 1? phan tram cac pic tinh theo ly thuyet va thyc nghigm doi vdi mlu OANH-MAUl
Cdc manh cua mlu OANH-MAUl CHuNjFeOCIj C„H,|NjFeOCl2 CHiiNjFeOCl CnHiiNjFeO CH.iNjO CjHsNiO CsHjN
m/z 434 399 364 329 273 145 128
M, %
100 100 100 100 100 100 100
M-2, % LT 6,32 6,32 6,32 6,32
TN 5,81 6,12 5,88 5,35 1,52
X
X
M+1,%
LT 20,69 20,68 22,58 19,67 18,28 10,87 9,46
TN 23,25 22,45 22,06 21,42 21,37 10,13 8,89
M+2, % LT 97,53 65,59 33,67 1,74 1,38 0,287 0,367
TN 94,18 63,26 33,82 3,57 0,76 0,267 0,36
m/z = 273 m/z = 329 Hinh 2: Sa d6 phan manh ciia phirc chat [FeLCb]
So sanh phd thiic nghi?m (hinh 4) cua phiic vai pho mo phong a tren, co th8 quy Icet cac tin hi?u xuat hi?n tren ph6 thirc nghi6m nhir sau: ^
Tin hieu singlet xuit hi?n a viing truong yeu nhdt CO dp chuyjn djch hoa hoc <5 11,64 ppm ung vdi proton H(ll) cua v6n§ isatin. Tin hifu doublet xuat hi|n cr vimg truang yeu eo d? chuyen djch hoa hgc .59,11 ppm ilng voti proton H(l) do tuan^g tac spin-spin v6i proton H(2). Cac tin hifu nay deu co dp chuyen djch hoa hpc 16n hom so vai a phoi t i . Dieu d6 c6 the giai thich nhu sau, khi tao phiic c4e electron se chuyen djch v6 phia ion kim loai, dong thdi do nguyen tii nito trong vong piridin hdt
electron n cua vong nho trang thai lai hoa sp lam cho nhan piridin bj thieu electron % nhat la tai nguyen tu cacbon lien ket true tiep voi di to N. Su chuyen djch electron ve phia nguyen tu nita lam giam tac dyng che chan doi vai proton H(l), tin hieu cpng huang se dich ve phia truang thap han.
Tin hieu doublet S 8,40 ppm dupc gan cho proton H(3) cung la do sir hut electron n ciia nguyen tu N sp^ lam cho mat dp electron tai nguyen tir cacbon nay thSp hon so vcri cac vj tri con lai.
Phd mo phong cho thay tin hieu triplet ciia proton
H(8), H(9) nam i> 57,03 ppm; 57,27 ppm. Tren cd scr
do ehiing toi c6 the ket luan rang tin hi?u triplet a
TCHH, T. 50(6), 2012 Duang Tudn Quang va cgngsi,
* , 9 2 ; 7,01 ppm tren pho thvc nghiam ciia phirc lan lirpt ilng vdi sir cpng hudng cua proton H(8), H(9).
ChemNMR <H Estiitiation W ffl ffl
(10) ( I I )
Eslimalion qtialriy blue = good, magenta = medium, red = rough
PPM
Hinh 3: Phd ' H - N M R mo phdng cua phoi tir L
1 2 X I l O 9
i iilsf ill
Hinh 4: Pho ' H - N M R cua phirc [FeLCIj]
Tin hiju a trong viing 7,78*8,01 ppm voi cudng hpc Ion han so vdi d phoi tu. Dieu nay co th6 giii t , « f L,S'j''"„r-,^* ™* ™' "*" P " ' ™ " ( ^ ' ' " ( 2 ' ' ^'"'"^ I* ''" 1^' •»» phiic, cac electron s5 chuySn dj*
H(4), H(6), H(7), H(10) trong phan tu phiic. Nhin v6 phia ion kim loai lam giam tac d\ing ehe chSn doi chung cae tin hieu nay deu co dp chuyen djch hoa vdi cac proton nay, nen tin hieu cpng hudng se dich
724
TCHH, T. 50(6), 2 0 1 2 v l phia t r u d n g t h a p h a n .
M$c dii tir pho khoi l u g n g c h o thay s y ton tgi hai phuc [FeLCb] v a [FeL(HS04)3]. T u y nhien, trong ph6 cgng h u d n g tir hgt n h a n k h o n g thdy tin hi?u H cua nhdm HSO4. Dieu n a y cd the d u g c giai thich la do phuc [FeL(HS04)3] c o h a m l u g n g be h o n n h i l u so vdi phuc [FeLCls], d o dd d u n g djch d e m d o pho cgng h u d n g tii hgt nhan chira [FeL(HS04)3] vdi n6ng dg rat thap iam c h o tin hi^u c g n g h u d n g ciia no khong xuat hign tren p h d .
Nhu'ng thdng tin ve p h o c g n g h u d n g tir hgt nhan 'H-NMR tren day c h o p h e p chiing toi mgt lan n u a khang djnh rang da tong h g p d u g c phirc [FeLCIj]
v d i t i I? p h i i tii b a z a SchifT:Fe(lII) la 1:1.
Tom lgi, cac dir kien pho khdi l u g n g va c g n g hudng tir hgt nhan c o the cho phep k h a n g djnh cong thirc cau tao p h u c [ F e L C b ] n h u d dudi day. C o n g thirc cau tgo ciia [FeL(HS04)5] t u o n g ty.
Phuc Fe(III) vdi baza Schiff...
Phoi t u va p h u c chat sau dd d u g c tham d o hogt tmh khang vi sinh vat k i l m djnh. Cac chiing vi sinh vgt kiem djnh bao gom: E. coli (E), P. aeruginosa (P), B. subtillis (B), S. aureus (S), Asp. niger (A). F.
oxysporum (F), C. albicans (C), S. cerevistae (S*).
K i t qua thir hogt tinh k h a n g vi sinh vgt kiem dinh ciia phoi tir va phuc chat d u g c trinh bay d bang 2.
TT 1 2 3
Bang 2: Hoat tinh
Hap chat Isatin 8-Aminoquinolin [FeLCIj]
khang vi s inh vat kiem djn 1 ciia phdi tii va phirc chat Nong do uc che toi thieu MIC, ^g/ml VKGr-
E
50 50 25
P
50
-
25
VKGr+
B
-
25 S
- -
50
Nam spi
A50 50 50
F
50 50 25
Nam men
s' -
25 C
- -
50
Ket qua tren c h o thay c a c phdi t u hau n h u khong CO boat tinh khang nam, k h a n g k h u a n . Chiing chi cho hoat tinh yeu doi vdi khuan Gr(-) va nam sgi.
Nhin chung, boat tinh k h a n g nam, k h a n g khuan cua phirc chat cao hon so vdi ciia p h i i tir. C a c phirc [FeLCls] cho pho rgng ddi vdi hoat tinh khang vi sinh vat kiem dinh. Dac bi?t, phirc tong h g p cho hoat tinh manh doi vdi khuan E. coli, day la loai khuan gay nguy hgi rat ldn ddi v d i sirc k h d e con n g u d i .
4. KET L U A N
Chiing toi da tong h g p thanh c o n g phirc tao thanh giua F e ( i n ) vdi b a z a Schiff isatin-8- aminoquinolin. P h d c chat cd m a u x a m , ben trong khong khi, co cau triic bat di?n. S y t6n tai cua phirc chat da d u g c xac minh bdi p h u o n g p h a p phd khdi lugng va pho c g n g h u d n g tir hgt nhan. Phirc chat da dugc tham do hoat tinh k h a n g vi sinh vgt kiem djnh va cho thay co p h 6 r d n g v d i k h u a n c u n g n h u n a m . Nhin chung hogt tinh ciia phirc chat m g n h h a n so vdi phoi di.
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