Nghiên cứu sự tạo phức của một số nguyên tố đất hiếm với Axit L-Aspactic và bước đầu thăm dò hoạt tính sinh học của chúng : Luận án PTS. Hóa học: 62 44 25 01

^ ,9 BO GíAO DUC VA DÁO lAO T R a Ó N G DAI IIOCTÓNG M O P M Á N Ó I KHOA HÓA - BÓ MÓN MOA VĨ CO LE XUAN rV' • • ' < Nc ' s ' -A ;;.yí t í ,, s m N > /~3S,9.5 '¿u aao tbánb cae pbúc ben giúa ^^i'DH vdi eác pbói tú da phói vi, d^ídc goi biéu 'laz cbelat, có bán cbat entropi Gbáng ban vdi pboi tú Dietylentriamin pentaaj^etie axit H.-LrP,; (8 cáng) cá abé tácn tú cáu pbói tri aqud eua ion dát biém pnan tú H^O : entropi táng 11 Ln(H,^G)^''"*' -!• GTPA^' = Ln(H^'^)^_^ DTFA"" + SH^O ( ) ^ Vdi cae p b o i t t co v i t r x p b o i t r i t h a p h d n , h i e u líng c b e l a t a se nbo b J n , b d i v i s-X tba.y d c i so t i e u pban k e t qua cua s'X t a o pbúc l a nbo b d n Gbána ban v d i p b ó i t ú c a n g T r i i m i n o d i a x e t i c axit(HpIiVrDA) co t n e t a c b tai 3aa p n o i t r i aqud caá cae i o n d a t biem p b n t ú nude Ln(H 0)^"^^ 3I^'iDA-~ = Ln(H.O) - IiaDA^' -^ 9H.0 (1.2) ¿ a ¿ n—::? x> tu,y nbien su: tbay doi só tieu pbán be la nbo bdn 3o tieu pbán d vaj^óar-c^ trinb (1.1) tang tú lea r, pbiídng trinb (1.2)látú -lea 10 Tea tó tbú aai ani dinb 3\i tao tbanb cae n'aiic ben cua cae NTDH v H eác rbéi tú da phói vi dien txcb cao cua cbung 'Ti.-fdn^: táe txnb dien ííiúa anión da rang dien ticb cao : cae polyamino polycacboxvli.c (complexcn), cae oxyaxit vdi cae ion dat biém Idn, kbi dó pbói t-'^ cáng cita thap , vi du nbií Gl~, J;CZ t^T:dng tac txnb dien d dá.y la yéu íjc tbu tac -obiíc cua Ln " la có so pbói tri Idn 'adn 5, cáe so pbói trx kbác eó tbe eó ^, ":, ^., IG, vá 12 /^35 ,?^í^-^di ta cao ring mot nbúng nguyen nban lám cbo ếc NTDH ce só oboi trx cao vá cnay doi la ion lát biém có bka kínn ldn(La : l, o A , Lu" : ",a3 A ), so vdx cae ion co kien tnxídc nno (ví-ia : Al^"^ : G,65 A^_, :u ""^ : C,34 A'^)ếe pbúc bát dien vji ấe pboi tú rang IDTA^~ aao znk'r.a d l^.:j ben ban co có s'/'kéo cáng''cáe >/on-^ etylendia.nin 3^1 va/ ebo aea ếc pnoi tú DDTA • eax anié.n mot pa-an cáu pnoi trx, pbán cáu pnoi tri lai co tne oi cniéii bdi paói tú /.nác, vá dieu náy giái tníeb sií tao tbánb pẳc bon bdp giúa eác Ln^* vdi SDTA vá cáe aminc -axit /"94, ;»ó,123,131^7 Gie tbú 30 pboi tri^ cao gán lien vái bán ebat ion (txnb.kbong bao boa vá kbong dinb hi^tdng cua lien két) eúa cáe pbúc dát biém Ban cbat náy ^'-n lien vdi viec eác orbital 4f a ếc ion dát biém cb^ía d-^dc lap dáy bi cbán manb bdi electrón 53 vá 3p, co dó ếc clp electrón cua pbói tú kbong tbe pbán bó tren orbital a^xj* Tuy nbién na-rdi ta ẳn.; dá kb^-n^r dinb mot 3^/ aong gep xac axnn cua cae Ixen ket cong boa tri tron^^ s-r tao tbánn pbúc _lát biém Z':íhxa,z ban nnj' daa váa pbo IR cua - lUi - Pang 29 - "V^ot só chi tiéu sinh hóa.(l) : Mau : Dung d i c h : ': tudi H^O : H^O - La(ilC ) , : L 'i(iIA3p),; lí^^Asp Xf X> : G(ppra) : : : : ""id • 0,8 : 0,61 0,65 : 0,75 : o,G0 0,28 : ?,4 1,3 : 1,1 : 1,70 : 1,17 t (ngáy) : m protein ' : (mp:) "^arainoaxi^^^) 250 : ¿30 : 712 : : ' "^ca.cbohyd^^^^J 1,P : 1,06 : 1,0 : E araylaza Ü'>'5 0,77 'ap : : : * :o,75 ' • ' (l)tính tren ral dich chiét Nhan xet : Trong cung mau so sanh : raau O va raáu 1, hara l-i'dng protein giára (phú hdp vdi / 2_7 ) va hám l^^dng arainoaxit tang theo tbdi gian náy mam 'i'u' raau 1-^ ta tbáy su' úc che lara giam náng phan giái protein vá tiídng úng vdi diéu dó hára lu'dng arainoaxit giám Tu'dng tu! cae arainoaxit ••^xf bien doi nam liídng cacboliydrat dien tudng tií nhu'ng vdi rauc nho hdn Hoat enzira amilaza thay dói khong dáng ké phu hóp vói su" thay dói hára lu'dng protein TÓm l^i, ta thay ion dat hiera La''^"'", Ge^" , 2A^' cung nhif phúc eúa chúng vdi axit L-aspaetic có táe dun;7 úc che su" n.íy mam a hat dau xanh Hong có tac dung úc che ro rft ln ?5 VP^^ ' Tac; dunr úc che eúa phúc Idn hdn chut ao vdi ion dát hiera vá Idn hdn phoi' t^-f :;i/ úc che lám giára l'T'dníZ cua c^y giá chieu cao eúa than vá chiéu dái eúa re, cung nh ^' lám thay iói ham Iwdng tu:dng dói thánh phán phan tú sinh h9c 102 111.4,2- BÜÍ3G DAU N G H I E N GTTU KOAT TÍTĐTH T?G Gílfe Sy IHÁT TRlfeN Tfe BAO UJ^G THU' GÜA PHL?G Ce(HAsp) - 3H ,0 VA Gd(HAap) ,^U ,0 TREN GHUpT Xuát phát tú eác két thu dude d cae tai nghiera chi hoat tinh úe ebé sií phát trien eúa mot só dat hiem aspactat su" náy mára eúa hgt dau xanh (phán III ¿| j, chúng toi manh dan nghién cúu hoat-tinh úc che náy len su' phát trien eúa té bao unp; thu' Sarcoma TG-130 (dang báng nu'dc) tren chuot nhát tráng Swiss Dáu tién chúng téi thú sd bo doc tinh cua phúc Ge(HAsp) 3H-jO le(2i^s]¿ly¿li^0_tren chuot: Gong trinh náy d-'óc th^fe bien tai Thónp thi nghiera thuoe bo mén rAién dich vá Sinh 1-v ^enh, d ^-ái SM tri cú-i Giao s-j* Tién si Iban Thi Phi Phi, Tr-'dng Dai hoc T khoa 'Tá "^oi III.4.2.1- Thú sd bo * ' Toe tính'^ a phúc •»iJoc tÍQh*' a Ge(HAsp) , • 3H.^0 G ídc thú tren chuot nhát • tráng Swiss có lu'dng 20 - 22 g /con d ? lieu ; sÓ chuét moi liéu thú 1- Tong liéu 2,5'-iig Oe'^^/con chuot 2- Tong lLéul,25mgGG^Vcon chuot Gác liéu tren du'dc ehia déu tiéra phúc jac ngáy lian tiép Dánh giá két thi nghifra diía váo : - Khám nghiera dai the chuot chét ti/ nbien hay giét sau thi nghiera váo ngáy thií báy - Déra só lu'dng hóng cáu, bach cáu - Th^T* uré huyét Két thu d^de nhu' sau : 1- Vdi tóng liéu ^,Smg (tiéra '.^ ngáy >c 0,416rag) - Gác chuot van sóng binh thudng suÓt Idt thi nghiera - Gác té bao rấu {hhn¿ cáu, D^xch cáu; hốn toan ninh ta.ídng -Uré máu binh thudng (40rag:) - vé dai thé nói chung phú tang vá nao binh th^fdng, chi có có vái dora xuat huyét phoi / 2- Vdi tong liéu 1,25 mg (tiém ngáy x 0,206mg) ' - Chuot sóng hoan toan binh thu'dng tbdi gian thi nghifm - Uré máu binh thiídng - Hong cáu, br^ch cau binh thifdng - D,^i thé : phú t^ng vá nao binh thu'dng TĨm I.7Í, vdi liéu 0,208mg Ge^Vngáy/chuot 20g- 22g, tién phúcra:jGtrong ngáy, chuot van sóng binh thirdng vá khong có biéu hifn bfnh ly III.4.2.2— Kháo sát hogt tinh úc che ung thif cua phúc Ge(HA3p) , 3H^0 vá Gd(HAsp) 5H^0 tren chuét Gong trinh dude thuc hifn t^i Phóng thi nghiem thuoe bé mon Dong vfit thu'c nghifra dudi su tri eúa Phó tién si T R M G O N Ü Y M , Khoa Sinh, Tru'dng D^i hoc TÓng hdp Ha Wéi 111.4.2.2.1- Xá^dinh lu'dnfT; té bao ung th\i : Lay 10 ^^1 dicb báng théra 1490 |H1 dunr dich PBS Do pha loángsi : 1/150 Lay óng hút tron déu: hon dich tren BÓ vái gi9t dáu roi nhó giot.tren kính lamel, l^in déu dé den phút cho té bao ung thií'láng xng rol dera rol vft kinh 40Z Dién tieh eúa moi é nhó l/40Qnra" Chiéu cao buóng dea 1/lOmm Thé tích a mol é l/4000ram3 Dém só lu'dng té bao 400 é (A) Ta có : A X ^!000 só t é bao ung thijf / ijim ' dich bang SÓ té bao ung thu! /mi , dich bang = 7|-^Y^ = A x I500 x l'SO 111.4.2.2.2- Phu'dng pháp'vá két thi nghifm : - Nuoi,té bao ung thu* xoang bung chuot tráng Swiss sau ngáy Lay dich báng, xác dinh liídng té bao ung thií , Hoi pha lống b^lng dung dich PBS de dude mot hon hdp ban dau co mat té bao ung tbií 25.lO"""^ eon/ml • - Ghuot tráng Swiss (gióng du'e) có lu'dng tú 20^- 22g, du'dc cay truyén xoang bung 0,2ml hon dich tren có 10 te bao - JLU4 - ung tbu' báng niídc Sarcoma TG-180.-Dan n{^,By t h ú t a i tiéra dung d i c h Ge(HAsp), vá Gd(HAsp;_ ( k h i u báng dá nhát t r i e n ; d day chúnf; t o i tiéra váo xoan' bini^ chuot v i hár" lifdnr t i n h t h e o c^c ion Ge ^ va Gd * ln l^/n:^/"\ ^ral'chuot '^ - ^ ^i- (nho hdn 20 l n so v d i l i é u tiéra O, 208!ng/n ú y / c h u o t •^•^' - i.:2-[ vá nho hón tóng l i é u l,25mg 125 l n ) 'au '"oi chúnr c h i tiéra 0,2ral dung d i c h PBS y c h i tiara l n - Sau '"í npay ké t ú np;áy tiéra, g i é t c h u o t vá horpt t i n h líe che 'vf p b a t t r i a n ene t e bao ung thií t h a y d o i t h e t i c h d i c h b-^n,!:^ va tnri»-^- có t é Láo un": u b-^ng so v d i l é Toi chifng ív'oi t h i nghifra góra ?o troní^, co 10 toi c h ú n g l'nh giá dua váo su th^í có t r o n g c h u o t , So l a n l p l a i t h í nghiem l 3- Ket d-rdc chi r a báng JO Banp 30 : J h i so p b a t t r i e n va tong só t é uáo un-, thu t r o n g u Lo t h l n>':hiém Lo d o i chung Lo tiéra GR (%) XTBUT (^0 100 : 100 ; Ce(HAsp) , 36 : 66,67 ; Lo tiéra Gd(HAsp), yi-,74 : 54,36 í ír'p GR V X 1' c h l so p h a t t r i e n eu ^ u ^^T : t h é t i e h khoi u sau d i e u - V^ : t h é t í c b khói u khong d i e u í l TBUT : tri' tri t o n g só t é bao ung tnu" t r o n g u • Nhan x e t : Khi ^o bung xoang c h u o t co tié'n cae rfiúc t r e n , chúng t o i nhan t h a y eó h.i é n t^/dng c c t é bao un- thu" c h é t don":- tu» l a i Hién tu'dnK l a ti^dnt^ tu' c^c k e t qua nh.^ui thay b d i t a c g i a Yan / " I _ k b i khao s a t h o a t t í n b chóng u a "'^ I va :fii to-nicia chúa g e l a t i n (-^^^I-mfiQ-.GM) len t é bao ung thif Hepatoma d c h u é t - 105 Du'di t e dung eúa cáe phúc t r e n , chl só ]Hiát.:tri'jn eúa u vá tóng s ó t é bao ung t h u giám r o r e t Tac dung úc ebé eúa phu'c 3d(HAsp) Idn hón phúc Ge(HAsp), eó l é gán l i e n v d i t í t i h n^.n(x tnag lecj k h i chuyén t ú Ge sang Gd Nhu' v a y , r o r n g r'^ng c e phuc ''/e(fl'V^p) _ Gcl(ifAs]0^ có t e dung úc che r o r f t su* pha,t trif?n cu-i t e bao xin-i th\i báng mide Sarcoma TG-I80 cá g i a i donn p h t t r i e n , ¡lúe dó úe che sau ngáy diéii t r i c^c pht/'c t r e n , t r e n chuét nhát tr-^np" Swiss ( - 22g) v i l i a n lu'dng CUR C^C ion d s t hiera / ^ g / e o n c h u o t / n g y ( t i é m l n ) mot cách tiídng úu;'; l 36,64;^^ vá 45,46::^ t h e o t h é t í c h u vá 3 , 33^^ vá 45,64'^ t h e o tóng só t é bao ung thTÍ 106 P H A N THÚ TU : KÉT LUÁN 1.- Da nghién cúu suf tao phúc eúa mot só ion dát hiém (La Ge P^, Nd, Tb, Dy, Ho, Er) vdi axit L-aspactic TÍnh toan háng só bén vá mét só théng só nhift dong eúa phúc t^o thánh - Fhúc t^o thánh yéu có thánb phán LnAsp*, vdi háng só bén táng dan phú hdp qui luft tú La - Er f- Sxi tfto phúc xáy tót vúng pH tú 6,2 - dói vdi cae ion dat hiera nh^ va t\í 6,2 — dat hiera náng doi vdi cae ion - Trong khoang nhiet khao sat 30 - 50.0G, kba náng t^o phúc táng theo nhift 2.- Da tóng hdp dude 11 phúc rán vá báng phu'dng pháp phan tich nguyen tó, phan tích nhiét, háp thu electrón, phó hong ngo^i vá dé dan dien cho phép két luán : - Phúc vdi ti le 1:2 có thánh phán NH¿^LnAspp.nH^0 (n : - ) Mói nhóm Asp ~ chiém3 vitri phói tri,lien két vdi ion Ln-^* diídc thxic hifn qua nguyen tú N a nhóm NHp va nguyen txi oxy d ¡2 nbom COO - Phúc vdi ti If 1:3 có thánh phán Ln(HAsp)^-3HpO Moi nhóm HAsp" chiéra vi tri phói tri , lien két vdi ion La dxióc thu'c hién qua nguyen tií N cua nbom NH^ va qua nguyen tú oxy eúa nhóra GOO" vi tri CK; S O vdi nhóm NHp 3.- Da chi dieu kifn thích hdp viéc tách nguyen tó La, Ce, Pr, Nd vá Sra báng phiídng pháp sác ki long cao áp pha ngu'dc eáp ion 4.- Da chi hoat tinh u'c che su mam cua b^t dfu xanh, déc tinh va hoat tinh chóng u cua mot so dat hiem aspactat tren chudt nhát tráng Swiss có lu'dng 20 - 22g - DÓi vdi sxi mam eúa h^t dau xanh mUe xic che cua phúc tu'dng dói Idn hdn ion kim loai vá Idn hdn hixn phói tií Hong dé T,a (HAsp)7.3HpO (tinh theo hára lu'dng ion La'''*") có tac dung líe che ro rft la 125 ppm - Doi v d i pbúc Ge(HAsp) 5HpO, v d i l i é u tiém l,25ffig Ge""'* / n g y / e o n c h u é t ( t i é m moi ngáy 0,208mg), chuot van sóng binh t h u d n g vá khéng có b i é u h i f n bfnh l í - phúc Ce(HAsp)^.3H^0 vá Gd(HAñp) 3H^0 t a c líe che r o r é t su" p h t t r i e n cua t é bao ung thu' báng mide TG-18Ó cá g i a i doan p h t t r i e n DÓi vdi chuot n h t Swiss ( - 2 g ) raúc úc che sau d i e u t r i vdi l i é u t i n h t h e o i o n d t hiém l a 10 n g / n ^ a y / c o n chuot ( c h i mét l n ) mot c c h tiídng úng l 38,64'?ÍÍ' vá 45,46% t h e o t h é dung Sarcoma tráng lu'dng tiéra tích u vá 33,33% vá 45,64*^0 t h e o t ó n g s é t é bao ung thií t r o n g u - 108 TAI L I U THAM KHAO TlfeNG VIST Acmetop HÓa Vé ed T2.ÍÍXB DH-THGN,Há Noi(1976), tr 323-329 Phan Thi Tran Gbau vá cong su! Nghién cúu enzim, cbúc úc ebé tripxin nbára nang cao ehát liídng bot dinh diídng cbo tré em Tap chi Khoa boe Triídng DHTH Há Noi 5, 39-46 (1991) Nguyen Lan Dúng vá cong suT Mot sé phu'dng pháp nghién cúu vi sinh boc T3 NXB Kboa hoc vá Ky thuat Há Noi (1978) Nguyen Quang Dat vá cong s^í Tong hdp mot só dan xt a isatin, 5-sunfamidoisatin vá N-aminometyl isatín có táe dung du'dcly Hoi nghi Khoa hoc Dai hoc D^rde khoa (Tbáng - 1978) Ferenman N.I So tay hóa hoc NXB Khoa boc vá Ky tbufit Ha Noi (1972), tr.376 Le HÚng Lufn án phó tién si HĨa b9c, Há Noi (1987) Tran ích Hoa sinh h9c NXBGD, Ha Noi (1979), tr.12-20 Lé Cbi Kién Giáo trinh HĨa hoc phúc chat T2 Triídng DHTH Ha Noi (1975), tr.6-71 BÚi Kim Lien Nghién cúu ehát chóng phán bao Thong bao Khoa hoc Dai hoc Diídc khoa, 27, tr 97-103 (1977) Mai Long HUdng dan thUe bánb Hoa LÍ NXB Y boc vá The duc^Thl tbao Há Noi (1964), tr.105-116,270 Pbam Luán • Giáo trinb cd s3 lí thuyét sác kí long cao áp Ha Nói U 9 ) Trinb Hong Ngoe Ln án phó tién si HĨa hoc Há Noi (1989) pban Tbi Phi Phi,Pbát bien dánh giá ehát chóng ung thif Trung táni nghién ciVu chat lu'dng dao t^o can bo y té Há Noi(1990) Nguyen Thi Quy va cong sri Tac dung cua cbe pbam HG-75 su" vaa^^ trien u bang Sarcoma TG - ISO tren cbuot nnát trlng Swiss Di truyén b9c vá úng dung 1, 30-4 (199^)* Phan TÓng Sdn vá cong sxi Gd s3 HÓa boc Húu cd LíXB DH-THCN Há Noi (1980), tr 416-3-4- Lé Nhií Thanb Nghién ciíu tách nguyen tó dát hiém báng pbifdng pbáp sác kí long cao áp, ki thuat cap ion Tap chi HÓa hoc 29, 3, 19-22 (1991)- Phan Van TUdng Giáo trinh Phan tícb HĨa LÍ, TI Trudng DHTH Há Noi (1973) • " * * • , Bao HÚU Vinh vá cong sU Các phu'dng pbáp sác kí N X B Há Noi (1985), tr.l44 KHKT - 109 - ' • , Tlg^G NGA BeíiGT P OnpoASJiGHHe pH Teopiin n npaKTHKa ViSTx "XiiMiifi", JleHi-iHppaTiCKoe OTziejieiHíe ( ) , CTp 7 , B:/cGB A.H., HpaKTnqGCKoe P^KOBOSCTBO no aHajiriTHqecKoü ^ xmmii poTlKiix ajieyeHTOB Hsa '*Xii¿aHH" MocKBa ( 6 ) , GTp BaTHOB M.iJ Od YcroímiiBOCTii KOMnjieKci-iHX coeaiiHemiíj JlaHiana, uepiiH, npasGOTíiiMa ii HeoaiiMa c acnapanmoBj KHOJIBI a ^ p Heopr XHivi., , I , 153 ( I I ) 2 rpiiEdspr A.A BBcacíH'is B xiimm i-íOLmjieKCHHX coeTULHOHHíí Visji "XnMHH", MocKBa (1966), c í p - Aparo P 3»ri3nqecKne ivie^Dosu HeopraHü^ecKoíí xiiuiui.H3fl " íinp " , MocKBa ( ) SBHrní-meE O.E O Bsaí-HoseücTBiin xTiopiisa neo^HMa c rjinunHOM Syp Heopr xivá , , I88I ( ) SBHrnHueB O.E S j p neopr xnw 7, , 1892 (1962) SBflrHHiíOB O.E - l y p Hoopr xiiu , , 3¿f9 (1963) ]¡[imQM Hw npwMSHeHi'ie KOtinjieKCOB B anajiUTn^ecKOií XHMHH H37T '» Mnp " , Mocoa (1979) KHJHHHU H J I , Kpa'TKOH xiiMn^ecKaH SHunKjionesiiH Haa CoEeTCKan aHmiKJionesiin, MocKBa ( I I ) , T I : ^-E , Cíp KopocTGjieB 11.ü PeoKTHBbi II pacTBOpu B MeTa.ujii'pnmecKOu anajinae Lí3/i "MeTajirijprnH", ívbcKBa (1977) Kpucc S S yiíp xiiM isyp , ¿f, 328-32 (196¿f) Jlepoíí AíápiiHr ycnexn B xnmHi ii TexHOJiornii pesKOsouejiLHHX ajieMCHTOB 1Í3S "MeTaJiJi:yprnn'*, M O G K B ( I ) ,CTp 156-7 JIjpBO 10.10 CnpaBO^HiiK no aHajiiiTi-mocKon xnivinn.Hsfl.'^XnívHiH" - MocKBa ( 9 ) 3 MCTpep A BnoxniJüH ainHiofuicjioT I/l3S iiHOCTpaHHotj JIHÍT MocKBa ( I I ) HaKarJOTO K WH^paKpacnbie cneKTpbi neopraHiiTOCKnx ii KoopíiiHamioHHux coGannem-ií-i Has "f/Hip", MocKBa (1966) , cTp - HanioiiixHH B T , KccriesoBQHne KorjnjieKcooOpasoBaHnfl pe^KoaeM8JILHHX sjivíeHTOB ií8pi'ie30& nozppynnbi c HGKOTopBíjn «, et al J Chromatogr 83, J9 {Xy7fy), 59 Evans et al Crystal strucbure of the njonopotn-auium salt of L-aspartic acid dihydrate Chom Abs 7b, 91303J (ra72; 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