L INTRODUCTION
2. MO HINH TINH TOAN
D6 nghien cuu c^u hinh cua nhom ạxetamido CH3C0-XH a phan tu N-axetyl-D- glucozamin. chung toi da su dung phucmg phap co hoc phan tu AMI va AMBER dua tren
ph4n m8m Hyper Chem 7.0. Vkn d§ vl cau hinh cua phan tu N-axetyl-D-glucozamin a day
dac biet dugc chu y a cho, tuong tu nhu 6 axetamit. nhom axetamido co the a bon dang cau hinh la (Z)-anti va (Z)-syn, (E)-anti va (E)-syn (xem hinh 1).
Danh phap (Z) va (E) dua tren su sip xep cua cac nhom the xung quanh lien ket N-C(O) trong khi do danh phap syn va anti thi dugc xet theo su dinh huong xung quanh lien kit C2(H)-N cua nguyen tu hidro cua vong piranozo va nguyen tu hidro ha> cua nhom thi R tren nguyen tu nito-aminọ Khi vong exo nam cung phia voi nhom C=0 so voi lien kit C-N thi ta co c^u hinh Z \'a nim khac phia thi ta co cau hinh Ẹ con danh phap s\n dc chi vi tri cua hai nguven tu hidro dinh voi C2 va N nim ciing phia voi nhau va neu chung nim khac phia thi se duoc goi la antị Cac anome cua N-axetyl-D-glucozamm dugc ki hieu nhu sau: N-axetyl-a-D-glucozamin la ADGLCNAc. N-axetyl-p-D-glucozamin la BDGLCNAc Tron^ cac tinh toan AMI d6i voi phan tu naỵ cau dang cua nhom hidroxylmetyl ngoai^ong doc theo lien kit C5-C6 la cau dang trans gauche [3.5]. trong do cac nguyen tu 0 5 va 0 6 o vi tri trans doi vol nhaụ con cac nguyen tu C4 va 0 6 a vi tn gauche voi nhaụ
HOnv/GHJ KHOA HQC VA rONG NGHE HOA HÚU CO TOAN QUOC L A N THU" III H CH3 X quay xung quanh N-C(O) N^ CH, R (Z)-anti quay xung quanh C(H)-N I R (E)-anti quay xung quanh C{H)-N quay xung quanh N-C(O) • N ' CH. (Z)-syn H3C ^ 0 (EJ-syn
Hmh L Cdn bdng nhan duac bdng su quay quanh cdc lien kit C(H)-N vd N-C(O) a axetamit (R^Hhay CH3).
3. KET QUA VA THAO LUAN
Ket qua tinh toan nang lugng cua cac cau hinh tren dugc dan ra trong bang 3, hinh dang cua cac ciu dang nhan dugc sau khi t6i uu hoa hinh hoc duoc dan ra trons hinh 2a \ a 2b. . . ^
ADGLCNAc-(E)-anti ADGLCNAc-) E)-s\n
ADGLCNAc-(Z)-ant. ADGLLNAc-(Zi-i>n
Hinh 2. Cdc cdu hinh co the c6 cua nhom axetamit a \-axetyl-a-D-olueozamm (tdi icu hod hinh hoc bdng phmvig phdp AMh.
228
HOI NGHI KHOA HOC vA CONG NGHE HOA HUU CO TOAN QUOC LAN THIJ" III
Dua vao bang s6 lieu tren ta co the so sanh nhu sau ve mat nang lugng cua cac cau hinh khac nhau cua hai anome a N-axetyl-D-glucozamin.
* Theo phiromg phdp AMBER
Ta nhan thay ring ca hai ciu hinh N-axetyl-a-D-glucozamin va N-axetyl-P-D- glucozamin 6 dang (E)-syn co muc nang lugng toi thieu thap hon ca, dieu do c6 nghia la cac dang nay co ciu hinh ben nhat. Trong khi cau hinh N-axetyl-a-D-glucozamin (Z)-anti va ciu hinh N-axetyl-P-D-glucozamin (Z)-syn co muc nang lugng cao nhit, nhu vay chung se kem ben nhat. Tuy nhien do phuang phap AMBER chi tdi uu hoa vl mat hinh hgc (tuc la coi cac nguyen tu trong phan tu nhu nhiing qua ciu) do do voi ciu hinh (E)-syn co su t6i uu nhat vai luc day giira cac qua cau nguyen tụ
BdngS. The ndng phdn tu, ndng luang tuyet doi vd tuang doi cua cdc cdu hinh co the co cua N-axetyl-a-D-glucozamin vd N-axetyl-P-D-glucozamin tinh theo phuang phdp AMBER
vdAMI
Cau hinh
Theo phucmg phap AMBER The nang E
(kcal/mol) AE (kcal/mol)
Theo phuong phap AMI Nhiet tao thanh
AH (kcal/mol) (kcal/mol) AG(kJ/mol) Anome a ADGLCNAc(E)-anti ADGLCNAc-(E)-syn ADGLCNAc(Z)-anti ADGLCNAc-(Z)-syn -22.752171 -16.681244 -26.455299 -23.277287 6.070927 0 9.774055 6.596043 -288.8976521 0 -283.6751875 -0.0835 -288.7447276 | 19.9295 -288.8210196 ' 0.8960 1 Anome (3 i BDGLCNAc-(E)-anti BDGLCNAc-(E)-syn BDGLCNAc-(Z)-anti BDGLCNAc-(Z)-syn -25.595922 -20.932409 -26.017303 -36.684071 4.663513 -286.7690256 ' 0 0 i -283.0558053 -0.19549 5.084894 i -289.5734293 -0.62127 15.75166 -287.0747285 1.76128
* Theo phirffng phdp AMI
Phucmg phap nay dugc sir dung sau khi phan tir da dugc toi uu hoa bang phucmg phap AMBER, do do ma cau tnic t6i uu trong phuang phap nay se co do chinh xac cao han. Tuy vay theo ca hai phuang phap nay ta thiy su sai lech ve cau hinh ben nhat va kem
bSn nh4t lákhong dang kk. Dua vao bang s6 lieu va d6 thi ta thdy cau true anome-p va
anome-a van se c6 c^u hinh bSn nh4t vai c4u hinh (E)-syn. Sir triing lap ve ca cau hinh kem
hkn nhat ciia N-axetyl-a-D-glucozamin (Z)-anti cang khang dinh them ve su dung dan cua
hai phuang phap. Tuy nhien dn hinh kem bin nhat theo phuong phap AMI cua N-axetyl-
P-D-glucozamin lai CO do chenh lech so vai su tinh toan theo phuang phap AMBER, dieu nay cung khong phai la v4n da quan trgng, do chi la su sai khac trong phep toan cua moi phuang phap ma thoị
HQl NGH{ KHOA HQC vACONG NGHE HOA HÚU CO TOAN QUOC LAN THÚ III
Nhu vay, bing tfnh toan cu the chung toi da nhan thiy ring N-axetyl-D-glucozamin CO ciu hinh b^n nhit la ciu hinh (E)-syn. Dieu nay co the dugc giai thich mot each don gian do su diy nhau giua cac nhom lan (coi Oxi la nhom lan trong lien k§t C-N cung voi vong exo) a ciu hinh (E) la be nhit, d6ng thai voi ciu hinh syn cua lien ket C2-N, nhom axetyl (CH3C0) cung khong bi tuang tac vai nhom hidroxi 6 Cl. Con trong tat ca cac cau hinh khac, sir tuang tac nay la dang ke, dac biet doi voi cau hinh (Z)-antị
Tom lai, qua tinh toan nang lugng cua he bang phuong phap AMI cho thay cau hinh b§n nhat ciia nhom N-axetyl trong N-axetyl-D-glucozamin la N-axetyl-D-glucozamin (E)-syn.
4. KET LUAN
Bang phuang phap toi uu hoa hinh hgc theo phuong phap co hgc phan tu AMBER va theo phuang phap co hgc lugng tu AMI, da nhan thay rang a phan tu N-axetyl-D- glucozamin, anome P ben hon anome a ve mat nang lugng (khi khong co anh huong cua dung moi) va doi voi cac anome thi cau hinh ben nhat la cau hinh (E)-syn.
Cong trinh duac hoan thanh vai su tdi tra kinh phi cua Trung tdm Ho tra Nghien ciru chau A (Dai hoc Quoc gia Hd Noi) vd De tdi nghien cim cap DHQG Hd Noi, md so QT-05-16.
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