Luận án Nghiên cứu thành phần hóa học và xây dựng quy trình công nghệ chiết xuất để tạo sản phẩm có giá trị từ quả táo mèo (docynia indica (wall.) decne) ở Việt Nam

àu sắc và mùi vị đặc trưng của táo mèo, dạng bột mịn, không vón cục. 137 KIẾN NGHỊ 1. Tiếp tục nghiên cứu và phân lập một số thành phần hóa học từ các phân đoạn cao chiết khác của quả táo mèo như phân đoạn nước, dicholoromethane. 2. Tiếp tục nghiên cứu thăm dò hoạt tính sinh học của các hợp chất phân lập được liên quan đến các bệnh tiểu đường, mỡ máu 3. Tiếp tục nghiên cứu, nâng cấp quy mô và hoàn thiện công nghệ để có thể triển khai sản xuất ở quy mô lớn NHỮNG ĐIỂM MỚI CỦA LUẬN ÁN 1. Lần đầu tiên áp dụng mô hình khảo sát thành phần hóa học quả táo mèo theo định hướng hoạt tính bảo vệ tim mạch. Từ phân đoạn ethyl acetate có tác dụng bảo vệ tim mạch mạnh nhất đã phân lập được 25 hợp chất trong đó có 1 hợp chất mới và 16 hợp chất khác lần đầu tiên phân lập từ quả táo mèo. 2. Lần đầu tiến hành nghiên cứu và tối ưu hóa thông số công nghệ quá trình chiết xuất phenolic bằng 3 phương pháp chiết khác nhau là chiết vi sóng, chiết siêu âm và chiết hồi lưu; Từ đó tiến hành so sánh, đánh giá và lựa chọn được phương pháp chiết xuất phù hợp nhất. 3. Lần đầu tiến hành nghiên cứu và tối ưu hóa thông số công nghệ quá trình sấy phun dịch chiết táo mèo thu bột cao chiết táo mèo giàu phenolic sử dụng cho mục đích bào chế tạo sản phẩm chăm sóc sức khỏe. 138 CÁC CÔNG TRÌNH KHOA HỌC CÔNG BỐ LIÊN QUAN ĐẾN LUẬN ÁN  BÀI BÁO QUỐC TẾ 1. Xuan Duy Le, Manh Cuong Nguyen, Dinh Hoang Vu, Minh Quan Pham, Quoc Long Pham, Quang Tung Nguyen, Tuan Anh Nguyen, Van Thinh Pham, Long Giang Bach, Tuong Van Nguyen. “Optimization of Microwave-Assisted Extraction of Total Phenolic and Total Flavonoid from Fruits of Docynia indica (Wall.) Decne. Using Response Surface Methodology”. Processes 7.8 (2019): 485. (SCI-E, Q2), Doi:10.3390/pr7080485. 2. Le Xuan Duy, Le Ba Vinh, Gao Dan, Vu Dinh Hoang, Tran Quoc Toan, Young Ho Kim, Nguyen Manh Cuong “Soluble epoxide hydrolase inhibitors from Docynia indica (Wall.) Decne.”. Nat. Prod. Res. (2020): 1-6 (SCI-E, Q2), DOI: 10.1080/14786419.2020.1774759.  BÀI BÁO TRONG NƯỚC 3. Lê Xuân Duy, Trần Quốc Toàn, Lê Tất Thành, Cầm Thị Ính, Đỗ Hữu Nghị, Hà Việt Hải, Vũ Đình Hoàng, Đỗ Thị Nguyệt, Phạm Quốc Long. “Một số kết quả nghiên cứu về thành phần hóa học quả táo mèo (Docynia indica Wall.) Việt Nam”. Tạp chí Khoa học công nghệ, tập 53 số 4C (2015) Tr 81-87. 4. Le Xuan Duy, Tran Quoc Toan, Do Huu Nghi, Le Tat Thanh, Vu Dinh Hoang, Young Ho Kim, Nguyen Manh Cuong. “Triterpene acids from Docynia indica fruits and their cytotoxic activity”. Vietnam J. Technol 56 (2018): 199-204 5. 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"Acretoside, a new sucrose ester from Aristolochia cretica." Journal of Asian natural products research 7.6 (2005): 799-803. 98. Jiang, Z. H., Hirose, Y., Iwata, H., Sakamoto, S. "Caffeoyl, coumaroyl, galloyl, and hexahydroxydiphenoyl glucoses from Balanophora japonica." Chemical and pharmaceutical bulletin 49.7 (2001): 887-892. 99. Foo, L. Y., Lu, Y., Molan, A. L., Woodfield, D. R. "The phenols and prodelphinidins of white clover flowers." Phytochemistry 54.5 (2000): 539-548. 100. Khanh, P. N., Duc, H. V., Huong, T. T., Son, N. T. "Alkylphloroglucinol derivatives and triterpenoids with soluble epoxide hydrolase inhibitory activity from Callistemon citrinus." Fitoterapia 109 (2016): 39-44 101. Vinh, L. B., Kim, J. H., Lee, J. S., Nguyet, N. T. M. "Soluble epoxide hydrolase inhibitory activity of phenolic glycosides from Polygala tenuifolia and in silico approach." Medicinal Chemistry Research 27.3 (2018): 726-734. 102. Aquino, R., Morelli, S., Lauro, M. R. "Phenolic constituents and antioxidant activity of an extract of anthurium v ersicolor leaves." Journal of Natural Products 64.8 (2001): 1019-1023. 103. Wang, L., Qin, P., & Hu, Y. "Study on the microwave-assisted extraction of polyphenols from tea." Frontiers of Chemical Engineering in China 4.3 (2010): 307-313. 104. Dent, M., Dragović-Uzelac, V., Penić, M. "The effect of extraction solvents, temperature and time on the composition and mass fraction of polyphenols in Dalmatian wild sage (Salvia officinalis L.) extracts." Food technology and biotechnology 51.1 (2013): 84-91. 105. Su, D., Li, H., & Lu, C. "Microwave Extraction of Polyphenol from Pomegranate Seed." Asian J. Bot.(Transferred) 1 (2018): 36-46. 106. Friedman, M., & Jürgens, H. S. "Effect of pH on the stability of plant phenolic compounds." Journal of agricultural and food chemistry 48.6 (2000): 2101-2110. 107. Guan, X., & Yao, H. "Optimization of Viscozyme L-assisted extraction of oat bran protein using response surface methodology." Food chemistry 106.1 (2008): 345-351. 108. Zabeti, M., Daud, W. M. A. W. "Optimization of the activity of CaO/Al2O3 catalyst for biodiesel production using response surface methodology." Applied Catalysis A: General 366.1 (2009): 154-159. 148 PHỤ LỤC PHỤ LỤC A: PHỔ CỦA CÁC HỢP CHẤT HÓA HỌC 149 PHỤ LỤC 1. PHỔ HỢP CHẤT TM1 1H-NMR-MEOD –TM1 13C-NMR-MEOD 150 PHỤ LỤC 2. PHỔ HỢP CHẤT TM2 151 PHỤ LỤC 3. PHỔ HỢP CHẤT TM3 152 PHỤ LỤC 4. PHỔ HỢP CHẤT TM5 1H-NMR-MEOD 13C-NMR-MEOD 153 PHỤ LỤC 5. PHỔ HỢP CHẤT TM6 154 PHỤ LỤC 6. PHỔ HỢP CHẤT TM7 155 156 PHỤ LỤC 7. PHỔ HỢP CHẤT TM8 1H-NMR-DMSO 13C-NMR-DMSO 157 PHỤ LỤC 8. PHỔ HỢP CHẤT TM9 158 PHỤ LỤC 9. PHỔ HỢP CHẤT TM10 159 160 PHỤ LỤC 10. PHỔ HỢP CHẤT TM12 161 PHỤ LỤC 11. PHỔ HỢP CHẤT TM13 1H-NMR-MEOD 13C-NMR-MEOD 162 PHỤ LỤC 12. PHỔ HỢP CHẤT TM15 163 PHỤ LỤC 13. PHỔ HỢP CHẤT TM16 164 PHỤ LỤC 14. PHỔ HỢP CHẤT TM17 165 166 167 168 169 170 171 172 PHỤ LỤC 15. PHỔ HỢP CHẤT TM18 173 174 175 PHỤ LỤC 16. PHỔ HỢP CHẤT TM20 176 PHỤ LỤC 17. PHỔ HỢP CHẤT TM22 1H-NMR-MEOD 13C-NMR-MEOD 177 PHỤ LỤC 18. PHỔ HỢP CHẤT TM23 1H, 13C-NMR-PYRIDIN 178 PHỤ LỤC 19. PHỔ HỢP CHẤT TM24 1H,13C-NMR-PYRIDIN 179 PHỤ LỤC 20. PHỔ HỢP CHẤT TM25 180 181 182 PHỤ LỤC 21. PHỔ HỢP CHẤT TM30 183 184 185 PHỤ LỤC 22. PHỔ HỢP CHẤT TM33 186 187 188 189 PHỤ LỤC 23. PHỔ HỢP CHẤT TM35 190 191 192 193 PHỤ LỤC 24. PHỔ HỢP CHẤT TM36 194 195 196 PHỤ LỤC 25. PHỔ HỢP CHẤT TM37 197 198 199 200 PHỤ LỤC B TÍNH TOÁN NĂNG LƯỢNG BỀN CÁC CẤU DẠNG CỦA HỢP CHẤT TM17 201 Cartesian coordinate and thermochemistry data of the five most stable boat- and chair-like conformers calculated at the M05-2X/6-311++G(d,p) level of theory in vacuo. Relative enthalpy of the conformer compared with the most stable one is also noted. Boat Conformer 1 kcal/mol 0 1 C -4.80872800 0.11321800 -0.58327400 C -4.19895600 -0.81119800 0.47419600 C -2.62909200 0.99270400 0.80799600 C -3.58409700 2.06593300 0.27560900 C -4.96210900 1.48323700 0.03817400 H -5.01711100 -1.13619400 1.11993000 H -4.15857700 0.17998000 -1.46261700 H -2.03499900 1.40725200 1.61964700 H -3.19695200 2.42239800 -0.68116300 H -5.47532300 1.37775700 1.00048100 O -3.28028600 -0.12667300 1.33660200 O -1.78425000 0.63140600 -0.27994000 O -3.61814900 3.11438800 1.22455200 H -4.26811500 3.75555400 0.92465500 O -5.66511000 2.37834300 -0.79974700 H -6.45732000 1.92325000 -1.10201900 O -6.10007600 -0.32691900 -0.96579200 H -5.99722300 -1.20689800 -1.34400400 C -3.53707100 -2.02925300 -0.15291800 H -2.74411800 -1.72099200 -0.83105900 H -3.10840600 -2.66842900 0.61908100 O -4.50986500 -2.72951000 -0.93729200 H -4.90981100 -3.41818100 -0.40505800 C -0.65702000 -0.08886900 -0.02328200 C 0.19682900 -0.25181500 -1.12412300 C -0.35766600 -0.63559600 1.21235500 C 1.37056100 -0.94905000 -0.96675000 H -0.08036200 0.19087300 -2.07041800 C 0.83368800 -1.34887500 1.36640100 H -1.02528600 -0.56922900 2.05628800 C 1.71559200 -1.49584700 0.28067300 C 2.96140500 -2.24543600 0.45649700 C 2.33335800 -1.17928100 -2.09664500 H 2.13370500 -2.15153700 -2.55305100 H 2.22410800 -0.42596200 -2.87405000 C 3.74945400 -1.20486700 -1.54941200 O 3.84274200 -2.25967600 -0.55884100 H 4.44167200 -1.53246800 -2.32198700 O 3.22493100 -2.87433600 1.46306800 C 4.23557300 0.09755300 -0.94333900 C 5.29759000 0.06775000 -0.04175600 C 3.68922900 1.33351500 -1.28311300 C 5.80156300 1.23741400 0.50676900 H 5.72662300 -0.88276800 0.24454400 C 4.18676700 2.50989600 -0.74385700 H 2.85501200 1.39750200 -1.96696300 C 5.24596800 2.46222000 0.15298400 H 6.62373600 1.19627100 1.21099800 H 3.76048700 3.46935000 -0.99913000 O 5.69708200 3.64350500 0.65872700 202 H 6.41126400 3.48186700 1.27810600 O 1.07905500 -1.88013000 2.56590300 H 1.91137000 -2.39270600 2.50076800 - Thermochemistry data - Zero-point correction= 0.425530 (Hartree/Particle) Thermal correction to Energy= 0.452847 Thermal correction to Enthalpy= 0.453791 Thermal correction to Gibbs Free Energy= 0.365566 Sum of electronic and zero-point Energies= -1565.600106 Sum of electronic and thermal Energies= -1565.572789 Sum of electronic and thermal Enthalpies= -1565.571845 Sum of electronic and thermal Free Energies= -1565.660070 Boat Conformer 2 0 1 C -4.83176500 0.11164000 -0.58894700 C -4.21810900 -0.80902600 0.46958200 C -2.65125500 0.99914600 0.79898800 C -3.60738400 2.06795500 0.25933000 C -4.98547300 1.48313400 0.02915000 H -5.03445200 -1.13564800 1.11661500 H -4.18355300 0.17703100 -1.46993800 H -2.06107900 1.41799300 1.61136300 H -3.22246300 2.41607100 -0.70144500 H -5.49563700 1.37993800 0.99330700 O -3.30087600 -0.11989000 1.32986600 O -1.80147300 0.63701500 -0.28475100 O -3.63985000 3.12534300 1.19855600 H -4.29781700 3.75836400 0.89862100 O -5.69204100 2.37511700 -0.80919500 H -6.48439000 1.91812400 -1.10831800 O -6.12316200 -0.33118300 -0.96742600 H -6.02034200 -1.21392800 -1.33931800 C -3.55292600 -2.02573600 -0.15648300 H -2.75797400 -1.71582800 -0.83164700 H -3.12632700 -2.66527100 0.61623900 O -4.52450700 -2.72521200 -0.94338200 H -4.90402000 -3.43436100 -0.42347200 C -0.67311300 -0.07993200 -0.02173800 C 0.18642600 -0.24161300 -1.11789200 C -0.37762700 -0.62394400 1.21605100 C 1.36225800 -0.93512200 -0.95397700 H -0.08774600 0.19821100 -2.06654800 C 0.81415800 -1.33557900 1.37592100 H -1.04925300 -0.55862100 2.05689700 C 1.70200400 -1.48114400 0.29448500 C 2.94498700 -2.23615300 0.47523600 C 2.33045100 -1.15926100 -2.08112600 H 2.12189400 -2.12280600 -2.55158400 H 2.23354700 -0.39313800 -2.84839700 C 3.74523800 -1.20408800 -1.53410500 O 3.82804700 -2.25659800 -0.53669800 H 4.43049000 -1.54822700 -2.30549800 O 3.19861200 -2.86683000 1.48293300 C 4.26217600 0.08946100 -0.93901800 203 C 3.63420400 1.31473600 -1.12329200 C 5.44349700 0.05176600 -0.19347200 C 4.16974700 2.47906900 -0.58370700 H 2.70898400 1.38426400 -1.67705400 C 5.98430300 1.20169100 0.35092000 H 5.93294500 -0.89878300 -0.02790900 C 5.34482100 2.42210000 0.15298800 H 3.66530200 3.42635000 -0.73052500 H 6.89432500 1.17653600 0.93293900 O 5.91551900 3.52627400 0.70891100 H 5.37671800 4.29894500 0.52866700 O 1.05402100 -1.86656300 2.57609400 H 1.88682800 -2.37959600 2.51437300 - Thermochemistry data - Zero-point correction= 0.425623 (Hartree/Particle) Thermal correction to Energy= 0.452856 Thermal correction to Enthalpy= 0.453800 Thermal correction to Gibbs Free Energy= 0.366223 Sum of electronic and zero-point Energies= -1565.599802 Sum of electronic and thermal Energies= -1565.572569 Sum of electronic and thermal Enthalpies= -1565.571625 Sum of electronic and thermal Free Energies= -1565.659202 Boat Conformer C3 0 1 C 3.57465800 0.69185900 -0.60544100 C 2.45805800 1.02583400 0.38464000 C 2.50766900 -1.34840800 0.86947100 C 3.96845100 -1.51324900 0.43997700 C 4.58582700 -0.16477600 0.12526000 H 2.81977000 1.84749700 1.00430100 H 3.18089200 0.14789000 -1.47090500 H 2.29875700 -1.99845000 1.71709000 H 3.98994800 -2.11942200 -0.46755500 H 4.84427100 0.33340200 1.06656900 O 2.19115600 -0.05412500 1.29174900 O 1.72609200 -1.74480000 -0.25455500 O 4.65223900 -2.16424500 1.49461000 H 5.58014600 -2.21378100 1.24986500 O 5.74990500 -0.39679800 -0.64221300 H 6.03284800 0.45381700 -0.99253700 O 4.24581300 1.86563100 -1.02761300 H 3.57821100 2.47170200 -1.37017400 C 1.17723400 1.46691200 -0.30125600 H 0.80879400 0.68618900 -0.97024500 H 0.41555700 1.67750500 0.45056900 O 1.52203500 2.64082300 -1.03934600 H 0.72704200 3.11466700 -1.30263900 C 0.37304000 -1.82013400 -0.14357700 C -0.33671200 -1.43178000 1.00255100 C -0.27869600 -2.28289500 -1.27676800 C -1.71482900 -1.43783200 0.94948700 H 0.17032700 -1.05910400 1.87758100 C -1.66686400 -2.31521700 -1.31312700 H 0.29000500 -2.60169000 -2.13727600 204 C -2.39626300 -1.84740100 -0.20154100 C -3.84352000 -1.66337400 -0.31737300 C -2.57005500 -0.94064000 2.07806800 H -3.03528100 -1.77672100 2.60491100 H -1.97987200 -0.36877700 2.79147400 C -3.66745000 -0.06367100 1.47847600 O -4.45481000 -0.84381000 0.56098700 O -4.51422300 -2.17004300 -1.19370700 H -4.37729800 0.23179400 2.24767900 C -3.08342200 1.17000800 0.81836200 C -2.50199300 2.14073500 1.63025900 C -3.03465800 1.34130600 -0.56182200 C -1.83645400 3.22974900 1.08480200 H -2.55366400 2.04451400 2.70807900 C -2.36592100 2.42095500 -1.12136500 H -3.52145200 0.63626000 -1.21992900 C -1.74535500 3.34700700 -0.29675600 H -1.37055500 3.96517900 1.72932200 H -2.31140800 2.54998900 -2.19320800 O -1.01353300 4.33737000 -0.90326400 H -0.73949800 4.99129700 -0.25569000 O -2.25946800 -2.75846100 -2.42626000 H -3.22564700 -2.73602800 -2.28435200 Zero-point correction= 0.426645 (Hartree/Particle) Thermal correction to Energy= 0.453141 Thermal correction to Enthalpy= 0.454085 Thermal correction to Gibbs Free Energy= 0.370887 Sum of electronic and zero-point Energies= -1565.604731 Sum of electronic and thermal Energies= -1565.578235 Sum of electronic and thermal Enthalpies= -1565.577291 Sum of electronic and thermal Free Energies= -1565.660489 Boat Conformer C4 0 1 C 4.01249600 1.07634300 -0.55081900 C 2.80707300 1.38074600 0.34408300 C 2.83799500 -0.98935700 0.78929700 C 4.32549400 -1.14488600 0.45987300 C 4.96678800 0.21023300 0.24087500 H 3.10012300 2.20710100 0.99556300 H 3.69978800 0.54513500 -1.45608600 H 2.57955200 -1.66623100 1.60062300 H 4.41098100 -1.71627100 -0.46656000 H 5.14415100 0.68101000 1.21437300 O 2.49152600 0.29514300 1.22761000 O 2.12599200 -1.33389500 -0.39100200 O 4.92829200 -1.83842000 1.53569900 H 5.87023800 -1.89370900 1.35368300 O 6.18941100 -0.00034700 -0.43480700 H 6.49689400 0.85760000 -0.74372300 O 4.70563600 2.26307800 -0.89766200 H 4.10530500 2.79785600 -1.42748600 C 1.58746500 1.78952700 -0.46993900 H 1.32136200 1.00872800 -1.17860800 H 0.73232200 1.96898100 0.18379100 205 O 1.91342500 2.94871700 -1.24322800 H 1.80087200 3.72966900 -0.69925700 C 0.77754200 -1.52353700 -0.31466200 C 0.03566900 -1.33209200 0.85851300 C 0.17410400 -1.91990300 -1.49661600 C -1.32772000 -1.54623300 0.81629300 H 0.49969300 -0.98752100 1.76907300 C -1.19830100 -2.13752900 -1.53414200 H 0.76708000 -2.07681700 -2.38506700 C -1.96574900 -1.93263600 -0.36829300 C -3.41588600 -2.13982700 -0.40948000 C -2.19546500 -1.38485000 2.03190800 H -2.34701500 -2.35825600 2.50419800 H -1.72948500 -0.73541700 2.76988300 C -3.55362900 -0.85570400 1.60688000 O -4.13947800 -1.79032600 0.66974700 O -3.99241600 -2.62897300 -1.36010100 H -4.24499200 -0.88184300 2.44650300 C -3.54087100 0.53372900 0.99678700 C -2.58332200 1.48322300 1.33546000 C -4.55112800 0.89948700 0.10432600 C -2.63039800 2.76693000 0.80374600 H -1.78029000 1.24027000 2.01708500 C -4.60405500 2.17219100 -0.43627600 H -5.29990800 0.17163400 -0.17629800 C -3.64174800 3.11177000 -0.08350500 H -1.88032500 3.49770300 1.08243700 H -5.38125400 2.45580200 -1.13131000 O -3.74014300 4.35140500 -0.63893300 H -3.02917200 4.91090500 -0.32148100 O -1.73770200 -2.53686600 -2.68768500 H -2.69040200 -2.69819700 -2.53428400 - Thermochemistry data - Zero-point correction= 0.425863 (Hartree/Particle) Thermal correction to Energy= 0.452929 Thermal correction to Enthalpy= 0.453873 Thermal correction to Gibbs Free Energy= 0.366571 Sum of electronic and zero-point Energies= -1565.598595 Sum of electronic and thermal Energies= -1565.571529 Sum of electronic and thermal Enthalpies= -1565.570585 Sum of electronic and thermal Free Energies= -1565.657887 Boat Conformer C5 206 0 1 C 3.62233000 0.73118200 -0.53838900 C 2.55305600 1.01818200 0.51533700 C 2.52246100 -1.39192700 0.78365700 C 3.96705000 -1.56725100 0.30512000 C 4.62312600 -0.21829400 0.08401000 H 2.96995700 1.76224900 1.19548100 H 3.18095300 0.27634600 -1.43186200 H 2.30740100 -2.10713300 1.57547300 H 3.94689400 -2.09774400 -0.64861900 H 4.92663500 0.18954900 1.05494700 O 2.26188000 -0.13066700 1.32614900 O 1.70379600 -1.66302900 -0.35161100 O 4.65181100 -2.32415100 1.28588200 H 5.57212500 -2.38183500 1.01562000 O 5.75530400 -0.42238200 -0.73734300 H 6.05770900 0.44550500 -1.02321400 O 4.32271000 1.91295600 -0.88345700 H 3.66739600 2.57616200 -1.13114400 C 1.27062500 1.57183100 -0.07762400 H 0.83987300 0.86594800 -0.79182900 H 0.55246500 1.74555100 0.72317400 O 1.63026700 2.79042300 -0.72932100 H 0.85447100 3.35022200 -0.83848800 C 0.35447700 -1.75249200 -0.20989700 C -0.33024500 -1.40135400 0.96352800 C -0.32139400 -2.18810400 -1.33977700 C -1.70942400 -1.42173500 0.94495300 H 0.19742200 -1.04675100 1.83409500 C -1.70936200 -2.23748200 -1.34127500 H 0.22870300 -2.47837500 -2.22215600 C -2.41567900 -1.81183100 -0.19826000 C -3.86879700 -1.65453200 -0.26856600 C -2.54107600 -0.95301600 2.10367100 H -2.98415700 -1.80156700 2.62952700 H -1.93854400 -0.38754300 2.81138600 C -3.66498800 -0.08380500 1.54267400 O -4.47215700 -0.87620700 0.65284800 O -4.55456700 -2.14945500 -1.14024700 H -4.35266500 0.20732700 2.33341800 C -3.11266400 1.14667200 0.84822500 C -3.23205900 1.35181200 -0.52077500 C -2.38701100 2.07077900 1.60012500 C -2.57324400 2.40715100 -1.14104200 H -3.83076500 0.68568500 -1.12522100 C -1.73900800 3.13653900 0.99686400 H -2.31325000 1.95458000 2.67444500 C -1.80237200 3.27473100 -0.38374300 H -2.64238100 2.53205300 -2.21470800 H -1.16389700 3.84813700 1.57294200 O -1.03800500 4.26526900 -0.95479000 H -1.31157600 4.40783200 -1.86432600 O -2.32511700 -2.65891700 -2.45070300 H -3.28696300 -2.65927100 -2.28109500 207 Zero-point correction= 0.426759 (Hartree/Particle) Thermal correction to Energy= 0.453188 Thermal correction to Enthalpy= 0.454132 Thermal correction to Gibbs Free Energy= 0.370858 Sum of electronic and zero-point Energies= -1565.604399 Sum of electronic and thermal Energies= -1565.577970 Sum of electronic and thermal Enthalpies= -1565.577025 Sum of electronic and thermal Free Energies= -1565.660300 Chair Conformer C1 0 1 C 5.00919300 -0.56472100 0.76378700 C 3.66674700 -1.08461000 1.28642300 C 2.93852300 -0.81818500 -0.99994200 C 4.35321100 -0.92982000 -1.57697700 C 5.33885100 -1.32936500 -0.49852300 H 3.87682800 -2.00298100 1.83819600 H 4.95031100 0.50588400 0.53889600 H 2.23587900 -1.28689600 -1.68542700 H 4.64460900 0.05118300 -1.95761000 H 5.23431700 -2.40167000 -0.29874400 O 2.77778300 -1.47073300 0.22794900 O 2.65871300 0.57109500 -0.88178000 O 4.31091000 -1.88184200 -2.62283400 H 5.20866300 -1.99701200 -2.94587700 O 6.63603000 -1.04182000 -0.97886000 H 7.23820200 -1.10402700 -0.23073000 O 6.05022700 -0.81004900 1.69296000 H 5.83620900 -0.31846300 2.49317500 C 2.99590500 -0.08067000 2.21250500 H 2.81835000 0.85667400 1.68962000 H 2.04129600 -0.46960800 2.56805900 O 3.88302400 0.20932300 3.29799900 H 3.69818200 -0.38486300 4.02628800 C 1.37250200 0.96635000 -0.66511400 C 0.31801800 0.07401800 -0.43259400 C 1.17115100 2.33764700 -0.68053600 C -0.95181100 0.58858500 -0.25093700 H 0.48537400 -0.98925800 -0.36286000 C -0.10286300 2.85265200 -0.47802700 H 2.00022500 3.00752600 -0.85228400 C -1.18689300 1.96804700 -0.28707300 C -2.53181400 2.50876900 -0.06620500 C -2.13261900 -0.29811600 0.02706500 H -1.98422500 -1.29235300 -0.39298400 H -2.28149000 -0.40838600 1.10504300 C -3.38390100 0.32321000 -0.57118200 O -3.56538000 1.65245700 -0.03906000 H -3.26052700 0.41812500 -1.65284500 O -2.75244500 3.69041000 0.10877700 C -4.62233700 -0.47173600 -0.26538200 C -5.41104800 -0.19346500 0.84383300 C -4.95512000 -1.55418500 -1.07708700 C -6.51203100 -0.98649900 1.14094700 208 H -5.17594900 0.65736300 1.46705400 C -6.04790200 -2.35413100 -0.78783200 H -4.35633300 -1.77240000 -1.95341300 C -6.82835700 -2.06779900 0.32705000 H -7.12830200 -0.75800500 2.00218800 H -6.31789100 -3.19186700 -1.41453700 O -7.89655600 -2.87855400 0.56929600 H -8.37267300 -2.56863500 1.34196900 O -0.25136500 4.17924700 -0.48091400 H -1.18299800 4.37754300 -0.25663400 Zero-point correction= 0.425282 (Hartree/Particle) Thermal correction to Energy= 0.452701 Thermal correction to Enthalpy= 0.453645 Thermal correction to Gibbs Free Energy= 0.365567 Sum of electronic and zero-point Energies= -1565.600609 Sum of electronic and thermal Energies= -1565.573191 Sum of electronic and thermal Enthalpies= -1565.572247 Sum of electronic and thermal Free Energies= -1565.660324 Chair Conformer C2 = 2.7 kcal/mol 0 1 C -4.78281900 -1.43579200 0.43522200 C -4.29907200 -0.22322200 1.23517700 C -3.62771700 0.63551000 -0.91935600 C -4.64207800 -0.21224200 -1.69369300 C -5.58243200 -0.92102700 -0.74064600 H -5.13140800 0.09068400 1.86823300 H -3.93408700 -2.02529400 0.07128400 H -3.51866800 1.60258200 -1.40562900 H -4.09352800 -0.97068400 -2.25601400 H -6.32613600 -0.20449300 -0.37452300 O -4.00889500 0.90498000 0.39882900 O -2.39404800 -0.07521800 -0.96404000 O -5.34045300 0.65289300 -2.56804200 H -6.01830700 0.13376300 -3.00907100 O -6.21270700 -1.96194800 -1.45918000 H -6.65573500 -2.52472900 -0.81644200 O -5.64404400 -2.25118700 1.21051100 H -5.13138500 -2.56991100 1.96110900 C -3.10046700 -0.56265400 2.10883400 H -2.27541000 -0.91883400 1.49561700 H -2.77146200 0.31783500 2.66112600 O -3.45762200 -1.63441500 2.98888100 H -3.79187600 -1.27098200 3.80989900 C -1.25218700 0.56773300 -0.59422900 C -0.07325300 -0.15750900 -0.81838500 C -1.22804100 1.83508600 -0.03684700 C 1.13564200 0.40052100 -0.47527600 H -0.13943800 -1.13717000 -1.26975500 C 0.00230700 2.40519500 0.29638800 H -2.12350400 2.39784500 0.17239500 C 1.19299700 1.68041500 0.10120800 C 2.47695300 2.28936200 0.45734500 C 2.44378100 -0.29500500 -0.71992100 H 2.31793800 -1.37712500 -0.73167200 209 H 2.85835000 0.00504500 -1.68645100 C 3.43218100 0.08955600 0.36899900 O 3.57983600 1.52496400 0.40561600 H 3.04200300 -0.22332100 1.34072800 O 2.59320200 3.45433200 0.78330800 C 4.79174600 -0.51158900 0.14777100 C 5.78475000 0.16745000 -0.54701000 C 5.04391600 -1.80728100 0.59346000 C 7.00877200 -0.43960500 -0.79709100 H 5.60777200 1.18083000 -0.87785600 C 6.25875900 -2.42406700 0.34548800 H 4.28249900 -2.34197700 1.14886000 C 7.24422900 -1.73572500 -0.35381800 H 7.78174800 0.09916400 -1.33183300 H 6.46603000 -3.42630500 0.69188900 O 8.42543100 -2.37997400 -0.56992700 H 9.03174600 -1.80171100 -1.03659700 O -0.01112400 3.63689200 0.81008000 H 0.91845500 3.92357700 0.92468400 Zero-point correction= 0.425068 (Hartree/Particle) Thermal correction to Energy= 0.452577 Thermal correction to Enthalpy= 0.453521 Thermal correction to Gibbs Free Energy= 0.365064 Sum of electronic and zero-point Energies= -1565.601456 Sum of electronic and thermal Energies= -1565.573948 Sum of electronic and thermal Enthalpies= -1565.573004 Sum of electronic and thermal Free Energies= -1565.661461 Chair Conformer C3 0 1 C 5.01305000 -0.57112800 0.75097800 C 3.67126900 -1.08778800 1.27862000 C 2.93573500 -0.82224400 -1.00547000 C 4.34837200 -0.93601400 -1.58709900 C 5.33668400 -1.33740800 -0.51186900 H 3.88139100 -2.00571900 1.83107000 H 4.95561800 0.49943600 0.52546700 H 2.23046500 -1.29082000 -1.68834200 H 4.64017200 0.04455800 -1.96852100 H 5.23024800 -2.40933400 -0.31106000 O 2.77840500 -1.47391400 0.22339200 O 2.65775000 0.56722700 -0.88727600 O 4.30140800 -1.88783200 -2.63307200 H 5.19822200 -2.00489000 -2.95805200 O 6.63296200 -1.05339400 -0.99679100 H 7.23731600 -1.11565900 -0.25041600 O 6.05678800 -0.81790600 1.67669800 H 5.84608200 -0.32574200 2.47746200 C 3.00553500 -0.08115700 2.20548700 H 2.82688400 0.85538100 1.68154600 H 2.05202400 -0.46815400 2.56598900 O 3.89804300 0.20941100 3.28647900 H 3.71142800 -0.37857100 4.01929600 C 1.37253800 0.96349300 -0.66525400 C 0.31774200 0.07174300 -0.43244600 210 C 1.17261000 2.33500000 -0.67607800 C -0.95110600 0.58728500 -0.24608800 H 0.48383000 -0.99194500 -0.36619700 C -0.10034000 2.85081300 -0.46809800 H 2.00192600 3.00455500 -0.84798400 C -1.18494500 1.96688700 -0.27729700 C -2.52905100 2.50850600 -0.05043500 C -2.13202300 -0.29980100 0.03016900 H -1.98580600 -1.29180800 -0.39580100 H -2.27733600 -0.41628900 1.10805900 C -3.38416700 0.32445600 -0.56227800 O -3.56331300 1.65354600 -0.02161600 H -3.26424400 0.42415800 -1.64352600 O -2.74626000 3.69039000 0.12767100 C -4.62370200 -0.46545500 -0.25654600 C -5.11190500 -1.37603800 -1.18380900 C -5.26269100 -0.34778500 0.97694800 C -6.21347500 -2.17032300 -0.88941800 H -4.63506100 -1.46835100 -2.15188700 C -6.36539500 -1.12767900 1.27875300 H -4.90509300 0.37818200 1.69425700 C -6.83902600 -2.04430000 0.34471300 H -6.58947900 -2.87480100 -1.62129600 H -6.87745700 -1.03829200 2.22607400 O -7.92635500 -2.78745500 0.69320400 H -8.17167500 -3.36773800 -0.02982900 O -0.24754700 4.17745500 -0.46607000 H -1.17874900 4.37524900 -0.23816800 Zero-point correction= 0.425166 (Hartree/Particle) Thermal correction to Energy= 0.452611 Thermal correction to Enthalpy= 0.453555 Thermal correction to Gibbs Free Energy= 0.365432 Sum of electronic and zero-point Energies= -1565.600499 Sum of electronic and thermal Energies= -1565.573053 Sum of electronic and thermal Enthalpies= -1565.572109 Sum of electronic and thermal Free Energies= -1565.660232 Chair Conformer C4 0 1 C -4.78706300 -1.44174000 0.42030200 C -4.30664600 -0.23417400 1.22976800 C -3.62731600 0.63781700 -0.91667500 C -4.63983900 -0.20378900 -1.70006500 C -5.58291500 -0.91961600 -0.75488600 H -5.14155200 0.07548200 1.86161300 H -3.93684900 -2.02845600 0.05539800 H -3.51526800 1.60792300 -1.39619500 H -4.08992500 -0.95804400 -2.26667100 H -6.32826300 -0.20594000 -0.38653200 O -4.01363800 0.89927100 0.40176700 O -2.39452000 -0.07413300 -0.96112000 O -5.33576600 0.66811000 -2.56961300 H -6.01210000 0.15242300 -3.01695400 O -6.21018600 -1.95610100 -1.48247000 H -6.65602700 -2.52273700 -0.84510900 211 O -5.65052000 -2.26263000 1.18743000 H -5.14011200 -2.58644700 1.93735400 C -3.11134400 -0.57864200 2.10599100 H -2.28458400 -0.93309300 1.49410300 H -2.78329500 0.29919200 2.66310500 O -3.47189800 -1.65391400 2.98038500 H -3.81805800 -1.29317600 3.79771000 C -1.25285100 0.56582400 -0.58461200 C -0.07356200 -0.15682000 -0.81453900 C -1.22963900 1.82785900 -0.01540000 C 1.13493500 0.39878800 -0.46558800 H -0.13891300 -1.13215800 -1.27530600 C 0.00032100 2.39537300 0.32405900 H -2.12553900 2.38831500 0.19814300 C 1.19148200 1.67302100 0.12284600 C 2.47530800 2.27956800 0.48524500 C 2.44312800 -0.29413600 -0.71734600 H 2.31792500 -1.37617900 -0.73743700 H 2.85453200 0.01336600 -1.68297900 C 3.43413300 0.08007700 0.37235000 O 3.57923500 1.51812000 0.42388400 H 3.04944000 -0.24458100 1.34196700 O 2.58844700 3.44109400 0.82469800 C 4.79539200 -0.50918500 0.14044100 C 5.15708900 -1.69122500 0.77213900 C 5.68683200 0.07882000 -0.75594000 C 6.38281300 -2.29170900 0.51080900 H 4.48119600 -2.15263000 1.48161100 C 6.91372200 -0.50511100 -1.01807900 H 5.42326500 1.01295300 -1.23276700 C 7.26048200 -1.69582700 -0.38632500 H 6.65752000 -3.21212800 1.01147000 H 7.61845100 -0.05405900 -1.70183400 O 8.47894100 -2.22888100 -0.68155700 H 8.61579200 -3.03245200 -0.17638600 O -0.01389500 3.62206200 0.84929100 H 0.91599300 3.90741900 0.96716300 Zero-point correction= 0.425079 (Hartree/Particle) Thermal correction to Energy= 0.452564 Thermal correction to Enthalpy= 0.453508 Thermal correction to Gibbs Free Energy= 0.365038 Sum of electronic and zero-point Energies= -1565.601136 Sum of electronic and thermal Energies= -1565.573651 Sum of electronic and thermal Enthalpies= -1565.572707 Sum of electronic and thermal Free Energies= -1565.661177 212 PHỤ LỤC C KẾT QUẢ XÁC ĐỊNH TÊN KHOA HỌC CỦA MẪU NGHIÊN CỨU 213 214 215 PHỤ LỤC D PHIẾU KẾT QUẢ THỬ HOẠT TÍNH GÂY ĐỘC TẾ BÀO