CC BY
21DOI: 10.6060/ivkkt.20206307.6253
УДК: 544.18
СРАВНИТЕЛЬНЫЕ ОСОБЕННОСТИ СТРУКТУРЫ И СВОЙСТВ БИОМАРКЕРОВ НАФТАЛАНСКОЙ НЕФТИ
Г.Ю. Колчина, Э.М. Мовсумзаде
Галина Юрьевна Колчина *
Кафедра химии и химической технологии, Стерлитамакский филиал Башкирского государственного университета, пр. Ленина, 49, Стерлитамак, Республика Башкортостан, Российская Федерация, 453100 E-mail: kolchina.GYu@mail.ru
Эльдар Мирсамедович Мовсумзаде
Кафедра общей, аналитической и прикладной химии, Уфимский государственный нефтяной технический университет, ул. Космонавтов, 1, Уфа, Республика Башкортостан, Российская Федерация, 450044 E-mail: eldarmm@yahoo.ru
Представлены результаты исследований структурных особенностей биомаркеров Нафталанской нефти (в частности, R, S-холестанов и гопанов с С28-С31) методом гибридного функционала плотности в приближении 6-311G+(d,p). Показано, что исследуемые вещества имеют четырехъядерную циклопентанопергидрофенантреновую систему, которая присуща смолам и асфальтенам тяжелых нефтей, а также характеризуется трехмерной пространственной конфигурацией. Соединения, содержащие такую кольцевую систему, имеют большое значение для организма, в том числе при воздействии антимикробных реагентов. Строение и положение примыкающих к основному циклу боковых групп и атомов, положение двойных связей в молекуле, пространственная конфигурация оказывают определенное влияние на биологическую активность биомаркеров Нафталанской нефти. Рассчитанные геометрические параметры исследуемых соединений показывают, что молекулы устойчивы, и устойчивость определяется конформацией колец (циклогекса-новые кольца имеют конформацию кресла, а циклопентановые — полукресла), характером соединения между собой и пространственным расположением атомов водорода, радикалов и функциональных групп. Из рассчитанных значений торсионных углов холестанов и гопанов показано, что сочленение циклов А/В, В/С и С/D находится в транс-конфигурации (118,37° - 129,94°). Исследуемые молекулы обладают транс-сочленением колец при 5,10-, 8,9-, и 13,14-положениях (в случае гопанов 5-10 также при 17,18-положении). Связи в молекулах, образующих кольца, незначительно искажены, а сами кольца не являются плоскими. Выявлена зависимость между биологической активностью тритерпенов и их значениями потенциалов ионизации и сродства к электрону. Исследуемые биомаркеры по геометрическим и энергетическим параметрам сходны с производными бетулина и могут проявлять биологическую активность.
Ключевые слова: биомаркеры, Нафталанская нефть, холестаны, гопаны, бетулин, метод гибридного функционала плотности, структура
COMPARATIVE FEATURES OF STRUCTURE AND PROPERTIES OF BIOMARKERS OF NAPHTHALAN PETROLEUM
G.Yu. Kolchina, E.M. Movsumzade
Galina Yu. Kolchina *
Department of Chemistry and Chemical Technology, Sterlitamak Branch of the Bashkir State University, Lenin ave., 49, Sterlitamak, 453100, Republic of Bashkortostan, Russia E-mail: kolchina.GYu@mail.ru*
Eldar M. Movsumzade
Department of General, Analytical and Applied Chemistry, Ufa State Petroleum Technical University, Kosmonavtov st., 1, Ufa, 450044, Republic of Bashkortostan, Russia E-mail: eldarmm@yahoo.ru
Г.Ю. Колчина, Э.М. Мовсумзаде
The results of studies of the structural features of the biomarkers of Naphthalan petroleum (in particular, R, S-cholestanes and hopanes with C28-C31) by the hybrid density functional in the approximation 6-311G+(d,p) are presented. It was shown that the studied substances have a quad-cyclopentanoperhydrophenanthrene system, which is inherent in resins and asphaltenes of heavy oils, and is also characterized by a three-dimensional spatial configuration. Compounds containing such a ring system are of great importance both for the body, including when exposed to antimicrobial reagents. The structure and position of the side groups and atoms adjacent to the main cycle, the position of double bonds in the molecule, and the spatial configuration have a definite effect on the biological activity of the biomarkers of Naphthalan petroleum. The calculated geometric parameters of the studied compounds show that the molecules are stable, and the stability is determined by the conformation of the rings (cyclohexane rings have the chair conformation, and cyclopentane rings have half-chairs), the nature of the connection between each other and the spatial arrangement of hydrogen atoms, radicals and functional groups. From the calculated values of the torsion angles of cholestanes and hopanes, it was shown that the junction of the A/B, B/C and C/D cycles is in the trans configuration (118.37° - 129.94°). The studied molecules possess a trans-articulation of the rings at the 5,10-, 8,9-, and 13,14-positions (in the case of 5-10 hopanes, also at the 17,18-position). The bonds in the molecules that form the rings are slightly distorted, and the rings themselves are not flat. A relationship was found between the biological activity of triterpenes and their values of ionization potentials and electron affinity. The studied biomarkers are similar in geometry and energy parameters to betulin derivatives and can exhibit biological activity.
Key words: biomarkers, Naphthalan petroleum, cholestans, hopanes, betulin, density functional hybrid method, structure
Для цитирования:
Колчина Г.Ю., Мовсумзаде Э.М. Сравнительные особенности структуры и свойств биомаркеров Нафталанской нефти. Изв. вузов. Химия и хим. технология. 2020. Т. 63. Вып. 7. С. 82-87
For citation:
Kolchina G.Yu., Movsumzade E.M. Comparative features of structure and properties of biomarkers of Naphthalan petroleum. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. [Russ. J. Chem. & Chem. Tech.]. 2020. V. 63. N 7. P. 82-87
INTRODUCTION
The composition of hydrocarbons and their ratio in oils are directly related to the conditions of their formation, namely: temperature and pressure (catagenesis), the effect of microorganisms (biodegradation), the composition and structure of the original organic matter [1-6].
Biomarkers (chemofossilia) are peculiar organic compounds and have a complex-built carbon skeleton
of biogenic nature, inherited in whole, or in the form of fragments from the precursor molecules of the original organisms. A large number of biomarkers in petroleum are polycyclic hydrocarbons (steranes and triter-pans), which are found in all living organisms [7-10].
Naphthalan oil its individual fractions obtained by distillation under vacuum or by the percolation method, as well as some organic compounds of non-hydrocarbon nature isolated from this oil, have significant biological activity [11-16].
14 a-17 a-cholestan-20R(S)(1,2) 14 p-17p-cholestan-20R(S) (3,4)
Fig. 1. Structures of the studied Naphthalan biomarker molecules Рис. 1. Структуры исследуемых молекул биомаркеров Нафталанской нефти
EXPERIMENTAL TECHNIQUE
The geometry of the molecules is fully optimized within the framework of the method of the hybrid density functional B3LYP/6-311+G(d,p). All calculations were performed using the FireFly program [16].
RESULTS AND DISCUSSION
The compounds contained in Naphthalan petroleum have a quad-cyclopentanoperhydrophenanth-rene system and are characterized by a three-dimensional spatial configuration (Fig. 1). The structure and position of the side groups and atoms adjacent to the main cycle, the position of double bonds in the molecule, the spatial configuration, etc., have a definite effect on the biological activity of these compounds.
The geometrical shape of the studied bi-omarkers is stable and is determined by the conformation of the rings (cyclohexane rings have the chair conformation, cyclopentane rings have half-chairs), the nature of their interconnection, and also the arrangement of hydrogen atoms, radicals and functional groups that are attached to the nucleus (Tables 1, 2).
Table 1
The geometric characteristics of cholestanes calculated
by the B3LYP/6-311+G(d,p) method Таблица 1. Геометрические характеристики холе-
Parameters Compounds
1 2 3 4
КС1-С2), Â 1.539 1.538 1.538 1.538
С2-С3 1.535 1.534 1.535 1.534
С3—С4 1.535 1.535 1.535 1.535
С4—С5 1.538 1.538 1.539 1.539
С5—С6 1.525 1.534 1.534 1.534
С6—С7 1.532 1.533 1.532 1.532
С7—С8 1.538 1.539 1.539 1.539
С8—С9 1.557 1.556 1.551 1.551
С9—С10 1.579 1.547 1.571 1.571
С10—С1 1.555 1.554 1.555 1.554
С9—С11 1.545 1.545 1.542 1.542
С11—С12 1.644 1.543 1.537 1.538
С12—С13 1.543 1.549 1.549 1.548
С13—С14 1.557 1.558 1.558 1.558
С14—С15 1.537 1.535 1.555 1.555
С15—С16 1.553 1.552 1.553 1.553
С16—С17 1.563 1.567 1.548 1.548
С13—С17 1.569 1.570 1.564 1.564
¿(С1С10С9), 0 110.25 110.08 109.86 109.85
¿С4С5С6 112.64 112.88 112.72 112.78
¿С10С9С11 114.60 114.51 114.37 114.49
¿С12С13С17 116.97 116.62 113.14 113.69
¿С7С8С14 111.71 111.75 111.20 111.18
¿С8С14С15 18.97 119.21 116.30 116.23
¿С13С17С20 120.61 120.34 118.67 119.18
¿(С1С10С9С19), 0 120.85 120.81 120.62 120.58
¿С1С10С9С5 -116.51 -116.57 -116.63 -116.64
¿С4С5С6С10 -129.3 -129.45 -129.27 -129.33
¿С9С8С14С7 -123.21 -123.09 -127.46 -112.88
¿С10С9С8С11 -130.31 -130.32 -128.51 -128.66
¿С12С13С17С18 127.10 127.12 124.91 125.16
¿С12С13С17С14 -114.10 -114.21 -116.48 -116.43
¿С8С14С15С13 -129.94 -129.89 128.30 128.33
¿С13С17С16С20 -131.40 -130.95 133.19 134.13
¿С17С20С22С21 125.89 -124.07 128.07 124.99
Angular ("angular") methyl groups at C10 and C13 atoms and a side chain at C17 consisting of eight carbon atoms are attached to the ring system of cholestanes 1-4. The side chain and two angular methyl groups are located above the plane in the molecules of cholestanes, and P-orientation is attributed to them. The hydrogen atom at Cs also has a P orientation. Hydrogen atoms at C9 and C14 are a-oriented. In cyclohexane rings, hydrogen atoms attached to adjacent carbon atoms are removed from each other at a distance of 2.46-2.48 Á, which indicates the stable position of cyclohexane rings in the chair conformation.
As can be seen, from the calculated values of the torsion angles of cholestanes 1-4 and hopanes 5-10, the junction of the A/B, B/C and C/D cycles is in the trans configuration (118.37°-129.94°). Eight carbon atoms form a zigzag chain, the hydrogen atoms of the individual units are maximally distant from each other, the methyl group at the C20 atom is removed from the angular methyl group at C13, and it follows that repulsions between the hydrogen atoms are minimized. This conformation is the most stable (Fig. 2).
Fig. 2. The structure of 14a-17a-cholestan-20R Рис. 2. Структура 14а-17а-холестана-20Я
The studied molecules possess a transarticulation of the rings at the 5,10-, 8,9-, and 13,14-positions (in the case of hopanes 5-10, also at the 17,18-position). The bonds in the molecules that form the rings are slightly distorted, and the rings themselves are not flat. The bonds C9-C10 and C8-C14 (and C13-C18 in the case of hopanes) connecting the two cycles have an anti-configuration. It has been shown that pairs of carbon atoms C2 and C3, C10 and C5, C8 and C7 are in the same plane, and carbon atoms C1, C9, C14, C13 and C11 are located in another plane parallel to the first and 0.84 away from it Â. In hopanes (510), the bond lengths between the carbons in the cycles remain unchanged, in addition to the E ring, where the radical fragment at the C21 atom affects the bond lengths and energies. In cholestanes, the bond
r.ro. Komma, Э.М. MoBcyM3age
lengths are distorted depending on the location relative to the plane of the hydrogen atoms at C14 and C17, as well as the influence of the position of the radical fragment. For example, in the case of the a-position
of hydrogen atoms at C14 and C17, the C14-C15 bond is significantly shortened to 1.535-1.537 A and a significant increase in the C11-C12 bond to 1.543-1.644 is observed.
Table 2
The geometric characteristics of hopanes calculated by the B3LYP/6-311+G(d,p) method
Parameters Compounds
5 6 7 8 9 10
C1-C2 1.535 1.535 1.535 1.535 1.535 1.535
C2 C3 1.530 1.530 1.530 1.530 1.530 1.530
C3—C4 1.550 1.550 1.550 1.549 1.550 1.550
C4—C5 1.571 1.570 1.570 1.570 1.570 1.570
C4—C23 1.545 1.544 1.544 1.545 1.544 1.544
C4—C24 1.547 1.547 1.547 1.547 1.547 1.547
C5—C6 1.537 1.537 1.537 1.537 1.537 1.537
C6—C7 1.536 1.536 1.536 1.536 1.536 1.536
C7—C8 1.553 1.554 1.554 1.553 1.554 1.554
C8—C9 1.576 1.577 1.576 1.577 1.576 1.577
C8—C26 1.555 1.555 1.555 1.555 1.555 1.556
C8—C14 1.618 1.618 1.618 1.617 1.617 1.618
C9—C10 1.585 1.586 1.585 1.585 1.585 1.585
C10—C1 1.556 1.556 1.556 1.556 1.556 1.556
C10—C25 1.551 1.551 1.551 1.550 1.551 1.551
C9—C11 1.546 1.546 1.546 1.546 1.546 1.546
C11—C12 1.540 1.539 1.540 1.540 1.540 1.539
C12—C13 1.539 1.538 1.539 1.539 1.539 1.538
C13—C18 1.561 1.560 1.560 1.560 1.560 1.557
C13—C14 1.574 1.578 1.575 1.575 1.575 1.578
C14—C15 1.559 1.562 1.558 1.559 1.558 1.563
C14—C27 1.557 1.557 1.558 1.555 1.558 1.558
C15—C16 1.545 1.545 1.545 1.545 1.545 1.545
C16—C17 1.529 1.525 1.530 1.529 1.530 1.523
C17—C18 1.554 1.551 - 1.554 1.547 1.551
C17—C21 1.567 1.554 1.570 1.569 1.571 1.534
C18—C19 1.549 1.552 1.549 1.549 1.549 1.553
C19—C20 1.548 1.554 1.547 1.548 1.546 1.561
ZC1C10C9 108.06 108.16 108.12 108.16 108.08 108.18
ZC4C5C6 114.72 114.65 114.65 114.66 114.68 114.63
ZC10C9C11 113.97 113.87 113.98 114.04 114.04 113.88
ZC12C13C18 114.41 114.70 114.49 114.43 114.52 114.64
ZC7C8C14 110.65 110.71 110.64 110.60 110.59 110.63
ZC8C14C15 110.84 110.66 110.79 110.81 110.78 110.76
ZC13C18C17 107.89 106.97 107.81 107.90 107.86 107.60
ZC17C16C15 109.34 108.82 109.29 109.27 109.31 109.05
ZC19C18C17 99.37 99.30 99.42 99.34 99.45 99.69
ZC18C17C21 107.16 107.07 107.20 107.17 107.05 104.57
ZC20C21C17 101.99 102.89 102.15 101.98 102.23 103.46
ZC1C10C9C25 118.79 118.80 118.80 118.75 118.75 118.77
ZC1C10C9C5 -115.61 -115.65 -115.61 -115.62 -115.65 -115.69
ZC4C5C6C10 -135.41 -135.29 -135.35 -135.50 -135.35 -135.30
ZC9C8C14C15 -175.50 -175.41 -175.69 -175.56 -175.83 -175.34
ZC10C9C8C11 -132.68 -132.58 -132.70 -132.80 -132.78 -132.58
ZC12C13C18C14 -130.98 -130.91 -130.95 -131.01 -130.98 -130.96
ZC8C14C15C13 -118.37 -118.62 -118.47 -118.38 -118.49 -118.50
ZC9C8C14C26 122.12 122.12 122.17 122.18 -122.16 122.18
ZC9C8C14C7 -120.31 -120.25 -120.27 -120.31 -120.32 -120.23
ZC8C14C15C13 -118.37 -118.62 -118.47 -118.38 -118.49 -118.50
ZC8C14C15C27 120.53 120.25 120.42 120.47 120.37 120.28
ZC13C18C17C28 127.46 127.06 127.34 127.41 127.24 127.31
ZC13C18C19C17 114.11 113.41 114.10 114.12 114.25 114.42
The studied structures are similar in structure with steroid hormones [18] and betulin (betulin derivatives) (Fig. 3), which also belong to the lupane series triterpenes [19-24].
R=CH2OH (11) COH (12) COOH (13)
Table 3.
Energy parameters of the studied molecules and betulin derivatives calculated by the B3LYP/6-311+G(d,p) method Таблица 3. Энергетические параметры исследуемых молекул и производных бетулина, рассчитанные
HO
Fig. 3. The structure of betulin and its derivatives Рис. 3. Структура бетулина и его производных
Table 3 shows the energy characteristics of the studied structures in comparison with the values of betulin and its derivatives. It has been established that betulin and its derivatives have a number of antibacterial and antimicrobial activities [19, 20].
The dependence of antimicrobial and antibacterial activity on the energy of the boundary molecular orbitals of betulin molecules and its derivatives 11-13 was studied. The dependence of the biological activity of betulin and its derivatives on their values of ionization potentials and electron affinity has been established.
Based on the results and comparing the values of the boundary orbitals with the orbits of the bio-markers, it can be assumed that the biomarkers of Nafta-lan oil, which have a similar structure with betulin derivatives, are also able to exhibit biological activity.
ЛИТЕРАТУРА
1. Петров А.А. Углеводороды нефти. М.: Наука. 1984. 264 с.
2. Рябов В.Д. Химия нефти и газа. М.: Техника, ТУМА Групп. 2004. 288 с.
3. Окунова Т.В., Бадмаев Ч.М., Гируц М.В., Эрдниева О.Г., Кошелев В.Н., Гордадзе Г.Н. Биометки нефтей Калмыкии. Нефтехимия. 2010. Т. 50. № 2. С. 99-106. DOI: 10.1134/S0965544110020015.
4. Гордадзе Г.Н., Чахмахчев В.А., Тихомиров В.И. Геохимическая типизация газоконденсатов нижнемеловых пластов Ясбургского месторождения Западной Сибири. Нефтехимия. 2004. Т. 44. № 3. С. 171-179.
5. Trejo F., Centeno G., Ancheyta J. Precipitation, fractionation and characterization of asphaltenes. Fuel. 2004. V. 83. N 16. P. 2169-2175. DOI: 10.1016/j.fuel.2004.06.008.
6. Полетаева О.Ю., Колчина Г.Ю., Леонтьев А.Ю., Бабаев Э.Р., Мовсумзаде Э.М., Хасанов И.И. Геометрическое и электронное строение компонентов тяжелых высоковязких нефтей. Изв. вузов. Химия и хим. технология. 2019. Т. 62. Вып. 9. С. 40-45. DOI: 10.6060/ivkkt20196209.6022.
7. Абрафикова И.М., Каюпова Г.П., Вандюкова И.И., Морозов В.И., Губайдуллин А. Т. Фракционный состав асфальтенов из природных битумов пермских отложений Татарстана. Вестн. Казан. технол. ун-та. 2011. № 3. С. 180-186.
Compound -Ehomo, eV Elumo, eV Ae, eV
1 7.094 -0.024 7.070
2 7.102 -0.046 7.56
3 7.151 -0.060 7.91
4 7.151 -0.063 7.88
5 6.961 -0.101 6.86
6 6.969 -0.101 6.868
7 6.955 -0.112 6.843
8 6.955 -0.106 6.849
9 6.953 -0.117 6.836
10 6.982 -0.095 6.887
11 6.550 -0.294 6.256
12 6.759 -0.909 5.85
13 6.651 -0.261 6.39
CONCLUSIONS
Quantum-chemical studies have made it possible to establish the structure of the biomarkers of Naftalan oil containing quad-cyclopentanoperhydro-phenanthrene systems. It was found that the geometric shape of the studied biomarkers is stable and is determined by the conformation of the rings that are located in the trans-conformation. The compounds under study are similar in structure to betulin derivatives and may possibly exhibit biological activity.
The reported study was funded by RFBR according to the research project № 19-29-074071/19.
REFERENCES
. Petrov A.A. Hydrocarbons of oil. M.: Nauka. 1984. 264 p. (in Russian).
:. Ryabov V.D. Chemistry of oil and gas. 2-e izd. M.:
Tekhnika, TUMA Grupp. 2004. 288 p. (in Russian). i. Okunova T.V., Badmaev Ch.M., Giruts M.V., Erdnieva O.G., Koshelev V.N., Gordadze G.N. Oil bio labels of Kalmykia. Neftekhimiya. 2010. V. 50. N 2. P. 99-106 (in Russian). DOI: 10.1134/S0965544110020015. k Gordadze G.N., Chakhmakhchev V.A., Tikhomirov V.I Geochemical typification of gas condensates of the Lower Cretaceous beds of the Yasburgskoye field in Western Siberia. Neftekhimiya. 2004. V. 44. N 3. P. 171-179 (in Russian). i. Trejo F., Centeno G., Ancheyta J. Precipitation, fractionation and characterization of asphaltenes. Fuel. 2004. V. 83. N 16. P. 2169-2175. DOI: 10.1016/j.fuel.2004.06.008. i. Poletaeva O.Yu., Kolchina G.Yu., Leontev A.Yu., Babayev E.R., Movsumzade E.M., Khasanov II Geometric and electronic structure of heavy highly viscous oil components. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2019. V. 62. N 9. P. 40-45 (in Russian). DOI: 10.6060/ivkkt.20196209.6022. '. Abrafikova I.M., Kayupova G.P., Vandyukova II, Morozov V.I, Gubaidullin A.T. Fractional composition of asphaltenes from natural bitumen of Permian deposits of Tatarstan. Vestn. Kazan Tekhnol. Un-ta. 2011. N 3. P. 180-186 (in Russian).
Г.Ю. Колчина, Э.М. Мовсумзаде
8. Mullins O.C., Sabbah H., Eyssautier J., Pomerantz A.E., Barre L., Andrews A.B., Ruiz-Morales Y., Mostowfi F., McFarlane R., Goual L., Lepkowicz R., Cooper T., Or-bulescu J., Leblanc R.M., Edwards J., Zare R.N. Advances in asphaltene science and the Yen-Mullins model. Energy Fuels. 2012. V. 26. N 7. P. 3986-4003. DOI: 10.1021/ef300185p.
9. Лурье М.А., Шмидт Ф.К. Генетические аспекты нефте-газообразования, серосодержания и металлоносность нефтей. Докл. АН. 2009. Т. 424. № 4. С. 534-537.
10. Киямова А.М., Каюкова Г.П., Романов Г.В. Состав высокомолекулярных компонентов нефте- и битумсо-держащих пород и продуктов их гидротермальных превращений. Нефтехимия. 2011. № 4. С. 243-253. DOI: 10.1134/S0965544111030078.
11. Мурадов А.Н., Анисимов А.В. Исследование химического состава лечебной нафталанской нефти. Вестник. 2006. Т. 47. № 3. С. 226-230.
12. Мурадов А.Н. Исследование химического состава лечебной Нафталанской нефти. Научные достижения биологии, химии, физики: сб. ст. по матер. VI междунар. науч.-практ. конф. Новосибирск: СибАК. 2012. С. 102-108.
13. Адигезалова В.А., Гашимова У. Ф., Полякова Л.П. Состав и свойства уникальной нефти Нафталанского месторождения Азербайджана. Рос. хим. журн. 2016. Т. 60. № 5-6. С. 100-109.
14. Мехдиев Д.И., Джафаров С.И., Адигезалова В.А., Мовсумзаде Э.М. Бальнеологические свойства Нафталанской нефти. М.: Медицина. 2002. 255 с.
15. Kolchina G.Yu., Movsumzade E.M, Adigezalova V.A., Poletaeva O.Yu. Theoretical and experimental study of the reactivity of Naftalan petroleum biomarkers. DGMK. 2018. P. 177-182.
16. Kolchina G.Yu., Adigozalova V.A., Movsumzade E.M
Indices of reactivity of biomarkers of naphthalan oil. DGMK. 2019. P. 179-184.
17. Granovsky A.A. http://assik/chem.msu.su/gran/amess/index.html.
18. Физер Л., Физер М. Стероиды. М.: Мир. 1964. 982 с.
19. Толстиков Г.А., Флехтер О.Б., Шульц Э.Э., Балтина Л.А., Толстиков А.Г. Бетулин и его производные. Химия и биологическая активность. Хим. в инт. уст. разе. 2005. № 1. С. 1-30.
20. Boryczka S., B^benek E., Wietrzyk J., Kempinska K., Jastrz^bska M., Kusz J., Nowak M Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin. Molecules. 2013. N 18 (4). Р. 4526-43. DOI: 10.3390/molecules 18044526.
21. Boryczka S., Michalik E., Jastrz^bska M., Kusz J., Zubko M., B^benek E. X-ray crystal structure of betulin-DMSO solvate. J. Chem. Crystallogr. 2012. N 42. Р. 345-351. DOI: 10.1007/s10870-011-0251-z.
22. Mullauer F.B., Kessler J.H., Medema J.P. Betulinic acid, a natural compound with potent anticancer effects. Anticancer Drugs. 2010. N 21. Р. 215-227. DOI: 10.1097/CAD. 0b013e3283357c62.
23. Alakurtti S., Heiska T., Kiriazis A., Sacerdoti-Sierra N., Jaife C.L., Yli-Kauhaluoma J. Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. Bioorg. Med. Chem. 2010. N 18. Р. 1573-1582. DOI: 10.1016/j.bmc.2010.01.003.
24. Urban M., Vlk M., Dzubak P., Hajduch M., Sarek J. Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid. Bioorg. Med. Chem. 2012. N 20. Р. 3666-3674. DOI: 10.1016/j.bmc.2012.03.066.
8. Mullins O.C., Sabbah H., Eyssautier J., Pomerantz A.E., Barre L., Andrews A.B., Ruiz-Morales Y., Mostowfi F., McFarlane R., Goual L., Lepkowicz R., Cooper T., Or-bulescu J., Leblanc RM, Edwards J., Zare R.N. Advances in asphaltene science and the Yen-Mullins model. Energy Fuels. 2012. V. 26. N 7. P. 3986-4003. DOI: 10.1021/ef300185p.
9. Lurie M.A., Schmidt F.K. Genetic aspects of oil and gas formation, sulfur content and metal content of oils. Dokl. AN. 2009. V. 424. N 4. P. 534-537 (in Russian).
10. Kiyamova A.M., Kayukova G.P., Romanov G.V. Composition of high molecular weight components of oil and bitumen-containing rocks and products of their hydrothermal transformations. Neftekhimiya. 2011. N 4. P. 243-253 (in Russian). DOI: 10.1134/S0965544111030078.
11. Muradov A.N., Anisimov A.V. Study of the chemical composition of medicinal Naftalan oil. Vestnik. 2006. V. 47. N 3. P. 226-230 (in Russian).
12. Muradov A.N. The study of the chemical composition of medicinal Naftalan oil. Scientific advances in biology, chemistry, physics: Sat. Art. by mater. VI int. scientific-practical conf. Novosibirsk: SibAK. 2012.P. 102-108 (in Russian).
13. Adigezalova V.A., Gashimova U.F., Polyakova L.P. Composition and properties of the unique oil of the Naftalan field of Azerbaijan. Ross. Khim. Zhurn. 2016. V. 60. N 5-6. P. 100-109 (in Russian).
14. Mehdiev D.I., Dzhafarov S.I., Adigezalova V.A., Movsumzade E.M. Balneological properties of Naftalan oil. M.: Meditsina. 2002. 255 p. (in Russian).
15. Kolchina G.Yu., Movsumzade E.M, Adigezalova V.A., Poletaeva O.Yu. Theoretical and experimental study of the reactivity of Naftalan petroleum biomarkers. DGMK. 2018. P. 177-182.
16. Kolchina G.Yu., Adigozalova V.A., Movsumzade E.M.
Indices of reactivity of biomarkers of naphthalan oil. DGMK. 2019. P. 179-184.
17. Granovsky A.A. http://assik/chem.msu.su/gran/amess/index.html.
18. Fizer L., Fizer M Steroids. M.: Mir. 1964. 982 p. (in Russian).
19. Tolstikov G.A., Flekhter O.B., Schulz E.E., Baltina L.A., Tolstikov A.G. Betulin and its derivatives. Chemistry and biological activity. Khim. Int. Ust. Razv. 2005. N 1. P. 1-30. (in Russian).
20. Boryczka S., Bçbenek E., Wietrzyk J., Kempinska K., Jastrzçbska M., Kusz J., Nowak M Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin. Molecules. 2013. N 18 (4). Р. 4526-43. DOI: 10.3390/molecules 18044526.
21. Boryczka S., Michalik E., Jastrzçbska M., Kusz J., Zubko M., Bçbenek E. X-ray crystal structure of betulin-DMSO solvate. J. Chem. Crystallogr. 2012. N 42. Р. 345-351. DOI: 10.1007/s10870-011-0251-z.
22. Mullauer F.B., Kessler J.H., Medema J.P. Betulinic acid, a natural compound with potent anticancer effects. Anticancer Drugs. 2010. N 21. Р. 215-227. DOI: 10.1097/CAD. 0b013e3283357c62.
23. Alakurtti S., Heiska T., Kiriazis A., Sacerdoti-Sierra N., Jaffe C.L., Yli-Kauhaluoma J. Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. Bioorg. Med. Chem. 2010. N 18. Р. 1573-1582. DOI: 10.1016/j.bmc.2010.01.003.
24. Urban M, Vlk M, Dzubak P., Hajduch M, Sarek J. Cyto-toxic heterocyclic triterpenoids derived from betulin and betu-linic acid. Bioorg. Med. Chem. 2012. N 20. Р. 3666-3674. DOI: 10.1016/j.bmc.2012.03.066.
Поступила в редакцию (Received) 05.02.2020 Принята к опубликованию (Accepted) 07.05.2020
