CC BY
10
AZERBAIJAN CHEMICAL JOURNAL № 3 2023 ISSN 2522-1841 (Online)
ISSN 0005-2531 (Print)
UDC 547.8
GRAPHENE OXIDE-MODIFIED DIHYDROPYRIMIDINES
1 2 3 4* 12 4 2
A.Huseynzada ''' , U.Hasanova '' , Z.Gakhramanova
1ICRL, Baku State University GPOGC SRI, Azerbaijan State Oil and Industry University 3Department of Chemistry, Azerbaijan Engineers Union 4ICESCO Biomedical Materials Department, Baku State University
Received 26.01.2023 Accepted 08.02.2023
This study is devoted to the synthesis of various ensembles on the basis of graphene oxide nanolayers and dihydropyrimidines and the investigation of their antimicrobial activity. The "building blocks" of ensembles, viz dihydropyrimidines were synthesized by the Biginelli reaction in the presence of low-toxic copper triflate under microwave conditions. The positive side of the reaction is the absence of any additional purification stage, formed after cooling the solution precipitate just washed with a few amount of distilled water. The structures of synthesized compounds were determined by 1H, 13C and dept135 NMR spectroscopy methods. The second component, viz graphene oxide nanolayers, was synthesized by a modified Hummer method. The modification of the method is caused by the increasing of the oxidizing agent (H2SO4+KMnO4) concentration, which allowed to receive purier nanolayers. The structure and morphology of nanolayers were investigated by SEM and XRD methods, according to which it was determined that the thickness of nanolayers is 1 nm. Subsequently, graphene oxide was modified with dihydropyrimidines. The synthesis of ensembles was performed by non-covalent coupling of dihydropyrimidines with graphene oxide nanolayers by sonication. In addition, the antimicrobial activity of ensembles against S. aureus, Ps. aeruginosa and E. coli was performed. Obtained during the analysis results were compared with the activity of pristine antibiotic ampicillin. It was found that the addition of graphene oxide nanolayers to the dihydropyrimidine molecule allowed to improve the antimicrobial activity of dihydropyrimidines.
Keywords: dihydropyrimidines, Biginelli reaction, graphene oxide nanolayers, antimicrobial activity.
doi.org/10.32737/0005-2531-2023-3-142-151
Introduction
One-pot multicomponent reactions are a very effective synthetic technique and a flexible tool for building different classes of compounds with a broad range of applications. Because multicomponent reactions provide a synthetic chemist intrinsically substantial benefits over traditional linear-type synthesis, such as straightforward operation, simple starting ingredients, high product complexity, and enormous product variety, interest in them is rising [1-4]. A three-component one-pot Biginelli reaction is one of these kinds of reactions that was used in the synthesis of heterocycles. Dihydro-pyrimidine is a family of chemical compounds with a wide range of biological activities that may be produced by combining an aldehyde, urea derivative, and a methylene active molecule [5-8]. The multicomponent character of this reaction, which enables the introduction of numerous pharmacophoric groups in the struc-
ture of dihydropyrimidines, accounts for their prominence in medicine. This class of compounds exhibits various antiviral, antifungal, an-ti-leishmanial, antiproliferative, antitumor, antibacterial, anti-inflammatory, anti-hypertensive, anti-HIV, antiepileptic, antidiabetic, anti-malarial, miscellaneous, potassium and calcium channels, and 1aadrenergic antagonist activities, according to numerous studies using molecular manipulations. On this premise, other medications were created and used in medicine, including terazosin, (S)-monastrol, (S)-enastron, mon-97, and batzelladine A and B [9-12].
Another perspective material is graphene oxide nanolayers, whose modification and chemical engineering lead to the production of new prospective materials having enormous potential in various areas of science, in particular, the pharmaceutical area [13-15]. Graphene oxide is an oxidized form of graphene, laced with oxygen-containing groups such as epoxide, carbon-yl, carboxyl and hydroxyl groups, which parti-
cipate in modification reactions [16-19]. One of the advantages of graphene oxide is its easy dispersibility in water and other organic solvents, as well as in different matrixes, due to the presence of oxygen functionalities. The func-tionalization of graphene oxide can fundamentally change its properties. The resulting chemically modified graphenes found their application in drug-delivery vehicles, biodevices, polymer composites and so on. Moreover, the usage of nano-sized particles reveals changes in the materials' properties due to their size approaches and the percentage of the surface in relation to the percentage of the volume of a material
o
J
hon
O
A
+ nh2
becomes significant. It is also another benefit of using graphene oxide nanolayers [20-23].
Taking into account the above-mentioned advantages of dihydropyrimidines and graphene oxide nanolayers, the novel ensembles on the basis of the mentioned "building blocks" were synthesized and their antimicrobial activity was investigated.
Experimental part
Synthesis of dihydropyrimidines
The existing procedure was modified slightly to produce the desired dihydropyrimi-dines (Scheme 1):
Cu(OTf)2, EtOH
o"'' 100°C, 2.5 h MW
Scheme 1. Synthesis of dihydropyrimidines in the presence of Cu(OTf)2.
0.5 mmol of the following aldehyde, 0.75 mmol (45 mg) of urea, and 0.08 mmol (30 mg) of Cu(OTf)2 were added to a microwave vial with a magnetic stirrer and dissolved in 1 ml of ethanol. A vial was then filled with 0.46 mmol (50 ^l) of methyl acetoacetate, sealed, and microwave-irradiated for 2.5 hours at 1000C with a maximum power of 200W (CEM DiscoverTM System). The precipitate was created at the conclusion of the reaction period, filtered, rinsed with distilled water, and dried.
Methyl 6-methyl-2-oxo-4-(2,4,6-trimeth-oxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-car-boxylate (1): The title compound was prepared according to the general procedure using 2,4,6-trimetoxybenzaldehyde to afford the title compound a light yellow precipitate. Yield 74 %. M.p. 252-2540C. 1H NMR spectrum (Figure 1): (DMSO-d6, 5, ppm), 2.15 s (3H, CH3), 3.39 s (3H, OCH3), 3.72 s (6H, 2OCH3), 3.75 s (3H, OCH3), 5.74 s (1H, CH), 6.18 s (2H, 2C ArH), 6.9 s (1H, NH), 8.95 s (1H, NH). 13C NMR
spectrum (Figure 2): (DMSO-d6, Ô, ppm), 17.78 (CH3), 45.03 (CH), 50.14 (OCH3), 55.1 (OCH3), 55.7 (2OCH3), 91.08 (2CATH), 96.03 (C), 113.71 (C), 147.84 (CAT), 152.12 (CAT), 158.99 (2Cat), 159.91 (COO), 166.25 (CO).
N
Methyl 4-(4-cyanophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2): The title compound was prepared according to the general procedure using 4-cyanobenz-aldehyde to afford the title compound a colorless precipitate. Yield 74 %. M.p. 212-2140C. 1H NMR spectrum (Figure 4): (DMSO-d6, 5, ppm), 2.26 s (3H, CH3), 3.54 s (3H, OCH3), 5.21-5.22 d (1H, CH, J=3 Hz), 7.41-7.44 d (2H, 2CArH, J=9 Hz), 7.8-7.83 d (2H, 2CArH, J=9 Hz), 7.86 s (1H, NH), 9.34 s (1H, NH). 13C NMR spectrum (Figure 5): (DMSO-d6, 5, ppm), 18.23 (CH3), 51.23 (CH), 54.03 (OCH3), 98.39 (C), 110.49 (C), 119.08 (CN), 127.61 (2CaH), 132.95 (2CArH), 149.88 (CAr), 150.18 (CAr), 152.2 (COO), 165.95 (CO).
Fig. 1. 1H NMR spectrum of compound 1 in DMSO-d6 solution
Fig. 2. 13C NMR spectrum of compound 1 in DMSO-d6 solution.
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Fig. 3. dept135 NMR spectrum of compound 1 in DMSO-d6 solution
Fig. 4. 1H NMR spectrum of compound 2 in DMSO-d6 solution
Fig. 5. C NMR spectrum of compound 2 in DMSO-d6 solution
NMR experiments
The NMR studies were carried out using Bruker Standard software (TopSpin 3.1) on a BRUKER FT NMR spectrometer AVANCE 300 (Bruker, Karlsruhe, Germany) (300 MHz for 1H and 75 MHz for 13C) with a BVT 3200 variable temperature unit in 5 mm sample tubes. Tetramethylsilane (TMS) was the internal standard, and chemical changes were expressed in parts per million (ppm). The following multiplicities are identified: singlet (s), doublet (d), triplet (t), quadruplet (q), and multiple (m).
The experimental parameters for 1H are as follows: digital resolution=0.23 Hz, SWH=7530 Hz, TD=32 K, SI=16 K, 90° pulse-length=10 ms, PL1=3 dB, ns=1, ds=0, d1=1 s
13
and for 13C as follows: digital resolution=0.27 Hz, SWH=17985 Hz, TD=64 K, SI=32 K, 90° pulse length=9 ms, PL1=1.5 dB, ns=100, ds=2, d1=3 s. The NMR-grade DMSO-d6 (99.7%, containing 0.3% H2O) was used for the solutions of synthesized compounds.
X-Ray Powder Diffraction Analysis (PXRD)
To examine the crystalline structure of the produced graphene oxide nanolayers, an
XRD investigation using a Rigaku Mini Flex 600 XRD diffractometer with CuK radiation was carried out at ambient temperature. The materials were scanned between 10 and 80 degrees Bragg at 15 milliamperes. The crystallite size was determined using the Williamson-Hall technique.
Scanning Electron Microscopy (SEM)
study
On a SEM JEOL-1400 (Japan) operating at 80-120 kV, the graphene oxide nanolayers were analyzed. On a carbon-coated grid, the eth-anol-based ultrasonicated graphene oxide solution was spread out to dry at room temperature. Utilizing the SEM Imaging Platform application from Olympus Soft Imaging Solutions GmbH (Germany), morphometric analysis of the pictures (electronograms) was performed.
Synthesis of graphene oxide nanolayers
The synthesis of graphene oxide nanolayers was carried out by modifying the Hummer method known in the literature. The modification of the method consisted in increasing the amount of oxidizing agents and their gradual addition. The synthesis of graphene oxide consists of two stages:
1. Synthesis of graphite oxide 10 g of finely ground graphite, 6 g of sodium nitrate and 300 ml of concentrated sulfuric acid are added to a three-necked flask equipped with a magnetic stirrer. After adding sulfuric acid, the reaction mass is lowered into an ice bath, the mixture is vigorously stirred, and the temperature is lowered to 00C. After the temperature has reached the required value, 35 g of potassium permanganate is added to the reaction medium within an hour. In this case, the temperature should be in the range of 17-200C. After all the potassium permanganate has been added, the ice bath is removed and the temperature is allowed to rise to 35±30C. After the temperature has reached the required value, the solution is stirred for 30 minutes. At this stage, intensive gas evolution occurs. Over time, the mixture gradually thickens, and its "hiss" decreases. After 20 minutes, the mixture becomes pasty with the release of a small amount of gas. The formed paste has a brownish-gray color. After 30 minutes, 460 ml of distilled water is added to the reaction mass very slowly (so that strong boiling and splashing does not occur) with vigorous stirring, as a result of which the temperature reaches 980C (if the reaction is set up with a small amount of graphite, additional heating may be required ). After adding the specified amount of water, the reaction mass becomes brown and at the specified temperature, intensively stirred for 15 minutes. Further, 1.4 l of warm water (40-500C) and 300 ml of 3% hydrogen peroxide are added to the solution with vigorous stirring and stirred for 5 minutes. After the addition of hydrogen peroxide, the color of the solution becomes yellowish. Further, the precipitate is filtered and a brownish-yellowish paste is obtained. Filtration must be carried out quickly while the solution is warm, because as it cools, the sparingly soluble salt of mellitic acid precipitates, which is formed as a by-product of the reaction. After filtration, the precipitate is washed with about 42 liters of warm (60-700C) distilled water. After the last wash, the solution is checked for the presence of sulfuric acid by adding barium nitrate. If no precipitate is formed, then the yellowish-
brownish mass is dried in a desiccator for 10 hours. Otherwise, additional washing of the obtained graphite oxide is necessary.
2. Synthesis of graphene oxide
In a 25 ml beaker add 10 mg of the obtained graphite oxide and 15 ml of DMSO. Next, the solution is sonified for 5 minutes, which results in the formation of graphite oxide nanolayers. The resulting solution is completely stable during the day. Complete precipitation of graphene oxide is observed after a month. The resulting solution can be used directly or subjected to centrifugation (9000 rpm) to isolate graphene oxide in solid form.
Antimicrobial activity
The 96-well microtiter assay was used to assess the supramolecular ensemble of synthesized graphene oxide nanolayers and Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The bacterial strains employed in the microbiological research were from the department of microbiology's culture collection at Baku State University in Azerbaijan. The inoculation of the new colony was done using Muller Hinton media (also known as "Li-ofilchem"). Various quantities of the evaluated compounds, ranging from 1024 to 8 pg/mL, were added to each well of the U-bottom micro-titer, and then 105 CFU of various bacterial strains were added to each well. After a 24-hour period of incubation at 370C, the resazurin dye was employed to measure the amount of bacterial growth.
Result and discussion
The research was first started with the synthesis of dihydropyrimidines. Due to the fact that using a microwave reactor for synthesis makes the process faster, more repeatable, and scaleable, it is becoming more common than using a traditional reactor. Given the benefits of microwave-assisted organic synthesis, we were able to produce certain dihydropyrimidines by carrying out the reaction in the presence of Cu(OTf)2 under microwave conditions. The advantage of this method is that the precipitate was simply rinsed with distilled water throughout the reactions carried out in order to create
dihydropyrimidines. Cu(OTf)2 is a great triflate substitute for other metal triflates since it is inexpensive, exhibits high activity, and has minimal toxicity, making the process more ecologically friendly. This is another benefit of employing Cu(OTf)2 as a catalyst. By using 1H and
13
C NMR spectroscopy, the structures of all
newly synthesized unique dihydropyrimidine molecules were identified.
Subsequently, the nanolayers of graphene oxide were synthesized by the modified Hummer method and analyzed by PXRD (Figure 6) and SEM (Figure 7) methods.
i-
(Л
с
I
20
2-theta (deg)
L
/
/ -V J
- ^У \ Г
\ * \ v
Юцт
Fig. 7. SEM image of graphene oxide
; Kai 2
60-
40-
20-
Ш Суммарный спектр карты С ^■
о
Zn I
Си ■ Ca I
Вес %
90%
O Kai
i Lai 2
Pt Mal
Cu Lc<l_2 i Kai Ca Kctl
О Г| i i i i i 11 i i I i
I I I I I I I
4
i i i i I i
5
Pt LhI Pt LSI
i i I i i i i I i i i
PtLyl
i I i i i i I i i
12
i I i i i
14
16
i I i i i i I i
18
■ i i
кзВ
Fig. 8. Elemental analysis of graphene oxide nanolayers.
Antimicrobial activity investigations
Investigated sample S. aureus E.coli Ps. aerugionosa
Dihydropyrimidine 1 64 128 128
Dihydropyrimidine 2 32 64 64
Dihydropyrimidine 1+graphene oxide 128 256 256
Dihydropyrimidine 2+graphene oxide 16 64 64
Ampicillin 32 64 64
SEM investigations allowed to say that the diameter of the layer is 1 nm.
In addition, elemental analysis (Figure 8) also confirms that during the synthesis graphene oxide nanolayers are formed.
Further, the sonication of graphene oxide solution (1 mg/mL) with subsequent addition of dihydropyrimidine solution (1 mg/mL) and son-ication allowed to receive supramolecular ensemble. Due to the fact that dihydropyrimidines demonstrate antimicrobial activity, it was decided to study the effect of graphene oxide addition (in an ensemble). That's why antimicrobial investigations of individual ensembles, as well as dihydropyrimidines were performed. The received results were compared with the activity results of Ampicillin.
As it can be seen from Table, ensemble 2 demonstrates improved activity in comparison with the pristine dihydropyrimidine 2 and Ampicillin.
Conclusion
Novel ensembles on the basis of dihydropyrimidines, synthesized by Biginelli reaction, and graphene oxide, synthesized by modified Hummer method, were received. Due to the fact that dihydropyrimidines demonstrate antimicrobial activity, it was decided to study how their properties will be changed in the case of the supramolecular ensemble. Antimicrobial activity investigations against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphy-lococcus aureus demonstrated that supramolec-ular ensemble 2 (dihydropyrimidine 2+gra-phene oxide) demonstrated improved biological
activity than that of pristine dihydropyrimidine 2 and Ampicillin. According to it, it is possible to say that GO improved the antimicrobial activity of dihydropyrimidine 2.
Funding
The research was founded by Azerbaijan Science Foundation in the frames of project number AEF-MCG-2022-1(42)-12/11/4-M-11.
References
1. Huseynzada, A., Mori, M., Meneghetti, F., Isra-yilova, A., Guney, E., Sayin, K., ... & Abbasov, V. Crystal Structure, Hirshfeld Surface Analysis, In-Silico and Antimycotic Investigations of Methyl 6 -methyl-4-(4 -nitrophenyl) -2-oxo-1, 2 -dihydropy -rimidine-5-carboxylate. Crystals. 2023. 13(1). 52. https://doi.org/10.3390/cryst13010052.
2. Huseynzada, A.E., Mori, M., Meneghetti, F., Israyilo-va, A.A., Tuzun, G., Sayin, K., ... & Abbasov, V. Synthesis, crystal structure, Hirshfeld surface, computational and antibacterial studies of a 9-phenan-threnecarboxaldehyde-based thiodihydropyrimidine derivative. J. Molecular Structure. 2022. 133571. https://doi.org/10.1016/j .molstruc. 2022.133571.
3. Huseynzada, A., Jelsch, C., Akhundzada, H. V., Soudani, S., Nasr, C. B., Sayin, K., ... & Abbasov, V. Crystal structure, Hirshfeld surface analysis, computational and antifungal studies of dihyd-ropyrimidines on the basis of salicylaldehyde derivatives. J. Iranian Chemical Society. 2022. 1-15. https://doi.org/10.1007/s13738-022-02659-9.
4. Huseynzada, A.E. Synthesis, crystal structure and antibacterial studies of 2, 4, 6-trimetoxybenzal-dehyde based dihydropyrimidine derivatives. J. Molecular Structure. 2021. 1241. 130678. https://doi.org/10.1016/j.molstruc.2021.130678.
5. Huseynzada, Alakbar E., et al. "Synthesis, crystal structure and antibacterial studies of dihyd-ropyrimidines and their regioselectively oxidized products." RSC Advances. 2021. 11.11. 63126329. https://doi.org/10.1039/D0RA10255E
6. Huseynzada, A.E. Synthesis, crystal structure and antibacterial properties of 6-methyl-2-oxo-4-(quinolin-2-yl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylate. J. Molecular Structure. 2020. 1219, 128581. https://doi.org/10.1016/j.molstruc.2020.128581
7. Zohny Y.M., Awad S.M., Rabie M.A., & Al-Saidan O.A. Synthesis of Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their Calcium Channel Blocking Efficiency. Molecules. 2023. 28(2), 784. https://doi.org/10.3390/molecules28020784
8. Hu, X., Chen, L., Li, H., Xu, Q., Liu, X., Feng, X. Enantioselective Catalytic Hantzsch Dihydropyridine Synthesis. ACS Catalysis. 2023. 13(10), 6675-6682. https://doi.org/10.1021/acscatal.2c05888.
9. Faizan, S., Roohi, T.F., Raju, R.M., Yuvaraj, S., Kumar, B.P. A Century-Old One-Pot Multicompo-nent Biginelli Reaction Products Still Finds a Niche in Drug Discoveries: Synthesis, Mechanistic studies and Diverse Biological Activities of Dihydro-pyrimidines. J.Molecular Structure, 2023, 136020. https://doi.org/10.1016/j.molstruc.2023.136020
10. Duraisamy, R., Al-Shar'i, N.A., Chandrashekha-rappa, S., Deb, P.K., Gleiser, R.M., Tratrat, C., ... & Venugopala, K.N. Synthesis, biological evaluation, and computational investigation of ethyl 2,4,6-trisubstituted-1, 4-dihydropyrimidine-5-carb-oxylates as potential larvicidal agents against Anopheles arabiensis. J. Biomolecular Structure and Dynamics. 2023. 1-13.
11. Guda, M.R., Zyryanov, G.V., Dubey, A., Muna-gapati, V.S., & Wen, J.C. Cytotoxic and Infection-Controlled Investigations of Novel Dihydropy-ridine Hybrids: An Efficient Synthesis and Molecular-Docking Studies. Pharmaceuticals. 2023. 16(8), 1159.
12. Talath, S., Wali, A.F., Nisar, B., Wani, H.A., Mush-taq, S., & Rehman, M.U. Novel dihydropyrimidine as potential cytotoxic agents in hepatic and blood cancers. In Dihydropyrimidinones as Potent Anticancer Agents. 2023. P. 199-222. Elsevier.
13. Yu, W., Sisi, L., Haiyan, Y., & Jie, L. Progress in the functional modification of graphene/graphene oxide: A review. RSC advances, 2020, 10(26), 1532815345. https://doi.org/10.1039/D0RA01068E.
14. Gao, W. The chemistry of graphene oxide. Gra-phene oxide: reduction recipes, spectroscopy, and applications, 2015, 61-95. DOI: 10.1007/978-3-319-15500-5_3.
15. Marcano, D.C., Kosynkin, D.V., Berlin, J.M., Sinitskii, A., Sun, Z., Slesarev, A., ... & Tour, J. M. Improved synthesis of graphene oxide. ACS nano. 2020. 4(8). 4806-4814. https://doi.org/10.1021/-nn1006368.
16. Chung, C., Kim, Y. K., Shin, D., Ryoo, S. R., Hong, B. H., & Min, D. H. Biomedical applications of graphene and graphene oxide. Accounts of chemical research, 2020, 46(10), 2211-2224. https://doi.org/10.1021/ar300159f.
17. Zhu, Y., Murali, S., Cai, W., Li, X., Suk, J. W., Potts, J. R., & Ruoff, R. S. Graphene and graphene oxide: synthesis, properties, and applications. Advanced materials. 2010. 22(35). 3906-3924. https://doi.org/10.1002/adma.201001068.
18. Parveen, K., Banse, V., & Ledwani, L. Green synthesis of nanoparticles: Their advantages and disadvantages. In AIP conference proceedings, 2016. V. 1724. No 1. P. 020048. AIP Publishing LLC.https://doi.org/10.1063/1.4945168.
19. Mohanraj, V.J., Chen, Y. Nanoparticles-a review. Tropical journal of pharmaceutical research. 2006. 5(1). 561-573. DOI: 10.4314/tjpr.v5i1.14634.
20. Seabra, A. B., Paula, A. J., de Lima, R., Alves, O. L., & Duran, N. Nanotoxicity of graphene and graphene oxide. Chemical research in toxicology. 2014. 27(2). 159-168. https://doi.org/10.1021/tx400385x.
21. Wu, J., Lin, H., Moss, D. J., Loh, K. P., & Jia, B. Graphene oxide for photonics, electronics and optoelectronics. Nature Reviews Chemistry. 2023. 7(3). 162-183.
22. Zhang, Y., Wu, J., Jia, L., Qu, Y., Yang, Y., Jia, B., & Moss, D. J. Graphene oxide for nonlinear integrated photonics. Laser & Photonics Reviews. 2023. 17(3). 2200512.
23. An, Y.C., Gao, X.X., Jiang, W.L., Han, J.L., Ye, Y., Chen, T. M., ... & Ren, N. Q. A critical review on graphene oxide membrane for industrial wastewater treatment. Environmental Research. 2023. 115409.
QRAFEN OKSiD MODÎFÎKASÎYA OLUNMU§ DiHiDROPiRlMiDiNLOR
O.Hüseynzada, Ü.Hasanova, Z.Qahramanova
Bu tadqiqat qrafen oksid nanolaylari va dihidropirimidinlar asasinda müxtalif ansambllann sintezina va onlarin antimikrob aktivliyinin tadqiqina hasr edilmiçdir. Ansambllarin "tikinti bloklari", yani dihidropirimidinlar mikrodalga çaraitda az toksikiliya malik mis triflatin içtiraki ila Biginelli reaksiyasi vasitasila sintez edilmiçdir. Reaksiyanrn müsbat tarafi, mahlulun soyudulmasindan sonra amala galan çôkûntûnûn müayyan miqdarda distilla edilmiç su ila yuyulmasindan sonra alava tamizlanma marhalasinin olmamasidir. Sintez edilmiç birlaçmalarin strukturlari 1H, 13C va dept135 NMR spektroskopiya üsullari ila müayyan edilmiçdir. ikinci komponent, yani qrafen oksid nanolaylari, modifikasiya olunmuç Hammer üsulu ila sintez edilmiçdir. Metodun modifikasiyasi daha tamiz nanolaylari alda etmaya imkan veran oksidlaçdirici qançigin (H2SO4+KMnO4) konsentrasiyasmrn artmasi ila alaqadardir. Nanolaylarin strukturu va morfologiyasi SEM va XRD üsullari ila tadqiq edilmiç, ona asasan nanolaylarin qalinliginin 1 nm oldugu müayyan edilmiçdir. Daha sonra, qrafen oksid dihidropirimidinlarla modifikasiya olunmuçdur. Ansambllarin sintezi sonifikasiya yolu ila dihidropirimidinlarin qrafen oksid nanolaylari ila qeyri-kovalent birlaçmasi yolu ila hayata keçirilmiçdir. Bundan alava, ansambllarin antimikrobial aktivliyi S. aureus, Ps. aeruginosa va E. coli bakteriyalarina qarçi apanlmiçdir. Tahlil zamani alda edilan naticalar tamiz antibiotik ampisillinin aktivliyi ila müqayisa edilmiçdir. Malum olmuçdur ki, dihidropirimidin molekuluna qrafen oksid nanolaylarinin alava edilmasi dihidropirimidinlarin antimikrob aktivliyini yaxçilaçdirmaga imkan verib.
Açar sözlar: dihidropirimidinlar, Biginelli reaksiyasi, qrafen oksid nanolaylari, antimikrobial aktivlik.
ГРАФЕН ОКСИД МОДИФИЦИРОВАННЫЕ ДИГИДРОПИРИМИДИНЫ
А.Гусейнзаде, У.Гасанова, З.Гахраманова
Данная работа посвящена синтезу различных ансамблей на основе нанослоев оксида графена и дигидропиримидинов и исследованию их антимикробной активности. «Строительными блоками» ансамблей являются дигидропиримидины, синтезированные реакцией Биджинелли в присутствии малотоксичного трифлата меди в микроволновых условиях. Положительной стороной реакции является отсутствие какой-либо дополнительной стадии очистки, образующийся после охлаждения раствора осадок только промывается небольшим количеством дистиллированной воды. Строение синтезированных соединений установлено методами ЯМР-спектроскопии 1Н, 13С и dept135. Второй компонент — нанослои оксида графена — был синтезирован модифицированным методом Хаммера. Модификация метода связана с увеличением концентрации окислительной смеси (H2SO4+KMnO4), что позволило получить более чистые нанослои. Структуру и морфологию нанослоев исследовали методами СЭМ и РФА, согласно которым было определено, что толщина нанослоев составляет 1 нм. Впоследствии оксид графена был модифицирован дигидропиримидинами. Синтез ансамблей осуществляли путем нековалентного связывания дигидропиримидинов с нанослоями оксида графена путем обработки ультразвуком. Кроме того, антимикробная активность ансамблей была изучена в отношении S. aureus, Ps. aeruginosa и E. Coli. Полученные в ходе анализа результаты сравнивали с активностью чистого антибиотика ампициллина. Установлено, что добавление к молекуле дигидропиримидина нанослоев оксида графена позволяет улучшить антимикробную активность дигидропиримидинов.
Ключевые слова: дигидропиримидины, реакция Биджинелли, нанослои оксида графена, антимикробная активность.
