Adsorption and Inhibition Mechanisms of Pyrazole Derivatives on Graphene Oxide Based on Theoretical Calculations

Abstract

Nanomaterials are increasingly being applied across various industries, including food processing, cosmetics, gene technology, and smart medicine. Their role in enhancing medical diagnosis, treatment, and prevention strategies is particularly notable. Among these materials, Graphene Oxide (GO), a derivative of graphene, has gained significant attention due to its unique properties and potential applications in the medical field, particularly for drug delivery and imaging. Graphene Oxide (GO) is a form of graphene that has been oxidized, resulting in a nanoscale material with distinctive physicochemical properties, such as electric charge and a high surface area. These properties make it a promising candidate for use in medical applications. However, the biocompatibility of GO remains a crucial consideration for its clinical use. While it can interact with live cells, its toxicity is generally low, though it depends heavily on factors like dosage and administration method. To optimize GO for safe and effective medical use, it is essential to understand its interactions with drug molecules and biological structures. Computational modeling plays a key role in this process. In this study, Density Functional Theory (DFT) was employed to calculate the electrical characteristics of commercially available pyrazole derivatives and to analyze their adsorption behavior on a graphene oxide nanocage. This approach offers valuable molecular-level insights into how GO functions as a drug carrier, providing a foundation for its safe and effective application in medicine.

Keywords

• Theoretical chemistry
• pyrazole
• adsorption
• graphene oxide

References

1. Akbas E., & Aslanoglu F. (2006). Syntheses of some new 1H-pyrazole, pyridazin-3(2H)-one, and oxazin-4-one derivatives. Heteroatom Chemistry,17 (1), 8-12. https://doi.org/ 10.1002/ hc.20170
2. Akbas E., Berber I., Sener A., Hasanov B. (2005). Synthesis and antibacterial activity of 4-benzoyl-1-methyl-5- phenyl-1H- pyrazole -3- carboxylic acid and derivatives. II. Farmaco 60, 23– 26. https://doi.org/10.1016/j.farmac.2004.09.003
3. Akbas E., Berber I. (2005). Antibacterial and antifungal activities of new pyrazolo[3,4-d]pyridazin derivatives. European Journal of Medicinal Chemistry,40,401-405. https://doi.org/ 10.1016/j. ejmech. 2004.12.001
4. Akbas E., Ruzgar A., Sahin E., Levent A. (2025). Metal–Organic Framework MIL-101 as an Efficient Heterogeneous Catalyst for Clean Synthesis of Benzothiazoles and Single Crystal X-ray Diffraction, Quantum Chemical Studies, Electrochemical Performance, Molecular Docking and DNA Interactions. Chemistry Select, 10, 1-12. https:// doi. org/ 10.1002/slct. 202405888
5. Akbas, E., Levent, A., Gumus, S., Sumer, M. R., Akyazi, I. (2010). Synthesis of Some Novel Pyrimidine Derivatives and Investigation of their Electrochemical Behavior. Bulletin of the Korean Chemical Society, 31, 3632. https:// doi.org/ 10.5012/BKCS.2010.31.12.3632
6. Akbas, E., Akbas, B. C. Investigation of the adsorption of dacarbazine (DTIC), which is used as an anticancer drug, on graphene oxide by DFT calculation method. (2023). International Journal of Chemistry and Technology, 7(2), 197. http://dx.doi.org/10.32571/ijct.1272379
7. Ansari A., Ali A., Asif M., Shamsuzzaman. (2017). Review: biologically active pyrazole derivatives. New Journal of Chemistry, 41, 16–41. https:// doi.org/ 10.1039/C6NJ03181A
8. Bai J., Zhong X., Jiang S., Huang Y., Duan X. (2010). Graphene nanomesh. Nature Nanotechnology, 5(3), 190–194. https://doi.org/ 10.1038/NNANO. 2010.8

9. Becke A, D. (1993). Density‐ functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics, 98, 5648–5652. https://doi.org/10.1063/1.464913
10. Burschka J., Kessler F., Nazeeruddin M. K., and Gratzel M. (2013). Co(III) Complexes as p-Dopants in Solid-State Dye-Sensitized Solar Cells. Chemistry of Materials, 25, 2986–2990. https:// doi.org/ 10.1021/cm400796u
11. Bratenko M. K., Chornous V. A., Panimarchuk O. I., Vovk M. V., Burdenyuk I. P. (2001). Synthesis and antimicrobial activity of N-benzyl-N-(4-pyrazolylmethyl)-benzenesulfamides. Pharma Chemistry, 35, 26–28. https://link.springer.com/ article/10.1007/s11094-006-0163-y
12. Eftekhari-Sis B., Zirak M., and Akbari A. (2013). Arylglyoxals in Synthesis of Heterocyclic Compounds. Chemistry Review, 113, 2958 –3043. https: // doi.org/ 10.1021/ cr300176g
13. El-Feky S. A. H., Abd El-Samii Z. K., Osman N. A., Lashine J., Kamel M. A., and Thabet H. K. (2015). Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II. Bioorganic Chemistry, 58, 104–116. https://doi.org/ 10.1016/j.bioorg. 2014. 12. 003
14. Fedotova А. K., Prischepa S. L., Fedotova J., et al. (2020). Effect of cobalt particle deposition on quantum corrections to Drude conductivity in twisted CVD grapheme. Physica E: Low-dimensional Systems and Nanostructures, 117, 113790. https:// doi.org/10.3897/ j.moem.5.4. 52068
15. Friedrich G., Rose T., Rissler K. J. (2002). Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection. Chromatography B., 766, 295–305. https:// doi.org/ 10.1016/s0378-4347 (01) 00514-x
16. Frisch, M. J., et al. (2009). Gaussian 09 (Revision D.01) [Computer software]. Gaussian Inc.e
17. Fu H., and Yao J. (2001). Size Effects on the Optical Properties of Organic Nanoparticles. Journal of the American Chemical Society, 123, 1434–1439. https: //doi.org/10.1021/ja0026298
18. Gordon E. M., Barrett R. W., Dower W. J., Fodor S. P. A., Gallop M. A. (1994). Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries. Journal of Medicinal Chemistry, 37, 1385–1401. https://doi.org/10.1021/ jm 00035 a 001
19. Hampp C., Hartzema A.G., Kauf T.L. (2008). Cost-Utility Analysis of Rimonabant in the Treatment of Obesity. Value Health, 11, 389–399. https:// doi.org/10.1111/j.1524-4733.2007.00281.x
20. Hoseini-Ghahfarokhi M., Mirkiani S., Mozaffari N., Abdolahi Sadatlu M.A., Ghasemi A., Abbaspour S., Akbarian M., Farjadian F., Karimi M. (2020). Applications of Graphene and Graphene Oxide in Smart Drug/Gene Delivery: Is the World Still Flat?. International Journal of Nanomedicine, 15, 9469–9496. https://doi.org/10.2147/ IJN. S 265876
21. Issa, R. M., Awad, M. K., Atlam, F. M. (2008). Study of the inhibition of the corrosion of copper and zinc in HNO3 solution by electrochemical technique and quantum chemical calculations. Applied Surface Science, 255, 2433. https:// doi.org/ 10.1016/j.arabjc.2009.12.009
22. Janak J. F. (1978). Proof that 𝜕𝐸𝜕𝑛𝑖=𝜀 in density-functional theory. Physica Review, 18 (12), 7165-7168.52. https://doi.org/ 10.1103/Phys Rev B. 18.7165
23. Jiang J.H., Pi J., Jin H., Cai J. Y. (2018). Advances in Lung Cancer Treatment Using Nanomedicines. Arti Cells Nanomed Biotechnol, 46(3), 297–307. https://doi.org/10.1021/acsomega.2c04078
24. Ju Y., and Varma R. S. (2006). Aqueous N-Heterocyclization of Primary Amines and Hydrazines with Dihalides:  Microwave-Assisted Syntheses of N-Azacycloalkanes, Isoindole, Pyrazole, Pyrazolidine, and Phthalazine Derivatives. Journal of Organic Chemistry, 71, 135–141. https://doi.org/10.1021/jo051878h
25. Khalil S. M. E. (2003). Synthesis, Spectroscopic and Magnetic Studies on Metal Complexes of 5-Methyl-3-(2-Hydroxyphenyl)Pyrazole. Journal of Coordination Chemistry, 56, 1013–1024. https:// doi.org/10.1080/0095897031000135289
26. Kiyani H., Albooyeh F., and Fallahnezhad S. (2015). Synthesis of new pyrazolyl-1,3-diazabicyclo[3.1.0]hexe-3-ene derivatives. Journal of Molecular Structure, 1091, 163–169. https:// doi.org/10.1016/j.molstruc.2015.02.069
27. Kishore N., Nagarajan V., Chandiramouli R. (2017). Exploring the Structural Stability and Electronic Properties of VS2 Nanostructures – a DFT Study. Journal of Nano- and Electronic Physics, 9,3,03008(4pp). https://doi.org/ 10.21272/jnep. 9 (3). 03008
28. Koopman T. (1934). Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms. Physica, 1(1-6), 104-113. https://doi.org/10.1016/S0031-8914(34)90011-2
29. Krishnamoorthy K., Kim G.S., Kim S.J. (2013). Graphene nanosheets: Ultrasound assisted synthesis and characterization. Ultrasonics Sonochem, 20, 644–649. https://doi.org/10.1016/ j. ultsonch. 2012.09.007
30. Leeson P. D., and Springthorpe B. (2007). The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug Discovery, 6, 881–890. https://doi.org/ 10. 1038/ nrd2445
31. Li Z., Fan J., Tong C., et al. (2019). A Smart Drug-Delivery Nanosystem Based on Carboxylated Graphene Quantum Dots for Tumor-Targeted Chemotherapy. Nanomedicine, 14(15), 2011–2025. https:// doi.org/10.2217/nnm-2018-0378
32. Li X., He L., Chen H., Wu W., and Jiang H. (2013). Copper-Catalyzed Aerobic C(sp2)–H Functionalization for C–N Bond Formation: Synthesis of Pyrazoles and Indazoles. Journal of Organic Chemistry, 78, 3636–3646. https:// doi. org/ 10.1021/jo400162d
33. Liu Z., Robinson J.T., Sun X., Dai H. (2008). PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs. Journal of the American Chemical Society, 130(33), 10876–10877. https://doi.org/10.1021/ja803688x
34. Luttinger D., Hlasta D.J. (1987). Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review. Annual Reports in Medicinal Chemistry, 21– 30. https:// doi. org / 10.3390/ molecules23010134
35. Lv P.-C., Sun J., Luo Y., Yang Y., and Zhu H.-L. (2010). Bioorganic & Medicinal Chemistry Letters, 20, 4657–4660. 10.1016/ j.bmcl. 2010. 05.105
36. Mert S., Kasimogullari R., Ica T., Colak F., Altun A., and Ok S. (2014). Synthesis, structure–activity relationships, and in vitro antibacterial and antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic acid derivatives. European Journal of Medicinal Chemistry, 78, 86–96. https://doi.org/ 10.1016/j.ejmech. 2014. 03. 033
37. Mennucci B., Tomasi J., Cammi R., Cheeseman J. R. J., Frisch M. J., Devlin F. J., Gabriel S., Stephens P. (2002). Polarizable Continuum Model (PCM) Calculations of Solvent Effects on Optical Rotations of Chiral Molecules. The Journal of Physical Chemistry A, 106, 6102-6113. https:/ /doi.org/ 10.1021/jp020124t
38. Mouhat F., Coudert F. X., Bocquet L. M. (2020). Structure and chemistry of graphene oxide in liquid water from first principles. Nature Communications, 11(1),1566. https://doi.org/ 10. 1038 / s41467-020-15381-y
39. Mubarik A., Mahmood S., Rasool N., Hashmi M. A., Ammar M., Mutahir S., Ghulam Ali K., Bilal M., Akhtar M. N., Ashraf G. A. (2022). Computational Study of Benzothiazole Derivatives for Conformational, Thermodynamic and Spectroscopic Features and Their Potential to Act as Antibacterials. Crystals, 12, 912. https ://doi. org/ 10.3390/cryst12070912
40. O'Boyle N. M., Tenderholt A. L., Langner K. M. (2008). cclib: A library for package-independent computational chemistry algorithms. Journal of Computational Chemistry, 29, 839-845. https: // doi. org/10.1002/jcc.20823
41. Perdew J. P., Wang Y. (1992). Accurate and simple analytic representation of the electron-gas correlation energy. Physical Review B, 45, 13244–13249. https://doi.org/ 10.1103/Phys Rev B. 45.13244
42. Sánchez-González A., A. G. Bandeira N., Ortiz de Luzuriaga I., F. Martins F., Elleuchi S., Jarraya K., Lanuza J., Lopez X., José Calhorda M., Gil A. (2021). New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes. Molecules, 26, 4737. https://doi.org/10.3390/molecules26164737
43. Simos T. E., Tsitouras C., Kovalnogov V. N., Fedorov R. V. Generalov D. A. (2021). Real-Time Estimation of R0 for COVID-19 Spread. Mathematics (Basel), 9, 664. https://doi.org/ 10. 3390/math9060664
44. Sönmez M., Berber I., Akbas E. (2006). Synthesis, antibacterial and antifungal activity of some new pyridazinone metal complexes. European Journal of Medicinal Chemistry, 41, 101–105. https://doi.org/10.1016/j.ejmech.2005.10.003
45. Spitz I., Novis B., Ebert R., Trestian S., LeRoith D., Creutzfeld W. (1982). Betazole-induced GIP secretion is not mediated by gastric HCl. Metabolism, 31, 380–382. https://doi.org/ 10. 1016 /0026-0495(82)90114-7
46. Steinbach G., Lynch P.M., Robin K.S.P., Wallace M.H., Hawk E., Gordon G.B., Wakabayashi N., Saunders B., Shen Y., Fujimura T., Su L.-K., Levin A.B. (2000). The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor, in Familial Adenomatous Polyposis. The New England Journal Of Medicine, 342, 1946–1952. https://doi.org/10.1056/NEJM200006293422603
47. Şener A., Akbas E., Şener M.K. (2004). Synthesis and Some Reactions of 4-Benzoyl-5-Phenyl-1-Pyridin-2-yl-1H- Pyrazole-3-Carboxylic Acid. Turkish Journal of Chemistry, 28, 271-277. https://journals.tubitak.gov.tr/chem/vol28/iss3/2/
48. Tewari A. K., Mishra A. (2001). Synthesis and anti-inflammatory activities of N4,N5-disubstituted-3-methyl-1H-pyrazolo[3,4-c]pyridazines. Bio organic & Medicinal Chemistry, 9, 715–718. https://doi.org/10.1016/S0968-0896(00)00285-6
49. Tiwari J.N., Mahesh K., Le N.H., Timilsina K.C.K.R., Tiwari R.N., Kim K.S. (2013). Reduced graphene oxide-based hydrogels for the efficient capture of dye pollutants from aqueous solutions. Carbon, 56, 173–182. https://doi.org/ 10.1016/j.carbon.2013.01.001
50. Tu X., Hao W., Ye Q., Wang S., Jiang B., Li G., and Tu S. (2014). Four-Component Bicyclization Approaches to Skeletally Diverse Pyrazolo[3,4-b]pyridine DerivativesClick to copy article link. Journal of Organic Chemistry, 79, 11110–11118. https://doi.org/10.1021/jo502096t
51. Walsh C. T. (2015). Nature loves nitrogen heterocycles. Tetrahedron Letters, 56 (23), 3075– 3081. https ://doi.org/ 10.1016/j.tetlet.2014.11.046
52. Wang, H., Wang, X., Wang, H., Wang, L., Liu, A. (2007). DFT study of new bipyrazole derivatives and their potential activity as corrosion inhibitors. Journal of Molecular Modeling, 13, 147. https://doi.org/10.1007/s00894-006-0135-x
53. Valentini L., Bittolo Bon S., Giorgi G. (2020). Engineering Graphene Oxide/Water Interface from First Principles to Experiments for Electrostatic Protective Composites. Polymers (Basel), 12(7), 1596. https://doi.org/ 10. 3390 /polym12071596
54. Zárate- Zárate D., Aguilar R., Hernández-Benitez R. I., Labarrios E. M., Delgado F., Tamariz J. (2015). Synthesis of α-ketols by functionalization of captodative alkenes and divergent preparation of heterocycles and natural products. Tetrahedron, 71, 6961–6978. https://doi.org/ 10.1016/j.tet. 2015.07.010
55. Zhu J., Wei S., Gu H., Rapole S.B., Wang Q., Luo Z., Haldolaarachchige N., Young D.P., Guo Z. (2012). One-Pot Synthesis of Magnetic Graphene Nanocomposites Decorated with Core@Double-shell Nanoparticles for Fast Chromium Removal. Environmental Science & Technology, (2), 977–985. https://doi.org/ 10. 1021/ es2014133