Skip to main content

Advertisement

SpringerLink
Log in

Oxidation process of 1,4-dihydropyridine, 1,4-dihydropyrimidine, and pyrrolo-1,4-dihydropyrimidine: quantum chemical study

  • Brief Report
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Derivatives of 1,4-dihydropyridine, 1,4-dihydropyrimidine, and its azolo analogs possess a wide range of biological activity and are involved in cellular bioenergetics. Dihydrocycles can be oxidized up to corresponding aromatic ones due to two one-electron transfers. Mechanism of the oxidation process was modeled as a stepwise change of the 1,4-dihydropyridine, 1,4-dihydropyrimidine, and pyrrolo-1,4-dihydropyrimidine using different levels of theory (Hartree–Fock, MP2, DFT), basis sets, and models of environment (vacuum approximation, PCM model describing a non-specific influence of polarizing environment, or PCM model with an explicit water molecule describing both non-specific and specific influence of neighboring molecules). It is shown that the potential of the first one-electron transfer I1 depends on the level of theory and the model of an environment used in calculations. The potential of the second one-electron transfer I2 depends only on the model of an environment. The analysis of their differences calculated using different approaches has revealed the dependence only from the level of theory. Since DFT methods provide the geometric characteristics of 1,4-dihydroheterocycles closest to the experimental data, it seems reasonable to use these relatively cheap calculations to study the oxidation process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Gui Y, Yao X, Guzei I, Aristov MM, Yu J, Yu L (2020) A mechanism for reversible solid-state transitions involving nitro torsion. Chem Mater 32:7754–7765

    Article  CAS  Google Scholar 

  2. Mishra MK, Desiraju GR, Ramamurty U, Bond AD (2014) Studying microstructure in molecular crystals with nanoindentation: intergrowth polymorphism in felodipine. Angew. Chem. Int Ed 53:13102–13105

    Article  CAS  Google Scholar 

  3. Rajendrakumar S, Durga ASVS, Nanubolu JB, Balasubramanian S (2020) Two novel polymorphic forms of iron-chelating agent deferiprone. Acta Cryst C: Structural Chemistry 76:193–200

    Article  CAS  Google Scholar 

  4. Wu JY, Zhang L, Cai LL, Zhang Y (2012) Catalyzing synthesis of chiral nitrendipine. Adv Mater Res 518:3943–3946

    Article  Google Scholar 

  5. Guo D, Song J-X, Li D, Chen J-M, Lin L-R, Lu T-B, Zhang H (2016) Determination and correlation of the absolute configuration of chiral nimodipine. Acta Phys Chim Sin 32:2241–2254

    Article  CAS  Google Scholar 

  6. Hu A-X, Wu X-Y, Cao G (2006) 3-Cinnamyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxyl-ate. Acta Crystallogr. Sect E:Struct Rep Online 62:o3161–o3162

    Article  CAS  Google Scholar 

  7. Druzbicki K, Mielcarek J, Kiwilsza A, Toupet L, Collet E, Pajzderska A, Wasicki J (2015) Computationally assisted (solid-state density functional theory) structural (X-ray) and Vibrational Spectroscopy (FT-IR, FT-RS, TDs-THz) characterization of the cardiovascular drug lacidipine. Cryst Growth Des 15:2817–2830

    Article  CAS  Google Scholar 

  8. Saad MH, El-Moselhy TF, El-Din NS, Mehany ABM, Belal A, Abourehab MAS, Tawfik HO, El-Hamamsy MH (2022) Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies. J Enzyme Inhib Med Chem 37:2489–2511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kumar R, Idhayadhulla A, Abdul Nasser A, Selvin J (2011) Synthesis and antimicrobial activity of a new series of 1,4-dihydropyridine derivatives. J Serb Chem Soc 76:1–11

    Article  CAS  Google Scholar 

  10. Reimão JQ, Scotti MT, Tempone AG (2010) Anti-leishmanial and anti-trypanosomal activities of 1,4-dihydropyridines: in vitro evaluation and structure-activity relationship study. Bioorg Med Chem 18:8044–8053

    Article  PubMed  Google Scholar 

  11. Guillemont J, Pasquier E, Palandjian P, Vernier D, Gaurrand S, Lewi PJ, Heeres J, De Jonge MR, Koymans LMH, Daeyaert FFD, Vinkers MH, Arnold E, Das K, Pauwels R, Andries K, De Béthune M-P, Bettens E, Hertogs K, Wigerinck P, Timmerman P, Janssen PAJ (2005) Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1. J Med Chem 48:2072–2079

    Article  CAS  PubMed  Google Scholar 

  12. Sayed AI, Mansour YE, Ali MA, Aly O, Khoder ZM, Said AM, Fatahala SS, Abd El-Hameed RH (2022) Novel pyrrolopyrimidine derivatives: design, synthesis, molecular docking, molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents. J Enzyme Inhib Med Chem 37:1821–1837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bhat MA, Al-Dhfyan A, Al-Omar MA (2016) targeting cancer stem cells with novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1h)-one/thiones. Molecules 21:1746

    Article  PubMed  PubMed Central  Google Scholar 

  14. Niemirowicz-Laskowska K, Głuszek K, Piktel E, Pajuste K, Durnaś B, Król G, Wilczewska AZ, Janmey PA, Plotniece A, Bucki R (2018) Bactericidal and immunomodulatory properties of magnetic nanoparticles functionalized by 1,4-dihydropyridines. Int J Nanomedicine 13:3411–3424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Prasanthi G, Prasad KV, Bharathi K (2014) Synthesis, anticonvulsant activity and molecular properties prediction of dialkyl 1-(di(ethoxycarbonyl) methyl)-2,6-dimethyl-4-substituted-1,4-dihydropyridine-3,5-dicarboxylates. Eur J Med Chem 73:97–104

    Article  CAS  PubMed  Google Scholar 

  16. Giffin MJ, Heaslet H, Brik A, Lin YC, Cauvi G, Wong CH, McRee DE, Elder JH, Stout CD, Torbett BE (2008) A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant. J Med Chem 51:6263–6270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yang Y, Sauve AA (2016) NAD+ metabolism: bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta Proteins Proteomics 1864:1787–1800

    Article  CAS  Google Scholar 

  18. Ludvik J, Volke J, Klima J (1987) Electrochemical oxidation mechanisms of different type 1,4-dihydropyridine derivatives in acetonitrile. Electrochim Acta 32:1063–1071

    Article  CAS  Google Scholar 

  19. Powell MF, Wu JC, Bruice TC (1984) ferricyanide oxidation of dihydropyridines and analogues. J Am Chem Soc 106:3850–3856

    Article  CAS  Google Scholar 

  20. Ogle J, Stradins J, Baumane L (1994) Formation and decay of free cation-radicals in the course of lector-oxidation of 1,2- and 1,4-dihydropyridines (Hantzch esters). Electrochim Acta 39:73–79

    Article  CAS  Google Scholar 

  21. Tavakkoli Z, Goljani H, Gunduz MG, Tahir MN, Nematollahi D (2020) Electrochemical studies of newly synthesized 1,4-dihydropyridine-based hexahydroquinoline derivatives. J Electrochem Soc 167:125502

    Article  CAS  Google Scholar 

  22. Ortiz ME, Núñez-Vergara LJ, Camargo C, Squella JA (2004) Oxidation of Hantzsch 1,4-dihydropyridines of pharmacological significance by electrogenerated superoxide. Pharm Res 21:428–435

    Article  CAS  PubMed  Google Scholar 

  23. Trofimov AB, Holland DMP, Powis I, Menzies RC, Potts AW, Kerisson L, Gromov EV, Badsyuk IL, Schirmer J (2017) Ionization of pyridine: interplay of orbital relaxation and electron correlation. J Chem Phys 146:244307

    Article  CAS  PubMed  Google Scholar 

  24. Trofimov AB, Skitnevskaya AD, Gridoricheva EK, Gromov EV, Köppel H (2020) Vibronic coupling in the ground and excited states of the pyridine radical cation. J Chem Phys 153:164307

    Article  CAS  PubMed  Google Scholar 

  25. Chong DP (2019) Computational study of the structure and photoelectron spectra of 12 azabenzenes. Can J Chem 97:697–703

    Article  CAS  Google Scholar 

  26. Arguello J, Núñez-Vergara LJ, Sturm JC, Squella JA (2004) Voltammetric oxidation of Hantzsch 1,4-dihydropyrimidines in protic media: substituent effect on positions 3, 4, 5 of the heterocyclic ring. Electrochim Acta 49:4849–4856

    Article  CAS  Google Scholar 

  27. Chebanov VA, Desenko SM, Gurley TW (2008) Azaheterocycles based on α, β-unsaturated carbonyls. Springer-Verlag, Berlin, Heidelberg

    Google Scholar 

  28. Berberova NT, Okhlobystin OY (1984) One-electron transfer during dehydroaromatization of heterocyclic compounds. Khim Geterotsikl Soedin 8:1011–1025

    Google Scholar 

  29. Morkovnik AS, Ivakhnenko EP, Bogachev YG, Tertov BA, Berberova NT, Okhlobystin OY (1988) Release of hydrogen during the interaction of some hydroheteroaromatic compounds with dehydrogenating reagents. Khim Geterotsikl Soedin 2:203–208

    Google Scholar 

  30. Fukuzumi S, Inada O, Suenobu T (2003) Mechanisms of electron-transfer oxidation of NADH analogues and chemiluminescence. Detection of the keto and enol radical cations. J Am Chem Soc 125:4808–4816

    Article  CAS  PubMed  Google Scholar 

  31. Desenko SM, Orlov VD, Lipson VV (1990) Chemical conversions of 5,7-disubstituted dihydro-1,2,4-triazolo[1,5-α]pyrimidines. Khim Geterotsikl Soedin 12:1638

    Google Scholar 

  32. Desenko SM, Orlov VD, Lipson VV, Shishkin OV, Lindeman SV, Struchkov YT (1993) 3-hydroxypyrimido[1,2- α]benzimidazoles. Khim Geterotsikl Soedin 5:688–692

    Google Scholar 

  33. Koopmans TA (1934) Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms. Physica 1:104–113

    Article  Google Scholar 

  34. Day OW, Smith DW, Garrod C (1974) A generalization of the Hartree-Fock one-particle potential. Int J Quantum Chem Symp 8:501–509

    Article  CAS  Google Scholar 

  35. Smith DW, Day OW (1975) Extension of Koopmans’ theorem. I Derivation J Chem Phys 62:113–114

    Article  CAS  Google Scholar 

  36. Morrell MM, Parr RG, Levy MJ (1975) Calculation of ionization potentials from density matrices and natural functions, and the long-range behavior of natural orbitals and electron density. J Chem Phys 62:549–554

    Article  CAS  Google Scholar 

  37. Ernzerhof M (2009) Validity of the extended Koopmans’ theorem. J Chem Theory Comput 5:793–797

    Article  CAS  PubMed  Google Scholar 

  38. Ermis B, Ekinci E, Bozkaya U (2021) State-Of-The-Art computations of vertical electron affinities with the extended Koopmans’ theorem integrated with the CCSD(T) method. J Chem Theory Comput 17:7648–7656

    Article  CAS  PubMed  Google Scholar 

  39. Shishkin OV, Konovalova IS, Zubatyuk RI, Palamarchuk GV, Shishkina SV, Biitseva AV, Rudenko IV, Tkachuk VA, Kornilov MYu, Hordiyenko OV, Leszczynski J (2013) Remarkably strong polarization of amidine fragment in the crystals of 1-imino-1H-isoindol-3-amine. Struct Chem 24:1089–1097

    Article  CAS  Google Scholar 

  40. Shishkina SV, Slabko AI, Shishkin OV (2013) Conjugation vs hyperconjugation in molecular structure of acrolein. Chem Phys Lett 556:18–22

    Article  CAS  Google Scholar 

  41. Yegorova TV, Kysil AI, Dyakonenko VV, Levkov IV, Karbovska RV, Shishkina SV, Voitenko ZV (2020) Azido-tetrazole isomerism in 2,2-dimethyl-1-(1-methyl-1H-tetrazolo[5,1-a]isoindol-5-yl)propan-1-one. J Mol Struct 1203:127469

    Article  CAS  Google Scholar 

  42. Handy NC, Marron MT, Silverstone HJ (1969) Long-range behavior of Hartree-Fock orbitals. Phys Rev 180:45–48

    Article  CAS  Google Scholar 

  43. Møller C, Plesset MS (1934) Note on an approximation treatment for many-electron systems. Phys Rev 46:618–622

    Article  Google Scholar 

  44. Parr RG, Yang W (1995) Density-functional theory of atoms and molecules. Oxford University Press, New York

    Book  Google Scholar 

  45. In; Labanowski JK, Andzelm JW, (ed) (1991) Density functional methods in chemistry. Springer-Verlag, New York

    Google Scholar 

  46. Mennucci B (2012) Polarizable continuum model. WIREs Comput Mol Sci 2:386–404

    Article  CAS  Google Scholar 

  47. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA Jr., Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) GAUSSIAN 09, Revision A.02, Gaussian Inc., Wallingford CT. https://gaussian.com/glossary/g09/

  48. Groom CR, Bruno IJ, Lightfoot MP, Ward SC (2016) The Cambridge Structural Database Acta Cryst B72:171–179

    Google Scholar 

  49. Kirby AJ (1996) Stereoelectronic Effects. Oxford University Press, New York. https://global.oup.com/academic/product/stereoelectronic-effects-9780198558934?cc=ua&lang=en&

Download references

Funding

This work was supported by the National Academy of Science of Ukraine (grant no. 0122U001857).

Author information

Authors and Affiliations

  1. SSI Institute for Single Crystals, National Academy of Sciences of Ukraine, 60 Nauky Ave, Kharkiv, 61072, Ukraine

    Mariia O. Shyshkina & Serhiy M. Desenko

Authors
  1. Mariia O. Shyshkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serhiy M. Desenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M. S.: calculations, preparation of figures and tables, and writing manuscript. S. D.: supervision of the research work and scientific discussion.

Corresponding author

Correspondence to Mariia O. Shyshkina.

Ethics declarations

Ethics approval

Not applicable; no human or animal studies have been carried out.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shyshkina, M.O., Desenko, S.M. Oxidation process of 1,4-dihydropyridine, 1,4-dihydropyrimidine, and pyrrolo-1,4-dihydropyrimidine: quantum chemical study. Struct Chem 35, 993–1002 (2024). https://doi.org/10.1007/s11224-024-02284-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-024-02284-7

Keywords

Search

Navigation