Document Type : Original Research Article


1 Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran

3 Biosensor Research Center, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran



The properties for 2(5H)-furanone and 2(5Methyl)- and 2(5Phenyl)-furanone derivatives have been explored by computational chemistry approach. The subatomic unit calculations have been done to optimize the models and to evaluate their corresponding properties, in which several achievements have been seen for the investigated models. The energy levels of molecular orbitals indicated the importance of structural modifications for obtaining better electronic properties. To this aim, total energy, energy levels of the highest occupied and the lowest unoccupied molecular orbitals, energy gap, ionization positional, electron affinity, hardness, softness and dipole moment have been evaluated in addition to the original molecular weight and LogP parameters. The results revealed better reactivity and antioxidativity for 2(5Phenyl)-furanone in comparison with two other models proposing it for various possible applications in biological systems. Moreover, hardness and softness properties were also seen more favorable for this model. As a conclusion, the importance of furanone could be very much increased regarding structural modification, which could be very well investigated by the computational chemistry approach.

Graphical Abstract

Computational Studies of Furanone and its 5Methyl/5Phenyl Derivatives


  1. Luo SH, Yang K, Lin JY, Gao JJ, Wu XY, Wang ZY. Synthesis of amino acid derivatives of 5-alkoxy-3, 4-dihalo-2 (5H)-furanones and their preliminary bioactivity investigation as linkers. Org. Biomol. Chem. 2019;17:5138-5147.
  2. Schwab W. Natural 4-hydroxy-2, 5-dimethyl-3(2H)-furanone (Furaneol®). Molecules 2013;18:6936-6951.
  3. Kozminykh VO, Igidov NM, Kozminykh EN, Konshina LO, Semenova ZN, Lyadova NV, Plaksina AN, Andreichikov YS. Synthesis and antimicrobial activity of 2-substituted-5-aryl-2,3-dihydro-3-furanones and 1,6-diaryl-3,4dihydroxy-2,4-hexadien-1,6-diones. Pharm. Chem. J. 1991;25:891-897.
  4. Cannon GW, Breedveld FC. Efficacy of cyclooxygenase-2 specific inhibitors. Am. J. Med. 2001;3: 6-12.
  5. Ogara JP, Humphreys H, Staphylococcus epidermidis biofilms importance and implications, J. Med. Microbiol. 2001;50:582-587.
  6. Futaki N, Yoshikawa K, Hamasaka Y, Arai I, Higuchi S, Iizuka H, Otomo S. A novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions. Gen. Pharmacol. 1997;24:105-110.
  7. Razet R, Thomet U, Furtmuller R, Chiaroni A, Sigel E, Sieghart W, Dodd RH. 5-[1-(2-N-arylsulfonyl-1,2,3,4-tetrahydroisoquinolyl)]-4,5dihydro-2(3H)-furanones: positive allosteric modulators of the GABA receptor with a new mode of action. J. Med. Chem. 2000;43:4363-4366.
  8. Abou-Elmagd WSI, Hashem AI. Synthesis and antitumor activity evaluation of some novel fused and spiro heterocycles derived from a 2(3H)-furanone derivative, J. Heterocycl. Chem. 2016;53: 202-208.
  9. Akhter M, Saha R, Tanwar O, Alam MM, Zaman MS. Synthesis and antimalarial activity of quinoline-substituted furanone derivatives and their identification as selective falcipain-2 inhibitors. Med. Chem. Res. 2015;24:879-890.
  10. Wang Y, Gloer JB, Scott JA, Malloch D, Appenolides AC. Three new antifungal furanones from the coprophilous fungus Podospora appendiculata. J. Nat. Prod. 1993;56:341-344.
  11. Husain A, Khan SA, Iram F, Iqbal MA, Asif M. Insights into the chemistry and therapeutic potential of furanones: A versatile pharmacophore. Eur. J. Med. Chem. 2019;171:66-92.
  12. Mardirossian N, Head-Gordon M. Thirty years of density functional theory in computational chemistry. Mol. Phy. 2017;115:2315-2372.
  13. Mirzaei M, Hadipour NL. Study of hydrogen bonds in crystalline 5-nitrouracil. Density functional theory calculations of the O-17, N-14, and H-2 nuclear quadrupole resonance parameters. J. Iran. Chem. Soc. 2009;6:195-199.
  14. Mirzaei M, Mirzaei M. The C-doped AlP nanotubes: A computational study. Solid State Sci. 2011;13:244-250.
  15. Behzadi H, Hadipour NL, Mirzaei M. A density functional study of 17O, 14N and 2H electric field gradient tensors in the real crystalline structure of α-glycine. Biophys. Chem. 2007;125:179-183.
  16. Mirzaei M, Yousefi M. Computational studies of the purine-functionalized graphene sheets. Superlat. Microstruct. 2012;52:612-617.
  17. Samadi Z, Mirzaei M, Hadipour NL, Khorami SA. Density functional calculations of oxygen, nitrogen and hydrogen electric field gradient and chemical shielding tensors to study hydrogen bonding properties of peptide group (OC–NH) in crystalline acetamide. J. Mol. Graph. Model. 2008;26:977-981.
  18. Mirzaei M. Effects of carbon nanotubes on properties of the fluorouracil anticancer drug: DFT studies of a CNT-fluorouracil compound. Int. J. Nano Dimens. 2013;3:175-179.
  19. Partovi T, Mirzaei M, Hadipour NL. The C–H···O hydrogen bonding effects on the 17O electric field gradient and chemical shielding tensors in crystalline 1-methyluracil: A DFT study. Z. Naturforsch. A. 2006;61:383-388.
  20. Harismah K, Sadeghi M, Baniasadi R, Mirzaei M. Adsorption of vitamin C on a fullerene surface: DFT studies. J. Nanoanal. 2017;4:1-7.
  21. Mokhtari A, Harismah K, Mirzaei M. Covalent addition of chitosan to graphene sheets: Density functional theory explorations of quadrupole coupling constants. Superlat. Microstruct. 2015;88:56-61.
  22. Harismah K, Ozkendir OM, Mirzaei M. Explorations of crystalline effects on 4-(benzyloxy) benzaldehyde properties. Z. Naturforsch. A. 2015;70:1013-1018.
  23. Mirzaei M, Harismah K, Jafari E, Gülseren O, Rad AS. Functionalization of (n, 0) CNTs (n= 3–16) by uracil: DFT studies. Eur. Phys. J. B. 2018;91:14.
  24. Harismah K, Mirzaei M, Sahebi H, Gülseren O, Rad AS. Chemically uracil–functionalized carbon and silicon carbide nanotubes: Computational studies. Mater. Chem. Phys. 2018;205:164-170.
  25. Harismah K, Mirzaei M, Ghasemi N, Nejati M. Non-covalent functionalisation of C30 fullerene by pyrrole-n-carboxylic acid (n= 2, 3): Density functional theory studies. Z. Naturforsch. A. 2017;73:51-56.
  26. Pence HE, Williams A. ChemSpider: An online chemical information resource. J. Chem. Edu. 2010;87:1123-1124.
  27. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery Jr JA, Stratmann RE, Burant JC, Dapprich S, et al. Gaussian 98, Revision A. 7. Pittsburgh, PA: Gaussian. Inc. Computer Program. 1998.
  28. Aramideh M, Mirzaei M, Khodarahmi G, Gülseren O. DFT Studies of Graphene-Functionalised Derivatives of Capecitabine. Z. Naturforsch. A. 2017;72:1131-1138.
  29. Aghazadeh M, Mirzaei M. Hydrogen bond interactions in sulfamerazine: DFT study of the O-17, N-14, and H-2 electric field gradient tensors. Chem. Phys. 2008;351:159-162.
  30. Soleimani M, Mirzaei M, Mofid MR, Khodarahmi G, Rahimpour SF. Lactoperoxidase inhibition by tautomeric propylthiouracils. Asian J. Green Chem. 2020;4:1-0.
  31. Alidoosti ZS, Mirzaei M. Comparative examination of moclobemide, tranylcypromine, phenelzine and isocarboxazid for monoamine oxidase–A inhibition. Adv. J. Chem. B. 2019;1:23-28.
  32. Esfahani AN, Mirzaei M. Flavonoid derivatives for monoamine oxidase–A inhibition. Adv. J. Chem. B. 2019;1:17-22.
  33. Ozkendir OM, Mirzaei M. Alkali metal chelation by 3–hydroxy–4–pyridinone. Adv. J. Chem. B. 2019;1:10-6.
  34. Nazemi H, Mirzaei M, Jafari E. Antidepressant activity of curcumin by monoamine oxidase–A inhibition. J. Adv. Chem. B. 2019;1:3-9.
  35. Mirzaei M, Meskinfam M. Computational studies of effects of tubular lengths on the NMR properties of pristine and carbon decorated boron phosphide nanotubes. Solid State Sci. 2011;13:1926-1930.
  36. Mirzaei M. Calculation of chemical shielding in C-doped zigzag BN nanotubes. Monatsh. Chem. 2009;140:1275-1278.
  37. Bagheri Z, Mirzaei M, Hadipour NL, Abolhassani MR. Density functional theory study of boron nitride nanotubes: calculations of the N-14 and B-11 nuclear quadrupole resonance parameters. J. Comput. Theor. Nanosci. 2008;5:614-618.
  38. Mirzaei M, Hadipour NL, Abolhassani MR. Influence of C-doping on the B-11 and N-14 quadrupole coupling constants in boron-nitride nanotubes: A DFT study. Z. Naturforsch. A 2007;62:56-60.
  39. Mirzaei M, Mirzaei M. The B-doped SiC nanotubes: A computational study. J. Mol. Struct. THEOCHEM 2010;953:134-138.
  40. Mirzaei M, Hadipour NL, Ahmadi K. Investigation of C–H… O=C and N–H… O=C hydrogen-bonding interactions in crystalline thymine by DFT calculations of O-17, N-14 and H-2 NQR parameters. Biophys. Chem. 2007;125:411-415.
  41. Acharya C, Coop A, E Polli J, D MacKerell A. Recent advances in ligand-based drug design: relevance and utility of the conformationally sampled pharmacophore approach. Cur. Comput. Aided Drug Design. 2011;7:10-22.
  42. Mirzaei M, Hadipour NL. A computational NQR study on the hydrogen‐bonded lattice of cytosine‐5‐acetic acid. J. Comput. Chem. 2008;29:832-838.
  43. Mirzaei M, Hadipour NL, Seif A, Giahi M. Density functional study of zigzag BN nanotubes with equivalent ends. Physica E 2008;40:3060-3063.
  44. Mirzaei M. Density functional study of defects in boron nitride nanotubes. Z. Phys. Chem. 2009;223:815-823.
  45. Mirzaei M. A computational NMR study of boron phosphide nanotubes. Z. Naturforsch. A 2010;65:844-848.
  46. Harismah K, Mirzaei M, Moradi R. DFT studies of single lithium adsorption on coronene. Z. Naturforsch. A 2018;73:685-691.
  47. Mirzaei M, Hadipour NL. Study of hydrogen bonds in 1-methyluracil by DFT calculations of oxygen, nitrogen, and hydrogen quadrupole coupling constants and isotropic chemical shifts. Chem. Phys. Lett. 2007;438:304-307.
  48. Harismah K, Mirzaei M, Samadizadeh M, Rad AS. DFT studies of stabilities and properties for X3Y6Z9 borazine–like structures (X= B/Al, Y= N/P, Z= H/Me). Superlat. Microstruct. 2017;109:360-365.