Structural Chemistry

, Volume 30, Issue 6, pp 2085–2092 | Cite as

Evaluation method of steric shielding effect around nitroxide radical reaction center based on molecular volume within a virtual ball

  • Jun Naganuma
  • Yudai Yamazaki
  • Hiroaki GotohEmail author
Original Research


Steric shielding affects the stability of various molecules such as nitroxide radicals, which have many applications in a variety of fields. Thus, the mechanisms that maintain molecular stability are of particular interest. A new method for nitroxide radicals to quantify the steric shielding effect around the reaction center in a molecule was developed. The steric hindrance in this method is defined as the volume of the molecules contained within a virtual ball centered on the radical atom. With the proposed method, it is possible to evaluate the influences of the β-substituent, the basic molecular skeleton, and other parameters on steric hindrance, which cannot be calculated with Esc, a known parameter that indicates bulkiness. This method can acquire more accurate data that more closely resembles the behavior of the actual molecule. Because this method is very simple in that it requires only the optimal stable structure of the molecule, it can be used to estimate the steric shielding of various nitroxide radicals as well as other molecules.


Steric hindrance Nitroxide radical Steric constant TEMPO Conformational analysis 



We thank Dr. Kazuhisa Sakakibara for helpful discussions. We would also like to thank Editage ( for English language editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11224_2019_1335_MOESM1_ESM.docx (919 kb)
ESM 1 (DOCX 918 kb)


  1. 1.
    Kirilyuk IA, Bobko AA, Grigor’ev IA, Khramtsov VV (2004) Synthesis of the tetraethyl substituted pH-sensitive nitroxides of imidazole series with enhanced stability towards reduction. Org Biomol Chem 2:1025–1030CrossRefGoogle Scholar
  2. 2.
    Paletta JT, Pink M, Foley B, Rajca S, Rajca A (2012) Synthesis and reduction kinetics of sterically shielded pyrrolidine nitroxides. Org Lett 14:5322–5325CrossRefGoogle Scholar
  3. 3.
    Komatsuzaki T, Sakakibara K, Hirota M (1989) A new method for evaluating the steric hindrance by substituent. Tetrahedron Lett 30:3309–3312CrossRefGoogle Scholar
  4. 4.
    Hirota M, Sakakibara K, Yuzuri T, Kuroda S (2005) Re-examination of steric substituent constants by molecular mechanics. Int J Mol Sci 6:18–29CrossRefGoogle Scholar
  5. 5.
    Hirota M, Sakakibara K, Yuzuri T, Kuroda S (2001) Evaluation of the steric substituent effect by ΩS: reinvestigation of the reaction dependency of the steric substituent constant. J Phys Org Chem 14:788–793CrossRefGoogle Scholar
  6. 6.
    Denisov ET, Denisova TG, Geletii YV, Balavuan Z (1997) Reactivity of nitroxyl radicals in reactions with phenols, amines and thiophenols. Neftekhimiya 37:402–412Google Scholar
  7. 7.
    Tolman CA (1977) Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis. Chem Rev 77:313–348CrossRefGoogle Scholar
  8. 8.
    Tomilin OB, Tanaseichuk BS, Boyarkina OV (2016) Estimation of steric hindrances at the dimerization of free organic radicals. Russ J Org Chem 52:1576–1586CrossRefGoogle Scholar
  9. 9.
    Cavallo L, Correa A, Costabile C, Jacobsen H (2005) Steric and electronic effects in the bonding of N-heterocyclic ligands to transition metals. J Organomet Chem 69:5407–5413CrossRefGoogle Scholar
  10. 10.
    Kirilyuk IA, Bobko AA, Semenov SV, Komarov DA, Irtegova IG, Grigor’ev IA, Bagryanskaya E (2015) Effect of sterical shielding on the redox properties of imidazoline and imidazolidine nitroxides. J Org Chem 80:9118–9125CrossRefGoogle Scholar
  11. 11.
    Bagryanskaya EG, Marque SRA, Tsentalovich YP (2012) Alkoxyamine re-formation reaction. Effects of the nitroxide fragment: a multiparameter analysis. J Org Chem 77:4996–5005CrossRefGoogle Scholar
  12. 12.
    Zubenko D, Tsentalovich Y, Lebedeva N, Kirilyuk I, Roshchupkina G, Zhurko I, Reznikov V, Marque SRA, Bagryanskaya E (2006) Laser flash photolysis and CIDNP studies of steric effects on coupling rate of imidazolidine nitroxide with carbon-centered radicals, methyl isobutyrate-2-yl and tert-butyl propionate-2-yl. J Org Chem 71:6044–6052CrossRefGoogle Scholar
  13. 13.
    Taft Jr RW (1952) Polar and steric substituent constants for aliphatic and o-benzoate groups from rates of esterification and hydrolysis of esters. J Am Chem Soc 74:3120–3128CrossRefGoogle Scholar
  14. 14.
    Taft Jr RW (1953) Linear steric energy relationships. J Am Chem Soc 75:4538–4539CrossRefGoogle Scholar
  15. 15.
    Fujita T, Takayama C, Nakajima M (1973) The nature and composition of Taft-Hancock steric constants. J Org Chem 38:1623–1630CrossRefGoogle Scholar
  16. 16.
    Allinger NL, Yuh YH, Lii JH (1989) Molecular mechanics. The MM3 force field for hydrocarbons. 1. J Am Chem Soc 111:8551–8566CrossRefGoogle Scholar
  17. 17.
    Frisch MJ et al (2009) Gaussian 09, Revision A.02. Gaussian, Inc., WallingfordGoogle Scholar
  18. 18.
    Winmostar Version 8 (2017) X-Ability Co. Ltd., TokyoGoogle Scholar
  19. 19.
    Shibuya M, Tomizawa M, Suzuki I, Iwabuchi Y (2006) 2-Azaadamantane N-oxyl (AZADO) and 1-Me-AZADO: highly efficient organocatalysts for oxidation of alcohols. J Am Chem Soc 128:8412–8413CrossRefGoogle Scholar
  20. 20.
    Marque S, Le Mercier C, Tordo P, Fischer H (2000) Factors influencing the C-O-bond homolysis of trialkylhydroxylamines. Macromolecules 33:4403–4410CrossRefGoogle Scholar
  21. 21.
    Sakai K, Yamada K, Yamasaki T, Kinoshita Y, Mito F, Utsumi H (2010) Effective 2,6-substitution of piperidine nitroxyl radical by carbonyl compound. Tetrahedron 66:2311–2315CrossRefGoogle Scholar
  22. 22.
    Sasaki K, Ito T, Fujii HG, Sato S (2016) Synthesis and reduction kinetics of five ibuprofen-nitroxides for ascorbic acid and methyl radicals. Chem Pharm Bull 64:1509–1513CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry and Life ScienceYokohama National UniversityYokohamaJapan

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