Effect of the alkyl substituent in NONOates derivatives on the reaction mechanism of NO liberation

  • Violeta Rangel-Galván
  • María Eugenia CastroEmail author
  • Jose Manuel Perez-Aguilar
  • Norma A. Caballero
  • Francisco Javier MeléndezEmail author
Regular Article
Part of the following topical collections:
  1. 11th Congress on Electronic Structure: Principles and Applications (ESPA-2018)


Nitric oxide (NO) is a small biological molecule dealing with several physiological processes. NO can be obtained from different donor compounds. In this work, an analysis of the reaction mechanism for the liberation of NO from a series of NONOates: 1,1-dimethyl-3-oxotriazan-2-olate (CH3)2N[N(O)NO] (1), 1,1-diethyl-3-oxotriazan-2-olate (CH2CH3)2N[N(O)NO] (2), 1,1-dipropyl-3-oxotriazan-2-olate (CH2CH2CH3)2 N[N(O)NO] (3), 1,1-dibutyl-3-oxotriazan-2-olate (CH2CH2CH2CH3)2N[N(O)NO] (4) and 1,1-dipenthyl-3-oxotriazan-2-olate (CH2CH2CH2CH2CH3)2N[N(O)NO] (5) is carried out. M06L/6-311++G(d,p) density functional theory calculations were performed for obtaining the geometries and energies of the involved species in the mechanism. Mechanism is proposed by protonation of 15, and then, their protonated tautomers are involved to obtain the intermediaries and transitions states. Tautomerization energies are found to be between 2.23 and 21.44 kcal mol−1 with respect to the lowest energy tautomer H1 in all NONOates structures. Finally, as products, the corresponding secondary amine and two molecules of NO are obtained. Geometry optimizations were carried out in aqueous solution using SMD. Current ΔG values take into account the thermochemical contributions of enthalpy and entropy at 298.15 K. The effect of substituent size on the dissociation energy barrier was analyzed finding similar values for dissociation of 15 NONOates. The NONOate 1 with smallest substituent has the lowest dissociation barrier of 4.78 kcal mol−1 and leads to most energetically stable products. As alkyl substituent is increased in size, the value of dissociation barrier is increased in 1.52.0 kcal mol−1 for 2–5 NONOates. Relative pka values and natural bond orbitals, NBO, are estimated using for the tautomers H5 where the protonation site has the most acid behavior causing the NO generation.


NONOate derivatives DFT methods Tautomers Energy profile Dissociation energy Relative pka 



VRG thanks CONACYT-México for financial support (PhD fellowship No. 286497). Authors thank the Laboratorio Nacional de Supercómputo del Sureste de México (LNS-BUAP) of the CONACYT network of national laboratories, for the computer resources and support provided. Authors thank to VIEP-BUAP for the financial support, project: 100256733-VIEP2019, as well as the PRODEP Academic Group BUAP-CA-263 (SEP, Mexico).

Supplementary material

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Supplementary material 1 (DOCX 3231 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Violeta Rangel-Galván
    • 1
  • María Eugenia Castro
    • 2
    Email author
  • Jose Manuel Perez-Aguilar
    • 1
  • Norma A. Caballero
    • 3
  • Francisco Javier Meléndez
    • 1
    Email author
  1. 1.Lab. de Química Teórica, Centro de Investigación, Depto. de Fisicoquímica, Facultad de Ciencias QuímicasBenemérita Universidad Autónoma de PueblaPueblaMexico
  2. 2.Centro de Química, Instituto de CienciasBenemérita Universidad Autónoma de PueblaPueblaMexico
  3. 3.Facultad de Ciencias BiológicasBenemérita Universidad Autónoma de PueblaPueblaMexico

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