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

• Published in: Theoretical chemistry accounts 2019-05, Vol.138 (5), p.1-11, Article 66
• Main Authors: Rangel-Galván, Violeta, Castro, María Eugenia, Perez-Aguilar, Jose Manuel, Caballero, Norma A., Meléndez, Francisco Javier
• Format: Article
• Language: English
• Subjects: 11th Congress on Electronic Structure: Principles and Applications (ESPA-2018); Aqueous solutions; Atomic/Molecular Structure and Spectra; Chemistry; Chemistry and Materials Science; Density functional theory; Energy of dissociation; Enthalpy; Free energy; Heat of formation; Inorganic Chemistry; Nitric oxide; Organic Chemistry; Physical Chemistry; Protonation; Reaction mechanisms; Regular Article; Tautomers; Theoretical and Computational Chemistry
• ISSN: 1432-881X; 1432-2234
• DOI: 10.1007/s00214-019-2453-y

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 (CH 3 ) 2 N[N(O)NO] − ( 1 ), 1,1-diethyl-3-oxotriazan-2-olate (CH 2 CH 3 ) 2 N[N(O)NO] − ( 2 ), 1,1-dipropyl-3-oxotriazan-2-olate (CH 2 CH 2 CH 3 ) 2 N[N(O)NO] − ( 3 ), 1,1-dibutyl-3-oxotriazan-2-olate (CH 2 CH 2 CH 2 CH 3 ) 2 N[N(O)NO] − ( 4 ) and 1,1-dipenthyl-3-oxotriazan-2-olate (CH 2 CH 2 CH 2 CH 2 CH 3 ) 2 N[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 1 – 5 , 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 Δ G 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 1 – 5 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 1.5 – 2.0 kcal mol −1 for 2–5 NONOates. Relative p k a 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.