New heteroaryl nitrone spin traps have an excellent ability to add free radicals to produce stable products. The effects of new heteroaryl (thiadiazoyl and furoxanyl) substituents on a parent nitrone spin trap have been computationally studied using <i>ab initio</i> methods at the Hartree-Fock (HF) and second-order Møller-Plesset (MP2) levels with the 6-31G(d), cc-pVDZ and cc-pVTZ basis sets. The calculations show that new heteroaryl nitrones are very reactive, with thiadiazoyl substituted-nitrones being the most reactive spin traps and 1,2,4 – thiadiazol -5-yl nitrone is the most polar spin trap This is due to the electronic natures of the new heteroaryl nitrones. Additionally, the thermodynamics of the spin trapping of new heteroaryl nitrones at C-site and O-site with the biologically relevant radicals has been studied using HF/6-31G(d). The calculations show that thermodynamically, the spin trapping of furoxan-3-yl nitrone with biologically relevant radicals gives the most stable spin adducts at the C site while furoxan-4-yl nitrone with these radicals gives the most stable spin adducts at the O-site. However, the spin trapping at the C-site of new heteroaryl nitrones is highly exothermic as compared to the O site of the nitrone, due to the presence of resonance stabilization in C-site spin adducts. Finally, the thermodynamics of the spin trapping of DMPO, PBN and FxBN with hydroxyl radical has also been studied using Density Functional Theory (DFT) with M06/6-31*. The spin trapping of FxBN with hydroxyl radical is thermodynamically favored over the spin trapping of DMPO and PBN with hydroxyl radical. The double spin adduct of FxBN with hydroxyl radical is thermodynamically favored over the monoadduct of FxBN with hydroxyl radical. This work provides the understanding of the chemical and physical basis that influences the spin trapping efficiency of the new heteroaryl nitrones with biologically relevant radicals and the corresponding stability of their spin adducts.

Computational studies of spin trapping of biologically relevant radicals by new heteroaryl nitrones

251st National Meeting (2016)

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