Calorimetric and computational studies for three nitroimidazole isomers

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Highlights

Abstract

In the present work, a combined experimental and computational thermochemical study of nitroimidazole isomers was carried out. The standard (p° = 0.1 MPa) molar enthalpy of combustion, in the crystalline phase, for 4-nitroimidazole was determined, at the temperature of 298.15 K, using a static bomb combustion calorimeter. Calvet microcalorimetry experiments were performed to measure its standard molar enthalpy of sublimation. The standard molar enthalpy of formation of 4-nitroimidazole, in the gaseous phase, at T = 298.15 K, (116.9 ± 2.9) kJ·mol−1, has been derived from the corresponding standard molar enthalpy of formation in the crystalline phase and the standard molar enthalpy of sublimation.

Computational studies for 4-nitroimidazole were performed to complement the experimental work. These were also extended to the 2- and 5-nitroimidazole isomers. The gas-phase enthalpies of formation were estimated from high level ab initio molecular orbital calculations, at the G3 level. Also investigated were the tautomeric equilibrium of 4(5)-nitroimidazole in the gaseous phase and it was concluded that the two tautomers are equally stable.

Introduction

Nitroimidazoles have been investigated extensively mainly due to their biological activity [1], [2], [3], in particular, their antibacterial properties [4], [5]. Since one of the many applications of this kind of compounds is to cure the infections induced by bacteria and to kill pathogenic protozoan parasites in human body [6], their toxicity and metabolism have been characterized [7]. Moreover they are promising candidates for high energy materials since they have favourable insensitivity and performance [8], [9], [10].

Also several studies [11], [12], [13], [14], [15], [16], [17], [18], [19] about tautomerism of these compounds have been carried out. For instance, the migration of the hydrogen atom to the nitrogen atoms in the imidazole ring can lead to the tautomeric forms. According to these studies, the 4-nitro isomer was found to predominate both in the crystal phase [12], [16] and in aqueous solution [11], [18]. Favouring the 4-nitro tautomer observed in the latter case seems to be principally a solvation phenomenon associated with its dipole moment which is much higher than that of the alternative tautomer. For the gaseous phase, the relative stability of both, 4- and 5-nitroimidazole is quite confusing; some results show that both tautomers are of similar energy [11], [19] while other results favour the tautomer 4 or 5 depending on the theoretical method used for calculating the energy [9], [17], [18], [19].

Knowledge of the energetic properties of the imidazole derivatives is important for the evaluation of their reactivity, therefore studies about the energy and structure of these compounds have been made [10], [17], [18], [19], [20], [21], [22].

In this work, we report the standard molar (p° = 0.1 MPa) enthalpy of formation of 4-nitroimidazole, in the gaseous phase, at T = 298.15 K, derived from measurements of the standard molar enthalpy of combustion by static bomb combustion calorimetry and from the standard molar enthalpy of sublimation as measured by Calvet microcalorimetry.

Additionally, standard ab initio molecular calculations, at the G3 level, were performed and the standard enthalpies of formation of 2-, 4- and 5-nitroimidazole were estimated. Estimates of the enthalpies of formation, obtained by using appropriate working reactions, were calculated and compared with the experimental data. The good agreement verified between computational and experimental results allows reliable estimates of the enthalpies of formation of the compounds which were not studied experimentally. The stability of the tautomeric forms, in the gaseous phase, has also been studied.

Section snippets

Compound and purity control

The compound was commercially obtained from TCI, with certified mole fraction purity of 1.000, and was purified by sublimation under reduced pressure. The purity of the sample was also checked by the amount of carbon dioxide recovered after the combustion experiments. The average ratio of the mass of carbon dioxide recovered to that calculated from the mass of sample was (0.9997 ± 0.0005), where the uncertainty is the standard deviation of the mean. Details of the origin and purification of the

Combustion calorimetry

The detailed results for the combustion experiments of 4-nitroimidazole are given in Table 2, together with the mean value of the standard massic energy of combustion Δcu°, and its standard deviation of the mean. Δm(H2O) is the deviation of the mass of water added to the calorimeter from 2900.0 g (the mass assigned for εcal), ΔU is the correction to the standard state and the remaining terms are as previously described [33], [45]. For the static-bomb measurements, as samples were ignited at T =

Final remarks

The experimental value of the standard molar enthalpy of formation, at T = 298.15 K, in the gaseous phase, for 4-nitroimidazole, (116.9 ± 2.9) kJ·mol−1, has been calculated from the result obtained for the standard molar enthalpy of formation, in the crystalline phase, together with the standard molar enthalpy of sublimation.

As can be seen from Table 5, Table 6, Table 7, by using appropriate reactions, we were able to calculate the enthalpy of formation for the compounds studied. A mean value was

Acknowledgments

Thanks are due to Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal, for the financial support to Project UID/QUI/0081/2013 and to FEDER through Program NORTE2020 for the financial support to Project POCI‐01‐0145‐FEDER‐006980 and to Project “Sustained Advanced Materials”, ref. NORTE-01-0145-FEDER-000028 (FCUP). LMPFA thanks to Programa Ciência 2008.

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    Present address: REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal.

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