Experimental study on the thermochemistry of some amino derivatives of uracil

doi:10.1016/j.jct.2011.06.003

The Journal of Chemical Thermodynamics

Volume 43, Issue 11, November 2011, Pages 1763-1767

https://doi.org/10.1016/j.jct.2011.06.003 Get rights and content

Abstract

Values of the standard (p^∘ = 0.1 MPa) molar enthalpy of combustion, $Δ_{c} H_{m}^{\circ}$ , of four crystalline compounds: 5-aminouracil, 6-aminouracil, 6-amino-1-methyluracil, and 6-amino-1,3-dimethyluracil, were determined, at T = 298.15 K, using a static bomb combustion calorimeter. The values obtained of standard molar enthalpy of combustion were used to derive the standard molar enthalpy of formation of the compounds investigated in their condensed phase and together with literature values of the standard molar enthalpy of sublimation, yielded the standard molar enthalpies of formation in the gaseous phase. These are discussed in terms of the effects of the molecular structure on the relative enthalpic stability.

Highlights

► Combustion calorimetry was used to determine $Δ_{f} H_{m}^{\circ} (cr)$ of amino derivatives of uracil. ► Gas-phase $Δ_{f} H_{m}^{\circ}$ of amino derivatives of uracil have been derived. ► The relative enthalpic stability of the title compounds is discussed in structural terms.

Introduction

The derivatives of uracil deserve particular attention among all series of derivatives of nucleic pyrimidine bases. The biological activity of 5-substituted derivatives of uracil has stimulated exceptional interest in biochemistry and pharmacology. The thermodynamic properties of different substituted derivatives of uracil are important in view of their medical application. Some of the derivatives of uracil exhibit significant pharmacological activity and have been used as antitumor, antibacterial, and antiviral drugs.

Also, amino derivatives of uracil exhibit significant biological activity. The 5-aminouracil is a pyrimidine nucleobase analogue to thymine in which an amino group replaces the methyl group, adding therefore new hydrogen bonding sites [1]. The 5-aminouracil has been used as a starting material for the synthesis of other pyrimidines [2] or transition metal complexes [3]. The 1-[(2-hydroxyethoxy)methyl]-5-aminouracil exhibited anti-mycobacterium activity against mycobacterium bovis [4].

The 6-aminouracil [5] and 6-amino substituted derivatives of thymine [6] have been found to be the competitive inhibitors of human thymidine phosphorylase.

The derivatives of uracils have very important applications in organic synthesis [7]. The 6-aminouracils find wide application as starting materials for the synthesis of many fused uracils of biological significance, for example, phenylazo- [7], pyrano-, pyrido-, pyrazolo-, pyrimido- and pyridazino-pyrimidines [8]. Some derivatives of 6-aminouracil were synthesized and their possible diuretic, smooth muscle relaxant, and cardiovascular effects were studied [9]. The 5-cinnamoyl-6-aminouracil derivatives have been investigated as anticancer agents [10]. The 6-aminouracil is used extensively as an intermediate in the synthesis of a number of compounds containing the pyrimidine ring, including the manufacture of the important sulphanilamide drug sulfadimethoxin [11]. 6-Aminouracil has been found to inhibit the uracil-DNA glycosylase [12] and the dihydropyrimidine dehydrogenase enzymes [13].

The determinations of the thermodynamic properties of uracil and its amino derivatives of uracil were the subject of previous research [14], [15], [16]. This research aimed at the experimental determinations of the apparent molar volumes, the heat capacities, the changes in the molar enthalpy of solution, solvation, and sublimation. Their purpose was also to study solute–solvent interactions. This work is part of a wider investigation on the thermodynamic properties of derivatives of uracil. Values of the standard molar enthalpy of formation of the compounds investigated, in the crystalline phase, at T = 298.15 K, were derived from the standard massic energies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The standard molar enthalpies of sublimation of the compounds at, T = 298.15 K, were previously obtained [16] by the application of the Clausius–Clapeyron equation to the values of the vapour pressure, at different temperatures, determined by the Knudsen mass-loss effusion technique. The combination of the values of the standard molar enthalpies of formation in the crystalline phase, and the standard molar enthalpies of sublimation, allowed the calculation of the standard molar enthalpies of formation, in the gaseous phase, at T = 298.15 K.

Section snippets

Materials and purity control

The object of the study was the four compounds, whose structural formulae are shown in figure 1. The compounds 5-aminouracil [CAS 932-52-5] and 6-amino-1,3-dimethyluracil [CAS 6642-31-5] were obtained from the Aldrich Chemical Co. with the assessed value of mass fraction purity of 0.98, whereas 6-aminouracil [CAS 873-83-6] and 6-amino-1-methyluracil [CAS 2434-53-9] were purchased from the Alfa Aesar®, with assessed values of mass fractions purity of 0.98 and 0.97, respectively. The

Results

Results for a typical combustion experiment of each compound studied are given in table 1, where Δm(H₂O) is the deviation of the mass of water added to the calorimeter from 3119.6 g, the mass assigned to ε_calor, and ΔU_Σ is the energy correction to the standard state. The remaining quantities are as previously defined [26]. As samples were ignited at T = (298.150 ± 0.001) K, $Δ U (IPB) = - {ε_{calor} + Δ m (H_{2} O) c_{p} (H_{2} O,l) + ε_{f}} Δ T_{ad} + Δ U (ign),$ where ΔU(IBP) is the energy associated with the isothermal bomb process, ε_f is

Discussion

Uracil may have different tautomeric forms differing each other by the position of the hydrogen that may be bond to either nitrogen or oxygen atoms [33], [34]. Theoretical calculations and some experimental data strongly suggest that the dioxo tautomer is the most stable form of uracil [35], [36], [37], [38]. However, the tautomeric equilibria between the forms can be influenced by the presence of different substituents. Many theoretical studies on the effect of substituents on the stability of

Acknowledgements

Thanks are due to Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal and to FEDER for financial support to Centro de Investigação em Química, University of Porto and Programa Ciência 2008. P. Szterner thanks Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal for the award of the post-doctoral fellowship with reference (SFRH/BPD/33863/2009).

References (50)

S. Noll et al.
Eur. J. Med. Chem.
(2009)
B. Taqui Khan et al.
Inorg. Chim. Acta
(1990)
N.C. Srivastav et al.
Bioorg. Med. Chem.
(2007)
P. Langen et al.
Biochem. Pharm.
(1967)
D.J. Brown
C.D. Mol et al.
J. Cell.
(1995)
M.A.V. Ribeiro da Silva et al.
J. Chem. Thermodyn.
(1984)
P. Szterner et al.
J. Chem. Thermodyn.
(2002)
A. Imamura et al.
J. Chem. Thermodyn.
(1989)
J.S. Kwiatkowski et al.
Adv. Quantum Chem.
(1986)

G. Ferenczy et al.

J. Mol. Struct.

(1986)

J.R. Sambrano et al.

Chem. Phys.

(2001)

F. Peral et al.

J. Mol. Struct. (THEOCHEM)

(2010)

A.K. Chandra et al.

J. Mol. Struct.

(2002)

M.A. Palafox et al.

Spectrochim. Acta, Part A

(2010)

E. Miszczak-Zaborska et al.

Z. Naturforsch. [C]

(1997)

Z. Serfoglu et al.

Cent. Eur. J. Chem.

(2008)

A.A. Mustafa et al.

Pharm. Res.

(1989)

I. Bernier et al.

J. Med. Chem.

(1985)

V.M. Nesterov et al.

Pharm. Chem. J.

(1981)

D. Dobritzsch et al.

EMBO J.

(2001)

W. Zielenkiewicz et al.

J. Solution Chem.

(2000)

W. Zielenkiewicz et al.

J. Chem. Eng. Data

(2007)

W. Zielenkiewicz et al.

J. Chem. Eng. Data

(2003)

http://www.lookchem.com, “lookchem“-look for chemicals (assessed in May...

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Experimental study on the thermochemistry of some amino derivatives of uracil

Abstract

Highlights

Introduction

Section snippets

Materials and purity control

Results

Discussion

Acknowledgements

Eur. J. Med. Chem.

Inorg. Chim. Acta

Bioorg. Med. Chem.

Biochem. Pharm.

J. Cell.

J. Chem. Thermodyn.

J. Chem. Thermodyn.

J. Chem. Thermodyn.

Adv. Quantum Chem.

J. Mol. Struct.

Chem. Phys.

J. Mol. Struct. (THEOCHEM)

J. Mol. Struct.

Spectrochim. Acta, Part A

Z. Naturforsch. [C]

Cent. Eur. J. Chem.

Pharm. Res.

J. Med. Chem.

Pharm. Chem. J.

EMBO J.

J. Solution Chem.

J. Chem. Eng. Data

J. Chem. Eng. Data