Enthalpies of Combustion and Formation of Histidine Stereoisomers

,e combustion energy of histidine enantiomers (L and D) and of their racemic mixture was measured experimentally. ,e following values for the enthalpies of formation corresponding to the crystalline state were derived (L � −451.7, D � −448.7, DL � −451.5 kJ·mol), and information concerning their stability was obtained by correlating the values of the above thermochemical quantity with the structure of the molecules by using the group additivity scheme. ,e samples were characterized using a simultaneous thermogravimetry (TG) coupled with differential scanning calorimetry (DSC) techniques in the temperature range between ambient and beyond melting-decomposition, and the corresponding parameters were calculated. ,e high values of the decomposition temperatures highlight the stability of the compounds.,e decomposition reactions are discussed in terms of DSC and TG data, obtained by us and other researchers.


Introduction
e aim of this study was a calorimetric characterization of L-, D-, and DL-histidine isomers.
Histidine is a heterocyclic amino acid containing an imidazole ring.e imidazole ring is aromatic, as it contains six π electrons.Histidine is a proteinogenic amino acid, and it is able to form π stacking interactions.Consequently, the side chain can have a role in stabilizing the folded structures of proteins.Histidine is an essential amino acid that is not synthesized de novo in humans and is needed for growth and tissue repair [1].
e imidazole ring allows histidine to act as a coordinating ligand in metal proteins, including certain enzymes.It is important in hemoglobin, as well.Histidine is involved in stabilizing oxyhemoglobin and destabilizing CO-bound hemoglobin.Histidine is important for maintenance of myelin membranes that protect nerve cells and is metabolized to the neurotransmitter histamine [2].
Two divergent values of the enthalpy of formation of L-histidine are found in the literature: −441.8 ± 2.6 kJ•mol −1 [3] and −466.7 ± 2.8 kJ•mol −1 [4].Vasilev et al. [3] were aware that their data differ from previously reported values [4] and considered that the difference is due to the inadequate purity of the sample of the later authors.No data about the enthalpy of formation of D-histidine and for the racemic are found in the literature.e main purpose of this work is to determine these parameters and to compare them with those calculated by the group additivity method.e paper brings more information about the thermal behavior of the investigated compounds in function of the isomer type.

Experimental
2.1.Materials.D-histidine and DL-histidine were obtained commercially from Sigma-Aldrich, mass fraction purities ≥98% and 99%, respectively, and L-histidine, assay >99%, from Fluka with M � 155.15 g•mol −1 .Samples were dried in a vacuum oven for 3 hours at 90 °C and preserved in a desiccator before use, in order to eliminate adsorbed water.e purity of samples was tested by DSC and polarimetry.
Our DSC data confirm the purity of over 99% for the DLand D-isomers (99.06 and 99.25%, respectively) while for the D-histidine, the purity was 98.86%.e data are shown in Table 1 of Supplementary materials.
Specific rotations [α] 25 λ of the investigated compounds were determined on solutions in deionized water for checking the amino acid optical purity.A 341 PerkinElmer polarimeter was used in the D line of sodium, with glass cells (1 cm path length), at 25 °C.Table 1 contains our values compared to literature data ( [5], p. C768).
Like in the case of other amino acids, the only impurities amounting at least 0.1% (other than water) certified by the manufacturer consist of other amino acids, with similar values of the massic heat of combustion.

Combustion Calorimetry.
e combustion experiments were performed using a Parr Instruments model 6200 microprocessor controlled isoperibol oxygen bomb calorimeter.Temperatures are measured with a high-precision electronic thermometer using a specially designed thermistor sensor sealed in a stainless steel probe which is fixed in the calorimeter cover.Measurements were taken with 0.0001 K resolution.e jacket temperature is held constant for isoperibol operation.e semimicro kit handling samples from 25 to 200 mg was used because of the small amounts of the studied compounds.High-purity oxygen 99.998% was used for combustion.Calorific grade benzoic acid supplied by Parr, with heat of combustion 26,454 J•g −1 , was used for the standardization of the combustion calorimeter.e determined calorimeter constant was ε calor � 2326.9 ± 1.9 J•K −1 .
e samples were pressed into pellets of 3 mm diameter.e pellets were weighed with a Mettler-Toledo analytical balance, model XP6 with an accuracy of ±2•10 −6 g. e final solution from the bomb was analyzed for the presence of nitric acid (about 20% from the total nitrogen) by titration with solution of Na 2 CO 3 0.1 mol•L −1 .e heat due to nitric acid formation was obtained using the value of the enthalpy of formation of nitric acid solution,

ermal Analysis.
For the thermal characterization of histidines, a simultaneous thermogravimetry (TG) and differential scanning calorimetry (DSC) TGA/DSC Setaram Setsys Evolution 17 analyzer was employed.ermal properties (temperatures, enthalpies, and mass losses) associated with melting and/or decomposition processes of the histidine stereoisomers were measured in the temperature ranging from 20 to 600 °C with a scanning rate of 10 °C min −1 in alumina crucibles, using Ar flow.Standard metallic substances of 99.999% purity (In, Sn, Pb, Zn, and Al) were used for the calibration in temperature.e melting onset temperatures and heats of fusion of standard materials were used for temperature correction and energy calibration.e sample mass for simultaneous TG-DSC measurements was about 1-2 mg. e error of TG measurement is ±0.154%.All thermal analysis (TG-DSC) data were processed using Calisto software.

Combustion Energy.
At least 6 runs were retained for each isomer.Some runs were rejected because of doubt about combustion completeness.In runs used in data calculation, there was no evidence of soot formation in the bomb.e data regarding the combustion measurements for the three isomers are given in Tables 2-4 in Supplementary materials.e assigned uncertainties are twice the standard error of the mean.∆U (fuse) and ∆U (ign) were calculated from the mass of cotton and ∆ c u (cotton) � 16240 ± 20 J•g −1 [7] and from the mass of the fire and ∆ c u (Ni-Cr) � 5.86 kJ•g −1 (certified by the fabricant), respectively.e values obtained experimentally for the combustion energy were reported to the standard state (T � 298.15K and p � 101.325 kPa).Corrections were performed using Washburn methodology [8].
In order to calculate the enthalpies of formation, the following values were used: In Table 2 are presented our data for the solid-state enthalpies of formation, together with literature values [3,4].
e values of the enthalpies of formation of the L-enantiomer are quasi-identical with that of racemic, while that of D-histidine is more negative (within the cumulated experimental errors). 1 presents the DSC curves of L-, D-, and DL-histidine isomers.A single-sharp peak is recorded for all three stereoisomers.e temperature ranges in which the decomposition processes (decomposition prevails due to the high temperature) of the three stereoisomers take place are similar (274-290 °C).

DSC. Figure
Our peak temperatures of the enantiomers (Table 3) are in reasonable agreement with the values reported by Olafsson and Bryan [10] (288 °C), Weiss et al. [11] (272 °C), and Anandan et al. [12] (275 °C) as well as with that included in the Handbook of Chemistry and Physics ( [5], p. C445) (287 °C), but not with the value of Wesolowski and Erecinska [13] (250 °C).e "melting" points usually found for amino acids are irrelevant since they decompose, so that the temperatures may vary according to the morphology of the sample and to the experimental conditions used by the researchers [13].

ermogravimetry.
Figure 2 shows the temperatures and weight losses in the TG and DTG curves.ermogravimetric records for samples show a first-step fast weight loss of 17-18% starting above 240 °C, followed by a continuous mass decrease of the sample.At 600 °C, a mass reduction of over 53% is observed for both L-and 2 Journal of Chemistry D-enantiomers and the racemic (Table 4).
e difference between the initial mass of samples and the mass loss due to decomposition was consistent with the mass of solid residue.
Table 5 shows comparative data of thermal analysis on histidine reported by different authors.

Discussion
e formation enthalpies in solid state experimentally found were compared with those obtained by means of the group additivity method, with parameters recommended by Domalski and Hearing [14].
e value of the solid-state group parameter corresponding to an imine nitrogen atom bound to a carbon atom (N I -(C)) is missing.A value of 67 kJ•mol −1 was assigned to this parameter, taking into account the values of the same parameter for the liquid and gaseous states.Generally, because of the presence of an α-amino acid moiety, a zwitterion contribution is considered.A comparison between experimental and calculated values in solid state is shown in Table 2. ) L-histidine D-histidine DL-histidine  e calculated enthalpy of formation [14] agrees fairly with our experimental values.Only four hydrogen bonds per molecule were reported, less than for other amino acids.One of them is intramolecular in the case of enantiomers [15,16] while all four are intermolecular for DL [17].ree of them are taken into account in the group additivity calculations.
e enthalpy of formation in the ideal gas state of the histidine stereoisomers was calculated by means of the same quantity in the crystalline state and of the standard enthalpy of sublimation (Table 6).Gaffney et al. [18] have derived a value of 142 ± 8 kJ•mol −1 from vapor pressure measurements in the temperature range 392-492 K.A positive correction to the standard state of 6 ± 2 kJ•mol −1 is obtained by means of the estimation methods, recommended by Chickos et al., for phase-change enthalpies and heat capacities [19,20].A much larger value of 182 kJ•mol −1 is predicted by Badelin et al. [21] by quantum chemical computations.
As it may be easily seen, the discrepancies with respect to the calculated value are mainly due to the large uncertainties in the evaluation of the standard enthalpy of sublimation.
A small molecule (possibly CO) is evolved during the first step and other gaseous molecules (H 2 O and NH 3 ) at higher temperatures.
e processes revealed by DSC and TG are essentially, if not exclusively due to decomposition.Bryan and Olafsson [22] state that the main decomposition reaction is decarboxylation, possibly preceded by deamination.Weiss et al. [11] consider that a single main reaction occurs, taking into account that a sharp peak is obtained during the DSC run.e weight loss in the case of decarboxylation reaction was the only one that would be about 28.4% (higher than our experimental value, about 18%).e calculated thermal effect of the decarboxylation reaction, by means of the group additivity method [14], is about 79 kJ•mol −1 (in standard conditions) comparable with our experimental values (Table 6).

Table 2 :
Enthalpies of combustion and formation in solid state of isomeric histidines.
[14]rtainty included the uncertainties of the enthalpies of formation of the reaction products H 2 O and CO 2 .bEstimatedvalue by means of the group additivity method, with parameters recommended by Domalski and Hearing[14]. a

Table 5 :
Comparative values of melting-decomposition parameters of L-histidine reported by different researchers.