Thermodynamic and Conformational Study of Proline Stereoisomers

Article pubs.acs.org/JPCB

Thermodynamic and Conformational Study of Proline Stereoisomers Ana Filipa L. O. M. Santos,*,† Rafael Notario,‡ and Manuel A. V. Ribeiro da Silva† †

Centro de Investigaçaõ em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal ‡ Instituto de Química Física “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain S Supporting Information *

ABSTRACT: Amino acids play fundamental roles both as building blocks of proteins and as intermediates in metabolism. Proline, one of the 20 natural amino acids, has a primordial function in enzymes, peptide hormones, and proteins. The energetic characterization of these molecules provides information concerning stability and reactivity and has great importance in understanding the activity and behavior of larger molecules containing these structures as fragments. In the present work, parallel experimental and computational studies have been performed. The experimental studies have been based on calorimetric and effusion techniques, from which the enthalpy of formation in the crystalline phase and the enthalpy of sublimation of the sterioisomers L-, D-, and the DL-mixture of proline have been derived. Additionally, vapor pressure measurements have also enabled the determination of the entropies and Gibbs energies of sublimation, at T = 298.15 K. From the former results, the experimental standard (po = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of L-proline, Dproline, and DL-proline have been calculated as −388.6 ± 2.3, −391.9 ± 2.0, and −391.5 ± 2.4 kJ·mol−1, respectively. A computational study at the G3 and G4 levels has been carried out. Conformational analysis has been done and the enthalpy of formation of proline as well as other intrinsic properties such as acidity, basicity, adiabatic ionization enthalpy, electron and proton affinities, and bond dissociation enthalpies have been calculated. There is a very good agreement between calculated and experimental values, when they are available.

1. INTRODUCTION Amino acids, as the molecular scaffolds of peptides, the backbones of proteins, are among the most important building blocks of living organisms playing, therefore, a very important role in many fundamental biochemical and metabolic processes. As the simplest models of peptides and proteins, amino acids are often object of intensive studies due to their high biochemical and biological importance, contributing to a deeper understanding of more complex structures. Proline, one of the 20 naturally occurring amino acids, has a peculiar structure, since it is the only cyclic amino acid among them; the amino group is part of a pyrrolidine ring, making it less flexible, restricting the local conformation freedom, and lowering the number of possible conformers. The ability of proline to form different intramolecular hydrogen bonds is due to its conformational versatility, caused by the capacity of reorientation of both −COOH and imine groups.1 The pyrrolidine ring in the proline residue is not planar; it may adopt two distinct down and up puckered conformations, which are almost equally favorable.2 This structure restricts the conformation that proline can adopt within a peptide or protein, giving proline an important and unique role in determining the secondary and tertiary structures of proline-containing peptides3,4 and proteins,5−8 and, consequently, their functional specificity. This cyclic amino acid is one of the main scaffolds of collagen, which is, in turn, the most abundant protein of connective tissue in mammals. The collagen stability is highly affected by the prolyl ring conformations;9,10 thus, the study of the conformational differences of proline is of extraordinary importance. © 2014 American Chemical Society

Due to its importance and particular structural properties, the structural features of proline have been the target of previously detailed studies by means of experimental X-ray diffraction,11−15 infrared spectroscopy,7,16,17 Raman spectroscopy,16 thermal decomposition (DTA, TG, and DTG),18 neutron diffraction,19 microwave spectroscopy, 1,20 and nuclear magnetic resonance,21−23 as well as by computational methods.7,8,12,14,17,24−31 Comprehension of the function of amino acids in biochemical processes depends on the knowledge of reliable thermodynamic data concerning the formation and dissociation of chemical bonds. In particular, the energetic characterization of these molecules provides information concerning stability and reactivity and has great importance for the understanding of the activity and behavior of larger molecules (such as proteins) containing these structures as fragments. In this context and following our previous studies on the thermodynamic properties of amino acids and their relationship with the corresponding molecular structures,32−37 we report, in the present work, a thermodynamic study of the sterioisomers L-, D-, and the DLracemic mixture of proline (Figure 1). As a consequence of the importance of proline, a great number of thermodynamic and thermochemical studies have appeared in the literature. For L-proline, there are four values reported of the standard molar enthalpy of formation, in the crystalline phase, ΔfHm°(cr),38−41 covering a range of 89 kJ·mol−1. In 1978 Sabbah Received: June 26, 2014 Revised: August 1, 2014 Published: August 2, 2014 10130

dx.doi.org/10.1021/jp5063594 | J. Phys. Chem. B 2014, 118, 10130−10141

The Journal of Physical Chemistry B

Article

respectively, the determination of the enthalpies of formation, in the crystalline phase, and the standard molar enthalpies of sublimation of the L-, D -, and DL -proline. From these experimental values, their gas-phase standard molar enthalpies of formation, at T = 298.15 K, have been derived. A computational study at the G3 and G4 levels has been carried out. A conformational analysis has been done and the gasphase enthalpy of formation has been calculated. We have also calculated other intrinsic properties of proline such as its acidity, basicity, adiabatic ionization enthalpy, electron and proton affinities, and bond dissociation enthalpy of different bonds.

Figure 1. Structural formula of proline.

and Laffitte,38 determined a value of Δf Hm°(cr) = −515.18 ± 0.52 kJ·mol−1 and Vasilev et al.,39 in 1989, obtained the value −507.6 ± 2.6 kJ·mol−1, both by static bomb calorimetry. More recently, Contineanu and collaborators performed a thermochemical study of proline stereoisomers.40 From combustion calorimetry, they reached to the following results for ΔfHm°(cr): −524.4 kJ·mol−1 for L-proline, −523.5 kJ·mol−1 for D-proline, and −520.4 kJ·mol−1 for DL-proline. In the past year, Ovchinnikov obtained a value of −596.6 kJ·mol−1, for both Land DL-proline, calculated using an equation based on Metzler’s monograph data, which is dependent on the number of valence electrons and the number of lone electron pairs of the molecule.41 For the DL-proline, there is also a value of ΔfHm°(cr) = −524.2 ± 0.9 kJ·mol−1, from Ponomarev and Migarskaya, measured by static bomb calorimetry (calculated from the standard molar enthalpy of combustion, ΔcHm° = −2729.6 ± 0.54 kJ·mol−1, reanalyzed by Cox and Pilcher;42 the original value of ΔcHm° = −3506.9 ± 0.63 kJ·mol−1 43). Values of vapor pressures or enthalpies of sublimation were found in the literature just for L-proline;44−46 they range around 48 kJ·mol−1. Svec and Clyde reported a value of enthalpy of sublimation, ΔgcrHm° = 101.3 ± 0.8 kJ·mol−1, determined by the Knudsen effusion method (value corrected to T = 298.15 K, see below; original value, 96.7 ± 0.8 kJ·mol−1 at T = 455 K).44 In 1978, Sabbah and Laffitte published a value of ΔgcrHm° = 149.0 ± 2.0 kJ·mol−1,45 measured calorimetrically, and one year later, De Kruif et al. measured the vapor pressures of several amino acids and peptides by simultaneous torsion and effusion techniques and a value of ΔgcrHm° = 130.6 ± 1.0 kJ·mol−1 was derived for Lproline (value corrected to T = 298.15 K, see below; original value 127.4 ± 1.0 kJ·mol−1 at T = 406.26 K).46 A value for the standard molar enthalpy of formation, in the gaseous phase, for Lproline is reported in the literature as −366.2 ± 4.0 kJ·mol−1.45 Computationally, Dorofeeva and collaborators performed a computational study to calculate the gas-phase enthalpy of formation of large organic molecules, at the G4 level of theory. For proline, the values calculated at this level were −387.6 kJ· mol−1, −386.0 kJ·mol−1, −394.7 kJ·mol−1 (values obtained using three different isodesmic reactions), and −387.6 kJ·mol−1 (value calculated through the respective atomization reaction).47 Recently, Dorofeeva and Ryzhova reported the gas-phase enthalpies of formation and of sublimation of several amino acids, based on isodesmic reaction calculations, at the G4 level of theory; for proline, they recommended a value of ΔfHm°(g) = −389.5 ± 4.0 kJ·mol−1.48 Based on theoretical calculations, they suggested a value for the enthalpy of sublimation of proline of 125.7 ± 4.0 kJ·mol−1. Therefore, due to the dispersion of thermodynamic values reported in the literature for proline stereoisomers, and since that knowledge of reliable thermodynamic data is of great importance to understand the behavior of proline containing macromolecules, we decide to perform the present study to get an accurate and complete thermodynamic and conformational characterization of this amino acid. In this work, static bomb combustion calorimetry and massloss Knudsen effusion experiments have been performed aiming,

2. EXPERIMENTAL SECTION 2.1. Materials and Purity Control. The compounds Lproline [CAS 147−85−3], D-proline [CAS 344−25−2], and DLproline [CAS 609−36−9] were purchased from Sigma-Aldrich Chemical Co., with initial mass fraction purities of 0.99. The solid samples of the sterioisomers L-, D-, and the DLracemic mixture of proline were purified by successive sublimations under reduced pressure. Their final purities were checked by gas−liquid chromatography (GLC), using an Agilent 4890 apparatus equipped with an HP-5 column, cross-linked, 5% diphenyl and 95% dimethylpolysiloxane (15 m × 0.530 mm i.d. × 1.5 μm film tickness), as well as by the percentage of carbon dioxide recovered during the combustion experiments. After purification, the three compounds were dried in vacuum and stored in nitrogen atmosphere, since they are highly hygroscopic. The final mass fraction purities obtained from the GLC analysis for L-proline, D-proline, and DL-proline were, respectively, 0.9998, 0.9996, and 0.9999. The average ratios of the mass of carbon dioxide recovered to those calculated from the mass of samples, used in each experiment, together with the uncertainties (twice the standard deviation of the mean) were: L-proline 0.9999 ± 0.0002, D-proline 0.9998 ± 0.0002, and DL-proline 1.0002 ± 0.0004. The specific densities, used to calculate the true mass from apparent mass in air, for L-proline, D-proline, and DL-proline were, respectively, ρ = 1.35 g·cm−3,11 ρ = 1.35 g·cm−3 (assumed to be equal to the L-isomer), and ρ = 1.409 g·cm−3.14 Throughout this paper, the values of the relative atomic masses of the elements were used according to the recommendations made by the IUPAC Commission in 2011.49 2.2. Combustion Calorimetry. The combustion experiments of the L-proline, D-proline, and DL-proline were performed in an isoperibol static bomb calorimetric system, equipped with a stainless steel twin valve bomb (Parr 1108 model), with an internal volume of 0.342 dm3. The description of the apparatus, as well as the operating technique have been previously reported.50,51 The energy equivalent of the calorimeter was determined, by the combustion of benzoic acid NIST Standard Reference Material, sample 39j, (under the bomb conditions, Δcu = −26 434 ± 3 J·g−1),52 according to Coops et al.;53 the value obtained was ε(calor) = 15 995.3 ± 2.0 J·K−1, as a mean of six calibration experiments, for an average mass of water added to the calorimeter of 3119.6 g (the quoted uncertainty refers the standard deviation of the mean). Pellets of crystalline L-, D-, and DL-proline were prepared in a nitrogen gas glovebag and subsequently enclosed in previously weighed polyester bags made of Melinex, with 0.025 mm thickness [Δcuo (Melinex) = −22902 ± 5 J·g−1], using the technique described by Skinner and Snelson,54 due to the high hygroscopicity of the compounds. The samples were ignited in 10131



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oxygen, at T = (298.150 ± 0.001) K, under a pressure of 3.04 MPa (the bomb was previously flushed to remove air), with 1.00 cm3 of deionized water introduced into the bomb. Details about calorimetric temperature measurements, electrical energy for ignition, cotton thread fuse, and the energetic effect for the amount of nitric acid produced in the combustion are described in previous works.55,56 The quantity of compound, m(cpd), burnt in each experiment and on which the energy of combustion was based, was determined from the mass of CO2 produced, taking into account that formed from the combustion of the cotton thread fuse and of the Melinex bags. The value for the pressure coefficient of specific energy, (∂u/ ∂p)T, at T = 298.15 K, was assumed to be −0.2 J·g−1·MPa−1, for the three studied compounds, a typical value for most organic compounds.57 Corrections to the standard state, ΔUΣ, used for the calculation of the standard mass energy of combustion, Δcuo, were made following the procedure proposed by Hubbard et al.58 2.3. Knudsen Effusion Technique. The study of the dependency of the vapor pressure with the temperature of the sterioisomers L-, D-, and the DL-mixture of proline was performed using the mass-loss Knudsen effusion method, which allowed the determination of their enthalpies of sublimation. The Knudsen apparatus used, fully described and tested before,59 enables the simultaneous operation of nine aluminum effusion cells, which are placed in cylindrical holes inside three aluminum blocks, each one with three cells, with different areas of the effusion orifices. Each block is maintained at a constant temperature, different from the other two blocks. The exact areas and the transmission probability factors of the nine effusion orifices, made of platinum foil of 0.0125 mm thickness, are presented in the Supporting Information, Table S1. In each effusion experiment, the loss of mass, Δm, of the samples, during a convenient effusion time period, t, is determined by weighing the effusion cells to ±0.01 mg, before and after the effusion period, in a system evacuated to a pressure near 1 × 10−4 Pa. At the temperature, T, of the experiment, the vapor pressure, p, is calculated by means of eq 1 p = (Δm /Aowot )(2πRT /M )1/2

Table 1. Typical Combustion Results, at T = 298.15 K, (p° = 0.1 MPa), for the Studied Compoundsa m(CO2, total)/g m(cpd)/g m′(fuse)/g m″(Melinex)/g ΔTad/K εf/J·K−1 Δm(H2O)/g −ΔU(IBP)b/J ΔU(fuse)/J ΔU(Melinex)/J ΔU(HNO3)/J ΔU(ign)/J ΔU∑/J −Δcuo/J·g−1

L-proline

D-proline

DL-proline

1.44562 0.70398 0.00321 0.04145 1.10956 16.26 0 17764.77 52.13 949.20 40.74 1.02 11.33 23738.42

1.35414 0.65339 0.00285 0.04398 1.03645 16.15 0 16594.12 46.28 1007.22 35.47 0.95 10.57 23714.14

1.05071 0.49694 0.00297 0.04196 0.80126 15.92 0 12827.96 48.23 961.08 29.37 1.19 8.04 23707.57

a m(CO2, total) is the mass of CO2 recovered in each combustion; m(cpd) is the mass of compound burnt in each experiment; m′(fuse) is the mass of the fuse (cotton) used in each experiment; m″(Melinex) is the mass of Melinex used in each experiment; ΔTad is the corrected temperature rise; εf is the energy equivalent of the contents in the final state; Δm(H2O) is the deviation of mass of water added to the calorimeter from 3119.6 g; ΔU(IBP) is the energy change for the isothermal combustion reaction under actual bomb conditions and includes ΔU(ignition); ΔU(fuse) is the energy of combustion of the fuse (cotton); ΔU(Melinex) is the energy of combustion of the Melinex; ΔU(HNO3) is the energy correction for the nitric acid formation; ΔU(ign) is the electric energy for the ignition; ΔU∑ is the standard state correction; Δcu° is the standard massic energy of combustion. bΔU(IBP) includes ΔU(ignition).

Table 2. Individual Values of Standard (p° = 0.1 MPa) Massic Energies of Combustion, Δcu°, of the Compounds, at T = 298.15 K L-proline

D-proline

23708.20 23741.59 23726.04 23757.36 23738.42 23752.59

(1)

where Ao represents the area of the effusion orifice, wo is the respective transmission probability factor (Clausing factor), R is the gas constant, and M is the molar mass of the effusing vapor.

(23737.4 ± 7.4)a

3. COMPUTATIONAL DETAILS Standard ab initio molecular orbital calculations60 were performed with the Gaussian 09 series of programs.61 The energies of the different conformers of proline were calculated using two different theoretical model chemistry Gaussian-n methods, at the G362 and G463 levels. We have optimized in this work the molecular structures of the four lowest-energy conformers of proline, taking into account only those conformers that contribute significantly to the populated states. We have also optimized the structures of protonated and deprotonated proline, its radical anion and cation, and the radicals formed by fission of the N−H, C2−H, and C−OH bonds.

a

DL-proline

−1

−Δcu /J·g 23722.57 23732.59 23739.33 23728.88 23708.28 23714.14 o

−⟨Δcuo⟩/(J·g−1) (23724.3 ± 4.8)a

23698.45 23702.73 23707.57 23687.06 23738.24 23687.20 23735.66 (23708.1 ± 8.0)a

Mean value and standard deviation of the mean.

crystalline phase, of the three compounds studied were derived from the respective massic energies of combustion, Δcuo, measured by static bomb combustion calorimetry. The combustion reaction of proline, to which are referred the values of Δcuo, is represented by the following equation: C5H 9NO2 (cr) + 6.25O2 (g) → 5CO2 (g) + 4.5H 2O(l) + 0.5N2(g)

(2)

In Table 1 are the results of one typical combustion experiment performed for each compound studied experimentally. The internal energy related to the isothermal bomb process, ΔU(IBP), was calculated according to eq 3, in which cp(H2O, l) is the massic heat capacity, at constant pressure, for the liquid

4. RESULTS AND DISCUSSION 4.1. Condensed Phase and Phase Transition. The standard (p° = 0.1 MPa) molar enthalpies of formation, in the 10132



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Table 3. Derived Standard (p° = 0.1 MPa) Molar Energies of Combustion, ΔcUm°, Standard Molar Enthalpies of Combustion, ΔcHm°, and Standard Molar Enthalpies of Formation, ΔfHm°, for the Compounds Studied, at T = 298.15 K compound L-proline D-proline DL-proline

−ΔcUm° (cr)/kJ·mol−1

−ΔcHm° (cr)/kJ·mol−1

−ΔfHm° (cr)/kJ·mol−1

2732.9 ± 2.0 2731.4 ± 1.6 2729.5 ± 2.1

2734.8 ± 2.0 2733.3 ± 1.6 2731.4 ± 2.1

519.0 ± 2.1 520.5 ± 1.7 522.4 ± 2.2

Table 4. Knudsen Effusion Results for the L-Proline, D-Proline, and DL-Proline 102·Δ ln(p/Pa)

p/Pa T/K

t/s

orifices

small

medium

large

small

medium

large

0.120 0.145 0.172 0.217 0.257 0.303 0.375 0.444 --0.677 0.774 0.915

4.0 2.3 --−3.6 2.8 4.3 1.6 1.4 2.8 3.3 2.9 3.2

2.2 3.2 −2.7 −0.2 3.1 −1.5 0.5 1.8 −0.5 0.9 −0.1 −0.7

−1.3 −2.9 −4.1 −0.6 −3.0 −5.0 −2.7 −4.7 --1.0 −3.8 −4.2

0.124 0.146 0.174 0.224 0.256 0.310 0.386 0.451 0.535 0.666 0.782 0.920

2.1 0.3 3.6 1.5 2.1 3.0 1.9 1.7 4.2 2.7 2.8 3.2

1.4 2.7 −2.1 0.5 2.6 −1.4 0.3 3.2 −2.1 1.9 3.6 −0.6

−0.1 −4.2 −5.5 0.9 −5.0 −4.4 −1.2 −4.5 −5.0 −1.9 −3.9 −4.4

0.110 0.131 0.155 0.196 0.238 0.285 0.343 0.418 0.490 0.616 0.732 0.867

−4.0 2.0 1.8 −3.7 0.8 0.8 0.3 2.3 −0.2 2.1 5.6 1.7

−0.6 4.8 −0.7 0.2 4.1 0.2 0.6 2.7 −2.7 1.7 3.9 −1.5

2.6 −0.8 −3.7 0.0 −0.8 −2.2 −2.6 −2.1 −5.1 −1.1 −2.5 −3.9

L-proline

393.19 395.24 397.14 399.17 401.20 403.14 405.18 407.21 409.15 411.21 413.23 415.14

21754 21754 21754 18122 18122 18122 13766 13766 13766 10555 10555 10555

A1−B4−C7 A2−B5−C8 A3−B6−C9 A1−B4−C7 A2−B5−C8 A3−B6−C9 A1−B4−C7 A2−B5−C8 A3−B6−C9 A1−B4−C7 A2−B5−C8 A3−B6−C9

0.127 0.152 --0.211 0.272 0.332 0.391 0.472 0.571 0.693 0.828 0.986

393.16 395.19 397.15 399.15 401.18 403.14 405.18 407.20 409.14 411.21 413.24 415.14

21612 21612 21612 18388 18388 18388 15180 15180 15180 10858 10858 10858


0.127 0.152 0.190 0.226 0.275 0.334 0.399 0.480 0.587 0.697 0.836 0.993

389.13 391.16 393.15 395.14 397.17 399.15 401.14 403.15 405.15 407.16 409.17 411.16

21615 21615 21615 16270 16270 16270 13319 13319 13319 10993 10993 10993


0.103 0.134 0.164 0.189 0.242 0.293 0.354 0.437 0.515 0.636 0.794 0.916

0.124 0.154 0.175 0.218 0.273 0.314 0.387 0.474 0.553 0.676 0.804 0.947 D-proline 0.126 0.156 0.180 0.224 0.276 0.319 0.393 0.487 0.551 0.692 0.843 0.956 DL-proline 0.107 0.138 0.160 0.197 0.250 0.292 0.355 0.439 0.502 0.634 0.781 0.888

Table 5. Values of the Standard (p° = 0.1 MPa) Molar Enthalpies, ΔgcrHm°, Entropies, ΔgcrSm°, and Gibbs Energies ΔgcrGm°, of Sublimation, at the Mean Temperature of the Experiments T = ⟨T⟩ and T = 298.15 K, for the Compounds Studied T = 298.15 K compound

⟨T⟩/K

ΔgcrHm°(⟨T⟩)/kJ·mol−1

L-proline

404.16 404.15 400.14

127.3 ± 1.0 126.2 ± 1.0 128.6 ± 0.9

D-proline DL-proline

ΔgcrSm(⟨T⟩,

−1

−1

p(⟨T⟩))/J·K ·mol

315.0 ± 2.5 312.3 ± 2.5 321.4 ± 2.2

water, Δm (H2O) represents the difference between the mass of water added to the calorimeter and the mass assigned for

ΔgcrHm°/kJ·mol−1

ΔgcrSm°/J·K−1·mol−1

ΔgcrGm°/kJ·mol−1

130.4 ± 1.0 128.6 ± 1.0 130.9 ± 0.9

219.4 ± 2.5 214.7 ± 2.5 222.7 ± 2.2

65.0 ± 1.2 64.6 ± 1.2 64.5 ± 1.1

ε(calor), εf is the energy equivalent of the bomb content in the final state, ΔTad is the calorimeter temperature change corrected 10133



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To derive the standard molar enthalpies of formation, in the crystalline phase, ΔfHm°(cr) from the standard molar enthalpies of combustion, ΔcHm°(cr), the standard molar enthalpies of formation of H2O(l) and CO2(g), at T = 298.15 K, −285.830 ± 0.042, and −393.51 ± 0.13 kJ·mol−1,64 respectively, were used. The derived values of the standard molar energies and enthalpies of combustion, respectively, ΔcUm°(cr) and ΔcHm°(cr), as well as the ΔfHm°(cr) of the L-proline, D-proline, and DL-proline, at T = 298.15 K, are given in Table 3. The uncertainties ascribed to the standard molar energies and enthalpies of combustion are twice the overall standard deviation of the mean and include the contribution from the calibration with benzoic acid and from the values of the auxiliary quantities used.65,66 The experimental results of the vapor pressure measurements at several temperatures for the sterioisomers L-, D-, and the DLmixture of proline, obtained from each effusion cell, together with the residuals of the Clausius−Clapeyron equation {102·Δln(p/Pa)}, derived from least-squares adjustments are summarized in Table 4. The integrated form of the Clausius−Clapeyron equation, ln(p/Pa) = a − b·(T/K)−1, where a is a constant and b = ΔgcrHm°(⟨T⟩)/R, was used to derive the standard molar enthalpies of sublimation at the mean temperature of the experimental temperature range ⟨T⟩. The equations obtained for L-proline (4), D-proline (5), and for DL-proline (6), together with the calculated uncertainties (standard deviations of the leastsquares regressions of the fittings) are as follows:

Figure 2. B3LYP/6-31G(2df,p)-optimized structures of the four lowestenergy conformers of proline.

Table 6. B3LYP/6-31G(2df,p)-Calculated and Experimental Structural Parameters of Neutral Prolinea calculatedb

experimentalc

1.484 1.480 1.544 1.537 1.532 1.545 1.336 1.203 123.9 113.5 122.7 105.8 110.1 109.2 103.6 102.9 102.5 121.3 1.8 0.0 0.7 1.850

--1.451 1.544 1.544 1.544 1.544 1.340 1.210 124.9 116.2 ----111.0 108.3 103.7 --101.9 121.0 0 --2.0 1.915

C2−N C5−N C2−C3 C3−C4 C4−C5 C2−C6 C−O CO OCO CCO CCO NC2C3 NC2C6 CNC C4C5N C2C3C4 C3C4C5 C5NC2C6 NCCO NCCO C3C2NC5 N···H−O a b

15307 ± 116 T

(4)

ln p = (36.53 ± 0.30) −

15183 ± 120 T

(5)

ln p = (37.50 ± 0.26) −

15461 ± 104 T

(6)

For the three compounds studied, the values of the standard (p° = 0.1 MPa) molar enthalpies, ΔgcrHm°, entropies, ΔgcrSm°, and Gibbs energies ΔgcrGm°, of sublimation, at the mean temperature of the experiments T = ⟨T⟩ and at T = 298.15 K are summarized in Table 5. The values of the enthalpies of sublimation, at T = 298.15 K, ΔgcrHm°, were calculated by eq 7, from the enthalpies of sublimation, at the mean temperature ⟨T⟩ of the experiment Δcrg Hm°(T = 298.15 K) = Δcrg Hm°(⟨T ⟩) + Δcrg Cp ,m°(298.15 − ⟨T ⟩) (7)

Bond lengths are in ångstroms and bond angles are in degrees. Correspond to the most stable conformer IIa. cTaken from ref 20.

The value of ΔgcrCp,m° = −29.3 ± 0.2 J·K−1·mol−1, for L-proline, was calculated from the respective molar heat capacity, in the crystalline phase, Cp,m°(cr)= 150.4 ± 0.2 J·K−1·mol−1, taken from the literature,67 and from the value of the gas phase molar heat capacity, Cp,m°(g) = 121.1 J·K−1·mol−1, at T = 298.15 K, derived from statistical thermodynamics, using the vibrational frequencies from B3LYP/6-31G(2df,p) calculations. For D-proline and g −1 −1 DL-proline, the value of ΔcrCp,m° = −22.2 J·K ·mol , was 68 calculated through eq 8, derived by Monte et al., as a rearrangement of eq 9, suggested by Chickos and collaborators,69 using the value of Cp,m°(g) = 121.1 J·K−1·mol−1, at T = 298.15 K, calculated in this work, at the B3LYP/6-31G(2df,p) level of theory.

for the heat exchange and the work of stirring, and ΔU(ign) is the electrical energy for ignition ΔU (IBP) = − {ε(calor) + cp(H 2O, l) ·Δm(H 2O) + εf }Δ Tad + ΔU (ign)

ln p = (36.82 ± 0.29) −

(3)

The individual values of Δcu , together with the respective mean values, ⟨Δcuo⟩, and their standard deviations are presented in Table 2. Detailed data of each combustion experiment, for the compounds studied, are given in the Supporting Information, Tables S2 to S4. o

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Table 7. G3 and G4 Results for Proline Conformers E0a

conformer

a

ΔΔHb

H298 Ka

IIa IIb Ia Ib

−400.871975 −400.870783 −400.869956 −400.869696

−400.863570 −400.862229 −400.861161 −400.861015

IIa IIb Ia Ib

−400.945746 −400.944685 −400.934373 −400.943605

−400.937507 −400.936361 −400.934956 −400.934980

G3 results 0.0 3.5 6.3 6.7 G4 results 0.0 3.0 6.7 6.6

Sc

ΔfH298 K°b

ΔfG298 K°b

χ

351.03 355.48 364.54 359.08

−390.63 −387.11 −384.31 −383.93

−221.70 −219.51 −219.41 −217.40

0.503 0.208 0.200 0.089

354.89 360.54 362.00 367.51

−389.55 −386.54 −382.85 −382.91

−221.78 −220.45 −217.19 −218.90

0.486 0.285 0.077 0.152

In Hartrees. bIn kJ·mol−1. cIn J·K−1·mol−1.

Table 8. Experimental Values for the Standard (p° = 0.1 MPa) Molar Enthalpies of Formation, in Crystalline and Gaseous Phase, and Standard Molar Enthalpy of Sublimation, at T = 298.15 K amino acid L-proline

D-proline

DL-proline

−ΔfHm°(cr)/kJ·mol−1

ΔgcrHm°/kJ·mol−1

−ΔfHm°(g)/kJ·mol−1

reference

--515.18 ± 0.52 507.6 ± 2.6

149.0 ± 2.0 ----101.3 ± 0.8a 130.6 ± 1.0a

366.2 ± 4.0 ---------

130.4 ± 1.0

388.6 ± 2.3

128.6 ± 1.0 ---

391.9 ± 2.0 ---

130.9 ± 0.9

391.5 ± 2.4

Sabbah, Laffitte (1978)45 Sabbah, Laffitte (1978)38 Vasilev et al. (1989)39 Svec, Clyde (1965)44 De Kruif et al. (1979)46 Contineanu et al. (2012)40 Ovchinnikov (2013)41 This work Contineanu et al. (2012)40 This work Ponomarev, et al. (1960)43 Contineanu et al. (2012)40 Ovchinnikov (2013)41 This work

524.4 596.6 ± 3.0 519.0 ± 2.1 523.5 520.5 ± 1.7 524.2 ± 0.9b 520.4 596.6 ± 3.0 522.4 ± 2.2

Value calculated from the results presented in the respective reference to T = 298.15 K using ΔcrCp,m° = −29.3 ± 0.2 J·K−1·mol−1. bValue derived from ΔcHm°(cr),43 and from the ΔfHm° of (H2O, l) = −285.830 ± 0.042 kJ·mol−1 and ΔfHm° (CO2, g) = −393.51 ± 0.13 kJ·mol−1, at T = 298.15 K.64 a

solution, stabilized by electrostatic, polarization, and hydrogenbonding interactions with their environment. In the gas phase, where the intermolecular interactions have no effect, amino acids are intrinsically flexible systems, existing as their non-ionized forms. Proline is the only natural amino acid which contains a secondary amino group as part of a flexible fivemembered ring. This makes proline conformationally somewhat less flexible than most of other amino acids. The structure of neutral proline in the gas phase has been experimentally determined by Lesarri et al. in 2002,20 by using laser-ablation molecular-beam Fourier-transform microwave spectroscopy (LA-MB-FTMW) in a supersonic jet. They first observed two conformers of proline, and two new conformers were observed1 after the introduction of changes in their instrument that increased the sensitivity efficiency. The pyrrolidine ring in the most stable conformer is bent, with atoms C3−C2−N−C5 in a plane and an endo-like puckering of 138°. The atoms involved in the intramolecular N···H−O hydrogen bond complete a fivemembered planar ring, with an hydrogen-bond length of r(N− H) = 1.915 Å.20 The earliest ab initio study for proline was performed by Sapse et al. in 1987,29 which resulted in an almost planar pyrrolidine ring. Several more elaborated theoretical studies followed. Ramek et al.,30 located 10 distinct conformers at the HF/6311++G(d,p) level. Császár et al.31 reported structural results for 12 conformers, including relative energies obtained at correlated

Table 9. G3- and G4-Calculated and Experimental Enthalpies of Formation of Proline in the Gas Phase, at T = 298.15 Ka atomization isodesmic (12) isodesmic (13) isodesmic (14) isodesmic (15) isodesmic (16)

G3

G4

−388.0 −390.6 −389.2 −389.9 −391.3 −386.3

−387.2 −390.8 −389.2 −390.7 −392.2 −386.9

experimental L-proline D-proline DL-proline

a

mean value −388.6 ± 2.3 −391.9 ± 2.0 −391.5 ± 2.4

−390.7 ± 3.9

All values in kJ·mol−1.

Δcrg Cp ,m°/J. K−1. mol−1 = − {0.9 + 0.176Cp ,m°(g)}

(8)

Δcrg Cp ,m°/J. K−1. mol−1 = − {0.75 + 0.15Cp ,m°(cr)}

(9)

4.2. Molecular Structure. The crystal structure of L-proline was determined by X-ray diffraction by Wright and Cole,11 in 1949, and later by Kayushina and Vainshtein, in 1965.15 The structure is orthorhombic with a = 11.55, b = 9.02, and c = 5.20 Å, and belongs to space group P212121.15 Amino acids exist as zwitterions in the crystalline state,70 as well as in aqueous 10135



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Figure 4. B3LYP/6-31G(2df,p)-optimized structures of the (a) deprotonated and (b) protonated species of proline.

Figure 3. Enthalpic increments, in kJ·mol−1, for the introduction of a −COOH group in 2-position of (a) pyrrolidine, (b) pyrrole, and (c) 1methylpyrrole.87

Table 10. G3- and G4-Calculated Gas-Phase Acidity, ΔGacid and ΔHacid, Gas-Phase Basicity, GB, Proton Affinity, PA, Adiabatic Ionization Enthalpy, IE, Electron Affinity, EA, and Bond Dissociation Enthalpies, BDE, at T = 298.15 K, for Prolinea G3

G4

experimental

ΔGacid

1395.1

1394.8

1395 ± 13

ΔHacid

1426.7

1426.3

1424 ± 13 1431 ± 9

GB

892.0

890.8

886.0 895.7 ± 1.6

PA

920.2

919.9

920.5 925.9 ± 1.6 920.1 ± 0.8 936.0

IE

8.38

8.31

8.3−9.0 9.36

EA BDE (N−H) BDE (C−OH) BDE (C2−H) a

−0.99 399.2 473.7 330.0

−0.84 389.9 463.4 322.6

---------

Figure 5. Bond dissociation reactions of proline for different types of bonds.

reference O’Hair et al. (1992)79 O’Hair et al. (1992)79 Jones et al. (2007)80 Hunter, Lias (1998)81 Bouchoux, Salpin (2003)82 Hunter, Lias (1998)81 Bouchoux, Salpin (2003)82 Mirza et al. (2001)83 Mezzache et al. (2003)84 Cannington, Ham (1983)85 Slifkin, Allison (1967)86 ---------

levels of electronic structure theory. Stepanian et al.7 determined 15 stable minima using DFT, and due to a more systematic search, Czinki and Császár8 located and characterized 18 conformers on the PES of proline at the B3LYP/6-311++G(d,p) level. The stable conformers of proline can be built up by considering puckering of the pyrrolidine ring, orientation of the COOH group (Z or E), orientation of the imino NH group (up or down with respect to the pyrrolidine ring), and torsions about the C−C and C−O bonds. All conformers thus built belong to the C1 point group.8 We have carried out G3 and G4 calculations on the four most stable conformers of proline, named IIa, IIb, Ia, and Ib, following the numbering used by Mata et al.1 (I, II, III, and IV in the article of Czinki and Császár8). They are the conformers that contribute significantly to the populated states. The next one is 15 kJ·mol−1 less stable than global minimum and its contribution to the population is very small. B3LYP/6-31G(2df,p)-optimized geometries of the four lowest-energy conformers of proline, obtained in this work, are shown in Figure 2. As can be observed, conformers IIa and IIb are characterized by hydrogen bonding between the lone pair of the nitrogen atom and the hydroxyl group hydrogen atom (N···H−O), while conformers Ia and Ib present hydrogen bonding between the imino group and the oxygen atom of the carbonyl group (N−H··· OC). The preference for the N···H−O interaction in proline should be attributed to the geometrical constraints imposed by the pyrrolidine ring.1 Conformers a and b differ in ring

All Values in kJ·mol−1 except IE and EA, in eV.

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Table 11. Enthalpies of Formation of Different Radicals Derived from Proline Calculated from Bond Dissociation Reactions (a) (Figure 5) and from Isogyric Reactions (b) (Figure 6)a

a

All Values are in kJ·mol−1.

molecules studied. Also included in this table are the experimental data for L-, D-, and the DL-proline available in the literature. As can be observed, our value for the Δf Hm°(cr) of Lproline, −519.0 ± 2.1 kJ·mol−1, is in reasonable agreement with the values measured by Sabbah and Laffitte38 and Contineanu et al.40 with differences of about 4 kJ·mol−1 and 5 kJ·mol−1, respectively. A huge deviation is found between our value and that reported by Ovchinnikov, ∼78 kJ·mol−1 (!!!).41 For D- and DL-proline, our results are in agreement with those determined by Contineanu et al.,40 and for DL-proline, the same great difference is observed when our result is compared with the one determined by Ovchinnikov.41 The value of Ponomarev et al. agrees very well with our result for DL-proline.43 Despite the concordance between our results, in the crystalline phase, and the ones determined by Contineanu et al.,40 their samples were burnt without previous purification (mass purities between 98% and 99.5%) and they were handled without taking into account the high hygroscopic character of proline. Moreover, it is possible to notice that there is a considerable dispersion in the individual combustion data obtained, mainly for DL-proline. These were the main reasons we decided to redetermine the enthalpies of formation, in the crystalline phase, of the proline stereoisomers. The only values for the enthalpies of sublimation, found in the literature, are for L-proline.44−46 Our experimental value 130.4 ± 1.0 kJ·mol−1 is in excellent agreement with that reported by De Kruif et al. of 130.6 ± 1.0 kJ·mol−1,46 but not with those reported by Sabbah et al.45 and Svec et al.44 in which the differences are ca. 19 kJ·mol−1 and 30 kJ·mol−1, respectively. No values of enthalpy of sublimation for D- and DL-prolines were found in the literature for comparison with our results. Regarding the gas-phase, the value reported for the enthalpy of formation of L-proline by Sabbah and Laffitte,45 based on the enthalpy of formation, in the crystalline phase,38 and enthalpy of sublimation,45 determined by those authors is 22.4 kJ·mol−1 more positive than the value determined in this work. The values of the enthalpies of formation of the different conformers of proline, calculated at the G3 and G4 levels using the standard procedure through atomization reactions,71 are shown in Table 7. Using eq 11:

Figure 6. Isogyric reactions for the calculation of the enthalpies of formation of different radicals derived from proline.

puckering. In all conformers the character of the nitrogen atom is pyramidal. Calculated and experimental structural parameters of the most stable conformer IIa of proline are shown in Table 6, and G3and G4-calculated energies and enthalpies of the four more stable conformers of proline are collected in Table 7. The conformational composition of proline in the gas phase, at T = 298 K, can be calculated through eq 10 xi =

e −[ n

ΔGrel(i) RT ]

∑i = 1 e−[

ΔGrel(i) RT ]

(10)

Boltzmann weighted populations derived from Gibbs energies have been collected in Table 7. As can be observed, populations follow the order IIa > IIb > Ia ≈ Ib. Conformers IIa and IIb account for more than 70% of the composition in the gas phase. Proline does not follow the trend observed by all the simplest αamino acids in that type I conformers are more populated than type II conformers.1 4.3. Gas-Phase Experimental and Theoretical Enthalpies of Formation. In Table 8 are summarized the experimentally derived standard molar enthalpies of formation in the gaseous phase, ΔfHm°(g), at T = 298.15 K, for the three 10137



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n

Δf Hm°(X ) =

∑ xiΔf Hm°(i) i=1

4.4. Other Gas-Phase Thermodynamic Properties. G3and G4-calculations have been extended to the determination of other thermodynamic properties of proline: gas-phase acidities, ΔGacid and ΔHacid; gas-phase basicity, GB; proton affinity, PA; electron affinity, EA; adiabatic ionization enthalpy, IE; and N−H, C−OH, and C2−H bond dissociation enthalpies, BDEs. The calculated values of these properties are collected in Table 10 together with the available experimental values, for comparison purposes. We have optimized the structures of protonated and deprotonated proline, its radical anion and cation, and the radicals formed by fission of the N−H, C2−H, and C−OH bonds. The B3LYP/6-31G(2df,p)-optimized structures of the deprotonated and protonated species of proline are shown in Figure 4. There are two possible deprotonation or protonation sites, the NH and COOH groups. The most stable deprotonated species is that with loss of the hydrogen atom of the COOH group. In the case of protonated species, the protonation is more favorable in NH group, contrary to the case of 2-pyrrolecarboxylic acid that protonates preferentially on the carbonyl oxygen atom.56 As can be seen in Figure 4, both protonated and deprotonated species are stabilized by N−H···O hydrogen bonding. The calculated gas-phase acidities, ΔGacid and ΔHacid, gas-phase basicity, GB, and proton affinity, PA, of proline are in very good agreement with the experimental values available in the literature. The addition of an electron to proline is more unfavorable than the addition of an electron to 2-pyrrolecarboxylic acid (calculated EA = −0.43 eV),56 but more favorable than the addition of an electron to pyrrole ring (calculated EA = −1.91 eV).55 The energy required to remove an electron from proline is lower than that required to remove an electron from 2-pyrrolecarboxylic acid (calculated IE = 8.63 eV),56 and slightly higher than that required to remove an electron from pyrrole ring (calculated IE = 8.28 eV).55 Bond dissociation enthalpies, BDE, for three different bonds in proline have been calculated through the reactions shown in Figure 5. Calculated BDE values are collected in Table 10. The H atom loss from the C2−H bond atom presents the lower BDE. More endothermic processes are the loss of an H atom from the NH group, and over all the loss of OH of the carboxylic group. The N−H bond dissociation in proline requires a lower enthalpy than required for the same bond dissociation in 2-pyrrolecarboxylic acid, calculated as 421.6 kJ·mol−1.56 We have also tried to calculated the BDE corresponding to the fission of the O−H bond of the carboxylic group, but this was not possible because in the calculations the radical pyrrolidine-COO• breaks in 2pyrrolidinyl radical plus CO2. Using the calculated bond dissociation enthalpies and the experimental enthalpies of formation of hydrogen and hydroxyl radicals, 218.076 and 37.377 kJ·mol−1, respectively, it is possible to calculate the enthalpies of formation of the different radicals derived from proline. The results are collected in Table 11. We can also use isogyric reactions, defined as those reactions conserving the number of electron pairs, to calculated the enthalpies of formation of radicals, expecting a cancellation of errors in the correlation energy.78 The results are shown in Table 11. As it can be observed, there is a good agreement between the enthalpies of formation of the radicals calculated from both series of reactions.

(11)

the final value for the enthalpy of formation of proline is calculated as −388.0 and −387.2 kJ·mol−1, at the G3 and G4 levels, respectively. Another possibility, suggested by Glukhovtsev and Laiter,72 as a better alternative for obtaining more accurate heats of formation, is the use of isodesmic or homodesmotic reactions.73 We have calculated the enthalpies of formation of proline using the isodesmic reactions 12−16:

G3- and G4-calculated enthalpies at T = 298.15 K, and experimental enthalpies of formation in the gas phase for the molecules used as references in isodesmic reactions 12−16 are collected in the Supporting Information (Table S5). G3- and G4calculated enthalpies of formation of proline, using isodesmic reactions 12−16, are collected in Table 9. As can be observed, there is a very good agreement between our experimental values for the three stereoisomers of proline and the calculated ones. The computational values estimated by Dorofeeva et al.47,48 are in very good agreement with our results, either the experimental or the computational ones. In the former study,47 they had already found a large discrepancy between theoretical and experimental literature data, suggesting an inaccuracy in the values of enthalpies of sublimation. In their recent publication,48 the value recommended for the enthalpy of sublimation, based on theoretical calculations, is underestimated by 3−5 kJ·mol−1, when compared with our experimental results. In terms of enthalpic increments, the substitution of a hydrogen atom by a carboxylic group produces a significant stabilization in the pyrrolidine ring. The enthalpic increment for the insertion of a −COOH group in position 2 of the pyrrolidine ring is between −385.2 ± 2.4 kJ·mol−1 for L-proline and −388.5 ± 2.2 kJ·mol−1 for D-proline, as shown in Figure 3. This large enthalpic stabilization may be due to an intramolecular hydrogen bond, which was already reported for 2-acetylpyrrole,55 2pyrrolecarboxylic acid,56 2-trichloroacetylpyrrole and 2-trifluoroacetylpyrrole,74 and 2-pyrrolecarboxaldehyde.75 However, the stabilization is lower than that observed when a hydrogen atom is substituted by a −COOH group in the 2-position of pyrrole and 1-methylpyrrole (see Figure 3), which can be explained by a more favorable electronic delocalization in the aromatic rings, since the pyrrole ring is planar and the pyrrolidine ring is puckered. 10138



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5. CONCLUSIONS In the present work, the standard (p° = 0.1 MPa) molar gasphase enthalpies of formation, at T = 298.15 K, of L-proline (−388.6 ± 2.3 kJ·mol−1), D-proline (−391.9 ± 2.0 kJ·mol−1), and −1 DL-proline (−391.5 ± 2.4 kJ·mol ) have been derived through the respective standard molar enthalpies of formation, in the crystalline phase and the standard molar enthalpies of sublimation measured, respectively, by combustion calorimetry and Knudsen effusion technique. Computational calculations at the G3 and G4 levels have been carried out and the estimated gas-phase enthalpies of formation for the different conformers of proline have been determined; experimental and computational data are in very good agreement. The optimized molecular structures of the lowest-energy conformers of proline have been established and the structural parameters have been determined at the B3LYP/6-31G(2df,p) level. The conformer which represents the absolute minimum (IIa) is characterized by hydrogen bonding between the lone pair of the nitrogen atom and the hydroxyl group hydrogen atom (N···H−O). Other thermodynamic properties, namely, gas-phase acidity, gas-phase basicity, proton and electron affinities, adiabatic ionization enthalpy, and bond dissociation enthalpies have also been determined by means of G3 and G4 calculations. Moreover, the enthalpies of formation of the different radicals derived from proline have also been calculated from bond dissociation reactions as well as from isogyric reactions. The new results presented for the stereoisomers of proline are a contribution to the thermodynamics−structure interplay of amino acids.

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REFERENCES

(1) Mata, S.; Vaquero, V.; Cabezas, C.; Peña, I.; Pérez, C.; López, J. C.; Alonso, J. L. Observation of Two New Conformers of Neutral Proline. Phys. Chem. Chem. Phys. 2009, 11, 4141−4144. (2) Momany, F. A.; McGuire, R. F.; Burgess, A. W.; Scheraga, H. A. Energy Parameters in Polypeptides. VII. Geometric Parameters, Partial Atomic Charges, Nonbonded Interactions, Hydrogen Bond Interactions, and Intrinsic Torsional Potentials for the Naturally Occurring Amino Acids. J. Phys. Chem. 1975, 79, 2361−2381. (3) Milner-White, E. J.; Bell, L. H.; Maccallum, P. H. Pyrrolidine Ring Puckering in Cis and Trans-proline Residues in Proteins and Polypeptides. Different Puckers are Favoured in Certain Situations. J. Mol. Biol. 1992, 228, 725−734. (4) Kang, Y. K. Ring Flip of Proline Residue via the Transition State with an Envelope Conformation. J. Phys. Chem. B 2004, 108, 5463− 5465. (5) Richardson, J. S.; Richardson, D. C. Amino Acid Preferences for Specific Locations at the Ends of Alpha Helices. Science 1988, 240, 1648−1652. (6) MacArthur, M. W.; Thornton, J. M. Influence of Proline Residues on Protein Conformation. J. Mol. Biol. 1991, 218, 397−412. (7) Stepanian, S. G.; Reva, I. D.; Radchenko, E. D.; Adamowicz, L. Conformers of Nonionized Proline. Matrix-Isolation Infrared and PostHartree-Fock Ab Initio Study. J. Phys. Chem. A 2001, 105, 10664− 10672. (8) Czinki, E.; Császár, A. G. Conformers of Gaseous Proline. Chem. Eur. J. 2003, 9, 1008−1019. (9) Improta, R.; Benzi, C.; Barone, V. Understanding the Role of Stereoelectronic Effects in Determining Collagen Stability. 1. A Quantum Mechanical Study of Proline, Hydroxyproline, and Fluoroproline Dipeptide Analogues in Aqueous Solution. J. Am. Chem. Soc. 2001, 123, 12568−12577. (10) DeRider, M. L.; Wilkens, S. J.; Waddell, M. J.; Bretscher, L. E.; Weinhold, F.; Raines, R. T.; Markley, J. L. Collagen Stability: Insights From NMR Spectroscopic and Hybrid Density Functional Computational Investigations of the Effect of Electronegative Substituents on Prolyl Ring Conformations. J. Am. Chem. Soc. 2002, 124, 2497−2505. (11) Wright, B. A.; Cole, P. A. Preliminary Examination of the Crystal structure of L-Proline. Acta Crystallogr. 1949, 2, 129−130. (12) DeTar, D. F.; Luthra, N. Conformations of Proline. P. J. Am. Chem. Soc. 1977, 99, 1232−1244. (13) Abramov, Y. A.; Volkov, A.; Wu, G.; Coppens, P. Use of X-Ray Charge Densities in the calculation of Intermolecular Interactions and Lattice Energies: Application to Glycylglycine, DL-Histidine, and DLProline and Comparison with Theory. J. Phys. Chem. B 2000, 104, 2183−2188. (14) Myung, S.; Pink, M.; Baik, M.-H.; Clemmer, D. E. DL-Proline. Acta Crystallogr. 2005, C61, 506−508. (15) Kayushina, R. L.; Vainshtein, B. K. Structure Determination of LProline by X-Ray Diffraction. Kristallografiya 1965, 10, 834−844; Sov. Phys. Crystallogr. (Engl. Transl.) 1966, 10, 698−706. (16) Kolbe, A.; Griehl, C.; Biehler, S. Molecular Interactions in Conjugates of Dicarboxylic Acids and Amino Acids. J. Mol. Struct. 2003, 661−662, 239−246. (17) Reva, I. D.; Stepanian, S. G.; Plokhotnichenko, A. M.; Radchenko, E. D.; Sheina, G. G.; Blagoi, Y. P. Infrared Matrix Isolation Studies of Amino Acids. Molecular Structure of Proline. J. Mol. Struct. 1994, 318, 1−13. (18) Wesolowski, M.; Erecińska, J. Relation Between Chemical Structure of Amino Acids and Their Thermal Decomposition. Analysis of the Data by Principal Component Analysis. J. Therm. Anal. Calorim. 2005, 82, 307−313. (19) McLain, S. E.; Soper, A. K.; Terry, A. N.; Watts, A. Structure and Hydration of L-Proline in Aqueous Solutions. J. Phys. Chem. B 2007, 111, 4568−4580. (20) Lesarri, A.; Mata, S.; Cocinero, E. J.; Blanco, S.; López, J. C.; Alonso, J. L. The Structure of Neutral Proline. Angew. Chem., Int. Ed. 2002, 41, 4673−4676.

ASSOCIATED CONTENT

S Supporting Information *

Detailed data of the effusion orifices (diameter and Clausing factors) of the Knudsen apparatus; data and details of all the combustion calorimetry experiments for L-proline, D-proline, and DL-proline; G3- and G4-calculated enthalpies at T = 298.15 K; experimental enthalpies of formation in the gas phase for the molecules used as references in isodesmic reactions (12)−(16); G3- and G4-calculated enthalpies and Gibbs energies at T = 298.15 K, in Hartrees, for species derived from proline; and Cartesian coordinates of all the species studied, optimized at the B3LYP/6-31G(2df,p) level. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*Phone: +351-22-0402 515. Fax: +351-22-0402 659. E-mail: ana. [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Thanks are due to Fundaçaõ para a Ciência e a Tecnologia, F.C.T., Lisbon, Portugal, and to FEDER for financial support to ́ Centro de Investigaçaõ em Quimica, University of Porto (strategic project PEst-C/QUI/UI0081/2013). A.F.L.O.M.S. thanks F.C.T. and the European Social Fund (ESF) under the Community Support Framework (CSF) for the award of the postdoctoral fellowship (SFRH/BPD/41601/2007). R.N. thanks the support of the Spanish Ministerio de Economiá y Competitividad under Project CTQ2010-16402. 10139



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(21) Haasnoot, C. A. G.; De Leeuw, F. A. A. M.; De Leeuw, H. P. M.; Altona, C. Relationship Between Proton−Proton NMR Coupling Constants and Substituent Electronegativities. III. Conformational Analysis of Proline Rings in Solution Using a Generalized Karplus Equation. Biopolymers 1981, 20, 1211−1245. (22) London, R. E. The Interpretation of Carbon-13 Spin-Lattice Relaxation Resulting From Ring Puckering in Proline. J. Am. Chem. Soc. 1978, 100, 2678−2685. (23) Pogliani, L.; Ellenberger, M.; Valat, J. A NMR Investigation of Proline and its Derivatives. IIConformational Implications of the 1H NMR Spectrum of L-Proline at Different pH. Org. Magn. Reson. 1975, 7, 61−71. (24) Marino, T.; Russo, N.; Tocci, E.; Toscano, M. Gas-Phase Acidity of Proline From Density Functional Computations. Int. J. Quantum Chem. 2001, 84, 264−268. (25) Tarakeshwar, P.; Manogaran, S. Vibrational Frequencies of Proline and Hydroxyproline. An Ab Initio Study. J. Mol. Struct. (Theochem) 1996, 365, 167−181. (26) Hudáky, I.; Baldoni, H. A.; Perczel, A. Peptide Models XXXVIII. Proline Conformers from X-Ray Crystallographic Database and From Ab Initio Computations. J. Mol. Struct. (Theochem) 2002, 582, 233−249. (27) Lee, K.-M.; Park, S.-W.; Jeon, I.-S.; Lee, B.-R.; Ahn, D.-S.; Lee, S. Computational Study of Proline − Water Cluster. Bull. Korean Chem. Soc. 2005, 26, 909−912. (28) Nasseri, S. M.; Hadipour, N. L.; Mohebbi, A. R. Investigation of the Effects of Ionic Hydrogen Bonds (CO−···H−C and +N− H···−OC) in Crystalline DL-Proline by Ab Initio and DFT Calculated NQR Parameters. J. Mol. Struct. 2007, 846, 119−122. (29) Sapse, A. M.; Mallah-Levy, L.; Daniels, S. B.; Erickson, B. W. The.Gamma. Turn: Ab Initio Calculations on Proline and NAcetylproline Amide. J. Am. Chem. Soc. 1987, 109, 3526−3529. (30) Ramek, M.; Kelterer, A.-M.; Nikolic, S. Ab Initio and Molecular Mechanics Conformational Analysis of Neutral L-Proline. Int. J. Quantum Chem. 1997, 65, 1033−1045. (31) Császár, A. G.; Perczel, A. Ab initio Characterization of Building Units in Peptides and Proteines. Prog. Biophys. Mol. Biol. 1999, 71, 243− 309. (32) Roux, M. V.; Foces-Foces, C.; Notario, R.; Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Santos, A. F. L. O. M.; Juaristi, E. Experimental and Computational Thermochemical Study of SulfurContaining Amino Acids: L-Cysteine, L-Cystine, and L-CysteineDerived Radicals. S−S, S−H, and C−S Bond Dissociation Enthalpies. J. Phys. Chem. B 2010, 114, 10530−10540. (33) Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Santos, A. F. L. O. M.; Roux, M. V.; Foces-Foces, C.; Notario, R.; Guzmán-Mejía, R.; Juaristi, E. Experimental and Computational Thermochemical Study of α-Alanine (DL) and β-Alanine. J. Phys. Chem. B 2010, 114, 16471− 16480. (34) Notario, R.; Roux, M. V.; Foces-Foces, C.; Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Santos, A. F. L. O. M.; Guzmán-Mejía, R.; Juaristi, E. Experimental and Computational Thermochemical Study of N-Benzylalanines. J. Phys. Chem. B 2011, 115, 9401−9409. (35) Santos, A. F. L. O. M.; Amaral, L. M. P. F.; Ribeiro da Silva, M. D. M. C.; Roux, M. V.; Notario, R. Experimental and Computational Study on the Energetics of the Cyclic Anhydrides of Glycine and Alanine. J. Chem. Thermodyn. 2013, 58, 29−35. (36) Amaral, L. M. P. F.; Santos, A. F. L. O. M.; Ribeiro da Silva, M. D. M. C.; Notario, R. Thermochemistry of Sarcosine and Sarcosine Anhydride: Theoretical and Experimental Studies. J. Chem. Thermodyn. 2013, 58, 315−321. (37) Notario, R.; Roux, M. V.; Santos, A. F. L. O. M.; Ribeiro da Silva, M. D. M. C. Experimental and Computational Study on the Energetics of N-Acetyl-L-cysteine. J. Chem. Thermodyn. 2014, 73, 57−61. (38) Sabbah, R.; Laffitte, M. Enthalpy of Formation of Solid L-Proline. J. Chem. Thermodyn. 1978, 10, 101−102. (39) Vasilev, V. P.; Borodin, V. A.; Kopnyshev, S. B. Standard Enthalpies of Formation of L-Histidine and L-Proline. Russ. J. Phys. Chem. (Engl. Transl.) 1989, 63, 891−892. In NIST Chemistry Webbook, NIST Standard Reference Database Number 69; Linstrom, P. J.;

Mallard, W. G., Eds.; National Institute of Standards and Technology: Gaithersburg, MD 20899, (http://webbook.nist.gov). (40) Contineanu, I.; Neacşu, A.; Zgîrian, R.; Tănăsescu, S.; Perişanu, Ş. The Standard Enthalpies of Formation of Proline Stereoisomers. Thermochim. Acta 2012, 537, 31−35. (41) Ovchinnikov, V. V. Thermochemistry of Heteroatomic Compounds: Analysis and calculation of Thermodynamic Functions of Amino Acids and Some Peptides of Different Space Structure. Am. J. Phys. Chem. 2013, 2, 8−15. (42) Cox, J. D.; Pilcher, G. Thermochemistry of Organic and Organometallic Compounds; Academic Press: New York, 1970. (43) Ponomarev, V. V.; Migarskaya, L. B. Heats of Combustion of Some Amino-Acids. Russ. J. Phys. Chem. (Engl. Transl.) 1960, 34, 1182− 1183. In NIST Chemistry Webbook, NIST Standard Reference Database Number 69; Linstrom, P. J.; Mallard, W. G., Eds.; National Institute of Standards and Technology: Gaithersburg, MD 20899, (http:// webbook.nist.gov). (44) Svec, H. J.; Clyde, D. D. Vapor Pressures of Some α-Amino Acids. J. Chem. Eng. Data 1965, 10, 151−152. (45) Sabbah, R.; Laffitte, M. Thermodynamique de Composes Azotes. IV. Étude Thermochimique de la Sarcosine et de la L-Proline. Bull. Soc. Chim. Fr. 1978, 1, 50−52. In NIST Chemistry Webbook, NIST Standard Reference Database Number 69; Linstrom, P. J.; Mallard, W. G., Eds.; National Institute of Standards and Technology: Gaithersburg, MD 20899, (http://webbook.nist.gov). (46) De Kruif, C. G.; Voogd, J.; Offringa, J. C. A. Enthalpies of Sublimation and vapour Pressures of 14 Amino Acids and Peptides. J. Chem. Thermodyn. 1979, 11, 651−656. (47) Dorofeeva, O. V.; Kolesnikova, I. N.; Marochkin, I. I.; Ryshova, O. N. Assessment of Gaussian-4 Theory for the Computation of Enthalpies of Formation of Large Organic Molecules. Struct. Chem. 2011, 22, 1303−1314. (48) Dorofeeva, O. V.; Ryshova, O. N. Gas-Phase Enthalpies of Formation and Enthalpies of Sublimation of amino acids Based on Isodesmic Reaction Calculations. J. Phys. Chem. A 2014, 118, 3490− 3502. (49) Wieser, M. E.; Holden, N.; Coplen, T. B.; Böhlke, J. K.; Berglund, M.; Brand, W. A.; De Bièvre, P.; Gröning, M.; Loss, R. D.; Meija, J.; et al. Atomic Weights of the Elements 2011 (IUPAC Technical Report). Pure Appl. Chem. 2013, 85, 1047−1078. (50) Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Pilcher, G. The Construction, Calibration and Use of a High-Precision Static-Bomb ́ 1984, 26, 163−172. Calorimeter. Rev. Port. Quim. (51) Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Pilcher, G. Enthalpies of Combustion of 1,2-Dihydroxybenzene and of Six Alkylsubstituted 1,2-Dihydroxybenzenes. J. Chem. Thermodyn. 1984, 16, 1149−1155. (52) Certificate of Analysis; Standard Reference Material 39j; Benzoic Acid; Calorimetric Standard; National Institutes of Standards and Technology: Washington, DC, 1995. (53) Coops, J.; Jessup, R. S.; van Nes, K. G. In Experimental Thermochemistry; Rossini, F. D., Ed.; Interscience: New York, 1956; Vol 1, Chapter 3. (54) Skinner, H. A.; Snelson, A. The Heats of Combustion of the Four Isomeric Butyl Alcohols. Trans Faraday Soc. 1960, 56, 1776−1783. (55) Santos, A. F. L. O. M.; Gomes, J. R. B.; Ribeiro da Silva, M. A. V. 2and 3-Acetylpyrroles: A Combined Calorimetric and Computational Study. J. Phys. Chem. A 2009, 113, 3630−3638. (56) Santos, A. F. L. O. M.; Ribeiro da Silva, M. A. V. Experimental and Computational Study on the Molecular Energetics of 2-Pyrrolecarboxylic Acid and 1-Methyl-2-pyrrolecarboxylic Acid. J. Phys. Chem. A 2009, 113, 9741−9750. (57) Washburn, E. W. Standard States for Bomb Calorimetry. J. Res. Natl. Bur. Stand. (U.S.) 1933, 10, 525−558. (58) Hubbard, W. N.; Scott, D. W.; Waddington, G. In Experimental Thermochemistry; Rossini, F. D., Ed.; Interscience: New York, 1956; Vol 1, Chapter 5. 10140



Article

(59) Ribeiro da Silva, M. A. V.; Monte, M. J. S.; Santos, L. M. N. B. F. The Design, Construction, and Testing of a New Knudsen Effusion Apparatus. J. Chem. Thermodyn. 2006, 38, 778−787. (60) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986. (61) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian 09, rev A.02; Gaussian, Inc., Wallingford, CT, 2009. (62) Curtiss, L. A.; Raghavachari, K.; Redfern, P. C.; Rassolov, V.; Pople, J. A. Gaussian-3 (G3) Theory for Molecules Containing First and Second-Row Atoms. J. Chem. Phys. 1998, 109, 7764−7776. (63) Curtiss, L. A.; Redfern, P. C.; Raghavachari, K. Gaussian-4 Theory. J. Chem. Phys. 2007, 126, 084108. (64) Cox, J. D., Wagman, D. D., Medvedev, V. A., Eds. CODATA Key Values for Thermodynamics; Hemisphere: New York, 1989. (65) Rossini, F. D. In Experimental Thermochemistry; Rossini, F. D., Ed.; Interscience: New York, 1956; Vol 1, Chapter 14. (66) Olofsson, G. In Combustion Calorimetry; Sunner, S., Månsson, M., Eds.; Pergamon: Oxford, 1979; Vol 1, Chapter 6. (67) Spink, C. H.; Wadsö, I. Thermochemistry of Solutions of Biochemical Model Compounds. 4. The Partial Molar Heat Capacities of Some Amino Acids in Aqueous Solution. J. Chem. Thermodyn. 1975, 7, 561−572. (68) Monte, M. J. S.; Almeida, A. R. R. P.; Matos, M. A. R. Thermodynamic Study on the Sublimation of Five Aminomethoxybenzoic Acids. J. Chem. Eng. Data 2010, 55, 419−423. (69) Chickos, J. S.; Hosseini, S.; Hesse, D. G.; Liebman, J. F. Heat Capacity Corrections to a Standard State: A Comparison of New and Some Literature Methods for Organic Liquids and Solids. Struct. Chem. 1993, 4, 271−278. (70) Allen, F. H. The Cambridge Structural Database: A Quarter of a Million Crystal Structures and Rising. Acta Crystallogr. 2003, B58, 380− 388. (71) Notario, R.; Castaño, O.; Gomperts, R.; Frutos, L. M.; Palmeiro, R. Organic Thermochemistry at High ab Initio Levels. 3. A G3 Study of Cyclic Saturated and Unsaturated Hydrocarbons (Including Aromatics). J. Org. Chem. 2000, 65, 4298−4302. (72) Glukhovtsev, M. N.; Laiter, S. High Level ab Initio Stabilization Energies of Benzene. Theor. Chim. Acta 1995, 92, 327−332. (73) Minkin, V. I. Glossary of Terms Used in Theoretical Organic Chemistry. Pure Appl. Chem. 1999, 71, 1919−1981. (74) Santos, A. F. L. O. M.; Ribeiro da Silva, M. A. V. Experimental and Computational Energetic Study of Two Halogenated 2-Acetylpyrrole Derivatives: 2-Trichloroacetylpyrrole and 2-Trifluoroacetylpyrrole. J. Chem. Thermodyn. 2010, 42, 1079−1086. (75) Santos, A. F. L. O. M.; Ribeiro da Silva, M. A. V. A Combined Experimental and Computational Thermodynamic Study of the isomers of Pyrrolecarboxaldehyde and 1-Methyl-2-pyrrolecarboxaldehyde. J. Phys. Chem. B 2011, 115, 12549−12557. (76) Chase, M. W., Jr. NIST-JANAF Thermochemical Tables, 4th Edition, J. Phys. Chem. Ref. Data, Monograph 9 1998, 1−1951. (77) Ruscic, B.; Wagner, A. F.; Harding, L. B.; Asher, R. L.; Feller, D.; Dixon, D. A.; Peterson, K. A.; Song, Y.; Qian, X.; Ng, C.-Y.; et al. On the Enthalpy of Formation of Hydroxyl Radical and Gas-Phase Bond Dissociation Energies of Water and Hydroxyl. J. Phys. Chem. A 2002, 106, 2727−2747. (78) Energetics of Organic Free Radicals; Martinho-Simões, J. A., Greenberg, A., Liebman, J. F., Eds.; Chapman & Hall: London, 1996. (79) O’Hair, R. J.; Bowie, J. H.; Gronert, S. Gas Phase Acidity of the alpha-Amino Acids. Int. J. Mass Spectrom. Ion Processes 1992, 117, 23−36. (80) Jones, C. M.; Bernier, M.; Carson, E.; Colyer, K. E.; Metz, R.; Pawlow, A.; Wischow, E. D.; Webb, I.; Andriole, E. J.; Poutsma, J. C. Gas-Phase Acidities of the 20 Protein Amino Acids. Int. J. Mass Spectrom. 2007, 267, 54−62. (81) Hunter, E. P.; Lias, S. G. Evaluated Gas Phase Basicities and proton Affinities of Molecules: An Update. J. Phys. Chem. Ref. Data 1998, 27, 413−656.

(82) Bouchoux, G.; Salpin, J. Y. Gas-Phase Basicity of Glycine, Alanine, Proline, Serine, Lysine, Histidine and some of their Peptides by the Thermokinetic Method. Eur. J. Mass Spectrom. 2003, 9, 391−402. (83) Mirza, S. P.; Prabhakar, S.; Vairamani, M. Estimation of Proton Affinity of Prolyne and Tryptophan under Electrospray Ionization Conditions Using the Extended Kinetic Method. Rapid Commun. Mass Spectrom. 2001, 15, 957−962. (84) Mezzache, S.; Afonso, C.; Pepe, C.; Karoyan, P.; Fournier, F.; Tabet, J. C. Proton Affinity of Proline and Modified Prolines Using the Kinetic Method: Role of the Conformation Investigated by ab initio Calculations. Rapid Commun. Mass Spectrom. 2003, 17, 1626−1632. (85) Cannington, P. H.; Ham, N. S. He(I) and He(II) Photoelectron Spectra of Glycine and Related Molecules. J. Electron Spectrosc. Relat. Phenom. 1983, 32, 139−151. (86) Slifkin, M. A.; Allison, A. C. Measurement of Ionization Potentials from Contact Charge Transfer Spectra. Nature 1967, 215, 949−950. (87) Pedley, J. B. Thermochemical Data and Structures of Organic Compounds, Vol. 1; TRC Data Series; National Institutes of Standards and Technology: Washington, DC, 1994.

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